Bio


Mark S. Blumenkranz, M.D., MMS, is HJ Smead Professor Emeritus in the Department of Ophthalmology at Stanford University. He received his Undergraduate, Master’s degree in Biochemical Pharmacology, and MD at Brown, his ophthalmic residency at Stanford and a fellowship in vitreoretinal diseases at the Bascom Palmer Eye Institute where he was appointed a member of the faculty in 1980. In 1985 he founded the Retinal Fellowship Training Program at the William Beaumont Eye Institute. He returned to Stanford in 1992 as head of the vitreoretinal service served as Department Chair from 1997 until 2015. He played a leading role in the planning, fundraising and construction of the Byers Eye Institute at Stanford and served as founding Director from its opening in September 2010 through June 2015.
He has served on the Editorial Boards of The American Journal of Ophthalmology, Retina, Ophthalmology, and Graefe’s Archives for Ophthalmology. He is a past President of the American University Professors of Ophthalmology (AUPO), and a past President of the Retina Society and the Macula Society. He was a past member of the Steering Committee of the Audacious Goals Initiative of the NEI, and was a Trustee and Fellow of the Corporation of Brown University from 2002 until 2019 where he was the Chair of the Corporation Medical School Committee for eleven years. Dr. Blumenkranz was an early innovator in vitrectomy techniques to treat complex forms of retinal detachment, and helped to usher in the modern era of intravitreal and surgical adjuvant drug therapy with laboratory and clinical studies identifying 5- fluorouracil and low molecular weight heparin as potent agents to inhibit ocular scarring. He was a member of the group that first reported the herpetic etiology and successful acyclovir treatment of acute retinal necrosis, the use of bioerodible polymers to deliver intraocular steroids for macular edema and published the first human safety study of ranibizumab (lucentis) and gene therapy based anti-VEGF therapy for age related macular degeneration.
He has published more than one hundred and sixty papers in peer-reviewed journals and multiple book chapters, abstracts and patents in the field. Dr. Blumenkranz has a longstanding interest and expertise in university corporate technology transfer. He was a Director and principal trial designer at Oculex Pharmaceuticals who were acquired by Allergan in 2003. He served as a co-founder, Director and Chairman of the SAB of Macusight, an ophthalmic pharmaceutical company, acquired by Santen in 2010. He was a founder and director of Peak Surgical, an innovator in pulsed plasma mediated electro-surgery that was acquired by Medtronics in 2011. In 2004 he co-founded Optimedica Corporation for which he co-wrote the foundational IP for the PASCAL and Catalys lasers, and which was acquired by AMO. In 2006 he co-founded and served as Chairman of the Board of Adverum Biotechnologies (ADVM:NASDAQ) until October 2016. He was a co-founder and director of Oculeve, a dry eye company which was acquired by Allergan in August of 2015. He was a founder and served as a Director of Verana Health (formerly Digisight Technologies) a digital medicine and health analytics company from 2009 until 2020. He served as the founding Chairman of Kedalion Therapeutics an ophthalmic drug delivery company from 2015 until 2022, and CEO from 2019 until 2022, when it was acquired by Novartis AG. He served as the founding Chairman of Combangio Inc, a topical ophthalmic biopharmaceutical company prior to its acquisition by Kala Therapeutics. He is a scientific founder of Eudora an ophthalmic gene therapy company. He currently serves as a director BVI Visitec, an ophthalmic surgical company, One Medical (ONEM:NASDAQ), Iveric Bio (ISEE:NASDAQ) and Kala Therapeutics (KALA:NASDAQ) He is a co-founder and the president of the Collaborative Community on Ophthalmic Imaging.

Academic Appointments


Administrative Appointments


  • HJ Smead Professor Emeritus, Stanford University School of Medicine (2017 - Present)
  • Director of Ophthalmic Innovation Program, Stanford University School of Medicine (2015 - 2017)
  • Founding Director, Byers Eye Institute at Stanford University (2010 - 2015)
  • HJ Smead Professor of Ophthalmology, Stanford University School of Medicine - Ophthalmology (2007 - 2017)
  • Chairman of Department of Ophthalmology, Stanford University School of Medicine (1997 - 2015)
  • Clinical Professor of Ophthalmology, Stanford University School of Medicine (1992 - 1997)
  • Head Vitreoretinal Service, Stanford University School of Medicine (1992 - 1997)

Honors & Awards


  • Albion Walter Hewlett Award, Stanford Medicine (2019)
  • Guest of Honor, American Academy of Ophthalmology (2019)
  • WW Keen Award, Warren Alpert School of Medicine Brown University (2019)
  • Lifetime Innovator Award, OIS (2017)
  • The Gass Award Lecture, The Retina Society (2016)
  • The Wacker Prize Lecture, The Club Jules Gonin (2016)
  • Charles Schepens Award Lecture, American Academy of Ophthalmology (2014)
  • Edward Jackson Memorial Award Lecture, American Academy of Ophthalmology (2013)
  • Kreissig Award Lecture, Euretina (2013)
  • The Visionary Award, Foundation Fighting Blindness (2009)
  • The Life Achievement Honor Award, The American Academy of Ophthalmology (2008)
  • The Ruth Sauber Distinguished Medical Alumni Award Lecture, Brown University (2008)
  • The Gertrude Pyron Award for Outstanding Achievement in Retina Research, The American Society of Retinal Specialists (2005)
  • Senior Honor Award, American Academy of Ophthalmology (2004)
  • The Rosenthal Foundation Award in Visual Science, The Rosenthal Foundation (1992)
  • The Heed Society Award, The Heed Society (1988)
  • The Special Manpower Award, Research to Prevent Blindness (1982)
  • Alpha Omega Alpha Scientific Honor Society Award, Brown University (1975/2011)
  • Sigma Xi Scientific Honor Society, Brown University (1975)

Boards, Advisory Committees, Professional Organizations


  • Steering Committee, Audacious Goals Initiative NEI/NIH (2015 - Present)
  • Member and Fellow, Association for Research in Visual Science and Ophthalmology (2014 - Present)
  • Past President, Macula Society (2011 - 2012)
  • Past President, Retina Society (2010 - 2011)
  • Past President, American University Professors of Ophthalmology (AUPO) (2009 - 2009)
  • Fellow, Brown University (2008 - Present)
  • Member Board of Directors, Macula Society (2006 - 2014)
  • Member of Board of Directors, Retina Society (2006 - 2010)
  • Board Member, American University of Professors (AUPO) (2004 - 2009)
  • Chairman Medical School Committee, Brown Corporation (2003 - Present)
  • Past Member Editorial Board, American Journal of Ophthalmology (2002 - 2008)
  • Trustee, Brown University (2002 - 2008)
  • Member, American University of Professors (AUPO) (1997 - 2015)
  • Member of Editorial Board, Retina (1992 - Present)
  • Past Member Editorial Board, Graefe's Archives of Ophthalmology (1992 - 1996)
  • Member, Macula Society (1987 - Present)
  • Member, Club Jules Gonin (1986 - Present)
  • Member, Retina Society (1984 - Present)
  • Member, American Academy of Ophthalmology (1981 - Present)

Professional Education


  • AB, Brown University, Biology (1972)
  • MD, Brown University, Medicine (1975)
  • MMS, Brown University, Biochemical Pharmacology (1976)
  • Internship, Stanford University, Surgery (1976)
  • Fellowship, Bascom Palmer Eye Institute, Vitreoretinal Surgery (1980)

Current Research and Scholarly Interests


Clinical Interest and Research
My primary areas of interest are in the diagnosis, medical and surgical treatment of vitreal retinal diseases. These principally include age-related macular degeneration and other diseases of the macula, and tractional syndromes, diabetic retinopathy, and complex forms of retinal detachment. I have been interested in the development of novel technology to diagnose and treat these diseases, including new forms of imaging, laser delivery systems, other microsurgical tools, and new drugs and drug delivery systems that inhibit new blood vessel growth, scarring and intraocular inflammation. I have been actively involved in translational research in the laboratory as well as technology transfer associated with that research for a variety of new therapies that have received FDA clearance and been introduced into clinical practice over the past 30 years.

Administrative and Community Service
I have served on the Board of Directors of a variety of voluntary education and service organizations, including the Corporation of Brown University, multiple scientific advisory boards and various philanthropic and research organizations.

2023-24 Courses


All Publications


  • Artificial Intelligence for Retinopathy of Prematurity: Validation of a Vascular Severity Scale against International Expert Diagnosis. Ophthalmology Campbell, J. P., Chiang, M. F., Chen, J. S., Moshfeghi, D. M., Nudleman, E., Ruambivoonsuk, P., Cherwek, H., Cheung, C. Y., Singh, P., Kalpathy-Cramer, J., Ostmo, S., Eydelman, M., Chan, R. V., Capone, A. J., CCOI Executive Committee and the CCOI Retinopathy of Prematurity Workgroup 2022

    Abstract

    OBJECTIVE: To validate a vascular severity score as an appropriate output for artificial intelligence (AI) Software as a Medical Device (SaMD) for retinopathy of prematurity (ROP) through comparison with ordinal disease severity labels for stage and plus disease assigned by the International Classification of ROP, 3rd edition (ICROP3) committee.DESIGN: Validation study of an AI-based ROP vascular severity score Subjects, Participants, and/or Controls: 34 ROP experts from the ICROP3 committee.METHODS: Two separate datasets of 30 fundus photographs each for stage (0-5) and plus disease (plus, pre-plus, neither) were labeled by members of the ICROP3 committee using an open-source platform. Averaging these results produced a continuous label for plus (1-9) and stage (1-3) for each image. Experts were also asked to compare each image to each other in terms of relative severity for plus disease. Each image was also labelled with a vascular severity score from the Imaging and Informatics in ROP deep learning (i-ROP DL) system, which was compared with each grader's diagnostic labels for correlation, as well as the ophthalmoscopic diagnosis of stage.MAIN OUTCOME MEASURES: Weighted kappa and Pearson correlation coefficients (CC) were calculated between each pair of grader classification labels for stage and plus disease. The Elo algorithm was also used to convert pairwise comparisons for each expert into an ordered set of images from least to most severe.RESULTS: The mean weighted kappa and CC for all inter-observer pairs for plus disease image comparison was 0.67 and 0.88 respectively. The vascular severity score was found to be highly correlated with both the average plus disease classification (CC = 0.90, p < 0.001) and the ophthalmoscopic diagnosis of stage (p < 0.001 by ANOVA) among all experts.CONCLUSIONS: The ROP vascular severity score correlates well with the ICROP committee member's labels for plus disease and stage, which had significant inter-grader variability. Generation of a consensus for a validated scoring system for ROP SaMD can facilitate global innovation and regulatory authorization of these technologies.

    View details for DOI 10.1016/j.ophtha.2022.02.008

    View details for PubMedID 35157950

  • The Collaborative Community on Ophthalmic Imaging: Accelerating Global Innovation and Clinical Utility OPHTHALMOLOGY Blumenkranz, M. S., Tarver, M. E., Myung, D., Eydelman, M. B., Collaborative Community Ophthalmic 2022; 129 (2): E9-E13

    View details for DOI 10.1016/j.ophtha.2021.10.001

    View details for Web of Science ID 000747770500001

    View details for PubMedID 34774340

  • A Smartphone-Based Near-Vision Testing System: Design, Accuracy, and Reproducibility Compared With Standard Clinical Measures OPHTHALMIC SURGERY LASERS & IMAGING RETINA Kim, D., Webel, A. D., Blumenkranz, M. S., Kim, Y., Yang, J., Yu, S., Kwak, H., Palanker, D., Toy, B., Myung, D. 2022; 53 (2): 79-84

    Abstract

    Ophthalmologic telemedicine has emerged during the COVID-19 pandemic. The objective of this study is to assess the accuracy and reproducibility of a smartphone-based home vision monitoring system (Sightbook) and to compare it with existing clinical standards.Near Snellen visual acuity (VA) was measured with Sightbook and compared with conventional measurements for distance and near VA at an academic medical center ophthalmology clinic in 200 patients with a variety of different specified preexisting ocular conditions. Measurements of contrast sensitivity were also compared by using an existing commercially available chart system in 15 normal patients and 15 patients with age-related macular degeneration.Sightbook VA tests were reproducible (SD = ±0.054 logMAR), and correlation with standard VA methods was significant (R > 0.87 and P < .001). Sightbook contrast sensitivity measurements were reproducible (SD/mean ratio, 0.02 to 0.04), yielding results similar to those of standard tests (R2 > 0.87 and P < .001).Smartphone-based VA and contrast sensitivity are highly correlated with standard charts and may be useful in augmenting limited inoffice care. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:79-84.].

    View details for DOI 10.3928/23258160-20220121-05

    View details for Web of Science ID 000768759200002

    View details for PubMedID 35148218

  • Foundational Considerations for Artificial Intelligence Utilizing Ophthalmic Images. Ophthalmology Abramoff, M. D., Cunningham, B., Patel, B., Eydelman, M. B., Leng, T., Sakamoto, T., Blodi, B., Grenon, S. M., Wolf, R. M., Manrai, A. K., Ko, J. M., Chiang, M. F., Char, D., Collaborative Community on Ophthalmic Imaging Executive Committee and Foundational Principles of Ophthalmic Imaging and Algorithmic Interpretation Working Group 2021

    Abstract

    IMPORTANCE: The development of Artificial Intelligence (AI) and other machine diagnostic systems, also known as Software as a Medical Device (SaMD), and its recent introduction into clinical practice, requires a deeply-rooted foundation in bioethics, for consideration by regulatory agencies and other stakeholders around the globe.OBJECTIVES: Initiate a dialogue on the issues to consider when developing a bioethically sound foundation for AI in medicine, based on images of eye structures, for discussion with all stakeholders.EVIDENCE REVIEW: The scope of the issues and summaries of the discussions under consideration by the Foundational Principles of Ophthalmic Imaging and Algorithmic Interpretation Working Group, as first presented during the Collaborative Community on Ophthalmic Imaging inaugural meeting on September 7, 2020, and afterwards in the working group.FINDINGS: AI has the potential to fundamentally improve the access to healthcare and patient outcomes, while decreasing disparities, lowering cost, as well as enhancing the care team. Nevertheless, substantial concerns exist. Ethicists, AI algorithm experts, as well as the Food and Drug Administration (FDA) and other regulatory agencies, industry, patient advocacy groups, clinicians and their professional societies, other provider groups, payors, and other healthcare stakeholders working together in collaborative communities to resolve such issues as non-maleficence, autonomy and equity, is essential to attain this potential, and impacts all levels of the design, validation and implementation of AI in medicine. Design, validation and implementation of AI warrant meticulous attention.CONCLUSIONS AND RELEVANCE: The development of a bioethically sound foundation may be possible if it is based in non-maleficence, autonomy and equity, for considerations for the design, validation and implementation for AI systems. Achieving such a foundation will be helpful for continuing successful introduction into medicine, before consideration by regulatory agencies around the globe.Fundamental improvements in accessibility and quality of healthcare, decrease in health disparities, and lower cost can thereby be achieved. These considerations should be discussed with all stakeholders and expanded upon as a useful initiation of this dialogue.

    View details for DOI 10.1016/j.ophtha.2021.08.023

    View details for PubMedID 34478784

  • Comparison of Telemedicine Screening of Diabetic Retinopathy by Mydriatic Smartphone-Based vs Nonmydriatic Tabletop Camera-Based Fundus Imaging. Journal of vitreoretinal diseases Han, Y. S., Pathipati, M., Pan, C., Leung, L., Blumenkranz, M. S., Myung, D., Toy, B. C. 2021; 5 (3): 199-207

    Abstract

    Purpose: To compare dilated smartphone-based imaging with a nonmydriatic, tabletop fundus camera as a teleophthalmology screening tool for diabetic retinopathy (DR).Methods: This was a single-institutional, cross-sectional, comparative-instrument study. Fifty-six patients at a safety-net hospital underwent teleophthalmology screening for DR using standard, nonmydriatic fundus photography with a tabletop camera (Nidek NM-1000) and dilated fundus photography using a smartphone camera with lens adapter (Paxos Scope, Verana Health). Masked graders performed standardized photo grading. Quantitative comparisons were performed employing descriptive, kappa, Bland-Altman, and receiver operating characteristic analyses.Results: Posterior segment photography was of sufficient quality to grade in 89% of mydriatic smartphone-imaged eyes and in 86% of nonmydriatic tabletop camera-imaged eyes (P = .03). Using the tabletop camera as the reference to detect moderate nonproliferative DR or worse (referral-warranted DR), mydriatic smartphone-acquired photographs were found to be 82% sensitive and 96% specific. Dilated smartphone imaging detected referral-warranted DR in 3 eyes whose tabletop camera imaging did not demonstrate referral-warranted DR. Secondary masked review of medical records for the discordances in referral-warranted status from the two imaging modalities was performed, and it revealed revised sensitivity and specificity values of 95% and 98%, respectively. Overall, there was good agreement between tabletop camera and smartphone-acquired photo grades (kappa = 0.91 ± 0.1, P < .001; area under the receiver operating characteristic curve = 0.99, 95% CI, 0.98-1.00).Conclusions: Mydriatic smartphone-based imaging resulted in fewer ungradable photos compared to nonmydriatic table-top camera imaging and detected more patients with referral-warranted DR. Our study supports the use of mydriatic smartphone teleophthalmology as an alternative method to screen for DR.

    View details for DOI 10.1177/2474126420958304

    View details for PubMedID 34632255

  • White Paper on Ophthalmic Imaging for Choroidal Nevus Identification and Transformation into Melanoma. Translational vision science & technology Shields, C. L., Lally, S. E., Dalvin, L. A., Sagoo, M. S., Pellegrini, M., Kaliki, S., Gündüz, A. K., Furuta, M., Mruthyunjaya, P., Fung, A. T., Duker, J. S., Selig, S. M., Yaghy, A., Ferenczy, S. R., Eydelman, M. B., Blumenkranz, M. S. 2021; 10 (2): 24

    Abstract

    To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process.White paper.Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use throughout the world. More recent publications have applied ocular diagnostic testing (fundus photography, ultrasound examination, autofluorescence, and optical coherence tomography) to identify risk factors for the malignant transformation of choroidal nevus based on multimodal imaging features. The widespread usage of ophthalmic imaging systems to identify and follow choroidal nevus, in conjunction with the characterization of malignant transformation risk factors via diagnostic imaging, presents a novel path to apply AI.AI applied to existing ophthalmic imaging systems could be used for both identification of choroidal nevus and as a tool to aid in earlier detection of transformation to malignant melanoma.Advances in AI models applied to ophthalmic imaging systems have the potential to improve patient care, because earlier detection and treatment of melanoma has been proven to improve long-term clinical outcomes.

    View details for DOI 10.1167/tvst.10.2.24

    View details for PubMedID 34003909

  • White Paper on Ophthalmic Imaging for Choroidal Nevus Identification and Transformation into Melanoma TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Shields, C. L., Lally, S. E., Dalvin, L. A., Sagoo, M. S., Pellegrini, M., Kaliki, S., Gunduz, A., Furuta, M., Mruthyunjaya, P., Fung, A. T., Duker, J. S., Selig, S. M., Yaghy, A., Ferenczy, S. R., Eydelman, M. B., Blumenkranz, M. S. 2021; 10 (2)
  • Development, Validation, and Innovation in Ophthalmic Laser-Based Imaging: Report From a US Food and Drug Administration-Cosponsored Forum. JAMA ophthalmology Brodie, F., Repka, M., Burns, S. A., Prakalapakorn, S. G., Morse, C., Schuman, J. S., Duenas, M. R., Afshari, N., Pollack, J. S., Thorne, J. E., Vitale, A., Sen, H. N., Myung, D., Blumenkranz, M. S., Tu, E., Hammer, D. X., Tarver, M., Cunningham, B., Kagemann, L., Sadda, S., Sarraf, D., Jaffe, G. J., Eydelman, M. 2020

    Abstract

    In April 2019, the US Food and Drug Administration, in conjunction with 11 professional ophthalmic, vision science, and optometric societies, convened a forum on laser-based imaging. The forum brought together the Food and Drug Administration, clinicians, researchers, industry members, and other stakeholders to stimulate innovation and ensure that patients in the US are the first in the world to have access to high-quality, safe, and effective medical devices. This conference focused on the technology, clinical applications, regulatory issues, and reimbursement issues surrounding innovative ocular imaging modalities. Furthermore, the emerging role of artificial intelligence in ophthalmic imaging was reviewed. This article summarizes the presentations, discussion, and future directions.

    View details for DOI 10.1001/jamaophthalmol.2020.4994

    View details for PubMedID 33211074

  • Assessment of Eye Disease and Visual Impairment in the Nursing Home Population Using Mobile Health Technology OPHTHALMIC SURGERY LASERS & IMAGING RETINA Lai, K. Y., Pathipati, M. P., Blumenkranz, M. S., Leung, L., Moshfeghi, D. M., Toy, B. C., Myung, D. 2020; 51 (5): 262–70

    Abstract

    To characterize the burden of eye disease and the utility of teleophthalmology in nursing home patients, a population with ophthalmic needs not commensurate with care received.Informed consent was obtained from 78 California Bay Area skilled nursing facility patients. Near visual acuity (VA) and anterior/posterior segment photographs were taken with a smartphone-based VA app and ophthalmic camera system. The Nursing Home Vision-Targeted Health-Related Quality of Life questionnaire was also administered. Risk factors for visual impairment were assessed. Institutional review board approval was obtained from Stanford University.Cataracts (51%), diabetic retinopathy (DR) (12%), optic neuropathy (12%), and age-related macular degeneration (AMD) (10%) were common findings; 11.7% had other referral-warranted findings. AMD and DR correlated with a higher risk of poor VA, with adjusted odds ratios of 22 (P = .01) and 43 (P = .004).This study demonstrated a high prevalence of poor VA and ophthalmic disease in the nursing home population impacting quality of life. Smartphone-based teleophthalmology platforms have the potential to increase access to eye care for nursing home patients. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:262-270.].

    View details for DOI 10.3928/23258160-20200501-03

    View details for Web of Science ID 000539315500003

    View details for PubMedID 32511729

  • Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration. American journal of ophthalmology Rakoczy, E. P., Magno, A. L., Lai, C., Pierce, C. M., Degli-Esposti, M. A., Blumenkranz, M. S., Constable, I. J. 2019; 204: 113–23

    Abstract

    PURPOSE: To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration.DESIGN: Phase 1/2a clinical trial.METHODS: Patients were prospectively randomized into control (n= 13) and GT (n= 24) groups. GT patients received 1X1011vg rAAV.sFLT-1 and were seen every month for 1 year then as needed every 1 to 2months. They were given retreatment anti-vascular endothelial growth factor injections according to predetermined criteria. At 12months, GT patients were divided into 2 groups: HD-1 (n= 14), requiring <2, and HD-2 (n= 10), requiring >2 retreatments.RESULTS: Between 1 year and 3 years there were 3 adverse events (AEs) and 33 serious AEs reported. Of these, 15 occurred in the 13 control subjects and 21 in the 24 GT patients. Except for 1 case of transient choroiditis in a control patient, serious AEs were deemed to be unrelated to the study. Control patients received a median of 7.0 retreatments and lost a median of 7.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, HD-1 patients received a median of 2.5 retreatments and lost a median of 4.0 ETDRS letters, and HD-2 patients received a median of 11.0 retreatments and lost a median of 7.0 ETDRS letters over 3 years. Center point thickness fluctuated. Thirty-three percent of control subjects, 44% of HD-2 patients, and 51% of HD-1 patients showed maintenance of baseline visual acuity. Four HD-1 patients (34%) maintained significant visual improvement at 3 years. None of these observations were statistically significant.CONCLUSIONS: Given the small number of patients, this study was unable to unequivocally confirm the existence of a biologic efficacy signal; however, it confirmed that rAAV.sFLT-1 gene delivery was well tolerated among the elderly.

    View details for DOI 10.1016/j.ajo.2019.03.006

    View details for PubMedID 30878487

  • A novel device for secondary intraocular lens placement: Design and Ex Vivo Evaluation Buickians, D., Myung, D., Blumenkranz, M. S., Brodie, F. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Evaluating New Ophthalmic Digital Devices for Safety and Effectiveness in the Context of Rapid Technological Development. JAMA ophthalmology Bodnar, Z. M., Schuchard, R. n., Myung, D. n., Tarver, M. E., Blumenkranz, M. S., Afshari, N. A., Humayun, M. S., Morse, C. n., Nischal, K. n., Repka, M. X., Sprunger, D. n., Trese, M. n., Eydelman, M. B. 2019

    Abstract

    The US Food and Drug Administration's medical device regulatory pathway was initially conceived with hardware devices in mind. The emerging market for ophthalmic digital devices necessitates an evolution of this paradigm.To facilitate innovation in ophthalmic digital health with attention to safety and effectiveness.This article presents a summary of the presentations, discussions, and literature review that occurred during a joint Ophthalmic Digital Health workshop of the American Academy of Ophthalmology, the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, the American Society of Cataract and Refractive Surgery, the American Society of Retina Specialists, the Byers Eye Institute at Stanford and the US Food and Drug Administration.Criterion standards and expert graders are critically important in the evaluation of automated systems and telemedicine platforms. Training at all levels is important for the safe and effective operation of digital health devices. The risks associated with automation are substantially increased in rapidly progressive diseases. Cybersecurity and patient privacy warrant meticulous attention.With appropriate attention to safety and effectiveness, digital health technology could improve screening and treatment of ophthalmic diseases and improve access to care.

    View details for DOI 10.1001/jamaophthalmol.2019.1576

    View details for PubMedID 31169870

  • Validity of the Red Reflex Exam in the Newborn Eye Screening Test Cohort. Ophthalmic surgery, lasers & imaging retina Ludwig, C. A., Callaway, N. F., Blumenkranz, M. S., Fredrick, D. R., Moshfeghi, D. M. 2018; 49 (2): 103–10

    Abstract

    The validity of the red reflex exam has yet to be tested against new methods of wide-angle imaging that may improve early detection of neonatal ocular pathology. The authors aimed to determine the validity of the pediatrician's red reflex exam using 130° wide-angle external and fundus digital imaging as a gold standard.This was a prospective cohort study of 194 healthy, term newborns enrolled in the Newborn Eye Screening Test study at Lucile Packard Children's Hospital from July 25, 2013, to July 25, 2014. Red reflex screening was performed by a pediatrician in the newborn nursery and wide-angle fundus digital imaging was performed by a neonatal intensive care unit-certified nurse. The main outcome measure was the validity of the pediatrician's red reflex exam (unweighted kappa [κ] statistic, sensitivity, specificity).Compared to no subjects with abnormal red reflex exams reported in the pediatrician's notes, 49 subjects demonstrated one or multiple ocular abnormalities on 130° wide-angle fundus imaging (κ = 0.00). The pediatrician's red reflex exam had a sensitivity of 0.0% (95% CI, 0.0%-7.3%) and specificity of 100.0% (95% CI, 97.5%-100.0%) for the detection of ocular abnormalities.This study demonstrates the ability of wide-angle fundus imaging to detect fundus abnormalities not otherwise identified by standard newborn red reflex screening prior to hospital discharge. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:103-110.].

    View details for DOI 10.3928/23258160-20180129-04

    View details for PubMedID 29443359

  • Laser for Vitreoretinal Diseases VITREORETINAL DISEASE: DIAGNOSIS, MANAGEMENT, AND CLINICAL PEARLS Paulus, Y. M., Blumenkranz, M. S., Scott, I. U., Regillo, C. D., Flynn, H. W., Brown, G. C. 2018: 576-596
  • Comparison of Pneumatic Retinopexy and Scleral Buckle for Primary Rhegmatogenous Retinal Detachment Repair OPHTHALMIC SURGERY LASERS & IMAGING RETINA Paulus, Y. M., Leung, L., Pilyugina, S., Blumenkranz, M. S. 2017; 48 (11): 887–93

    Abstract

    To compare pneumatic retinopexy (PR) and scleral buckle for the repair of primary rhegmatogenous retinal detachment.Retrospective analysis of 90 patients undergoing surgery for primary rhegmatogenous retinal detachment, with 46 patients undergoing PR compared with 44 patients undergoing scleral buckle procedure (SBP).Both groups had similar baseline characteristics. Single surgery reattachment rate was 95.5% with SBP and 67% with PR (P = .00057). Final reattachment rate was 100% with SBP and 97.8% with PR. A final visual acuity (VA) of 20/40 or better occurred in 89% of patients with SBP and 72% of patients with PR (P = .04). PR and SBP had a similar mean VA if the primary procedures were successful, whereas those patients with unsuccessful PR had lower mean final acuities.This study demonstrates that SBP has a significantly higher rate of single surgery reattachment than PR, along with improved final VA. Initial success of PR may be an important predictor of final visual outcome. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:887-893.].

    View details for DOI 10.3928/23258160-20171030-03

    View details for Web of Science ID 000418012200003

    View details for PubMedID 29121357

  • Reply. Retina (Philadelphia, Pa.) He, L., Toy, B., Blumenkranz, M., Chang, R., Myung, D. 2017; 37 (6)

    View details for DOI 10.1097/IAE.0000000000001642

    View details for PubMedID 28376047

  • Safety and post hoc analysis of subretinal rAAV.sFLT-1 for wet age-related macular degeneration following a phase 2a randomized clinical trial Rakoczy, E. P., Lai, C., Magno, A., French, M., Butler, S., Barone, S., Schwartz, S. D., Blumenkranz, M., Degli-Esposti, M., Constable, I. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Optical Coherence Tomography Profiles, Visual Acuity and Ranibizumab Usage During 3-Year Follow-Up in a rAAV.sFLT-1 Gene Therapy Clinical Trial for Wet Age-Related Macular Degeneration Lai, C., Magno, A. L., Barone, S. B., Schwartz, S. D., Blumenkranz, M. S., Constable, I. J., Rakoczy, E. P. CELL PRESS. 2017: 315
  • Engineered ligand-based VEGFR antagonists with increased receptor binding affinity more effectively inhibit angiogenesis. Bioengineering & translational medicine Kapur, S., Silverman, A. P., Ye, A. Z., Papo, N., Jindal, D., Blumenkranz, M. S., Cochran, J. R. 2017; 2 (1): 81-91

    Abstract

    Pathologic angiogenesis is mediated by the coordinated action of the vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling axis, along with crosstalk contributed by other receptors, notably αvβ3 integrin. We build on earlier work demonstrating that point mutations can be introduced into the homodimeric VEGF ligand to convert it into an antagonist through disruption of binding to one copy of VEGFR2. This inhibitor has limited potency, however, due to loss of avidity effects from bivalent VEGFR2 binding. Here, we used yeast surface display to engineer a variant with VEGFR2 binding affinity approximately 40-fold higher than the parental antagonist, and 14-fold higher than the natural bivalent VEGF ligand. Increased VEGFR2 binding affinity correlated with the ability to more effectively inhibit VEGF-mediated signaling, both in vitro and in vivo, as measured using VEGFR2 phosphorylation and Matrigel implantation assays. High affinity mutations found in this variant were then incorporated into a dual-specific antagonist that we previously designed to simultaneously bind to and inhibit VEGFR2 and αvβ3 integrin. The resulting dual-specific protein bound to human and murine endothelial cells with relative affinities of 120 ± 10 pM and 360 ± 50 pM, respectively, which is at least 30-fold tighter than wild-type VEGF (3.8 ± 0.5 nM). Finally, we demonstrated that this engineered high-affinity dual-specific protein could inhibit angiogenesis in a murine corneal neovascularization model. Taken together, these data indicate that protein engineering strategies can be combined to generate unique antiangiogenic candidates for further clinical development.

    View details for DOI 10.1002/btm2.10051

    View details for PubMedID 28516164

  • Gene Therapy in Neovascular Age-related Macular Degeneration: Three Year Follow-up of a Phase 1 Randomised Dose Escalation Trial. American journal of ophthalmology Constable, I. J., Lai, C., Magno, A. L., French, M. A., Barone, S. B., Schwartz, S. D., Blumenkranz, M. S., Degli-Esposti, M. A., Rakoczy, E. P. 2017

    Abstract

    To assess the safety of rAAV.sFlt-1 subretinal injection in neovascular age-related macular degeneration (wet AMD) over 36 months.Phase 1 dose escalation trial.Eight subjects with advanced, treatment-experienced wet AMD were randomly assigned (3:1) to treatment and non-gene therapy control groups. Eligible subjects were ≥65 years, had wet AMD, and had best-corrected visual acuity (BCVA) 10/200 to 20/80 in the study eye and 20/200 or better in the other eye. Three of the treatment group subjects received low-dose (1 × 10(10) vector genomes) and 3 high-dose (1 × 10(11) vector genomes) rAAV.sFLT-1 via subretinal injection. Study monitoring was monthly to the primary endpoint at month 12 and then protocol-driven follow-up study visits were conducted at months 18 and 36. All subjects received intravitreal ranibizumab at baseline and at week 4, and retreatment injections at subsequent visits based on prespecified criteria for active wet AMD. The primary endpoint was ocular and systemic safety, but exploratory data including BCVA, retinal center point thickness, and the number of ranibizumab retreatments at and between study visits were also analyzed.Six of the 8 subjects completed the 36-month study. Subretinal injection with pars plana vitrectomy was well tolerated in this cohort. No ocular or systemic safety signals were observed during the long-term follow-up period. Exploratory data analysis suggests stability of wet AMD over the 36-month period.Subretinal delivery of rAAV.sFLT-1 was well tolerated and demonstrated a favourable safety profile through month 36. Thus, rAAV.sFLT-1 could be safely considered for future evaluation in the treatment of wet AMD.

    View details for DOI 10.1016/j.ajo.2017.02.018

    View details for PubMedID 28245970

  • Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. EBioMedicine Constable, I. J., Pierce, C. M., Lai, C., Magno, A. L., Degli-Esposti, M. A., French, M. A., McAllister, I. L., Butler, S., Barone, S. B., Schwartz, S. D., Blumenkranz, M. S., Rakoczy, E. P. 2016; 14: 168-175

    Abstract

    We present the results of a Phase 2a randomized controlled trial investigating the safety, and secondary endpoints of subretinal rAAV.sFLT-1 gene therapy in patients with active wet age-related macular degeneration (wAMD).All patients (n=32), (ClinicalTrials.gov; NCT01494805), received ranibizumab injections at baseline and week 4, and thereafter according to prespecified criteria. Patients in the gene therapy group (n=21) received rAAV.sFLT-1 (1×10(11)vg). All patients were assessed every 4weeks to the week 52 primary endpoint.Ocular adverse events (AEs) in the rAAV.sFLT-1 group were mainly procedure related and self-resolved. All 11 phakic patients in the rAAV.sFLT-1 group showed progression of cataract following vitrectomy. No systemic safety signals were observed and none of the serious AEs were associated with rAAV.sFLT-1. AAV2 capsid was not detected and rAAV.sFLT-1 DNA was detected transiently in the tears of 13 patients. ELISPOT analysis did not identify any notable changes in T-cell response. In the rAAV.sFLT-1 group 12 patients had neutralizing antibodies (nAb) to AAV2. There was no change in sFLT-1 levels in bodily fluids. In the rAAV.sFLT-1 group, Best Corrected Visual Acuity (BCVA) improved by a median of 1.0 (IQR: -3.0 to 9.0) Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline compared to a median of -5.0 (IQR: -17.5 to 1.0) ETDRS letters change in the control group. Twelve (57%) patients in the rAAV.sFLT-1 group maintained or improved vision compared to 4 (36%) in the control group. The median number of ranibizumab retreatments was 2.0 (IQR: 1.0 to 6.0) for the gene therapy group compared to 4.0 (IQR: 3.5 to 4.0) for the control group. Interpretation rAAV.sFLT-1 combined with the option for co-treatment appears to be a safe and promising approach to the treatment of wAMD.National Health and Medical Research Council of Australia (AP1010405), Lions Eye Institute, Perth Australia, Avalanche Biotechnologies, Menlo Pk, CA, USA.

    View details for DOI 10.1016/j.ebiom.2016.11.016

    View details for PubMedID 27865764

    View details for PubMedCentralID PMC5161436

  • Association of serum neutralizing antibodies with safety and efficacy outcomes in a Phase 2a trial of rAAV.sFlt-1 in the treatment of wet AMD Rakoczy, E. P., Lai, C., Magno, A., French, M., Barone, S., Schwartz, S. D., Blumenkranz, M., Degli-Esposti, M., Constable, I. J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016
  • What colour are newborns' eyes? Prevalence of iris colour in the Newborn Eye Screening Test (NEST) study. Acta ophthalmologica Ludwig, C. A., Callaway, N. F., Fredrick, D. R., Blumenkranz, M. S., Moshfeghi, D. M. 2016; 94 (5): 485-488

    Abstract

    This study aims to assess the birth prevalence of iris colour among newborns in a prospective, healthy, full-term newborn cohort.The Newborn Eye Screening Test (NEST) study is a prospective cohort study conducted at Lucile Packard Children's Hospital at Stanford University School of Medicine. A paediatric vitreoretinal specialist (DMM) reviewed images sent to the Byers Eye Institute telemedicine reading centre and recorded eye colour for every infant screened. Variables were graphed to assess for normality, and frequencies per subject were reported for eye colour, sex, ethnicity and race.Among 192 subjects screened in the first year of the NEST study with external images of appropriate quality for visualization of the irides, the birth prevalence of iris colour was 63.0% brown, 20.8% blue, 5.7% green/hazel, 9.9% indeterminate and 0.5% partial heterochromia. The study population was derived from a quaternary care children's hospital. We report the birth prevalence of iris colour among full-term newborns in a diverse prospective cohort.The study demonstrates a broad range of iris colour prevalence at birth with a predominance of brown iris coloration. Future studies with the NEST cohort will assess the change in iris colour over time and whether the frequencies of eye colour change as the child ages.

    View details for DOI 10.1111/aos.13006

    View details for PubMedID 27061128

  • Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration. American journal of ophthalmology Rodrigues, I. A., Sprinkhuizen, S. M., Barthelmes, D., Blumenkranz, M., Cheung, G., Haller, J., Johnston, R., Kim, R., Klaver, C., McKibbin, M., Ngah, N. F., Pershing, S., Shankar, D., Tamura, H., Tufail, A., Weng, C. Y., Westborg, I., Yelf, C., Yoshimura, N., Gillies, M. C. 2016; 168: 1-12

    Abstract

    To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care.Recommendations from working-group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM).Modified Delphi technique, supported by structured teleconferences, followed by online-surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working-group and selected based upon impact on patients, relationship to good clinical care and feasibility of measurement in routine clinical practice.Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease-control. Proposed data-collection sources include administrative, clinical data during routine clinical visits and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk-adjustment: age; gender; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis or pigment epithelial detachment; previous macular degeneration treatment; ocular co-morbidities.The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data-gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses.

    View details for DOI 10.1016/j.ajo.2016.04.012

    View details for PubMedID 27131774

  • Gene Therapy for Age-Related Macular Degeneration. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) Constable, I. J., Blumenkranz, M. S., Schwartz, S. D., Barone, S., Lai, C., Rakoczy, E. P. 2016; 5 (4): 300-303

    Abstract

    The purpose of this article was to evaluate safety and signals of efficacy of gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration (wet AMD). A phase 1 dose-escalating single-center controlled unmasked human clinical trial was followed up by extension of the protocol to a phase 2A single-center trial. rAAV.sFlt-1 vector was used to deliver a naturally occurring anti-vascular endothelial growth factor agent, sFlt-1, into the subretinal space. In phase 1, step 1 randomized 3 subjects to low-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm; step 2 randomized an additional 3 subjects to treatment with high-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm. Follow-up studies demonstrated that rAAV.sFlt-1 was well tolerated with a favorable safety profile in these elderly subjects with wet AMD. Subretinal injection was highly reproducible, and no drug-related adverse events were reported. Procedure-related adverse events were mild and self-resolving. Two phakic patients developed cataract and underwent cataract surgery. Four of the 6 patients responded better than the small control group in this study and historical controls in terms of maintaining vision and a relatively dry retina with zero ranibizumab retreatments per annum. Two patients required 1 ranibizumab injection over the 52-week follow-up period. rAAV.sFlt-1 gene therapy may prove to be a potential adjunct or alternative to conventional intravitreal injection for patients with wet AMD by providing extended delivery of a naturally occurring antiangiogenic protein.

    View details for DOI 10.1097/APO.0000000000000222

    View details for PubMedID 27488071

  • Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-Year Results of the Newborn Eye Screen Test Study. Ophthalmology Callaway, N. F., Ludwig, C. A., Blumenkranz, M. S., Jones, J. M., Fredrick, D. R., Moshfeghi, D. M. 2016; 123 (5): 1043-1052

    Abstract

    To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth.Prospective cohort study at Stanford University School of Medicine.All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded.Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist.Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events.The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant.Fundus hemorrhages are common among newborns. They often involve multiple areas and layers of the retina. Vaginal delivery was associated with a significantly increased risk of FH, whereas self-identified Hispanic or Latino ethnicity was protective against FH in this study. The long-term consequences of FH on visual development remain unknown.

    View details for DOI 10.1016/j.ophtha.2016.01.004

    View details for PubMedID 26875004

  • SMARTPHONE-BASED DILATED FUNDUS PHOTOGRAPHY AND NEAR VISUAL ACUITY TESTING AS INEXPENSIVE SCREENING TOOLS TO DETECT REFERRAL WARRANTED DIABETIC EYE DISEASE RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Toy, B. C., Myung, D. J., He, L., Pan, C. K., Chang, R. T., Polkinhorne, A., Merrell, D., Foster, D., Blumenkranz, M. S. 2016; 36 (5): 1000-1008

    Abstract

    To compare clinical assessment of diabetic eye disease by standard dilated examination with data gathered using a smartphone-based store-and-forward teleophthalmology platform.100 eyes of 50 adult patients with diabetes from a health care safety-net ophthalmology clinic. All patients underwent comprehensive ophthalmic examination. Concurrently, a smartphone was used to estimate near visual acuity and capture anterior and dilated posterior segment photographs, which underwent masked, standardized review. Quantitative comparison of clinic and smartphone-based data using descriptive, kappa, Bland-Altman, and receiver operating characteristic analyses was performed.Smartphone visual acuity was successfully measured in all eyes. Anterior and posterior segment photography was of sufficient quality to grade in 96 and 98 eyes, respectively. There was good correlation between clinical Snellen and smartphone visual acuity measurements (rho = 0.91). Smartphone-acquired fundus photographs demonstrated 91% sensitivity and 99% specificity to detect moderate nonproliferative and worse diabetic retinopathy, with good agreement between clinic and photograph grades (kappa = 0.91 ± 0.1, P < 0.001; AUROC = 0.97, 95% confidence interval, 0.93-1).The authors report a smartphone-based telemedicine system that demonstrated sensitivity and specificity to detect referral-warranted diabetic eye disease as a proof-of-concept. Additional studies are warranted to evaluate this approach to expanding screening for diabetic retinopathy.

    View details for Web of Science ID 000375482100029

    View details for PubMedID 26807627

  • Retinal and Optic Nerve Hemorrhages in the Newborn Infant OPHTHALMOLOGY Callaway, N. F., Ludwig, C. A., Blumenkranz, M. S., Jones, J. M., Fredrick, D. R., Moshfeghi, D. M. 2016; 123 (5): 1043-1052

    Abstract

    To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth.Prospective cohort study at Stanford University School of Medicine.All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded.Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist.Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events.The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant.Fundus hemorrhages are common among newborns. They often involve multiple areas and layers of the retina. Vaginal delivery was associated with a significantly increased risk of FH, whereas self-identified Hispanic or Latino ethnicity was protective against FH in this study. The long-term consequences of FH on visual development remain unknown.

    View details for DOI 10.1016/j.ophtha.2016.01.004

    View details for Web of Science ID 000375942300026

  • AFLIBERCEPT FOR THE TREATMENT OF RETINAL PIGMENT EPITHELIAL DETACHMENTS. Retina (Philadelphia, Pa.) He, L., Silva, R. A., Moshfeghi, D. M., Blumenkranz, M. S., Leng, T. 2016; 36 (3): 492-498

    Abstract

    To compare anatomical and visual acuity outcomes of eyes with persistent pigment epithelial detachments (PEDs) secondary to exudative age-related macular degeneration despite ranibizumab or bevacizumab treatment.After institutional review board approval, 40 eyes with PEDs switched from ranibizumab or bevacizumab to intravitreal aflibercept were compared for logMAR visual acuity, central subfield thickness on spectral domain optical coherence tomography, and PED height. Using paired t-tests, these parameters at baseline, after 3 consecutive injections, and 1 year after the switch were compared.Baseline visions of 20/61 ± 3.99 lines declined after 3 injections with aflibercept by 0.39 ± 2.43 lines (P = 0.32) and continued to fall after 1 year by 1.27 ± 3.48 lines (P = 0.03). Central subfield thickness was reduced after 3 injections (9.1 ± 52.0 μm, P = 0.27) and after 1 year (24.4 ± 55.3 μm, P = 0.01). The height of PEDs decreased by 31.7 ± 71.53 μm (P = 0.008) after 3 injections and by 47.81 ± 77.94 μm (P < 0.001) after 1 year.Switching to aflibercept from ranibizumab or bevacizumab resulted in a reduction in the height of PED and central subfield thickness, but a trend toward worse visual acuity 1 year after the switch.

    View details for DOI 10.1097/IAE.0000000000000749

    View details for PubMedID 26398694

  • Report on the National Eye Institute Audacious Goals Initiative: Regenerating the Optic Nerve. Investigative ophthalmology & visual science Goldberg, J. L., Guido, W., For The Agi Workshop Participants 2016; 57 (3): 1271-1275

    Abstract

    The National Eye Institute (NEI) hosted a workshop on November 19, 2014, as part of the Audacious Goals Initiative (AGI), an NEI-led effort to rapidly expand therapies for eye diseases through coordinated research funding. The central audacious goal aims to demonstrate by 2025 the restoration of usable vision in humans through the regeneration of neurons and neural connections in the eye and visual system. This workshop focused on identifying promising strategies for optic nerve regeneration. Its principal objective was to solicit input on future AGI-related funding announcements, and specifically to ask, where are we now in our scientific progress, and what progress should we reach for in the coming years? A full report was generated as a white paper posted on the NEI Web site; this report summarizes the discussion and outcomes from the meeting and serves as guidance for future funding of research that focuses on optic nerve regeneration.

    View details for DOI 10.1167/iovs.15-18500

    View details for PubMedID 26990163

  • Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial LANCET Rakoczy, E. P., Lai, C., Magno, A. L., Wikstrom, M. E., French, M. A., Pierce, C. M., Schwartz, S. D., Blumenkranz, M. S., Chalberg, T. W., Degli-Esposti, M. A., Constable, I. J. 2015; 386 (10011): 2395-2403

    Abstract

    Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related macular degeneration with a single subretinal injection.In this single-centre, phase 1, randomised controlled trial, we enrolled patients with wet age-related macular degeneration at the Lions Eye Institute and the Sir Charles Gairdner Hospital (Nedlands, WA, Australia). Eligible patients had to be aged 65 years or older, have age-related macular degeneration secondary to active subfoveal choroidal neovascularisation, with best corrected visual acuity (BCVA) of 3/60-6/24 and 6/60 or better in the other eye. Patients were randomly assigned (3:1) to receive either 1 × 10(10) vector genomes (vg; low-dose rAAV.sFLT-1 group) or 1 × 10(11) vg (high-dose rAAV.sFLT-1 group), or no gene-therapy treatment (control group). Randomisation was done by sequential group assignment. All patients and investigators were unmasked. Staff doing the assessments were masked to the study group at study visits. All patients received ranibizumab at baseline and week 4, and rescue treatment during follow-up based on prespecified criteria including BCVA measured on the Early Treatment Diabetic Retinopathy Study (EDTRS) scale, optical coherence tomography, and fluorescein angiography. The primary endpoint was ocular and systemic safety. This trial is registered with ClinicalTrials.gov, number NCT01494805.From Dec 16, 2011, to April 5, 2012, we enrolled nine patients of whom eight were randomly assigned to receive either intervention (three patients in the low-dose rAAV.sFLT-1 group and three patients in the high-dose rAAV.sFLT-1 group) or no treatment (two patients in the control group). Subretinal injection of rAAV.sFLT-1 was highly reproducible. No drug-related adverse events were noted; procedure-related adverse events (subconjunctival or subretinal haemorrhage and mild cell debris in the anterior vitreous) were generally mild and self-resolving. There was no evidence of chorioretinal atrophy. Clinical laboratory assessments generally remained unchanged from baseline. Four (67%) of six patients in the treatment group required zero rescue injections, and the other two (33%) required only one rescue injection each.rAAV.sFLT-1 was safe and well tolerated. These results support ocular gene therapy as a potential long-term treatment option for wet age-related macular degeneration.National Health and Medical Research Council of Australia, Richard Pearce Bequest, Lions Save Sight Foundation, Brian King Fellowship, and Avalanche Biotechnologies, Inc.

    View details for DOI 10.1016/S0140-6736(15)00345-1

    View details for Web of Science ID 000366290400033

    View details for PubMedID 26431823

  • One-year analysis of sFlt-1 and VEGF proteins and immunological markers in the bodily fluids of subjects participating in the Phase I rAAV.sFlt-1 trial Rakoczy, E. P., Lai, C., Magno, A., Wikstrom, M., French, M., Schwartz, S. D., Blumenkranz, M. S., Chalberg, T., Degli-Espoti, M., Constable, I. J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Incidence and clinical characteristics of epiretinal membrane developing after posterior vitreous detachment Tan, G. S., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Cost and Utility Analysis of Treatments for Macular Edema in Central Retinal Vein Occlusion Karth, P. A., Moshfeghi, D. M., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Baseline Data for Patients Participating in the Phase 2a rAAV.sFlt-1 Gene Therapy Trial for Exudative Age-Related Macular Degeneration Rakoczy, E. P., Lai, C., Magno, A. L., French, M. A., Chalberg, T. W., Schwartz, S. D., Blumenkranz, M. S., Constable, I. J. NATURE PUBLISHING GROUP. 2015: S156–S157
  • Serum Inflammatory Markers After Rupture Retinal Laser Injury in Mice OPHTHALMIC SURGERY LASERS & IMAGING RETINA Paulus, Y. M., Kuo, C., Morohoshi, K., Nugent, A., Zheng, L. L., Nomoto, H., Blumenkranz, M. S., Palanker, D., Ono, S. J. 2015; 46 (3): 362-368

    Abstract

    To characterize the cellular, immunological, and inflammatory response to retinal photocoagulation of intense rupture laser lesions as a model of retinal degenerative diseases.Seven C57BL/6 mice were irradiated using a 532-nm laser to induce 10 retinal burns per eye that ruptured Bruch's membrane. Blood was drawn from the saphenous vein before and 2 months after laser treatment. The serum was run on antigen microarrays with 85 molecular markers associated with retinal degenerative diseases.Rupture laser resulted in dramatic changes in the immunoglobulin reactivity of most inflammatory markers 2 months after laser injury. Approximately two-thirds increased expression and one-third decreased expression. Notable markers that were increased included complement C3, CRP, PKM2, and aldolase.Rupture laser injury causes a change in the serum inflammatory markers after 2 months similar to macular degeneration, diabetic retinopathy, and cancer-associated retinopathy. This animal model could be used as a biomarker for disease stage and activity in retinal degenerations.

    View details for DOI 10.3928/23258160-20150323-11

    View details for Web of Science ID 000359291400012

    View details for PubMedID 25856824

  • INTRAVITREAL INJECTION TECHNIQUE AND MONITORING: Updated Guidelines of an Expert Panel. Retina (Philadelphia, Pa.) Avery, R. L., Bakri, S. J., Blumenkranz, M. S., Brucker, A. J., Cunningham, E. T., D'Amico, D. J., Dugel, P. U., Flynn, H. W., Freund, K. B., Haller, J. A., Jumper, J. M., Liebmann, J. M., McCannel, C. A., Mieler, W. F., Ta, C. N., Williams, G. A. 2014; 34: S1-S18

    Abstract

    To review evidence and provide updated guidelines on intravitreal (IVT) injection technique and monitoring.A review of the published literature on IVT injection from 2004 to 2014 formed the basis for round table deliberations by an expert panel of ophthalmologists.The dramatic increase in the number of IVT injections has been accompanied by a comparable increase in evidence surrounding IVT practice patterns and techniques. The expert panel identified a number of areas that have evolved since publication of the original IVT injection guidelines in 2004, the most notable of which were a lack of evidence to support the routine use of pre-, peri-, and postinjection antibiotics to reduce the risk of endophthalmitis, and the role of aerosolized droplets containing oral contaminants from the patient and/or providers as a potential source of infection. The panel emphasized the continued importance of applying povidone-iodine to and avoiding eyelid contact with the intended injection site and needle.Updated guidelines on IVT injection technique and monitoring are proposed based on a review of published literature and expert panel deliberations.

    View details for DOI 10.1097/IAE.0000000000000399

    View details for PubMedID 25489719

  • The Evolution of Laser Therapy in Ophthalmology: A Perspective on the Interactions Between Photons, Patients, Physicians, and Physicists: The LXX Edward Jackson Memorial Lecture AMERICAN JOURNAL OF OPHTHALMOLOGY Blumenkranz, M. S. 2014; 158 (1): 12-25

    Abstract

    To present the evolution of laser therapy in modern ophthalmic practice.Review of published experimental and clinical studies.A review was undertaken of the work of multiple investigators leading to the invention of the laser, its biophysical effects on ocular tissues from which it derives its name (light-amplified stimulation of emitted radiation), and the development of various laser-based devices and methods to treat common ophthalmologic disorders, with particular emphasis on new and emerging retinal and anterior segment applications.Because the eye is optimized for the transmission of light and its transduction into neural signals, lasers are particularly well suited for ophthalmic therapy. This fact and the high demands for precision in therapy have inspired the development of highly sophisticated laser systems that have impacted the treatment of common diseases. These include diabetic retinopathy, age-related macular degeneration, retinal venous occlusive disease, retinopathy of prematurity, and optical aberrations including ametropia, cataract, and glaucoma, among others. Recent developments in scanning laser systems, including image-guided systems with eye tracking, real-time feedback, and ultra-short pulse durations, have enabled increased selectivity, precision, and safety in ocular therapy. However, improved outcomes have been associated with increased cost of medical care, and attention to and optimization of their cost effectiveness will continue to be required in the future.The invention and evolution of modern ophthalmic lasers have enhanced therapeutic options and can serve as a heuristic model for better understanding the process of innovation, including the societal benefits and also unintended consequences, including increased costs.

    View details for DOI 10.1016/j.ajo.2014.03.013

    View details for Web of Science ID 000338097300004

    View details for PubMedID 24699157

  • Reliability of Smartphone-Based Electronic Visual Acuity Testing: (Applications in Remote Monitoring and Clinical Research of Macular Pathology) Yu, S., Yang, J., Kim, Y., Kwak, H., Blumenkranz, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2014
  • One Year Follow-Up Report on the rAAV.sFlt-1 Phase I Gene Therapy Trial for Exudative Age-Related Macular Degeneration Rakoczy, E. P., Lai, M., Magno, A. L., French, M., Chalberg, T., Blumenkranz, M., Schwartz, S. D., Constable, I. J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2014
  • RESULTS FROM A PHASE I/II CLINICAL TRIAL ON ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR GENE THERAPY IN PATIENTS WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION Lai, C., Magno, A., Pierce, C., Samulski, R. J., Chalberg, T. W., Blumenkranz, M. S., Constable, I. J., Rakoczy, E. P. WILEY-BLACKWELL. 2013: 319
  • Anti-VEGF Gene Therapy for Wet AMD: Safety and Tolerability of Subretinal Delivery in a Phase I/II Clinical Trial Constable, I., Pierce, C., Somasundaram, S., Lai, M., Chalberg, T., Blumenkranz, M., Samulski, R., Rakoczy, E. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Anti-VEGF Gene Therapy for Wet AMD: Phase I/II Safety and Pharmacology Results Rakoczy, E., Lai, M., Pierce, C., Magno, A., Samulski, R., Chalberg, T., Blumenkranz, M., Constable, I. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Serum Autoantibody Evaluation after Retinal Laser Injury in Mice Paulus, Y., Kuo, C., Morohoshi, K., Nugent, A., Zheng, L., Nomoto, H., Blumenkranz, M., Palanker, D., Ono, S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2013
  • Herpes simplex virus type 2 mediated acute retinal necrosis in a pediatric population: case series and review GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Silva, R. A., Berrocal, A. M., Moshfeghi, D. M., Blumenkranz, M. S., Sanislo, S., Davis, J. L. 2013; 251 (2): 559-566

    Abstract

    We report 15 eyes with herpes simples virus type 2 (HSV-2) mediated acute retinal necrosis (ARN) in order to better characterize pathogenesis, clinical course, diagnosis, and outcomes of the disease.Retrospective observational case series of 14 patients (15 eyes) all aged 21 years or younger with acute retinal necrosis resulting from HSV-2 and examined between 1995 and 2009. Patients were diagnosed by various techniques, including polymerase chain reaction (PCR) of aqueous, vitreous, and serum, antibody determination of serum and intraocular fluids, fundoscopic exam, a therapeutic trial of antivirals active against HSV-2, or a combination thereof.Mean age of presentation was 11.7 years (range, newborn to 21.0 years) with a standard deviation of 7.0 years. Mean initial vision was 20/200 (median, 20/400; range, 20/20 to LP). Eleven patients (73.3 %) had received oral, injectable, or topical corticosteroids, and 14 (93.3 %) had received antiviral therapy. All patients were diagnosed based on evaluation of intraocular fluids and tissue by antibody determinations, culture, PCR, histopathologic examination, or a combination thereof. Mean final visual acuity was 20/400 (median, CF; range, 20/25 to LP) with worsened visual acuity in five eyes (33.3 %). Anatomically, 14 of 15 eyes had healed or improved retinal appearance.In a pediatric population with acute retinal necrosis, HSV-2 should be considered as the prime candidate virus. Diagnosis of HSV-2 acute retinal necrosis is accomplished mainly by PCR of ocular specimens. Prompt diagnosis may lead to appropriate anti-viral therapy.

    View details for DOI 10.1007/s00417-012-2164-8

    View details for PubMedID 23052715

  • Human histopathology of PASCAL laser burns. Eye (London, England) Paulus, Y. M., Kaur, K. n., Egbert, P. R., Blumenkranz, M. S., Moshfeghi, D. M. 2013

    View details for DOI 10.1038/eye.2013.100

    View details for PubMedID 23722723

  • EFFECT OF INTRAVITREAL TRIAMCINOLONE ACETONIDE ON HEALING OF RETINAL PHOTOCOAGULATION LESIONS RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Nomoto, H., Lavinsky, D., Paulus, Y. M., Leung, L., Dalal, R., Blumenkranz, M. S., Palanker, D. 2013; 33 (1): 63-70

    Abstract

    To evaluate the effect of intravitreal triamcinolone acetonide (TA) on healing of retinal photocoagulation lesions using drug and laser dosing typically employed in clinical practice.Laser burns with a 267-μm retinal beam size at 532-nm wavelength were applied to 40 eyes of Dutch belted rabbits. Barely visible to intense lesions were produced with pulses of 5, 10, 20, and 50 milliseconds and power of 175 mW. Eyes received intravitreal injections of either 2 mg TA/50 μL or balanced salt solution administered either 1 week before or immediately after laser treatment. Lesion grades were assessed acutely ophthalmoscopically and by a masked observer histologically at 1, 3, 7, 30, and 60 days.Both TA groups demonstrated significant reduction in retinal thickness throughout follow-up compared with balanced salt solution groups (P < 0.001). The width of the lesions at 1 day after injection was not significantly different between groups. However, by 7 days, the lesions in balanced salt solution groups contracted much more than in the TA groups, especially the more intense burns, and this difference persisted to 2 months. The healing rate of the barely visible burns was not significantly affected by TA compared with the balanced salt solution control eyes.Triamcinolone acetonide injection previously or concurrently with photocoagulation significantly decreases laser-induced edema but interferes with lesions healing, thereby leaving wider residual scarring, especially persistent in more intense burns.

    View details for DOI 10.1097/IAE.0b013e318261e34b

    View details for Web of Science ID 000313422500008

    View details for PubMedID 23026846

  • Panretinal Photocoagulation for Proliferative Diabetic Retinopathy AMERICAN JOURNAL OF OPHTHALMOLOGY Palanker, D., Blumenkranz, M. S. 2012; 153 (4): 780-781

    View details for Web of Science ID 000302387100035

    View details for PubMedID 22445637

  • Longterm cultures of the aged human RPE do not maintain epithelial morphology and high transepithelial resistance GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Stanzel, B. V., Blumenkranz, M. S., Binder, S., Marmor, M. F. 2012; 250 (2): 313-315

    View details for DOI 10.1007/s00417-011-1624-x

    View details for Web of Science ID 000300290600021

    View details for PubMedID 21279375

  • Tennis partners. Retina (Philadelphia, Pa.) Flynn, H. W., Blumenkranz, M. S. 2012; 32: S12-4

    View details for DOI 10.1097/IAE.0b013e31823daa6f

    View details for PubMedID 22270764

  • Macular infarction following intravitreal bevacizumab for treatment of central retinal vein occlusion. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye Leung, L. B., Silva, R. A., Blumenkranz, M. S., Flynn, H. W., Sanislo, S. R. 2012; 43: e73-9

    Abstract

    Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is widely used for the treatment of macular edema associated with central retinal vein occlusion (CRVO). The authors present a series of three patients with CRVO who suffered apparent macular infarction within weeks of intravitreal administration of bevacizumab. Of the nearly 200 patients undergoing intravitreal injections of bevacizumab for this indication over a surveillance period of 3 years, this event occurred in three patients. This has not been described in the natural history of the disease and is associated with poor visual outcomes.

    View details for DOI 10.3928/15428877-20120712-05

    View details for PubMedID 22823029

  • A Randomized, Dose-Escalation Study of Subconjunctival and Intravitreal Injections of Sirolimus in Patients with Diabetic Macular Edema OPHTHALMOLOGY Dugel, P. U., Blumenkranz, M. S., Haller, J. A., Williams, G. A., Solley, W. A., Kleinman, D. M., Naor, J. 2012; 119 (1): 124-131

    Abstract

    To evaluate the safety and tolerability of a single subconjunctival (SCJ) or intravitreal (IVT) injection of an ophthalmic sirolimus formulation in eyes with diabetic macular edema (DME).Randomized, open-label, dose-escalating phase I study.Fifty eyes among 50 patients with DME, retinal thickness ≥ 300 microns and best-corrected visual acuity (BCVA) 20/40 to 20/200.A single dose of sirolimus administered SCJ (220, 440, 880, 1320, or 1760 μg) or IVT (44, 110, 176, 264, or 352 μg) on day 0; observation through day 90.Primary end points were the frequency and severity of ocular and systemic adverse events. Secondary end points were changes in BCVA and retinal thickness.No dose-limiting toxicities were observed and ocular adverse events were mostly mild and transient. Conjunctival hyperemia, hemorrhage, and edema were common after the SCJ injection procedure and conjunctival hemorrhage was common after the IVT injection procedure. Three patients experienced ocular adverse events considered possibly related to study drug: Conjunctival edema and reduced visual acuity were reported in 1 SCJ patient each and iritis was reported in 1 IVT patient. No serious ocular adverse events were reported. No nonocular adverse events were considered related to study drug. Systemic exposure to sirolimus was low, with blood concentrations below levels necessary for systemic immunosuppression. For the SCJ group (n = 25), a median increase in BCVA started at day 7 (5.0 letters) and was 3.0, 4.0, and 4.0 letters at days 14, 45 and 90, respectively. At day 45, median decrease in retinal thickness was -23.7 μm. For the IVT group (n = 25), the median increase in BCVA was 2.0 letters at day 7; at days 14, 45, and 90, the median increase was maintained (4.0 letters); the median decrease in retinal thickness was -52.0 μm at day 45.Locally administered sirolimus was well-tolerated with minimal systemic exposure at all doses tested in this small phase I population. These findings support advancing the present sirolimus formulation into phase II studies.Proprietary or commercial disclosure may be found after the references.

    View details for DOI 10.1016/j.ophtha.2011.07.034

    View details for Web of Science ID 000298639500020

    View details for PubMedID 22115710

  • Fifty Years of Ophthalmic Laser Therapy ARCHIVES OF OPHTHALMOLOGY Palanker, D. V., Blumenkranz, M. S., Marmor, M. F. 2011; 129 (12): 1613-1619

    View details for Web of Science ID 000297995000016

    View details for PubMedID 22159684

  • Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology Haller, J. A., Bandello, F., Belfort, R., Blumenkranz, M. S., Gillies, M., Heier, J., Loewenstein, A., Yoon, Y. H., Jiao, J., Li, X., Whitcup, S. M., Li, J. 2011; 118 (12): 2453-2460

    Abstract

    To evaluate the safety and efficacy of 1 or 2 treatments with dexamethasone intravitreal implant (DEX implant) over 12 months in eyes with macular edema owing to branch or central retinal vein occlusion (BRVO or CRVO).Two identical, multicenter, prospective studies included a randomized, 6-month, double-masked, sham-controlled phase followed by a 6-month open-label extension.We included 1256 patients with vision loss owing to macular edema associated with BRVO or CRVO.At baseline, patients received DEX implant 0.7 mg (n = 421), DEX implant 0.35 mg (n = 412), or sham (n = 423) in the study eye. At day 180, patients could receive DEX implant 0.7 mg if best-corrected visual acuity (BCVA) was <84 letters or retinal thickness was >250 μm.The primary outcome for the open-label extension was safety; BCVA was also evaluated.At day 180, 997 patients received open-label DEX implant. Except for cataract, the incidence of ocular adverse events was similar in patients who received their first or second DEX implant. Over 12 months, cataract progression occurred in 90 of 302 phakic eyes (29.8%) that received 2 DEX implant 0.7 mg injections versus 5 of 88 sham-treated phakic eyes (5.7%); cataract surgery was performed in 4 of 302 (1.3%) and 1 of 88 (1.1%) eyes, respectively. In the group receiving two 0.7-mg DEX implants (n = 341), a ≥ 10-mmHg intraocular pressure (IOP) increase from baseline was observed in (12.6% after the first treatment, and 15.4% after the second). The IOP increases were usually transient and controlled with medication or observation; an additional 10.3% of patients initiated IOP-lowering medications after the second treatment. A ≥ 15-letter improvement in BCVA from baseline was achieved by 30% and 32% of patients 60 days after the first and second DEX implant, respectively.Among patients with macular edema owing to BRVO or CRVO, single and repeated treatment with DEX implant had a favorable safety profile over 12 months. In patients who qualified for and received 2 DEX implant injections, the efficacy and safety of the 2 implants were similar with the exception of cataract progression.Proprietary or commercial disclosure may be found after the references.

    View details for DOI 10.1016/j.ophtha.2011.05.014

    View details for PubMedID 21764136

  • Dexamethasone Intravitreal Implant in Patients with Macular Edema Related to Branch or Central Retinal Vein Occlusion OPHTHALMOLOGY Haller, J. A., Bandello, F., Belfort, R., Blumenkranz, M. S., Gillies, M., Heier, J., Loewenstein, A., Yoon, Y. H., Jiao, J., Li, X., Whitcup, S. M. 2011; 118 (12): 2453-2460

    Abstract

    To evaluate the safety and efficacy of 1 or 2 treatments with dexamethasone intravitreal implant (DEX implant) over 12 months in eyes with macular edema owing to branch or central retinal vein occlusion (BRVO or CRVO).Two identical, multicenter, prospective studies included a randomized, 6-month, double-masked, sham-controlled phase followed by a 6-month open-label extension.We included 1256 patients with vision loss owing to macular edema associated with BRVO or CRVO.At baseline, patients received DEX implant 0.7 mg (n = 421), DEX implant 0.35 mg (n = 412), or sham (n = 423) in the study eye. At day 180, patients could receive DEX implant 0.7 mg if best-corrected visual acuity (BCVA) was <84 letters or retinal thickness was >250 μm.The primary outcome for the open-label extension was safety; BCVA was also evaluated.At day 180, 997 patients received open-label DEX implant. Except for cataract, the incidence of ocular adverse events was similar in patients who received their first or second DEX implant. Over 12 months, cataract progression occurred in 90 of 302 phakic eyes (29.8%) that received 2 DEX implant 0.7 mg injections versus 5 of 88 sham-treated phakic eyes (5.7%); cataract surgery was performed in 4 of 302 (1.3%) and 1 of 88 (1.1%) eyes, respectively. In the group receiving two 0.7-mg DEX implants (n = 341), a ≥ 10-mmHg intraocular pressure (IOP) increase from baseline was observed in (12.6% after the first treatment, and 15.4% after the second). The IOP increases were usually transient and controlled with medication or observation; an additional 10.3% of patients initiated IOP-lowering medications after the second treatment. A ≥ 15-letter improvement in BCVA from baseline was achieved by 30% and 32% of patients 60 days after the first and second DEX implant, respectively.Among patients with macular edema owing to BRVO or CRVO, single and repeated treatment with DEX implant had a favorable safety profile over 12 months. In patients who qualified for and received 2 DEX implant injections, the efficacy and safety of the 2 implants were similar with the exception of cataract progression.Proprietary or commercial disclosure may be found after the references.

    View details for DOI 10.1016/j.ophtha.2011.05.014

    View details for Web of Science ID 000298138000022

  • THE IMPACT OF PULSE DURATION AND BURN GRADE ON SIZE OF RETINAL PHOTOCOAGULATION LESION Implications for Pattern Density RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Palanker, D., Lavinsky, D., Blumenkranz, M. S., Marcellino, G. 2011; 31 (8): 1664-1669

    Abstract

    Shorter pulses used in pattern scanning photocoagulation (10-20 milliseconds [ms]) tend to produce lighter and smaller lesions than the Early Treatment Diabetic Retinopathy Study standard 100-ms exposures. Smaller lesions result in fewer complications but may potentially reduce clinical efficacy. It is worthwhile to reevaluate existing standards for the number and size of lesions needed.The width of the coagulated zone in patients undergoing retinal photocoagulation was measured using optical coherence tomography. Lesions of "moderate," "light," and "barely visible" clinical grades were compared for 100, 200, and 400 μm spot sizes and pulse durations of 20 ms and 100 ms.To maintain the same total area as in 1,000 standard burns (100 ms, moderate) with a 400-μm beam, a larger number of 20-ms lesions are required: 1,464, 1,979, and 3,520 for moderate, light, and barely visible grades, respectively. Because of stronger relative effect of heat diffusion with a smaller beam, with 200 μm this ratio increases: 1,932, 2,783, and 5,017 lesions of 20 ms with moderate, light, and barely visible grades correspond to the area of 1,000 standard burns.A simple formula is derived for calculation of the required spot spacing in the laser pattern for panretinal photocoagulation with various laser parameters to maintain the same total coagulated area.

    View details for Web of Science ID 000294456100027

    View details for PubMedID 21642898

  • Femtosecond laser capsulotomy JOURNAL OF CATARACT AND REFRACTIVE SURGERY Friedman, N. J., Palanker, D. V., Schuele, G., Andersen, D., Marcellino, G., Seibel, B. S., Battle, J., Feliz, R., Talamo, J. H., Blumenkranz, M. S., Culbertson, W. W. 2011; 37 (7): 1189-1198

    Abstract

    To evaluate a femtosecond laser system to create the capsulotomy.Porcine and cadaver eye studies were performed at OptiMedica Corp., Santa Clara, California, USA; the human trial was performed at the Centro Laser, Santo Domingo, Dominican Republic.Experimental and clinical study.Capsulotomies performed by an optical coherence tomography-guided femtosecond laser were evaluated in porcine and human cadaver eyes. Subsequently, the procedure was performed in 39 patients as part of a prospective randomized study of femtosecond laser-assisted cataract surgery. The accuracy of the capsulotomy size, shape, and centration were quantified and capsulotomy strength was assessed in the porcine eyes.Laser-created capsulotomies were significantly more precise in size and shape than manually created capsulorhexes. In the patient eyes, the deviation from the intended diameter of the resected capsule disk was 29 μm ± 26 (SD) for the laser technique and 337 ± 258 μm for the manual technique. The mean deviation from circularity was 6% and 20%, respectively. The center of the laser capsulotomies was within 77 ± 47 μm of the intended position. All capsulotomies were complete, with no radial nicks or tears. The strength of laser capsulotomies (porcine subgroup) decreased with increasing pulse energy: 152 ± 21 mN for 3 μJ, 121 ± 16 mN for 6 μJ, and 113 ± 23 mN for 10 μJ. The strength of the manual capsulorhexes was 65 ± 21 mN.The femtosecond laser produced capsulotomies that were more precise, accurate, reproducible, and stronger than those created with the conventional manual technique.

    View details for DOI 10.1016/j.jcrs.2011.04.022

    View details for Web of Science ID 000292783100004

    View details for PubMedID 21700099

  • Untitled Reply RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Blumenkranz, M. S. 2011; 31 (4): 815-816
  • Critical appraisal of the clinical utility of the dexamethasone intravitreal implant (Ozurdex) for the treatment of macular edema related to branch retinal vein occlusion or central retinal vein occlusion. Clinical ophthalmology (Auckland, N.Z.) Chan, A., Leung, L., Blumenkranz, M. S. 2011; 5: 1043-1049

    Abstract

    Macular edema is a common cause of visual loss in patients with retinal vein occlusions. Ozurdex(®), a dexamethasone intravitreal implant, has been shown in randomized controlled trials to reduce macular edema and improve visual acuity in patients with either branch retinal vein occlusions or central retinal vein occlusions. It was approved in the United States in 2009. Since then, new therapeutic agents and clinical data have emerged. The purpose of this review is to critically evaluate the clinical utility of Ozurdex(®) in the current treatment strategy of macular edema related to retinal vein occlusion.

    View details for DOI 10.2147/OPTH.S13775

    View details for PubMedID 21845032

    View details for PubMedCentralID PMC3151568

  • Kinetics of central macular thickness reduction in patients with macular edema after intravitreal drug therapy. Clinical ophthalmology (Auckland, N.Z.) He, L., Chan, A., Leng, T., Blumenkranz, M. S. 2011; 5: 1751-1758

    Abstract

    The purpose of this study was to characterize central macular thickness and retinal volume following intravitreal injections using time domain and spectral domain optical coherence tomography (TD-OCT and SD-OCT, respectively).Nine patients with macular edema secondary to diabetes or retinal vein occlusion treated with intravitreal triamcinolone 4.0 mg and/or bevacizumab 1.25 mg were enrolled. Central macular thickness and volume was measured by SD-OCT and TD-OCT scan at baseline, and 1, 3, 6, 24, 48 hours, and 1 week postinjection.Equations were derived to describe central macular thickness and volume reduction in the hours following intravitreal injection. Measurements of central macular thickness by SD-OCT were significantly reduced by 3 hours (P = 0.03) and retinal volume by 6 hours (P = 0.03). Central macular thickness measured 40.9 (28.6-53.2) μm thicker on the SD-OCT instrument while volume measured 3.47 (3.27-3.66) mm(3) higher.Significant central macular thickness and volume reductions occur in the first hours after injection with triamcinolone and/or bevacizumab.

    View details for DOI 10.2147/OPTH.S26631

    View details for PubMedID 22205836

    View details for PubMedCentralID PMC3245197

  • Femtosecond Laser-Assisted Cataract Surgery with Integrated Optical Coherence Tomography SCIENCE TRANSLATIONAL MEDICINE Palanker, D. V., Blumenkranz, M. S., Andersen, D., Wiltberger, M., Marcellino, G., Gooding, P., Angeley, D., Schuele, G., Woodley, B., Simoneau, M., Friedman, N. J., Seibel, B., Batlle, J., Feliz, R., Talamo, J., Culbertson, W. 2010; 2 (58)

    Abstract

    About one-third of people in the developed world will undergo cataract surgery in their lifetime. Although marked improvements in surgical technique have occurred since the development of the current approach to lens replacement in the late 1960s and early 1970s, some critical steps of the procedure can still only be executed with limited precision. Current practice requires manual formation of an opening in the anterior lens capsule, fragmentation and evacuation of the lens tissue with an ultrasound probe, and implantation of a plastic intraocular lens into the remaining capsular bag. The size, shape, and position of the anterior capsular opening (one of the most critical steps in the procedure) are controlled by freehand pulling and tearing of the capsular tissue. Here, we report a technique that improves the precision and reproducibility of cataract surgery by performing anterior capsulotomy, lens segmentation, and corneal incisions with a femtosecond laser. The placement of the cuts was determined by imaging the anterior segment of the eye with integrated optical coherence tomography. Femtosecond laser produced continuous anterior capsular incisions, which were twice as strong and more than five times as precise in size and shape than manual capsulorhexis. Lens segmentation and softening simplified its emulsification and removal, decreasing the perceived cataract hardness by two grades. Three-dimensional cutting of the cornea guided by diagnostic imaging creates multiplanar self-sealing incisions and allows exact placement of the limbal relaxing incisions, potentially increasing the safety and performance of cataract surgery.

    View details for DOI 10.1126/scitranslmed.3001305

    View details for Web of Science ID 000288441800003

    View details for PubMedID 21084720

  • An extensive case of acute posterior multifocal placoid pigment epitheliopathy. Retinal cases & brief reports Chan, A., Blumenkranz, M. S., Sanislo, S. R. 2010; 4 (4): 336-338

    Abstract

    To report a case of extensive acute posterior multifocal placoid pigment epitheliopathy (APMPPE).Case report.An 18-year-old girl was admitted and treated with intravenous acyclovir and intravitreal gancyclovir for presumed acute retinal necrosis. As the lesions faded and vision improved, the findings became more consistent with an extensive form of APMPPE.Acute posterior multifocal placoid pigment epitheliopathy can present very aggressively early in its course. Despite macular involvement, as in this patient, vision can improve significantly.

    View details for DOI 10.1097/ICB.0b013e3181aff47e

    View details for PubMedID 25390912

  • CORRELATION OF VISUAL ACUITY AND MACULAR THICKNESS MEASURED BY OPTICAL COHERENCE TOMOGRAPHY IN PATIENTS WITH PERSISTENT MACULAR EDEMA RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Blumenkranz, M. S., Haller, J. A., Kuppermann, B. D., Williams, G. A., Ip, M., Davis, M., Weinberg, D. V., Chou, C., Whitcup, S. M. 2010; 30 (7): 1090-1094

    Abstract

    The purpose of this study was to evaluate the correlation between best-corrected visual acuity (BCVA) and macular thickness in patients with persistent macular edema treated with a dexamethasone intravitreal drug delivery system (dexamethasone DDS).In a randomized, multicenter, controlled, parallel-group, dose-ranging study, patients with macular edema lasting at least 90 days despite treatment were randomized to observation or treatment with 350- or 700-microg dexamethasone DDS. Macular thickness was assessed in 80 patients using optical coherence tomography. Best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study methodology.At baseline, macular thickness was significantly inversely correlated with BCVA (r = -0.406, P < 0.001). Patients treated with 350- or 700-microg dexamethasone DDS showed a significant decrease in macular thickness from baseline to Day 90 (P = 0.002). In the 700-microg dexamethasone DDS treatment group, there was a modest inverse correlation between changes in macular thickness from baseline to Day 90 and improvement in BCVA (r = -0.530, P = 0.009). In the 350-microg dexamethasone DDS treatment group, the correlation was weaker and not statistically significant (r = -0.206, P = 0.304).The correlation between baseline BCVA and macular thickness in patients with persistent macular edema was modest. Improvement in BCVA after treatment with 700-microg dexamethasone DDS was consistent with changes in macular thickness measured using optical coherence tomography.

    View details for DOI 10.1097/IAE.0b013e3181dcfaf3

    View details for Web of Science ID 000279635600015

    View details for PubMedID 20616686

  • Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Macular Edema Due to Retinal Vein Occlusion OPHTHALMOLOGY Haller, J. A., Bandello, F., Belfort, R., Blumenkranz, M. S., Gillies, M., Heier, J., Loewenstein, A., Yoon, Y., Jacques, M., Jiao, J., Li, X., Whitcup, S. M. 2010; 117 (6): 1134-U164

    Abstract

    To evaluate the safety and efficacy of dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc., Irvine, CA) compared with sham in eyes with vision loss due to macular edema (ME) associated with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).Two identical, multicenter, masked, randomized, 6-month, sham-controlled clinical trials (each of which included patients with BRVO and patients with CRVO).A total of 1267 patients with vision loss due to ME associated with BRVO or CRVO.A single treatment with DEX implant 0.7 mg (n = 427), DEX implant 0.35 mg (n = 414), or sham (n = 426).The primary outcome measure for the pooled data from the 2 studies was time to achieve a > or =15-letter improvement in best-corrected visual acuity (BCVA). Secondary end points included BCVA, central retinal thickness, and safety.After a single administration, the time to achieve a > or =15-letter improvement in BCVA was significantly less in both DEX implant groups compared with sham (P<0.001). The percentage of eyes with a > or =15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90 (P<0.001). The percentage of eyes with a > or =15-letter loss in BCVA was significantly lower in the DEX implant 0.7-mg group compared with sham at all follow-up visits (P< or =0.036). Improvement in mean BCVA was greater in both DEX implant groups compared with sham at all follow-up visits (P< or =0.006). Improvements in BCVA with DEX implant were seen in patients with BRVO and patients with CRVO, although the patterns of response differed. The percentage of DEX implant-treated eyes with intraocular pressure (IOP) of > or =25 mmHg peaked at 16% at day 60 (both doses) and was not different from sham by day 180. There was no significant between-group difference in the occurrence of cataract or cataract surgery.Dexamethasone intravitreal implant can both reduce the risk of vision loss and improve the speed and incidence of visual improvement in eyes with ME secondary to BRVO or CRVO and may be a useful therapeutic option for eyes with these conditions.

    View details for DOI 10.1016/j.ophtha.2010.03.032

    View details for Web of Science ID 000278224400008

    View details for PubMedID 20417567

  • Randomized Controlled Trial of an Intravitreous Dexamethasone Drug Delivery System in Patients With Diabetic Macular Edema ARCHIVES OF OPHTHALMOLOGY Haller, J. A., Kuppermann, B. D., Blumenkranz, M. S., Williams, G. A., Weinberg, D. V., Chou, C., Whitcup, S. M. 2010; 128 (3): 289-296

    Abstract

    To evaluate the safety and efficacy of a dexamethasone intravitreous drug delivery system (DDS) in eyes with diabetic macular edema (DME).Patients with persistent macular edema (> or = 90 days' duration) were randomized to treatment with 700 microg or 350 microg of dexamethasone DDS or observation. One eye from each patient was designated as the study eye. The analysis is of the eyes in this study with DME (n = 171).The primary outcome measure was the proportion of eyes that achieved an improvement in best-corrected visual acuity (BCVA) of 10 letters or more from baseline at day 90. Other outcome measures included fluorescein leakage, central retinal thickness, and safety parameters.At day 90, a BCVA improvement of 10 letters or more was seen in more eyes in the 700-microg group (33.3%) and 350-microg group (21.1%) than the observation group (12.3%; P = .007 vs 700-microg group). At day 180, a BCVA improvement of 10 letters or more was seen in 30% of eyes in the 700-microg group, 19% in the 350-microg group, and 23% in the observation group (P > or = .4 for treated vs observed eyes). There were also significantly greater improvements in central retinal thickness and fluorescein leakage in treated eyes than observed eyes (P = .03; day 90). Dexamethasone DDS was well tolerated.In eyes with persistent DME, treatment with 700 microg of intravitreal dexamethasone DDS is well tolerated and produces significant improvements in BCVA, central retinal thickness, and fluorescein leakage compared with observation (statistically significant at day 90).Dexamethasone DDS, 700 microg, may have potential as a treatment for persistent DME.clinicaltrials.gov Identifier: NCT00035906.

    View details for Web of Science ID 000275308100002

    View details for PubMedID 20212197

  • Optimal current and future treatments for diabetic macular oedema 39th Cambridge Ophthalmology Symposium Blumenkranz, M. S. NATURE PUBLISHING GROUP. 2010: 428–34

    Abstract

    Diabetic retinopathy is the most common cause of vision loss in working-age adults. Both inflammation and vascular endothelial growth factor (VEGF) play a critical role, modern and emerging treatments have centred on both laser photocoagulation and new pharmacologic strategies to improve the prognosis. Focal and grid photocoagulation, as described in the ETDRS trials, remain the gold standard of treatment. New classes of agents include long-acting steroid formulations delivered as intravitreal injections and also anti-VEGF agents. In addition, studies are under way to evaluate potential benefits from other novel agents, including those acting on the mammalian target of rapamycin pathway. In limited numbers of direct head-to-head comparisons, both steroids and anti-VEGF agents appear to be superior to conventional photocoagulation in reducing macular oedema in the first 4-6 months after treatment, although laser photocoagulation appears to be superior at time points of 1-2 years. In addition, there appear to be significant potential long-term complications of steroids including cataracts and glaucoma that may limit their use in certain patients. New methods of the laser delivery including shorter pulse durations and pattern scanning may also improve the effectiveness and risk profile of laser from the patient prospective. Finally, multi-modality therapy may play an increasingly important role.

    View details for DOI 10.1038/eye.2009.335

    View details for Web of Science ID 000275447200005

    View details for PubMedID 20075969

  • Photoacoustic ocular imaging OPTICS LETTERS de la Zerda, A., Paulus, Y. M., Teed, R., Bodapati, S., Dollberg, Y., Khuri-Yakub, B. T., Blumenkranz, M. S., Moshfeghi, D. M., Gambhir, S. S. 2010; 35 (3): 270-272

    Abstract

    We developed a photoacoustic ocular imaging device and demonstrated its utility in imaging the deeper layers of the eye including the retina, choroid, and optic nerve. Using safe laser intensity, the photoacoustic system was able to visualize the blood distribution of an enucleated pig's eye and an eye of a living rabbit. Ultrasound images, which were simultaneously acquired, were overlaid on the photoacoustic images to visualize the eye's anatomy. Such a system may be used in the future for early detection and improved management of neovascular ocular diseases, including wet age-related macular degeneration and proliferative diabetic retinopathy.

    View details for PubMedID 20125691

  • Photodynamic Therapy With and Without Adjunctive Intravitreal Triamcinolone Acetonide: A Retrospective Comparative Study OPHTHALMIC SURGERY LASERS & IMAGING Chan, A., Blumenkranz, M. S., Wu, K. H., Wang, G., Berker, N., Parast, L. M., Sanislo, S. R. 2009; 40 (6): 561-569

    Abstract

    To compare photodynamic therapy (PDT) with and without adjunctive intravitreal triamcinolone acetonide (IVTA) in the treatment of choroidal neovascularization secondary to age-related macular degeneration.Sixty-six eyes received PDT with IVTA and 73 eyes received PDT only. Outcome measures included changes in visual acuity and greatest linear dimension (GLD), the presence of angiographic leakage, the re-treatment rate, and adverse events.Patients treated with PDT with IVTA had reduced mean GLD compared to patients treated with PDT only at all study time points (3 [P = .0049], 6 [P = .003], and 12 [P = .05] months). Forty-four percent of patients in the PDT with IVTA group and 22% of patients in the PDT only group achieved angiographic closure at 3 months (P = .027). There were no significant differences in the final visual acuity outcome or the re-treatment rate between the two groups.PDT with IVTA therapy has a favorable outcome on GLD. There is a modest improvement in visual acuity with PDT with IVTA therapy, which diminishes over time.

    View details for DOI 10.3928/15428877-20091030-05

    View details for PubMedID 19928721

  • Dexamethasone Posterior-Segment Drug Delivery System in the Treatment of Macular Edema Resulting from Uveitis or Irvine-Gass Syndrome AMERICAN JOURNAL OF OPHTHALMOLOGY Williams, G. A., Haller, J. A., Kuppermann, B. D., Blumenkranz, M. S., Weinberg, D. V., Chou, C., Whitcup, S. M. 2009; 147 (6): 1048-1054

    Abstract

    To evaluate the effects of a dexamethasone intravitreous drug delivery system (dexamethasone DDS) in patients with persistent macular edema (ME) resulting from uveitis or Irvine-Gass syndrome.Randomized, prospective, single-masked, controlled trial.Three hundred and fifteen patients with persistent (>or= 90 days) ME were randomized in a multicenter study to surgical placement of 350 or 700 microg dexamethasone DDS or observation. This study evaluated the subset of patients with uveitis or Irvine-Gass syndrome (n = 41). The primary outcome measure was the proportion of patients achieving a 10-letter or more improvement in best-corrected visual acuity (BCVA) at day 90. Change in fluorescein angiographic leakage and safety also were evaluated.At day 90, a 10-letter or more BCVA improvement was seen in 41.7% (5/12) of patients in the 350-microg group, in 53.8% (7/13) of patients in the 700-microg group, and in 14.3% (2/14) of patients in the observation group (P = .029 vs the 700-microg group). Improvement in visual acuity persisted to day 180. A 15-letter or more improvement was achieved in 53.8% (7/13) of 700-microg patients vs 7.1% (1/14) of observed patients (P = .008). There were significantly greater reductions in fluorescein leakage in treated patients than in observed patients. Dexamethasone DDS was well tolerated. Throughout the study, an increase in intraocular pressure of 10 mm Hg or more was seen in 5 of 13 patients in the 700-microg group, in 1 of 12 patients in the 350-microg group, and in no patients in the observation group. There were no reports of endophthalmitis.In patients with persistent ME resulting from uveitis or Irvine-Gass syndrome, 700-microg dexamethasone DDS was well tolerated and produced statistically significant improvements in visual acuity and fluorescein leakage.

    View details for DOI 10.1016/j.ajo.2008.12.033

    View details for Web of Science ID 000266508600019

    View details for PubMedID 19268890

  • Healing of Retinal Photocoagulation Lesions INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Paulus, Y. M., Jain, A., Gariano, R. F., Stanzel, B. V., Marmor, M., Blumenkranz, M. S., Palanker, D. 2008; 49 (12): 5540-5545

    Abstract

    To systematically assess the changes in retinal morphology during the healing of retinal photocoagulation lesions of various clinical grades.Rabbits were irradiated with a 532-nm Nd:YAG laser with a beam diameter of 330 microm at the retinal surface, a power of 175 mW, and pulse durations between 5 and 100 ms. Retinal lesions were clinically graded 1 minute after placement as invisible, barely visible, light, moderate, intense, very intense, and rupture and were assessed histologically at six time points from 1 hour to 4 months.At all pulse durations, the width of the retinal lesions decreased over time. At clinical grades of light and more severe (pulse durations, 10-100 ms), retinal scarring stabilized at 1 month at approximately 35% of the initial lesion diameter. Lesions clinically categorized as barely visible and invisible (pulse durations of 7 and 5 ms) exhibited coagulation of the photoreceptor layer but did not result in permanent scarring. In these lesions, photoreceptors completely filled in the damaged areas by 4 months.The decreasing width of the retinal damage zone suggests that photoreceptors migrating from unaffected areas fill in the gap in the photoreceptor layer. Laser photocoagulation parameters can be specified to avoid not only the inner retinal damage, but also permanent disorganization and scarring in the photoreceptor layer. These data may facilitate studies to determine those aspects of laser treatment necessary for beneficial clinical response and those that result in extraneous retinal damage.

    View details for DOI 10.1167/iovs.08-1928

    View details for PubMedID 18757510

  • Severe surfing-related ocular injuries: the Stanford Northern Californian experience BRITISH JOURNAL OF SPORTS MEDICINE Zoumalan, C. I., Blumenkranz, M. S., McCulley, T. J., Moshfeghi, D. M. 2008; 42 (10): 855-857

    Abstract

    There is a growing body of literature describing severe surfing-related ocular injuries that result in permanent vision loss. We describe three severe surfing-related ocular injuries that occurred on beaches in northern California. One particular case stresses the need to tailor treatment to the patient and injury because of the possibility of good outcomes despite severe injury. Attention should also be directed towards commercially available safety gear and providing additional safety measures to prevent other orbital and ocular injuries.

    View details for DOI 10.1136/bjsm.2007.041657

    View details for PubMedID 18198199

  • Posterior retinal breaks as a cause of vitreous hemorrhage in diabetes. Retinal cases & brief reports Hwang, T. N., Moshfeghi, D. M., Blumenkranz, M. S. 2008; 2 (4): 335-337

    Abstract

    To describe posterior retinal breaks as a cause of vitreous hemorrhage in diabetic patients.In two institutional practices, six posterior retinal breaks were identified in five eyes of five diabetic patients with vitreous hemorrhage. All eyes underwent fundus photography and fluorescein angiography. Four eyes received barrier photocoagulation. The outcome measures included retinal nonperfusion, proximity to retinal vessels, and progression to retinal detachment.All six posterior breaks were in areas of retinal ischemia. No eyes had neovascularization. Three breaks had a bridging vessel, and three were in a paravascular location. One untreated eye had progression to a retinal detachment.The differential diagnosis for vitreous hemorrhage in diabetic patients should include posterior retinal breaks, particularly in the absence of proliferative disease. These breaks are paravascular, are located in areas of retinal ischemia, and may involve avulsed bridging vessels. We suggest treatment with barrier rather than panretinal photocoagulation.

    View details for DOI 10.1097/ICB.0b013e318150697d

    View details for PubMedID 25390607

  • Surveillance for potential adverse events associated with the use of intravitreal bevacizumab for retinal and choroidal vascular disease RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Wong, L. J., Desai, R. U., Jain, A., Feliciano, D., Moshfeghi, D. M., Sanislo, S. R., Blumenkranz, M. S. 2008; 28 (8): 1151-1158

    Abstract

    To systematically study potential adverse events associated with the use of intraocular bevacizumab at a single medical center.Retrospective study of all consecutive patients receiving intraocular bevacizumab injections at the Stanford University Department of Ophthalmology between November 15, 2005 and July 14, 2006. Bevacizumab was given for exudative age-related macular degeneration, retinal vascular occlusion, diabetic macular edema, neovascular glaucoma, and five other indications.We analyzed medical records of 186 subjects (203 eyes) who received a total of 578 injections of 1.25 mg of bevacizumab. The average follow-up was approximately 6 months. Five eyes with exudative age-related macular degeneration developed retinal pigment epithelial (RPE) tears, all with preexisting RPE detachments. These five eyes represented 2.9% of all age-related macular degeneration eyes treated and 7% of the age-related macular degeneration eyes with preexisting RPE detachments at initiation of treatment. Other adverse events were rare and included retinal ischemia, subretinal hemorrhage, vitreous hemorrhage, ocular irritation or pain, worsened hypertension, and headache. No death or thromboembolic events were observed.Intraocular bevacizumab appears to be well tolerated for the treatment of a variety of retinal and choroidal vascular diseases. RPE tears may occur when treating choroidal neovascularization, particularly in patients with preexisting RPE detachment.

    View details for PubMedID 18685542

  • Bacterial contamination of ocular surface and needles in patients undergoing intravitreal injections 109th Annual Meeting of the American-Academy-of-Ophthalmology De Caro, J. J., Ta, C. N., Ho, H. V., Cabael, L., Hu, N., Sanislo, S. R., Blumenkranz, M. S., Moshfeghi, D. M., Jack, R., de Kaspar, H. M. LIPPINCOTT WILLIAMS & WILKINS. 2008: 877–83

    Abstract

    To evaluate potential sources of bacterial contamination during intravitreal (IVT) injection procedures.Patients scheduled for IVT injection were asked to enroll in the study at the California Vitreoretinal Center (Menlo Park, CA) and the Vantage Eye Center (Salinas, CA) between October 2004 and April 2005. A total of 104 patients participated in the study, with a total of 118 IVT injection procedures performed on 107 eyes. Standard microbiological techniques were used to culture, identify, and quantify bacterial contamination of injection needles and the bulbar conjunctiva at the injection site in patients undergoing IVT injections. The main outcomes measured were type and quantity of bacterial isolates.Two (2%) of 114 needles collected were contaminated with bacteria. The prevalence of bacterial contamination of the injection site on the bulbar conjunctiva was 43% before prophylaxis on the day of the injection with topical antibiotics and povidone-iodine, with a statistically significant reduction to 13% after prophylaxis (P < 0.0001). Coagulase-negative Staphylococcus, the most common bacterium isolated from the ocular surface, was isolated from both culture-positive needles.IVT injection needles became contaminated with bacteria during the injection procedure. Although the contamination rate was low, this supports a mechanism of postinjection endophthalmitis in which there is direct inoculation of ocular surface flora into the vitreous cavity by the injection needle.

    View details for PubMedID 18536606

  • Towards prosthetic replacement of Bruch's membrane: Comparison of polyester and electrospun nanofiber substrates Annual Tissue-Engineering-and-Regenerative-Medicine-International-Society-European-Chapter Meeting Stanzel, B. V., Englander, M., Strick, D. J., Blumenkranz, M. S., Binder, S., Marmor, M. F. MARY ANN LIEBERT INC. 2008: 791–91
  • Effect of pulse duration on size and character of the lesion in retinal photocoagulation ARCHIVES OF OPHTHALMOLOGY Jain, A., Blumenkranz, M. S., Paulus, Y., Wiltberger, M. W., Andersen, D. E., Huie, P., Palanker, D. 2008; 126 (1): 78-85

    Abstract

    To systematically evaluate the effects of laser beam size, power, and pulse duration of 1 to 100 milliseconds on the characteristics of ophthalmoscopically visible retinal coagulation lesions.A 532-nm Nd:YAG laser was used to irradiate 36 retinas in Dutch Belt rabbits with retinal beam sizes of 66, 132, and 330 mum. Lesions were clinically graded 1 minute after placement, their size measured by digital imaging, and their depth assessed histologically at different time points.Retinal lesion size increased linearly with laser power and logarithmically with pulse duration. The width of the therapeutic window, defined by the ratio of the threshold power for producing a rupture to that of a mild coagulation, decreased with decreasing pulse durations. For 132- and 330-mum retinal beam sizes, the therapeutic window declined from 3.9 to 3.0 and 5.4 to 3.7, respectively, as pulse duration decreased from 100 to 20 ms. At pulse durations of 1 millisecond, the therapeutic window decreased to unity, at which point rupture and a mild lesion were equally likely to occur.At shorter pulse durations, the width and axial extent of the retinal lesions are smaller and less dependent on variations in laser power than at longer durations. The width of the therapeutic window, a measure of relative safety, increases with the beam size.Pulse durations of approximately 20 milliseconds represent an optimal compromise between the favorable impact of speed, higher spatial localization, and reduced collateral damage on one hand, and sufficient width of the therapeutic window (> 3) on the other.

    View details for Web of Science ID 000252312800011

    View details for PubMedID 18195222

  • Perspective: Tissue engineering for RPE transplantation in AMD SPEKTRUM DER AUGENHEILKUNDE Stanzel, B. V., Englander, M., Strick, D. J., Sanislo, S. S., Huie, P., Blumenkranz, M. S., Binder, S., Marmor, M. F. 2007; 21 (4): 212-217
  • Endogenous Scedosporium apiospermum endophthalmitis ARCHIVES OF OPHTHALMOLOGY Jain, A. T., Egbert, P., McCulley, T. J., Blumenkranz, M. S., Moshfeghi, D. M. 2007; 125 (9): 1286-1289

    View details for Web of Science ID 000249342100023

    View details for PubMedID 17846376

  • Retinal pigment epithelium tears after intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Ronan, S. M., Yoganathan, P., Chien, F. Y., Corcostegui, I. A., Blumenkranz, M. S., Deramo, V. A., Elner, S. G., Fastenberg, D. A., Johnson, M. W., Lopez, M., Mateo, C., Moshfeghi, D. M., Navarro, R., Rosenblatt, B. J., Sanislo, S. R., Saxe, S. J., Zacks, D. N. 2007; 27 (5): 535-540

    Abstract

    Intravitreal bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA) treatment of neovascular age-related macular degeneration (AMD) has become an important part of clinical retinal practice. We describe retinal pigment epithelium (RPE) tears that were noted after intravitreal injection of bevacizumab.In this multimember, retrospective case series, data on eyes that developed RPE tears after intravitreal bevacizumab injection were collected and analyzed. Previous treatments, type of lesion, time to tear, and preinjection and final visual acuities were all compared. The total numbers of bevacizumab injections were available from all four institutions and compiled to estimate the incidence rate.Four retina centers administered a total of 1,455 intravitreal 1.25-mg bevacizumab injections for neovascular AMD during the 9-month study period. Twelve patients presented with RPE tears within 4 days to 8 weeks of injection (mean +/- SD, 24.3 +/- 15.2 days from injection to tear). In each case, the RPE tear was preceded by an RPE detachment, and all had a component of serous sub-RPE fluid. On the basis of our collective data, we estimate an incidence rate of approximately 0.8%.RPE tears can occur after intravitreal injection of bevacizumab. The low incidence of this adverse event should not preclude anti-vascular endothelial growth factor therapy counseling for patients with neovascular AMD, but eyes with serous RPE detachments appear to be most vulnerable to this adverse event.

    View details for Web of Science ID 000247259400002

    View details for PubMedID 17558313

  • Role of genetic factors and inflammation in age-related macular degeneration RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Moshfeghi, D. M., Blumenkranz, M. S. 2007; 27 (3): 269-275

    Abstract

    Complement factor H (CFH) has been implicated in the predisposition to advanced forms of age-related macular degeneration (AMD). The purpose of this review is to highlight recent discoveries implicating single nucleotide polymorphisms on 1q32, 6p21, and 10q26 in the risk for development of AMD. In addition, the central role of CFH in the complement cascade and its role in the inflammatory hypothesis for AMD are reviewed.

    View details for PubMedID 17460581

  • Effect of ruboxistaurin in patients with diabetic macular edema - Thirty-month results of the randomized PKC-DMES clinical trial ARCHIVES OF OPHTHALMOLOGY Aiello, L. P., Ai, E., Aiello, L. M., Anand, R., Blumenkranz, M., Boyer, D., Brucker, A. J., Chandler, T., Chong, L., Connor, T., Danis, R., Dehning, D., Dodson, P., Eaton, A., Faber, D., Finkelstein, D., Forrester, J. V., Frank, R. N., Garcia, C., Gardner, T. W., Gehrs, K. M., Goodart, R. A., Gottlieb, J., Greven, C. M., Guyer, D. R., Hainsworth, D., Hooper, P., Jackson, W. E., Kinyoun, J. L., Kipnes, M., Klein, M. L., Kohner, E. M., Kuppermann, B., Lewis, H., Li, H. K., Lund-Anderson, H., Ma, C., Martin, D. F., Orellana, J., Paden, P. Y., Polak, B., Ross, S. A., Sharuk, G., Singerman, L. J., Smiddy, W. E., Trese, M., Tweeten, J. P., Vine, A., Vora, J., Wolffenbuttel, B. 2007; 125 (3): 318-324

    Abstract

    To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME).Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally (4, 16, or 32 mg/d) for 30 months. At baseline, patients had DME farther than 300 mum from the center of the macula, an Early Treatment Diabetic Retinopathy Study retinopathy severity level from 20 to 47A without prior photocoagulation, and an Early Treatment Diabetic Retinopathy Study visual acuity of 75 or more letters in the study eye. The primary study outcome was progression to sight-threatening DME or application of focal/grid photocoagulation for DME. Main Outcome Measure Masked grading of stereoscopic fundus photographs.The delay in progression to the primary outcome was not statistically significant (32 mg of RBX vs placebo, P = .14 [unadjusted]; Cox proportional hazards model adjusted for covariates, hazards ratio = 0.73; 95% confidence interval, 0.53-1.0; P = .06). However, application of focal/grid photocoagulation prior to progression to sight-threatening DME varied by site, and a secondary analysis of progression to sight-threatening DME alone showed that 32 mg of RBX per day reduced progression, compared with placebo (P = .054 [unadjusted]; Cox proportional hazards model, hazards ratio = 0.66; 95% confidence interval, 0.47-0.93; P = .02).Although progression to the primary outcome was not delayed, daily oral administration of RBX may delay progression of DME to a sight-threatening stage. Ruboxistaurin was well tolerated in this study.

    View details for Web of Science ID 000244846000003

    View details for PubMedID 17353401

  • Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema ARCHIVES OF OPHTHALMOLOGY Kuppermann, B. D., Blumenkranz, M. S., Haller, J. A., Williams, G. A., Weinberg, D. V., Chou, C., Whitcup, S. M. 2007; 125 (3): 309-317

    Abstract

    To evaluate a dexamethasone intravitreous drug delivery system (DDS) in patients with persistent (> or =90 days despite treatment) macular edema.This 6-month study randomized 315 patients with persistent macular edema with best-corrected visual acuity (BCVA) of 20/40 to 20/200 in the study eye to observation or a single treatment with dexamethasone DDS, 350 or 700 microg.Proportion of patients achieving a BCVA improvement of 10 or more letters or 15 or more letters, safety measures, change in fluorescein angiographic leakage, and central retinal thickness.At day 90 (primary end point), an improvement in BCVA of 10 letters or more was achieved by a greater proportion of patients treated with dexamethasone DDS, 700 microg (35%) or 350 microg (24%), than observed patients (13%; P<.001 vs 700-microg group; P = .04 vs 350-microg group); an improvement in BCVA of 15 letters or more was achieved in 18% of patients treated with dexamethasone DDS, 700 microg, vs 6% of observed patients (P = .006). Results were similar in patients with diabetic retinopathy, vein occlusion, or uveitis or Irvine-Gass syndrome. During 3 months of observation, 11% of treated patients and 2% of observed patients had intraocular pressure increases of 10 mm Hg or higher.In persistent macular edema, a single dexamethasone DDS treatment produced statistically significant BCVA improvements 90 days after treatment and was well tolerated for 180 days. Application to Clinical Practice Dexamethasone DDS, 700 microg, may have potential as a treatment for persistent macular edema.

    View details for Web of Science ID 000244846000002

    View details for PubMedID 17353400

  • The effectiveness of the new fluoroquinolones against the normal bacterial flora of the conjunctiva OPHTHALMOLOGE Koss, M. J., Eder, M., Blumenkranz, M. S., Klauss, V., Ta, C. N., de Kaspar, H. M. 2007; 104 (1): 21-27

    Abstract

    Our aim was to determine the antibiotic susceptibility of the preoperative conjunctival bacterial flora against 25 commonly used antibiotics, especially the new fluoroquinolones levofloxacin, gatifloxacin, and moxifloxacin.The Kirby-Bauer disk-diffusion technique was used to test for the in vitro antibiotic susceptibility of conjunctival bacterial strains isolated from 160 patients (median=74 years, mean=71 years) undergoing cataract surgery at the Department of Ophthalmology, Stanford University, CA, USA.Among the 256 bacteria isolated, 201 (79%) were coagulase-negative staphylococci (CNS), 26 Staphylococcus aureus, 15 Streptococcus group D and 14 gram-negative rods. A total of 100 of these 256 strains (39%) were classified as multiresitant (resistant to>or=five antibiotics). The resistance rate (RR) of commonly used antibiotics for all CNS was: gatifloxacin=moxifloxacin

    View details for DOI 10.1007/s00347-006-1453-1

    View details for Web of Science ID 000243817700003

    View details for PubMedID 17160378

  • Patterned retinal coagulation with a scanning laser 17th Conference on Ophthalmic Technologies Palanker, D., Jain, A., Paulus, Y., Andersen, D., Blumenkranz, M. S. SPIE-INT SOC OPTICAL ENGINEERING. 2007

    View details for DOI 10.1117/12.701708

    View details for Web of Science ID 000246519000036

  • A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus dystrophy AMERICAN JOURNAL OF OPHTHALMOLOGY Lin, R. J., Blumenkranz, M. S., Binkley, J., Wu, K., Vollrath, D. 2006; 142 (5): 839-848

    Abstract

    To describe the phenotype and genotype of a family with suspected Sorsby fundus dystrophy (SFD).Case reports and results of deoxyribonucleic acid (DNA) analysis.Clinical features were determined by complete ophthalmologic examination or by review of medical records. Mutational analysis of the tissue inhibitor of metalloproteinase (TIMP)3 gene was performed by DNA resequencing. Biochemical properties of the mutant TIMP3 protein were studied, and phylogenetic and molecular modeling analyses of TIMP proteins were performed.Fundi of four affected family members demonstrated active or regressed bilateral choroidal neovascularization, whereas another affected individual displayed severe diffuse pigmentary degeneration associated with nyctalopia characteristic of SFD. Onset of disease occurred in the fifth to seventh decades of life. A heterozygous His158Arg mutation was found in seven affected family members and was absent from an unaffected member and 98 unrelated controls. Bioinformatic analyses indicate that histidine 158 is an evolutionarily conserved residue in most vertebrate TIMP homologs and predict that substitution by arginine disrupts TIMP3 function. The mutant protein appears to be expressed by fibroblasts from an affected family member. Molecular modeling suggests that TIMP3 residue 158 may be part of a protein-protein interaction interface.A novel mutation in TIMP3 causes a late-onset form of SFD in this family. His158Arg is the first reported TIMP3 SFD coding sequence mutation that does not create an unpaired cysteine. Further study of this unusual mutation may provide insight into the mechanism of SFD pathogenesis.

    View details for DOI 10.1016/j.ajo.2006.06.003

    View details for Web of Science ID 000242142900019

    View details for PubMedID 16989765

  • Development of a high-resolution optoelectronic retinal prosthesis Palanker, D., Vankov, A., Huie, P., Chan, Butterwick, A., Marmor, M. F., Blumenkranz, M. S. FEDERATION AMER SOC EXP BIOL. 2006: A844
  • Semiautomated patterned scanning laser for retinal photocoagulation RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Blumenkranz, M. S., Yellachich, D., Andersen, D. E., Wiltberger, M. W., Mordaunt, D., Marcellino, G. R., Palanker, D. 2006; 26 (3): 370-376

    View details for Web of Science ID 000241684700024

    View details for PubMedID 16508446

  • Plasma-mediated transfection of RPE 16th Conference on Ophthalmic Technologies Palanker, D., Chalberg, T., Vankov, A., Huie, P., Molnar, F. E., Butterwick, A., Calos, M., Marmor, M., Blumenkranz, M. S. SPIE-INT SOC OPTICAL ENGINEERING. 2006

    View details for DOI 10.1117/12.649624

    View details for Web of Science ID 000237708800038

  • Antibiotic susceptibility of preoperative normal conjunctival bacteria 107th Annual Meeting of the American-Academy-of-Ophthalmology/Annual Meeting of the ISRS de Kaspar, H. M., Koss, M. J., Blumenkranz, M. S., Ta, C. N. ELSEVIER SCIENCE INC. 2005: 730–33

    Abstract

    To determine the antibiotic susceptibility of preoperative conjunctival bacterial flora.In vitro study.Antibiotic susceptibility of conjunctival bacterial strains isolated from 164 patients undergoing intraocular surgery was determined using the Kirby-Bauer disk-diffusion technique.Among the 162 bacteria isolated, 124 (76%) were coagulase-negative staphylococci (CNS), with 2% resistant to gatifloxacin and moxifloxacin, and none were resistant to vancomycin or minocycline. Other bacteria isolated were 19 Staphylococcus aureus (S. aureus), 8 Streptococcus Group D, and 11 gram-negative rods. Most S. aureus (>85%) were susceptible to all antibiotics except for the penicillin and macrolide groups. No streptococci were resistant to gatifloxacin, levofloxacin, moxifloxacin, mezlocillin, imipenem, or vancomycin. None of the gram-negative rods were resistant to the fluoroquinolones. Approximately one half of all bacteria were resistant to erythromycin. One in three patients harbored multi-resistant bacteria (resistant to > or = five antibiotics).Newer-generation fluoroquinolones provide excellent broad-spectrum coverage against conjunctival bacterial flora.

    View details for PubMedID 15808182

  • Prospective randomized comparison of 2 different methods of 5% povidone-iodine applications for anterior segment intraocular surgery. Archives of ophthalmology Miño de Kaspar, H., Chang, R. T., Singh, K., Egbert, P. R., Blumenkranz, M. S., Ta, C. N. 2005; 123 (2): 161-165

    Abstract

    To determine the efficacy of reducing conjunctival bacteria flora with 2 different regimens of 5% povidone-iodine application: 2 drops on the conjunctiva cul-de-sac vs a 10-mL conjunctival irrigation of the fornices.In this prospective controlled trial, 200 eyes undergoing anterior segment intraocular surgery were randomized to control and study groups. All patients from both groups received topical ofloxacin and a povidone-iodine scrub of the periorbital area before the surgical procedure. The eyes in the control group received 2 drops of povidone-iodine on the conjunctiva preoperatively, whereas eyes in the study group had irrigation of the fornices with 10 mL of povidone-iodine. Conjunctival cultures were obtained at 4 separate time points before and after surgery.Twenty (26%) of 78 eyes in the study group had positive conjunctival cultures immediately prior to surgery compared with 40 (43%) of 94 eyes in the control group (P = .02). At the conclusion of the surgery, 14 (18%) of 78 eyes and 30 (32%) of 94 eyes had positive cultures in the study and control groups, respectively (P = .05).Irrigation of the fornices with 5% povidone-iodine was associated with significantly fewer positive conjunctival cultures at the time of surgery compared with the application of 2 drops on the conjunctiva.

    View details for PubMedID 15710810

  • New therapy for central retinal vein occlusion - Are intravitreal steroids a possible answer? ARCHIVES OF OPHTHALMOLOGY Blumenkranz, M. S. 2005; 123 (2): 259-261

    View details for Web of Science ID 000226755000018

    View details for PubMedID 15710826

  • Prospective Randomized comparison of 2 different methods of 5% povidone-lodine applications for anterior segment, Intraocular surgery 106th Annual Meeting of the American-Academy-of-Ophthalmology de Kaspar, H. M., Chang, R. T., Singh, K., Egbert, P. R., Blumenkranz, M. S., Ta, C. N. AMER MEDICAL ASSOC. 2005: 161–65

    Abstract

    To determine the efficacy of reducing conjunctival bacteria flora with 2 different regimens of 5% povidone-iodine application: 2 drops on the conjunctiva cul-de-sac vs a 10-mL conjunctival irrigation of the fornices.In this prospective controlled trial, 200 eyes undergoing anterior segment intraocular surgery were randomized to control and study groups. All patients from both groups received topical ofloxacin and a povidone-iodine scrub of the periorbital area before the surgical procedure. The eyes in the control group received 2 drops of povidone-iodine on the conjunctiva preoperatively, whereas eyes in the study group had irrigation of the fornices with 10 mL of povidone-iodine. Conjunctival cultures were obtained at 4 separate time points before and after surgery.Twenty (26%) of 78 eyes in the study group had positive conjunctival cultures immediately prior to surgery compared with 40 (43%) of 94 eyes in the control group (P = .02). At the conclusion of the surgery, 14 (18%) of 78 eyes and 30 (32%) of 94 eyes had positive cultures in the study and control groups, respectively (P = .05).Irrigation of the fornices with 5% povidone-iodine was associated with significantly fewer positive conjunctival cultures at the time of surgery compared with the application of 2 drops on the conjunctiva.

    View details for Web of Science ID 000226755000002

  • Full thickness retinal pigment epithelium explants proliferate into epithelial monolayers on synthetic Bruch's membrane substitutes Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Lombardi, L., Leng, T., Yeh, E., Molnar, F., Noolandi, J., Marmor, M. F., Fishman, H. A., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2005
  • Synthetic Bruch's membrane substitutes: Comparisons after subretinal transplantation with cultured iris pigment epithelium Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Molnar, F. E., Lombardi, L., Berker, N., Yeh, E., Yellachich, D., Leng, T., Dalal, R., Marmor, M. F., Fishman, H. A., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2005
  • Directed retinal nerve cell growth for use in a retinal prosthesis interface INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Leng, T., Wu, P., Mehenti, N. Z., Bent, S. F., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. 2004; 45 (11): 4132-4137

    Abstract

    Retinal prosthetic devices that use microelectrode arrays to stimulate retinal nerve cells may provide a viable treatment for degenerative retinal diseases. Current devices are based on electrical field-effect stimulation of remaining functional neural elements. However, the distance between target neurons and electrodes limits the potential density of electrodes and the ability to stimulate specific types of retinal neurons that contribute to visual perceptions. This study was conducted to investigate the use of microcontact printing (muCP) to direct cultured or explant retinal ganglion cell (RGC) neurites to precise and close stimulation positions and to evaluate the cell types that grow from a retinal explant.RGCs and whole retinal explants were isolated from postnatal day-7 Sprague-Dawley rats using immunopanning purification and microdissection, respectively. Aligned muCP was used to direct the growth of RGC neurites from pure cultures (n=105) and retinal explants (n=64) along laminin patterns and to individual microelectrodes. Immunofluorescence stains (n=39) were used to determine the cell types that grew out from the retinal explants.RGC neurite growth was directed reproducibly along aligned laminin micropatterns to individual microelectrodes in pure RGC cultures and from full-thickness explanted rat retinas in 92% of experiments, neurites from pure RGC cultures extended along the laminin lines with an average length of 263 +/- 118 microm (SD; n=27) after 24 hours. Neurites from retinal explants extended in more than 80% of experiments and were observed to grow to an average length of 279 +/- 78 microm (n=64) after 2 days in culture. These neurites grew up to 3 mm after 1 month of culture on the laminin micropatterns. Immunohistochemical stains demonstrated that extended processes from both RGCs and glial cells grew out of retinal explants onto stamped laminin lines.Using muCP to pattern surfaces with growth factors, individual neuronal processes from pure RGC culture and whole retinal explants can be directed to discrete sites on a microelectronic chip surface. By directing RGC neurite processes to specific sites, single cell stimulation becomes possible. This may allow discrete populations of retinal neurons to be addressed so that physiologic retinal processing of visual information can be achieved.

    View details for DOI 10.1167/iovs.03-1335

    View details for PubMedID 15505066

  • Migration of retinal cells through a perforated membrane: Implications for a high-resolution prosthesis INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Palanker, D., Huie, P., Vankov, A., Aramant, R., Seiler, M., Fishman, H., Marmor, M., Blumenkranz, M. 2004; 45 (9): 3266-3270

    Abstract

    One of the critical difficulties in design of a high-resolution retinal implant is the proximity of stimulating electrodes to the target cells. This is a report of a phenomenon of retinal cellular migration into a perforated membrane that may help to address this problem.Mylar membranes with an array of perforations (3-40 microm in diameter) were used as a substrate for in vitro retinal culture (chicken, rats) and were also transplanted into the subretinal space of adult RCS rats. A membrane was also constructed with a seal on one side to restrict the migration.Retinal tissue in vitro grew within 3 days through perforations of greater than 5 microm in diameter when the membranes were positioned on the photoreceptor side, but no migration occurred if the implant was placed on the inner retinal surface. Histology with light microscopy and transmission electron microscopy (TEM) demonstrated that migrating cells retain neuronal structures for signal transduction. Similar growth of RCS rat retinal cells occurred in vivo within 5 days of implantation. A basal seal kept the migrating tissue within a small membrane compartment.Retinal neurons migrate within a few days into perforations (> 5 microm in diameter) of a membrane placed into the subretinal space. This may provide a means of gaining close proximity between electrodes in a retinal prosthetic chip and target cells, and thus allow a greater density of stimulating elements to subserve higher resolution. Further studies are needed to explore the long-term stability of the retinal migration.

    View details for DOI 10.1167/iovs.03-1327

    View details for PubMedID 15326150

  • Localized chemical release from an artificial synapse chip PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Peterman, M. C., Noolandi, J., Blumenkranz, M. S., Fishman, H. A. 2004; 101 (27): 9951-9954

    Abstract

    A device that releases chemical compounds in small volumes and at multiple, well defined locations would be a powerful tool for clinical therapeutics and biological research. Many biomedical devices such as neurotransmitter-based prostheses or drug delivery devices require precise release of chemical compounds. Additionally, the ability to control chemical gradients will have applications in basic research such as studies of cell microenvironments, stem cell niches, metaplasia, or chemotaxis. We present such a device with repeatable delivery of chemical compounds at multiple locations on a chip surface. Using electroosmosis to drive flow through microfluidic channels, we pulse minute quantities of a bradykinin solution through four 5-microm apertures onto PC12 cells and show stimulation of individual cells using a Ca(2+)-sensitive fluorescent dye. We also present basic computational results with experimental verification of both fluid ejection and fluid withdrawal by imaging pH changes by using a fluorescent dye. This "artificial synapse chip" is a prototype neural interface that introduces a new paradigm for neural stimulation, with eventual application in treating macular degeneration and other neurological disorders.

    View details for DOI 10.1073/pnas.0402089101

    View details for Web of Science ID 000222534200003

    View details for PubMedID 15218102

    View details for PubMedCentralID PMC454196

  • Three-day application of topical ofloxacin reduces the contamination rate of microsurgical knives in cataract surgery - A prospective randomized study Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology de Kaspar, H. M., Chang, R. T., Shriver, E. M., Singh, K., Egbert, P. R., Blumenkranz, M. S., Ta, C. N. ELSEVIER SCIENCE INC. 2004: 1352–55

    Abstract

    To determine the rate of contamination of microsurgical knives during cataract surgery and the benefit of a 3-day versus a 1-hour preoperative application of topical ofloxacin in reducing the contamination rate.Prospective, randomized controlled trial.Seventy-eight eyes of 75 patients were randomly assigned to control (39 eyes) or study groups (39 eyes).All patients from both groups received 0.3% topical ofloxacin 1 hour before surgery, 5% povidone-iodine (PVI) scrub of the periorbital area, and 2 drops of PVI onto the ocular surface preoperatively. The patients in the study group also received ofloxacin 4 times a day for 3 days before surgery.Microsurgical knives were placed in blood culture broth media immediately after the incision had been made. The number of positive cultures and types of bacteria isolated were determined.Ten of 39 knives (26%) in the control group were found to be positive for bacterial growth compared with only 2 of 39 (5%) in the study group (P = 0.028).The initial paracentesis incision frequently results in contamination of the microsurgical knife and may serve as a mechanism for introducing bacteria from the ocular surface into the anterior chamber. The application of topical ofloxacin for 3 days before surgery significantly reduces the contamination rate of the microsurgical knives, compared with a preoperative application of ofloxacin given 1 hour before surgery.

    View details for PubMedID 15234136

  • Health- and vision-related quality of life among patients with choroidal neovascularization secondary to age-related macular degeneration at enrollment in randomized trials of submacular surgery: SST report no. 4 AMERICAN JOURNAL OF OPHTHALMOLOGY Hubbard, B., Sternberg, P., Capone, A., AABERG, T. M., Brown, J. M., DuBois, L. G., Johnson, J., Schmitz, N., Haller, J. A., Campochiaro, P. A., de Juan, E., Pieramici, D., Zimmer-Galler, I., Hartnett, M., Hawse, P., Porter, T., Youngblood, A. E., Orr, P. R., Arroyo, J., MacCumber, M. W., Civantos, J., Packo, K. H., De Alba, M., Franzyck, M., Gaynes, B. L., Morrison, C., Rago, L., Violetto, C., Bryant, D. A., Doherty, D., Morini, F., Weinberg, D. V., SCHROEDER, R., Koecher, J., Strugala, Z., Lewis, H., Kaiser, P. K., Holody, L., Schaaf, L. S., Ambrose, G., Fatori, A., Bartram, G. M., Burke, S. L., Fecko, T., Ross, D. J., Singerman, L. J., Novak, M. A., Pendergast, S., Campana, L. M., Tilocco, K., Rath, S. C., Tanner, V., Greanoff, G., Lehnhardt, D., Smith-Brewer, S., Spagnoletta, K., Davidorf, F. H., Chambers, R., Milliron, J., Perry, J., Callanan, D. G., Creighton, J. R., Resmini, N., Rollins, R., Andrews, M., Toth, C., ANDERSON, M. W., Caldwell, J. V., Atebara, N. H., Pelke, S., Rosenthal, W. N., Dyer, D. S., Moore, D., Petro, B., Thibodeaux, D. J., Hoskins, J. C., Googe, J. M., Carter, K. E., Evans, S. M., Higdon, T. T., Holton, J. L., Gilliland, B. D., WOOD, W. J., Isernhagen, R., Cruz, J. L., Buck, M. L., James, J. D., Jordan, T. L., Wolfe, J. L., Brown, C., Heath, W., Millet, C., REID, M., SLADE, E., Schwartz, S. D., Engstrom, R., Small, K., EURE, J., Hsu, J., Ostrick, R., Tran, D., Wong, T., Barnhart, L., Chen, J., Chun, M., Johnson, L., Kageyama, J. Y., Tetreault, M., THAYER, D., Trump, B., Blumenkranz, M. S., Mattio, P., WILLIAMS, D. F., Mittra, R. A., Dev, S., Enloe, J., Marella, S. D., Oestrich, N., Bradford, R. H., Nanda, S. K., Monlux, A., Ogilbee, L. M., Sipperley, J. O., Sneed, S. R., Jacobsen, J. J., Tysiac, E., Freistroffer, D., Perez, N., Rosas, P., Tomaszewski, T., Bergren, R. L., Doft, B., Metz, D. J., Sedory, K., Trombetta, C., Rigoni, G., Wellman, L., Wilcox, L., Campbell, A., STEINBERG, D., VAGSTAD, G., Wilson, D. J., Redenbo, E., Steinkamp, P., Wallace, P., WILLIAMS, G. A., Garretson, B. R., Ruby, A., Cumming, K. L., Lewis, B., Manatry, P., Zajechewski, M., Holekamp, N. M., Thomas, M. A., Joseph, D. P., Boyd, L., Gualdoni, J., Nobel, V., Allen, R., Barts, B., Dahl, J., Holle, T. S., Ort, E., Raeber, M., Rogers, J. M., McDonald, H. R., Johnson, R. N., Stolarczuk, M., Wood, P., Curren, K. E., DeBoer, K. A., Huggans, S. M., Miller, J. R., Uy, J., Pesin, S. R., Leonardy, N. J., Dabbs, C. K., Haener, J. M., Bressler, N. M., Cumming, L., Orr, P. R., Haener, J. M., Hartnett, M., Hawse, P., Bass, E. B., Childs, D., Lawson, C., Goldsborough, I. L., Staflin, P., Hawkins, B. S., Dong, L. M., Marsh, M. J., Miskala, H., Casper, R. G., Keith, A. D., Smith, D. K., McCaffrey, L. D., Newhouse, M. M., Dreger, K., Jaffee, H. A., Grubb, S. C., Lassiter, L., James, P. A., Alden, C. B., Kiah, T. R., Prusakowski, N. A., Pieramici, D., Sadda, S., Schein, O. D., Solomon, S. D., Mbah, L., Strozykowski, R. W., Mills, I., Sieving, P. A., Kupfer, C., McLaughlin, J. A., Redford, M., Cotch, M. F., Childs, A. L., Mangione, C. M., Bass, E. B., Bressler, N. M., Hawkins, B. S., Marsh, M. J., Miskala, P. H., Jaffee, A., McCaffrey, L. D., Hillis, A. I., ABRAMS, G. W., Connett, J. E., Grady, C., Harrison, E. G., Jampol, L. M., Bressler, N. M., Marsh, M. J., Redford, M., Sternberg, P., Thomas, M. A., Redford, M., Grossniklaus, H. E., Halter, J. A., Mangione, C. M., Brown, J. M., Holekamp, N. M., Pesin, S. R., Wilson, D. J. 2004; 138 (1): 91-108

    Abstract

    To describe the effect of subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD) on health-related quality of life (HRQOL) of patients at enrollment in two randomized clinical trials; to examine the relation of visual acuity to HRQOL; to compare HRQOL scores between participants with unilateral and bilateral CNV independent of other characteristics.Randomized clinical trials.Two Submacular Surgery Trials (SST) recruited patients with AMD and either new subfoveal CNV (Group N Trial) or predominantly hemorrhagic CNV (Group B Trial). Health-related quality of life interviews included the National Eye Institute Visual Function Questionnaire [NEI-VFQ], the SF-36 Health Survey, and the Hospital Anxiety and Depression Scale [HADS]. Linear correlation and regression analyses were used to relate baseline HRQOL scores to visual acuity and bilateral disease.Interview data were analyzed for 789 AMD patients: 454 patients in the Group N Trial and 335 patients in the Group B Trial. Participants reported poor vision-related functioning in many domains measured by the NEI-VFQ (mean overall scores of 65 for Group N and 63 for Group B). Visual acuity of the better eye was strongly associated with NEI-VFQ scores but not with SF-36 or HADS scores. After adjusting for visual acuity of the better eye and other factors, bilateral cases had NEI-VFQ overall scores six points lower than unilateral cases in Group N Trial and 10 points lower than unilateral cases in the Group B Trial.Subfoveal CNV profoundly affects vision-related quality of life. The effect is more pronounced with bilateral disease, even after controlling for visual acuity.

    View details for DOI 10.1016/j.ajo.2004.02.011

    View details for Web of Science ID 000222568200012

    View details for PubMedID 15234287

  • The chick chorioallantoic membrane as a model tissue for surgical retinal research and simulation RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., MILLER, J. M., Bilbao, K. V., Palanker, D. V., Huie, P., Blumenkranz, M. S. 2004; 24 (3): 427-434

    Abstract

    We describe the use of chick chorioallantoic membrane (CAM) as a model system for the study of the precision and safety of vitreoretinal microsurgical instruments and techniques.The CAM was prepared for experimentation with and without its inner shell membrane (ISM) attached for in vivo and in vitro experiments that simulated medical and surgical interventions on the retina.The CAM's ease of use, low cost, and anatomic structure make it a convenient model for surgical retinal and retinal vascular modeling.While CAM has been used extensively in the past for ocular angiogenesis studies, we describe the tissue as a useful tool for a variety of other applications, including (1) testing of novel surgical tools and techniques for cutting and coagulating retina and its vasculature, (2) testing vessel cannulation and injection techniques, (3) angiographic studies, and (4) endoscopic surgery.

    View details for Web of Science ID 000222156800014

    View details for PubMedID 15187666

  • Controlling cell adhesion on human tissue by soft lithography LANGMUIR Lee, C. J., Blumenkranz, M. S., Fishman, H. A., Bent, S. F. 2004; 20 (10): 4155-4161

    Abstract

    Soft lithographic techniques are widely used for fundamental biological applications. This study investigates the extension of soft lithography for use on human tissue to create a biological implant by systematically studying the effect of pattern size on cellular morphology. We focus on mimicking a key layer of the physiological retina with an organized monolayer of epithelial cells to act as a new treatment for age-related macular degeneration. We show that epithelial cells can be confined to cytophilic islands defined on lens capsule by the inhibitory polymer poly(vinyl alcohol). In addition, as the size of the cytophilic islands grows, both the fraction of islands with cells attached and the number of cells adhered to each island increase. High densities of cell adhesion and single cell attachment per island were achieved with a 25 microm pattern size. Over time, the cells spread over the 5 microm wide barriers to form a confluent monolayer that may eventually serve as a functional retinal implant. With the ability to apply soft lithography to tissue samples, human tissue may become a universal membrane substrate for other ocular diseases or in tissue engineering applications elsewhere in the body.

    View details for DOI 10.1021/la035467c

    View details for Web of Science ID 000221319400049

    View details for PubMedID 15969410

  • The challenge of determining aqueous contamination rate in anterior segment intraocular surgery AMERICAN JOURNAL OF OPHTHALMOLOGY Ta, C. N., Egbert, P. R., Singh, K., Blumenkranz, M. S., de Kaspar, H. M. 2004; 137 (4): 662-667

    Abstract

    To determine aqueous contamination rate in anterior segment intraocular surgery using two different techniques of obtaining aqueous fluid and to assess whether a 3-day application of topical 0.3% ofloxacin reduces this contamination rate compared with a 1-hour application.Randomized clinical trial.One hundred and thirty-three eyes of 130 patients undergoing anterior segment intraocular surgery were randomized to either control (64 eyes received topical ofloxacin 1 hour before surgery) or study groups (69 eyes received topical ofloxacin four times a day for 3 days before surgery in addition to 1 hour preoperatively). Eyes in both groups received a periorbital iodine scrub and two drops of topical 5% iodine. Aqueous fluid was obtained at the beginning and conclusion of surgery using a cannula passed through a paracentesis or a needle passed through clear cornea. The aqueous, cannula, and needles were inoculated in blood culture media broth and bacterial growth was identified.Overall, eight of 89 aqueous samples (9%) obtained using a cannula at the beginning of surgery were culture-positive. Similarly, six of 41 aqueous samples (15%) obtained through a needle through clear cornea at the beginning of surgery showed contamination. At the conclusion of surgery, nine of 112 samples (8%) showed positive cultures. There was no difference in the aqueous contamination rates between the control and study groups.Despite the use of a needle to obtain aqueous fluid at the beginning of surgery before creating a paracentesis, the aqueous contamination rate remained higher than that found at the conclusion of surgery. A 3-day application of topical ofloxacin before surgery did not reduce the anterior chamber aqueous contamination rate relative to a 1-hour application.

    View details for DOI 10.1016/j.ajo.2003.11.057

    View details for PubMedID 15059705

  • Design of a neurotransmitter-based retinal prosthetic chip powered by the ambient light. Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Fishman, H. A., Palanker, D. V., Mehenti, N. Z., Marmor, M. F., Bent, S. F., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2004: U126–U126
  • Development of a flexible, microfabricated retinal interface Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Mehenti, N. Z., Marmor, M. F., Blumenkranz, M. S., Bent, S. F., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2004: U381–U381
  • Fluid flow past an aperture in a microfluidic channel ANALYTICAL CHEMISTRY Peterman, M. C., Noolandi, J., Blumenkranz, M. S., Fishman, H. A. 2004; 76 (7): 1850-1856

    Abstract

    Electroosmotically driven flow in neurotransmitter-based retinal prostheses offers a novel approach to interfacing the nervous system. Here, we show that electroosmotically driven flow in a microfluidic channel can be used either to eject or to withdraw fluid through a small aperture in the channel wall. We study this fluid movement numerically using a finite-element method and experimentally using microfabricated channels and apertures. Two devices are used to test the concept of fluid ejection and withdrawal: (1) a single, large channel with four apertures and (2) a prototype neural interface with four individually addressable apertures. We compared experimental and numerical results in microchannels using the observed pH dependence of the fluorescent dye fluorescein, finding good agreement between the results. Because of the simplicity and rapid response of electroosmotic flow, this technique may be useful for neurotransmitter-based neural interfaces.

    View details for DOI 10.1021/ac035154m

    View details for Web of Science ID 000220618400016

    View details for PubMedID 15053643

  • Attracting retinal cells to electrodes for high-resolution stimulation 14th Conference on Ophthalmic Technologies Palanker, D. V., Huie, P., Vankov, A., Freyvert, Y., Fishman, H., Marmor, M. F., Blumenkranz, M. S. SPIE-INT SOC OPTICAL ENGINEERING. 2004: 306–314

    View details for DOI 10.1117/12.529757

    View details for Web of Science ID 000223299200039

  • Electro-adhesive forceps for tissue manipulation 14th Conference on Ophthalmic Technologies Vankov, A., Huie, P., Blumenkranz, M., Palanker, D. SPIE-INT SOC OPTICAL ENGINEERING. 2004: 270–274

    View details for DOI 10.1117/12.529723

    View details for Web of Science ID 000223299200035

  • Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration - Twelve-month clinical outcomes Retina Congress 2002 Russell, S., Boldt, H. C., Folk, J. C., Gehrs, K. M., Stone, E. M., Weingeist, T. A., Lotery, A. J., Goerdt, C. J., Wiblin, R. T., Fountain, C. N., Groben, L., Vogel, C., Heffron, E., Verdick, R., Karakas, S., Harker, M., Montague, P. R., Singerman, L. J., Novak, M., Zegarra, H., Pendergast, S. D., MILLER, D. G., Stanescu, G. L., Zakov, Z. N., Koletsky, R., Tanner, V., Ilc, M., Schura, S., Hursky, J., Dubois, K., Dubois, J., Greanoff, G., Yannuzzi, L. A., Sorenson, J., Spaide, R., Freund, K. B., Katz, L., Goldberg, H., Guyer, D., Smithen, C., Fisher, Y., Klein, R. W., Gross, N., Frank, J., Koenig, T., Daly, J., Schnipper, L., Maranan, L., Burke, K., Scolaro, M., Costa, D., Huang, S., Saroj, N., Riff, M., Agresta, G., Ho, A. C., Belmont, J., Lucier, A., McNamara, A., Sivalingham, A., Connolly, B., Blade, K., Shuler, M., Borrillo, L., Moran, H., Sklyar, A., Lambert, J., Lambert, R., Curtain, B., Godley, B., van Kuijk, E., Wong, B. R., Uwaydat, S., Gold, D., Li, H., Vogelpohl, E., Ebert, B., Ekelund, M., Steding, M., Krason, Z., Friedlander, M., Oster, A., Riley, R., Trombley, J., Chan, R., Young, M., Holquin, A., Lewis, M. L., Rosenfeld, P., Dubovy, S., Diaz, Y., Davis, M., Mendez, P., Coleman, G., Davis, J., Auerbach, E., Guzman, L., Thomas, R., Boulanger, C., Marcus, E., Manjarrez, E., Fierer, E. M., Berrocal, A., Espana, L., Blanco, M., Torres, A., Contreras, T., Rams-McPhee, I., Lipka, K., Cuvillas, A. V., Gitter, K., Cohen, G., Ross, R. D., Batlle, I. R., Tareef, R., Knighten, M., Ebanks, C. M., Vining, C., Shoemaker, K., Soubrane, G., Coscas, G., Glacet-Bernard, A., Haddad, W. M., Tran, M. H., Delhoste, B., Kunsch, A., Lasnier, M., Lejeune, J., Fish, G. E., Fuller, D., JOST, B., Goodman, P., Spencer, R., Hutton, W., Anand, R., Arnwine, J., Arceneaux, S., Sanchez, B., Pierce, D., AGUADO, H., Ellenich, P., Creighton, J., Schwartz, S., Gonzales, C., Gupta, A., Small, K. W., Estafanous, M., Shpiner, R., Levine, M. S., Kreiger, A. E., Engstrom, R. E., Heckenlively, J. R., Yoshizumi, M. O., Tran, D., Ostrick, R., Peaco, M., Chun, M., Kagenama, J., Ho, S., LeBeck, D., Blinder, K., Burges, D., Boniuk, I., Meredith, T., Thomas, M., Holekamp, N., Grand, G., Shah, G., Daniels, J., Berk, M., Joseph, D., Skor, D., Binning, J., Light, P., Gualdoni, J., Nobel, G., Boyd, L., Barts, B., Ort, E., Rogers, M., Hudson, H., Novalis, G. S., Storrie, M., Hindenlang, R., Novalis, C., Padilla, R., Cota, D., Gomez, R., Schachat, A. P., Goldberg, M. F., Bressler, N., Bressler, S., Hause, L., Suness, J. S., Petty, B., Morris, B., Donohue, D., Cain, D., Emmert, D., de Smet, M. D., Verbraak, F. D., Tan, H., Schlingemann, R. O., Sital, O. N., Eveleens, A., Kruissel, N., Vermeulen, M., Schmidt-Erfurth, U., Michels, S., Kusserow, C., Muller-Velten, R., Neppert, B., Kollner, Behneke, Sabates, F., Sabates, N., Poulose, A., Thaker, J., Keeling, M., Rucker, T., Gallimore, G., Desai, K., Blumenkranz, M., Sanislo, S., Little, H., Rice, T., Hansen, D., Jack, R., Mattio, P., Lamborn, L., Cabrera, O., Cabael, L., Rudy, N., Murphy, R., Slakter, J. S., Ciardella, A., Orlock, D., Drosnes, B., D'Amico, D. J., Regillo, C., MIELER, W. F., Schneebaum, C., Beasley, C. ELSEVIER SCIENCE INC. 2003: 2372–83

    Abstract

    To evaluate safety and efficacy of the angiostatic agent anecortave acetate, compared with a placebo, for treatment of subfoveal choroidal neovascularization (CNV).Ongoing masked, randomized, placebo-controlled, parallel evaluation of anecortave acetate (30 mg, 15 mg, and 3 mg) versus a placebo.There were 128 eyes of 128 patients with subfoveal CNV secondary to age-related macular degeneration who were enrolled and treated, with 80% (102/128) of eyes presenting with predominantly classic lesions at baseline.All eyes received a posterior juxtascleral depot application of masked study medication or a placebo, with retreatment at 6-month intervals if the masked investigator believed the patient could benefit. Patients received periodic detailed ophthalmic examinations with both fluorescein and indocyanine green angiography, general physical examinations with electrocardiograms, and hematology/serum chemistry/urinalysis. All ophthalmic and systemic safety data were periodically reviewed by the Independent Safety Committee overseeing the study.Best-corrected logarithm of the minimum angle of resolution (logMAR) vision and fluorescein angiographic lesion characteristics were compared over time and among treatment groups.At month 12, anecortave acetate (15 mg) administered at 6-month intervals was statistically superior to the placebo for 3 measures of clinical efficacy: mean change from baseline vision (P = 0.0131), stabilization of vision (<3 logMAR line change; P = 0.0323), and prevention of severe vision loss (decrease of > or = 6 logMAR lines from baseline; P = 0.0224). Subgroup analysis of predominantly classic lesions revealed that anecortave acetate (15 mg) was also superior to the placebo at 1 year for each of these 3 measures of visual outcome (Ps = 0.0022, 0.0100, and 0.0299, respectively). Anecortave acetate (15 mg) trended toward significance over the placebo at month 12 for inhibition of total lesion growth and for inhibition of both the total CNV component and the classic CNV component in both the overall and subgroup analyses. The Independent Safety Committee identified no clinically relevant treatment-related safety issues.Anecortave acetate (15 mg) is safe and clinically efficacious at 1 year for maintaining vision, preventing severe vision loss, and inhibiting subfoveal CNV lesion growth.

    View details for DOI 10.1016/j.ophtha.2003.08.020

    View details for Web of Science ID 000186875400014

    View details for PubMedID 14644721

  • The artificial synapse chip: A flexible retinal interface based on directed retinal cell growth and neurotransmitter stimulation ARTIFICIAL ORGANS Peterman, M. C., Mehenti, N. Z., Bilbao, K. V., Lee, C. J., Leng, T., Noolandi, J., Bent, S. F., Blumenkranz, M. S., Fishman, H. A. 2003; 27 (11): 975-985

    Abstract

    The Artificial Synapse Chip is an evolving design for a flexible retinal interface that aims to improve visual resolution of an electronic retinal prosthesis by addressing cells individually and mimicking the physiological stimulation achieved in synaptic transmission. We describe three novel approaches employed in the development of the Artificial Synapse Chip: (i) micropatterned substrates to direct retinal cell neurite growth to individual stimulation sites; (ii) a prototype retinal interface based on localized neurotransmitter delivery; and (iii) the use of soft materials to fabricate these devices. By patterning the growth of cells to individual stimulation sites, we can improve the selectivity of stimulation and decrease the associated power requirements. Moreover, we have microfabricated a neurotransmitter delivery system based on a 5- micro m aperture in a 500-nm-thick silicon nitride membrane overlying a microfluidic channel. This device can release neurotransmitter volumes as small as 2 pL, demonstrating the possibility of chemical-based prostheses. Finally, we have fabricated and implanted an equivalent device using soft flexible materials that conform to the retinal tissue more effectively. As many of the current retinal prosthesis devices use hard materials and electrical excitation at a lower resolution, our approach may provide more physiologic retinal stimulation.

    View details for Web of Science ID 000186491900003

    View details for PubMedID 14616516

  • Antibiotic resistance patterns of ocular bacterial flora - A prospective study of patients undergoing anterior segment surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Ta, C. N., Chang, R. T., Singh, K., Egbert, P. R., Shriver, E. M., Blumenkranz, M. S., de Kaspar, H. M. ELSEVIER SCIENCE INC. 2003: 1946–51

    Abstract

    To determine the antibiotic susceptibility patterns of conjunctival bacterial flora isolated preoperatively from patients undergoing anterior segment surgery.Prospective observational study.One hundred fifty-six eyes from 139 patients scheduled for anterior segment surgery were enrolled over a 6-month period from August 2001 to February 2002.Conjunctival cultures were obtained on the day of surgery before povidone-iodine or antibiotic application.Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique.Among the 156 eyes studied, 36 were from patients who had undergone either bilateral surgery or more than one surgery in the same eye. Only the first eyes of the 120 patients that underwent initial ocular surgery were included in our analysis. Of these 120 eyes, 21 (18%) showed no bacterial growth. Of the 143 bacterial strains isolated from the remaining 99 eyes, 112 (78%) were coagulase-negative staphylococci (CNS). Among the CNS, greater than 90% were susceptible to cefotaxime, levofloxacin, imipenem, meropenem, vancomycin, and each of the aminoglycosides except neomycin. Between 70% and 90% of the CNS were susceptible to cefazolin, neomycin, ciprofloxacin, ofloxacin, norfloxacin, and chloramphenicol. Less than 70% of the isolated CNS were sensitive to the penicillin analogues, ceftazidime, erythromycin, and tetracycline.Preoperative conjunctival isolates of CNS seem to be most sensitive to vancomycin, the aminoglycosides (except neomycin), and levofloxacin.

    View details for DOI 10.1016/S0161-6420(03)00735-8

    View details for PubMedID 14522770

  • Risk factors for antibiotic-resistant conjunctival bacterial flora in patients undergoing intraocular surgery 100th Annual Meeting of the Deutsche-Ophthalmologische-Gesellschaft de Kaspar, H. M., Shriver, E. M., Nguyen, E. V., Egbert, P. R., Singh, K., Blumenkranz, M. S., Ta, C. N. SPRINGER. 2003: 730–33

    Abstract

    The purpose of this study was to determine if patients with certain risk factors are more likely to harbor conjunctival bacterial flora resistant to multiple antibiotics.In this prospective study, detailed medical history and slit-lamp examination were performed on all patients prior to intraocular surgery. Patients with local risk factors were defined as those with chronic blepharitis, conjunctivitis or discharge. Those with systemic risk factors were patients with diabetes, autoimmune, immunodeficient or skin disorders, asthma and those taking immunosuppressant medications. Conjunctival cultures were obtained prior to preoperative antibiotics and povidone-iodine. Bacteria isolated were identified and antibiotic susceptibility was determined. Bacteria resistant to five or more antibiotics were defined as multi-resistant (MR).Among the 207 patients enrolled in the study, 73 patients had local risk factors. Of these patients, 32 patients (44%) carried MR organisms, compared to 32 of the 134 patients (24%) without local risk factors (P=0.0049). Thirty-two of 71 patients (45%) with systemic risk factors harbored MR organisms, compared to 32 of 136 patients (24%) without systemic risk factors (P=0.0025). Seventeen of 93 patients (18%) who had neither local nor systemic risk factors had MR organisms on their conjunctiva. In contrast, 17 of the 30 patients (57%) with both local and systemic risk factors (57%) carried MR bacteria (P=0.0001).Patients with local and/or systemic risk factors are more likely to harbor MR organisms. This may be one mechanism for the reported increased risk of postoperative endophthalmitis in this group of patients.

    View details for DOI 10.1007/s00417-003-0742-5

    View details for PubMedID 12928904

  • Towards a neurotransmitter-based retinal prosthesis using an inkjet print-head BIOMEDICAL MICRODEVICES Noolandi, J., Peterman, M. C., Huie, P., Lee, C., Blumenkranz, M. S., Fishman, H. A. 2003; 5 (3): 195-199
  • Localized neurotransmitter release for use in a prototype retinal interface INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Peterman, M. C., Bloom, D. M., Lee, C., Bent, S. F., Marmor, M. E., Blumenkranz, M. S., Fishman, H. A. 2003; 44 (7): 3144-3149

    Abstract

    Current neural prostheses use electricity as the mode of stimulation, yet information transfer in neural circuitry is primarily through chemical transmitters. To address this disparity, this study was conducted to devise a prototype interface for a retinal prosthetic based on localized chemical delivery. The goal was to determine whether fluidic delivery through microfabricated apertures could be used to stimulate at single-cell dimensions.A drug delivery system was microfabricated based on a 5- or 10- microm aperture in a 500-nm thick silicon nitride membrane to localize and limit transmitter release. The aperture overlies a microfluidic delivery channel in a silicone elastomer. To demonstrate the effectiveness of this transmitter-based prosthesis, rat pheochromocytoma cells (PC12 cell line) were grown on the surface of the device to test the precision of stimulation, using bradykinin as a stimulant and measuring fluorescence from the calcium indicator, fluo-4.The extent of stimulation could be controlled accurately by varying the concentration of stimulant, from a single cell adjacent to the aperture to a broad area of cells. The stimulation radius was as small as 10 microm, corresponding to stimulation volumes as small as 2 pL. The relationship between the extent of stimulation and concentration was linear.The demonstration of localized chemical stimulation of excitable cells illustrates the potential of this technology for retinal prostheses. Although this is only a proof of concept of neurotransmitter stimulation for a retinal prosthesis, it is a significant first step toward mimicking neurotransmitter release during synaptic transmission.

    View details for DOI 10.1167/iovs.02-1097

    View details for PubMedID 12824264

  • Precision and safety of the pulsed electron avalanche knife in vitreoretinal surgery ARCHIVES OF OPHTHALMOLOGY MILLER, J. M., Palanker, D. V., Vankov, A., Marmor, M. F., Blumenkranz, M. S. 2003; 121 (6): 871-877

    Abstract

    We have developed a new surgical instrument, called the pulsed electron avalanche knife (PEAK; Carl Zeiss Meditec, Jena, Germany), for precise, "cold," and tractionless dissection of tissue in liquid media.To evaluate the 3-dimensional damage zone induced by the PEAK compared with 2 other standard intraocular surgical instruments, diathermy and retinal scissors.Damage zone and minimum safe distance were measured in vitro on chick chorioallantoic membrane and in vivo on rabbit retina with the use of propidium iodide staining.The PEAK produced a paracentral zone of cellular structure disruption surrounding a crater and a peripheral zone of structurally intact but abnormally permeable cells. The instrument induced a damage radius that varied from 55 to 300 micro m for the range of voltages and pulses typically used during surgery. For comparison, damage radius for microsurgical scissors was 50 micro m, and for diathermy, 400 to 850 micro m. The PEAK also damaged tissue up to 1.4 mm away by the creation of water flow that formed at the tip of convex probes during collapse of a cavitation bubble. Concave probes, which prevent formation of the water jet, eliminated this effect.The PEAK operated well within accept-able safety limits and may greatly facilitate both posterior segment surgeries (eg, membrane dissection and sheathotomy) and anterior segment procedures (eg, capsulotomy, nonpenetrating trabeculectomy, and iridectomy).

    View details for PubMedID 12796261

  • Retinal evaluation of patients on chronic amiodarone therapy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Shaikh, S., Shaikh, N., Chun, S. H., Spin, J. M., Blumenkranz, M. S., Marmor, M. F. 2003; 23 (3): 354-359

    Abstract

    To determine whether retinal electrophysiologic changes can be detected and correlated with funduscopic findings in patients with the long-term use of amiodarone.Eleven patients ranging in age from 52 to 67 years were recruited from the Stanford University Medical Center Department of Cardiology for ophthalmologic examination. Patients had received amiodarone at various dosages ranging from 100 to 800 mg daily for at least 15 months. Clinical indications for the use of amiodarone included atrial fibrillation, ventricular arrhythmias, and congestive heart failure. All patients underwent retinal electrophysiology studies (full-field and multifocal electroretinograms) in addition to a complete ophthalmologic examination and fluorescein angiography.No patients were found to have significant vision loss. Funduscopic examination and fluorescein angiography showed mild age-related changes in four patients, three of whom had nonspecific foveal pigmentary alterations. Multifocal and full-field electroretinograms were mostly unremarkable, and the mildly subnormal findings in a few patients showed no consistent pattern to suggest a toxic cause. Dosage, duration of amiodarone exposure, patient age, and underlying cardiac disease did not appear to correlate with these findings.No significant adverse retinal funduscopic changes or electrophysiologic effects could be correlated with amiodarone exposure in this small series of patients. Routine electrophysiologic and funduscopic screening of patients receiving amiodarone does not seem warranted, although future prospective controlled studies may be required to exclude the possibility of progressive abnormalities in patients with preexisting age-related macular degeneration.

    View details for PubMedID 12824836

  • Quantitative verteporfin angiography in humans Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Moshfeghi, D. M., Blumenkranz, M. S., Sanislo, S. R., Hnik, P. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U698–U698
  • Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration - Phase II study results 105th Annual Meeting of the American-Academy-of-Ophthalmology Fish, G., Haller, J. A., Ho, A. C., Klein, M., Loewenstein, J., Martin, D., Orth, D., Rosen, R. B., Sanislo, S., Schwartz, S. D., Singerman, L. J., Williams, G., Adamis, A. P., Blumenkranz, M., Goldberg, M., Gragoudas, E. S., Miller, J. W., Yannuzzi, L., Guyer, D. R., O'Shaughnessy, D., Patel, S. ELSEVIER SCIENCE INC. 2003: 979–86

    Abstract

    There is evidence to suggest that anti-vascular endothelial growth factor (anti-VEGF) therapy may be useful in treating ocular neovascularization. A phase IA single intravitreal injection study of anti-VEGF therapy for patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) revealed a good safety profile. We performed a phase II multiple injection study of anti-VEGF therapy with and without photodynamic therapy for patients with subfoveal CNV secondary to AMD to determine the safety profile of multiple injection therapy.A phase II multiple-dose safety study.Twenty-one patients were treated with intravitreal injection with and without photodynamic therapy.Clinical evidence of toxicity and complications.No drug-related serious adverse events were revealed. Ophthalmic evaluation revealed that 87.5% of patients who received the anti-VEGF aptamer alone showed stabilized or improved vision 3 months after treatment and that 25% of eyes demonstrated a 3 line or greater improvement in vision on the Early Treatment of Diabetic Retinopathy Study chart during this period. A 60% 3 line gain at 3 months was noted in patients who received both the anti-VEGF aptamer and photodynamic therapy.Anti-VEGF therapy is a promising treatment for various forms of ocular neovascularization, including AMD. Multiple intravitreal injections of the anti-VEGF aptamer were well tolerated in this phase II study. Further clinical trials are necessary to demonstrate the efficacy and long-term safety of anti-VEGF therapy for AMD.

    View details for DOI 10.1016/S0161-6420(03)00085-X

    View details for Web of Science ID 000182754600032

    View details for PubMedID 12750101

  • A retinal interface based on neurite micropatterning for single cell stimulation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Mehenti, N. Z., Peterman, M. C., Leng, T., Marmor, M. F., Blumenkranz, M. S., Bent, S. F. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U704–U704
  • The pulsed electron avalanche knife in human vitreoretinal surgery; A status report Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Blumenkranz, M. S., Palanker, D., Sanislo, S. S., Marmor, M. H., Quiroz-Mercado, H., Koch, F., Kampik, A., Miesner, H., Amend, P. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U99–U99
  • Bubble-free plasma blade for posterior segment surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Sanislo, S. R., Palanker, D., Vankov, A., Bilbao, K., Marmor, M., Blumenkranz, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U665–U665
  • RPE cell adhesion on spatially patterned lens capsule Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Lee, C. J., Bent, S. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U100–U100
  • Laser treatment in fellow eyes with large drusen: updated findings from a pilot randomized clinical trial Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) Sternberg, P., AABERG, T. M., Martin, D., Saperstein, D., Hyatt, M., Gilman, J., SWORDS, R., Nemes, G., Singerman, L. J., Rice, T. A., Zegarra, H., Novak, M. A., Pendergast, S., Zakov, Z. N., Niffenegger, J., Bartel, M., LICHTERMAN, S., Knight, D., Tilocco-DuBois, K., Ilk, M., Daley, G., Greanoff, G., Dubois, J., Weiss, D., Lyon, A., Jampol, L., Weinberg, D., Chiapetta, B., Strugala, Z., Richine, L., Fish, G. E., Callanan, D., JOST, B., Anand, R., Snyder, W. B., Fuller, D., ANDERSON, T., Arceneaux, S., AGUADO, H., NORK, C., Boleman, B., Avery, P., Solomon, S., KING, J., Orth, D., Packo, K., Cohen, J., DEBUSTROS, S., Figliulo, C., Morrison, C., Lluen-Johnson, K., Bryant, D., Doherty, D., Folk, J., Boldt, H. C., Gehrs, K., Russell, S., Fountain, C., Griffin, M., Heffron, E., Vogel, C., Ward, B., Northway, R., Sabates, F., Schuchard, R., Sabates, N., Poulose, A., Crosser, V., Matta, C., Keeling, M., Lei, H., Gallimore, G., Holz, E. R., Wood, W., Isernhagen, R., Wolfe, J., Hawkins, L., Taul, Y., Oldroyd, M., Cornett, L., Van Arsdall, J., SLADE, E., Harris, M., Chandra, S., Stevens, T., Meyers, F., Olsen, T., Blodi, B., Gottlieb, J., Walker, W., Perry, J., Knutson, G., Harrison, R., Neider, M., Wabers, H., Little, H., Blumenkranz, M., Jack, R., Zweng, H. C., Showman, J., Hahn, T., JIMENEZ, L., Mattio, P., Cabrera, O., Gitter, K., Cohen, G., Ross, R., Newell, K., Schomaker, K., Fine, S. L., Brucker, A., Ho, A. C., Maguire, A., GRUNWALD, J., Dupont, J., Kirschner, J., Sterling, E., Goller, G., Sheehan, M., Nyberg, B., Weeney, L., Reynolds, J., Elkins, D., Klein, M., Wilson, D., Nolte, S., Evans, M., Wallace, P., MARGHERIO, R. R., TRESE, M. T., Hassan, T. S., Margherio, A., Capone, A., CUMMING, K., Mitchell, B., STREASICK, P., Bridges, C., Huston, G., Szydlowski, L., Medina, T., McDonald, H. R., SCHATZ, H., Johnson, R., Ai, E., Wood, P., Di Angelo, M., Stolarczuk, M., Rosenfeld, I., Wild, S., Uy, J., Maguire, M. G., Ying, G. S., Brightwell-Arnold, M., Stanford, N. N., Dallas, V., Wheary, C., Fine, S. L., Reich, A., Fatula, E., Katz, M., Ho, A. C., Javornik, N. B., Alexander, J., Begley, S., Elsner, K. S., McWilliams, K. C., Whitlock, E. R., FINKELSTEIN, D., Hawkins, B. S. ELSEVIER SCIENCE INC. 2003: 971–78

    Abstract

    To update the findings from the Choroidal Neovascularization Prevention Trial (CNVPT) with respect to resolution of drusen, incidence of choroidal neovascularization, and visual function.A multicenter, randomized, controlled, pilot clinical trial.The 120 patients enrolled in the CNVPT. Patients had signs of choroidal neovascularization or retinal pigment epithelial detachment in 1 eye and had >/=10 large (>63- micro m) drusen in the contralateral, or fellow, eye.The fellow eye of 59 patients was assigned randomly to argon green laser treatment consisting of multiple 100- micro m spots at least 750 micro m from the center of the fovea. The fellow eye of the remaining 61 patients was assigned randomly to observation.Change in visual acuity was the primary outcome measure. Incidence of choroidal neovascularization, resolution of drusen, change in contrast threshold, change in critical print size for reading, and incidence of geographic atrophy were secondary outcome measures.Throughout 4 years of follow-up, there were no statistically significant differences in change in visual acuity, contrast threshold, critical print size, or incidence of geographic atrophy. With additional follow-up, the large increase in the incidence of choroidal neovascularization observed within 18 months of treatment was maintained; however, by 30 months, the incidence in the two treatment groups was the same. Most drusen resolution in treated eyes occurred within 24 months of the initial treatment. Treated eyes that received higher-intensity laser burns had an increased risk of choroidal neovascularization. Among eyes developing choroidal neovascularization in each treatment group, most lesions (two thirds or more) were composed of occult neovascularization only.Laser treatment as applied in the CNVPT caused an excess risk of choroidal neovascularization in the first year or so after treatment. The increased early incidence of choroidal neovascularization was not associated with either a harmful or beneficial effect in this pilot study.

    View details for DOI 10.1016/S0161-6420(03)00098-8

    View details for Web of Science ID 000182754600031

    View details for PubMedID 12750100

  • Cell demographics from full thickness retinal explant growth on micropatterned surfaces Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Wu, P., Mehenti, N. Z., Leng, T., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U692–U692
  • Ten-fold reduction of conjunctival bacterial contamination rate using a combined 3-day application of topical ofloxacin and iodine irrigation in patients undergoing anterior segment intraocular surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology de Kaspar, H. M., Singh, G., Egbert, P. R., Haw, W. W., Nguyen, E. V., Singh, K., Blumenkranz, M. S., Ta, C. N. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U344–U344
  • Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia - 2-year results of a randomized clinical Trial - VIP report no. 3 OPHTHALMOLOGY Blinder, K. J., Blumenkranz, M. S., Bressler, N. M., Bressler, S. B., Donati, G., Lewis, H., Lim, J. I., Menchini, U., Miller, J. W., Mones, J. M., Potter, M. J., Pournaras, C., Reaves, A., Rosenfeld, P., Schachat, A. P., Schmidt-Erfurth, U., Sickenberg, M., Singerman, L. J., Slakter, J., Strong, H. A., Virgili, G., WILLIAMS, G. A. 2003; 110 (4): 667-673

    Abstract

    To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia.Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America.Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better.Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV.The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data.Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up.Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

    View details for DOI 10.1016/S0161-6420(02)01998-X

    View details for Web of Science ID 000182566600023

    View details for PubMedID 12689884

  • Clinicopathologic study after submacular removal of choroidal neovascular membranes treated with verteporfin ocular photodynamic therapy AMERICAN JOURNAL OF OPHTHALMOLOGY Moshfeghi, D. M., Kaiser, P. K., Grossniklaus, H. E., Sternberg, P., Sears, J. E., Johnson, M. W., Ratliff, N., Branco, A., Blumenkranz, M. S., Lewis, H. 2003; 135 (3): 343-350

    Abstract

    To report the clinicopathologic findings after submacular removal of choroidal neovascular membranes (CNV) treated with verteporfin ocular photodynamic therapy.Interventional case series.Retrospective review of eight eyes of eight patients who underwent submacular surgery for CNV after having previously received verteporfin ocular photodynamic therapy for presumed ocular histoplasmosis (one patient), age-related macular degeneration ([AMD] three patients) pathologic myopia (two patients), punctate inner choroiditis (one patient), and idiopathic CNV (one patient). All cases had undergone ocular photodynamic therapy with verteporfin using standard protocols. Six of eight patients suffered a submacular hemorrhage after ocular photodynamic therapy, and two of eight patients refused further ocular photodynamic therapy. All patients subsequently had submacular surgery with removal of the CNV. One membrane was routinely processed, sectioned, and stained with hematoxylin and eosin. Five membranes were stained with toluidine blue for light microscopic examination. Semithin (1.0 microm) sections were cut and stained with uranyl acetate-lead citrate for transmission electron microscopy.Choroidal neovascular membranes were removed at 3 days (presumed ocular histoplasmosis), 29 days (punctate inner choroiditis), 63 days (AMD, pathologic myopia), 66 days (AMD), 107 days (pathologic myopia), 116 days (AMD), and 152 days (idiopathic) after verteporfin ocular photodynamic therapy. Histopathologic and ultrastructural examination showed areas of vascular occlusion at 3 days that were not seen at later time points. All specimens had patent CNV. There were signs of vascular damage with extravasated erythrocytes and fibrin, pigment clumping in cells, and inflammatory cells in all but the 3-day specimen.This case series presents data only from patients who refused repeat treatment with ocular photodynamic therapy or who developed submacular hemorrhage after initial photodynamic therapy. Histopathologic evaluation of CNV 3 days after verteporfin ocular photodynamic therapy showed partial vascular occlusion that was not present in later specimens. These later specimens demonstrated evidence of vascular damage. Verteporfin ocular photodynamic therapy does not appear to lead to permanent and complete occlusion of the CNV. Thus, treatments that lead to permanent closure of CNV without damage to the retinal pigment epithelium and sensory retina are still needed.

    View details for Web of Science ID 000181258100012

    View details for PubMedID 12614752

  • Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD) - Interim (month 6) analysis of clinical safety and efficacy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Blinder, K., Blumenkranz, M., Desmet, M., Fish, G., Friedlander, M., Gitter, K., Godley, B., Ho, A., Hudson, H., van Kuijk, E., Lewis, M. L., Rosenfeld, P., Russell, S., Sabates, F., Schachat, A., Schmidt-Erfurth, U., Schwartz, S., Singerman, L., Soubrane, G., Yannuzzi, L., D'Amico, D. J., Regillo, C., MIELER, W. F., Schneebaum, C., Beasley, C., Slakter, J. S., Ciardella, A., Goldberg, M. F., Hudson, H., Jerdan, J. A., Krueger, S., Luna, S., Robertson, S. M., Russell, S., Singerman, L., Slakter, J. S., Sullivan, E. K., Yannuzzi, L., Zilliox, P. 2003; 23 (1): 14-23

    Abstract

    To evaluate clinical safety and efficacy of the angiostatic agent anecortave acetate for treatment of subfoveal choroidal neovascularization secondary to AMD.128 patients were randomized to placebo treatment or one of three anecortave acetate doses. Study medication was administered as a posterior juxtascleral injection onto the posterior scleral surface. Best-corrected logMAR vision was obtained at baseline and follow-up visits. Fluorescein angiograms were evaluated for eligibility before enrollment and posttreatment.Six months after a single treatment, visual acuity (mean change from baseline logMAR values) was significantly better (P = 0.003) after anecortave acetate 15 mg than placebo. More patients treated with anecortave acetate 15 mg than placebo maintained vision (88% versus 70%, P = 0.080), especially those with predominantly classic lesions (92% versus 65%, P = 0.021). Anecortave acetate 15 mg inhibited lesion growth significantly better than placebo (P = 0.001). Trends favoring the other doses over placebo were observed for vision preservation and lesion inhibition, but statistical significance was not achieved. The Independent Safety Committee overseeing this study identified no clinically relevant treatment-related changes.Anecortave acetate 15 mg is safe and effective for preserving or improving vision and for inhibiting lesion growth in patients with subfoveal AMD.

    View details for Web of Science ID 000182898500003

    View details for PubMedID 12652226

  • Optimization of the pulsed electron avalanche knife for anterior segment surgery 13th Conference on Ophthalmic Technologies Palanker, D., Vankov, A., Bilbao, K., Marmor, M., Blumenkranz, M. SPIE-INT SOC OPTICAL ENGINEERING. 2003: 56–61
  • Microcontact printing on human tissue for retinal cell transplantation ARCHIVES OF OPHTHALMOLOGY Lee, C. J., Huie, P., Leng, T., Peterman, M. C., Marmor, M. F., Blumenkranz, M. S., Bent, S. F., Fishman, H. A. 2002; 120 (12): 1714-1718

    Abstract

    To demonstrate that microcontact printing, a modern materials fabrication technique, can be used to engineer the surface of human tissue and to show that inhibitory molecules can be used to pattern the growth of retinal pigment epithelial cells or iris pigment epithelial cells on human lens capsule for transplantation.Photolithographic techniques were used to fabricate photoresist-coated silicon substrates into molds. Poly(dimethylsiloxane)stamps for microcontact printing were made from these molds. The poly(dimethylsiloxane) stamps were then used to "wet-transfer" growth inhibitory molecules to the surface of prepared human lens capsules that were obtained during cataract surgery. Human retinal pigment epithelial and rabbit iris pigment epithelial cells were grown on a lens capsule substrate in the presence and absence of a patterned array of inhibitory factors.We found that human lens capsule could be microprinted with a precision similar to that obtained on glass or synthetic polymers. Retinal pigment epithelial cells and iris pigment epithelial cells cultured onto an untreated lens capsule showed spreading and formed into fusiform-appearing cells. In contrast, cells cultured on a lens capsule with a hexagonal micropattern of growth inhibitory molecules retained an epithelioid form within the inhibitory hexagons.Inhibitory growth molecules can be micropatterned onto human lens capsule, and these micropatterns can control the organization of retinal pigment epithelial cells or iris pigment epithelial cells cultured onto the lens capsule surface.Microprinting on autologous human tissue may facilitate efforts to effectively organize cell cultures and transplantations for the replacement of vital ocular tissues such as the retinal pigment epithelium in age-related macular degeneration.

    View details for PubMedID 12470147

  • Prospective randomized comparison of 3-day versus 1-hour preoperative ofloxacin prophylaxis for cataract surgery 105th Annual Meeting of the American-Academy-of-Ophthalmology Ta, C. N., Egbert, P. R., Singh, K., Shriver, E. M., Blumenkranz, M. S., de Kaspar, H. M. ELSEVIER SCIENCE INC. 2002: 2036–40

    Abstract

    To determine the efficacy of reducing conjunctival bacterial flora with topical ofloxacin when given for 3 days compared with 1 hour before surgery.Prospective, randomized, controlled trial.Ninety-two eyes from 89 patients were randomized to a control group (48 eyes) or study group (44 eyes).All patients from both groups received topical ofloxacin 0.3% 1 hour before surgery and a 5% povidone iodine scrub of the periorbital area before surgery. The patients in the study group received additional ofloxacin four times daily for 3 days before surgery.Conjunctival cultures were obtained at five separate time points and were inoculated in solid and liquid culture media. The presence of bacteria was determined, quantified, and identified.Forty-two percent of eyes in the control group had positive conjunctival culture immediately before surgery, compared with 19% of eyes in the study group (P < 0.05). Immediately after surgery, 34% and 14% of eyes had positive cultures in the control and study groups, respectively (P < 0.05). Quantitatively, fewer bacteria were isolated from eyes in the study group compared with those in the control group for culture samples that were obtained both before povidone iodine scrub and at the conclusion of surgery (P

    View details for PubMedID 12414411

  • Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration - Additional information regarding baseline lesion composition's impact on vision outcomes - TAP report No. 3 ARCHIVES OF OPHTHALMOLOGY Bressler, N. M., Arnold, J., Benchaboune, M., Blumenkranz, M. S., Fish, G. E., Gragoudas, E. S., Lewis, H., Schmidt-Erfurth, U., Slakter, J. S., Bressler, S. B., Manos, K., Hao, Y., Haynes, L., Koester, J., Reaves, A., Strong, H. A. 2002; 120 (11): 1443-1454

    Abstract

    To explore how baseline lesion composition influenced vision outcomes in patients with age-related macular degeneration (AMD) undergoing photodynamic therapy with verteporfin (Visudyne) for subfoveal choroidal neovascularization (CNV) in the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Investigation.Patients with subfoveal lesions secondary to AMD with evidence of classic CNV were categorized into 2 subgroups based on baseline color photographs and fluorescein angiograms assessed by graders at the Wilmer Photograph Reading Center (The Johns Hopkins University School of Medicine) before any outcome analyses as follows: (1) predominantly classic CNV (area of classic CNV >/=50% of the area of the entire lesion) or (2) minimally classic CNV (area of classic CNV <50% but >0% of the area of the entire lesion). Additional exploratory analyses were performed in the predominantly classic subgroup to investigate the effects of visual acuity, lesion size, prior laser photocoagulation, phakic status, micronutrient use, and presence of occult CNV on vision outcomes.Subgroup analyses of vision and fluorescein angiographic outcomes at 1 and 2 years after study enrollment were examined in an intent-to-treat analysis from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials.Compared with patients who had minimally classic CNV, patients with predominantly classic CNV had a worse initial mean visual acuity and smaller lesions and were more likely to have lesions that included blood or blocked fluorescence. When evaluated by treatment assignment and lesion composition, 84% to 88% completed the month 24 examination. In the subgroup with predominantly classic lesions, visual acuity outcomes were consistently better in verteporfin-treated patients. Outcomes for patients with predominantly classic lesions without occult CNV tended to be better than outcomes for patients with predominantly classic lesions with occult CNV, although the former tended to have smaller lesions and lower levels of visual acuity at baseline. Contrast sensitivity and fluorescein angiographic outcomes (total lesion size, progression of classic CNV, and absence of classic CNV) were better in verteporfin-treated patients than in placebo-treated patients in the predominantly classic and the minimally classic CNV subgroups. In patients with predominantly classic CNV, no interaction of the treatment benefit by phakic status, micronutrient use, or prior laser photocoagulation therapy was noted.Verteporfin therapy can safely reduce the risk of moderate and severe vision loss in patients with subfoveal lesions that are predominantly classic CNV secondary to AMD. While this benefit seemed to be even greater in the absence of occult CNV, the effect may be related to the smaller lesions and worse visual acuity associated with predominantly classic lesions without occult CNV and not solely to the lesion composition itself. These analyses support initial reports that verteporfin therapy should be used to treat patients with AMD who have predominantly classic CNV, with or without occult CNV, but suggest that further investigations should be performed to determine if lesions with a minimally classic composition might benefit when they are smaller and have lower levels of visual acuity.

    View details for Web of Science ID 000179203400002

    View details for PubMedID 12427056

  • Treatment of central retinal vein occlusion by vitrectomy with lysis of vitreopapillary and epipapillary adhesions, subretinal peripapillary tissue plasminogen activator injection, and photocoagulation AMERICAN JOURNAL OF OPHTHALMOLOGY Lam, H. D., Blumenkranz, M. S. 2002; 134 (4): 609-611

    Abstract

    To report a case of subretinal peripapillary tissue plasminogen activator (tPA) injection with vitreopapillary and epipapillary membrane dissection and peripheral photocoagulation in the treatment of central retinal vein occlusion.Interventional case report.A 79-year-old woman with a history of branch vein occlusion in the left eye presented with visual loss in the right eye for 4 months secondary to unresolved central retinal vein occlusion. She underwent vitrectomy, right eye, with lysis of vitreopapillary and epipapillary adhesions and hyaloid separation, subretinal peripapillary tissue tPA injection, peripheral photocoagulation, and air-fluid exchange.Postoperatively, funduscopic and fluorescein angiographic features of venous obstruction improved rapidly, with prompt reduction in intraretinal hemorrhages and disk and macular edema. The patient reported subjective improvement of vision in her right eye, although measured improvement was modest, from finger counting to 20/400.Subretinal administration of tPA, lysis of adhesions, and endophotocoagulation may be of value in resolving the obstructive component of selected cases of chronic central retinal vein occlusion associated with vitreopapillary and epipapillary traction.

    View details for Web of Science ID 000178446100019

    View details for PubMedID 12383824

  • Intravascular drug delivery with a pulsed liquid microjet ARCHIVES OF OPHTHALMOLOGY Fletcher, D. A., Palanker, D. V., Huie, P., Miller, J., Marmor, M. F., Blumenkranz, M. S. 2002; 120 (9): 1206-1208

    Abstract

    Occlusions of the retinal veins and arteries, associated with diseases such as hypertension and arteriosclerosis, are a major cause of severe and irreversible loss of vision. Treatments for retinal vascular diseases have been unsatisfactory owing in part to the difficulty of delivering drugs to the site of disease within the eye. In this article, we demonstrate that a new device, the vapor bubble-driven pulsed liquid microjet, can deliver drugs into the lumen of small vessels such as those found in the retina. A 15- micro m-diameter liquid jet traveling at more than 60 m/s was shown to penetrate and deliver fluid through the wall of a blood vessel that was 60 micro m in diameter. Perforation of the wall of the blood vessel did not extend beyond the jet diameter.

    View details for Web of Science ID 000178022300013

    View details for PubMedID 12215096

  • CME photodynamic therapy for choroidal neovascularization - A review RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Woodburn, K. W., Engelman, C. J., Blumenkranz, M. S. 2002; 22 (4): 391-405

    Abstract

    To review the biophysical basis and current state of therapy for photodynamic closure of subfoveal choroidal neovascularization in the eye.A review of the literature is included, which encompasses the chemical structure, biophysical mechanism of action, range of available agents, status of clinical trials, clinical indications, results of treatments, complications, and future directions.Photodynamic therapy has been shown to be effective in closing both experimental choroidal neovascularization in animal models as well as subfoveal choroidal neovascularization in humans. The therapy results in temporary closure of choroidal new vessels for a period of approximately 1 to 4 weeks. By 12 weeks, most patients have reperfusion or reproliferation of choroidal new vessels resulting in the need for retreatment to achieve continued closure and visual stabilization. Differences exist in the quantum yield, clinical efficiency, and light and sensitizer dose requirements between different classes of agents. Further clinical trials will be required to determine the optimal form of therapy, with verteporfin (Visudyne) as the only currently approved agent. Other agents, including tin etiopurpurin (Purlytin) and motexafin lutetium (Optrin), are currently undergoing phase III, and phase II trials, respectively.Photodynamic therapy is a promising treatment modality shown to be effective in achieving closure and stabilization of vision loss compared with placebo control in eyes with subfoveal choroidal neovascularization.

    View details for Web of Science ID 000177437200001

    View details for PubMedID 12172104

  • The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: A comparison with ophthalmoscopy and standardized mydriatic color photography AMERICAN JOURNAL OF OPHTHALMOLOGY Lin, D. Y., Blumenkranz, M. S., Brothers, R. J., Grosvenor, D. M. 2002; 134 (2): 204-213

    Abstract

    To evaluate single-field digital monochromatic nonmydriatic fundus photography as an adjunct in the screening of diabetic retinopathy.Prospective, comparative, observational case series.Patients with type I and type II diabetes mellitus (n = 197) were sequentially evaluated by three different techniques: single-field digital monochromatic nonmydriatic photography; dilated ophthalmoscopy by an ophthalmologist; and seven Early Treatment Diabetic Retinopathy Study (ETDRS) standardized 35-mm color stereoscopic mydriatic images. The seven stereoscopic color photographs served as the reference standard and were compared with either ophthalmoscopy or a single digital photograph transmitted electronically to a reading site. Levels of agreement were determined by kappa analyses. The sensitivity and specificity of the three methods were compared based on a threshold for referral to further ophthalmologic evaluation (ETDRS level > or =35).There was highly significant agreement (kappa = 0.97, P =.0001) between the degree of retinopathy detected by a single nonmydriatic monochromatic digital photograph and that seen in seven standard 35-mm color stereoscopic mydriatic fields. The sensitivity of digital photography compared with color photography was 78%, with a specificity of 86%. Agreement was poor (kappa = 0.40, P =.0001) between mydriatic ophthalmoscopy and the seven-field standard 35-mm color photographs. Sensitivity of ophthalmoscopy compared with color photography was 34%, with a specificity of 100%.A single nonmydriatic monochromatic wide-field digital photograph of the disk and macula was more sensitive for diabetic retinopathy screening than mydriatic ophthalmoscopy, the currently accepted screening method. When adjudicated by standard seven-field color photographs, the higher sensitivity of digital photography primarily reflected the reduced sensitivity of ophthalmoscopy in detecting early retinopathy.

    View details for Web of Science ID 000177169300008

    View details for PubMedID 12140027

  • Surgical therapy of central retinal vein occlusion by creation of choroidal retinal anastomosis Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Quiroz-Mercado, H., Blumenkranz, M. S., Palanker, D. V., Sanislo, S. R., Garcia-Aguirre, G., Magdalenic, R., Araya-Munoz, C. E., Ruiz, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U431–U431
  • A biodegradable matrix facilitates the use of lens capsule as a substrate for subretinal cell transplantation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Bilbao, K. V., Leng, T., Fung, A. E., Huie, P., Sanislo, S. R., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U972–U972
  • Directed ganglion cell growth and stimulation with microcontact printing as a prototype visual prosthesis interface Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Leng, T., Huie, P., Mehenti, N. Z., Peterman, M. C., Lee, C. J., Marmor, M. F., Sanislo, S. R., Beni, S. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U1279–U1279
  • The Pulsed Electron Avalanche Knife (PEAK (TM)) for intraocular surgery in patients with proliferative vitreoretinal disorders Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Blumenkranz, M. S., Quiroz-Mercado, H., Sanislo, S. R., Garcia, G., Dubnack, S., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U845–U845
  • The artificial synapse chip: A novel interface for a retinal prosthesis based on neurotransmitter stimulation and nerve regeneration Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Fishman, H. A., Peterman, M. C., Leng, T., Huie, P., Lee, C. J., Bloom, D. M., Sanislo, S. R., Marmor, M. F., Bent, S. F., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U803–U803
  • Tissue engineered lens capsule as a substrate for IPE and RPE transplantation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Fung, A. E., Lee, C. J., Leng, T., Bilbao, L. V., Peterman, M. C., Blumenkranz, M. S., Bent, S. F., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U973–U973
  • A new pulsed liquid microjet lot potential treatment of retinal vascular occlusions Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Sanislo, S. R., Blumenkranz, M. S., Vankov, A., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U988–U988
  • Effects of the pulsed electron avalanche knife on retinal tissue ARCHIVES OF OPHTHALMOLOGY Palanker, D. V., Marmor, M. F., Branco, A., Huie, P., MILLER, J. M., Sanislo, S. R., Vankov, A., Blumenkranz, M. S. 2002; 120 (5): 636-640

    Abstract

    To evaluate the precision of retinal tissue dissection by the pulsed electron avalanche knife (PEAK) and to assess possible toxic effects from this device.To demonstrate precision of cutting, bovine retina (in vitro) and rabbit retina (in vivo) were incised with the PEAK. Samples were examined by scanning electron microscopy and histologic examination (light microscopy). To evaluate possible toxic effects in rabbit eyes, 30 000 pulses were delivered into the vitreous 1 cm above the retina. Histologic examinations and electroretinography were performed at intervals up to 1 month after exposure.Cuts in postmortem bovine retina showed extremely sharp edges with no signs of thermal damage. Full-thickness cuts in living attached rabbit retina were similarly sharp and were typically less than 100 microm wide. No signs of retinal toxic effects were detected by histologic examination or electroretinography.The PEAK is capable of precise cutting through retinal tissue, and there are no demonstrable retinal toxic effects from its use. The precision and tractionless nature of PEAK cutting offers advantages over mechanical tools and laser-based instrumentation. We believe this new device will prove useful in a variety of vitreoretinal surgical applications.

    View details for PubMedID 12003616

  • Antibiotic susceptibility pattern of coagulase-negative staphylococci in patients undergoing Intraocular surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Ta, C. N., de Kaspar, H. M., Chang, R. T., Shriver, E. M., Egbert, P. R., Singh, K., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U1275–U1275
  • Bacterial contamination of paracentesis blades used in cataract surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Chang, R. T., Ta, C. N., Egbert, P. R., Singh, K., Haw, W. W., Shriver, E. M., Espinosa, L., Williams, D. Y., Blumenkranz, M. S., de Kaspar, H. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U73–U73
  • Multiresistant Staphylococcus epidermidis on the conjunctiva prior to intraocular surgery Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Shriver, E. M., Ta, C. N., Egbert, P. R., Singh, K., Chang, R. T., Blumenkranz, M. S., de Kaspar, H. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U860–U860
  • Guidelines for using verteporfin (Visudyne (R)) in photodynamic therapy to treat choroidal neovascularization due to age-related macular degeneration and other causes RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Arnold, J., Bauer, B., Blumenkranz, M. S., Bressler, N. M., Bressler, S. B., CHADER, G. J., Chakravarthy, U., Corcostegui, B., Fine, S. L., Foerster, M. H., Gragoudas, E. S., Harvey, P. T., Hendrikse, F., Immonen, I., Johnson, M., Kaiser, P. K., Kieselbach, G. F., Larsen, M., Leys, A., MARGHERIO, R. R., Menchini, U., MIELER, W. F., Mones, J., Moreira, C., Ohji, M., Prunte, C., Rosenfeld, P., Saperstein, D. A., Singerman, L., Soubrane, G., Straatsma, B. R., Syrdalen, P., Tornambe, P. E., Verdaguer, J., Wolf, S., Olson, J., Aabert, T. M., Schachat, A. P., Bressler, S. B., Mones, J., Miller, J. W., Lewis, H., Singerman, L., Soubrane, G., Fish, G. E., Jurklies, B., Pournaras, C. J., Sickenberg, M., Lim, J. I., Schmidt-Erfurth, U., Blumenkranz, M. S., Rosenfeld, P. J., Slakter, J. S., Johansson, I., Lobes, L., Ma, C., MARGHERIO, R. R., WILLIAMS, G. A., Koenig, F., Meredith, T., Harvey, P. T., Menchini, U., Potter, M. J., Stur, M., Bressler, N. M., Bressler, S. B., Deslandes, J. Y., Huber, G., Manjuris, U., Miller, J. W., Reaves, A., Sickenberg, M., Schmidt-Erfurth, U., Strong, A., Terlouw, G. 2002; 22 (1): 6-18
  • Pulsed liquid microjet for intravascular injection 12th Conference on Ophthalmic Technologies Palanker, D., Fletcher, D., Miller, J., Huie, P., Marmor, M., Blumenkranz, M. SPIE-INT SOC OPTICAL ENGINEERING. 2002: 72–75
  • Pulsed Electron Avalanche Knife (PEAK) for intraocular surgery INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Palanker, D. V., MILLER, J. M., Marmor, M. F., Sanislo, S. R., Huie, P., Blumenkranz, M. S. 2001; 42 (11): 2673-2678

    Abstract

    To develop a better and more economical instrument for precise, tractionless, "cold" cutting during intraocular surgery. The use of highly localized electric fields rather than laser light as the means of tissue dissection was investigated.A high electric field at the tip of a fine wire can, like lasers, initiate plasma formation. Micrometer-length plasma streamers are generated when an insulated 25 micron (microm) wire, exposed to physiological medium at one end, is subjected to nanosecond electrical pulses between 1 and 8 kV in magnitude. The explosive evaporation of water in the vicinity of these streamers cuts soft tissue without heat deposition into surrounding material (cold cutting). Streamers of plasma and the dynamics of water evaporation were imaged using an inverted microscope and fast flash photography. Cutting effectiveness was evaluated on both polyacrylamide gels, on different tissues from excised bovine eyes, and in vivo on rabbit retina. Standard histology techniques were used to examine the tissue.Electric pulses with energies between 150 and 670 microJ produced plasma streamers in saline between 10 and 200 microm in length. Application of electric discharges to dense (10%) polyacrylamide gels resulted in fracturing of the gel without ejection of bulk material. In both dense and softer (6%) gels, layer by layer shaving was possible with pulse energy rather than number of pulses as the determinant of ultimate cutting depth. The instrument made precise partial or full-thickness cuts of retina, iris, lens, and lens capsule without any evidence of thermal damage. Because different tissues require distinct energies for dissection, tissue-selective cutting on complex structures can be performed if the appropriate pulse energies are used; for example, retina can be dissected without damage to the major retinal vessels.This instrument, called the Pulsed Electron Avalanche Knife (PEAK), can quickly and precisely cut intraocular tissues without traction. The small delivery probe and modest cost make it promising for many ophthalmic applications, including retinal, cataract, and glaucoma surgery. In addition, the instrument may be useful in nonophthalmic procedures such as intravascular surgery and neurosurgery.

    View details for Web of Science ID 000171433300037

    View details for PubMedID 11581215

  • Terson's syndrome following epidural saline injection NEUROLOGY Naseri, A., Blumenkranz, M. S., Horton, J. C. 2001; 57 (2): 364

    View details for DOI 10.1212/WNL.57.2.364

    View details for Web of Science ID 000169994300041

    View details for PubMedID 11468336

  • Adjuvant methods in macular hole surgery: Intraoperative plasma-thrombin mixture and postoperative fluid-gas exchange OPHTHALMIC SURGERY AND LASERS Blumenkranz, M. S., Ohana, E., Shaikh, S., Chang, S., Coll, G., Morse, L. S., De Bustros, S. 2001; 32 (3): 198-207

    Abstract

    The optimal method for surgical management of idiopathic macular holes remains unknown. Adjuvant methods including intraoperative cytokines and postoperative fluid-gas exchange with and without laser have been described. We report on the safety and final results of routine intraoperative autologous plasma-thrombin mixture and postoperative fluid-gas exchange when necessary as an adjunct to the surgical therapy of this disease.A consecutive series of 114 patients (mean age 66.9 years) with primary idiopathic full thickness Stage II, III, and IV macular holes were primarily treated by vitrectomy, fluid/perfluorocarbon gas exchange, and application of autologous plasma-thrombin mixture to the macular hole. Visible epiretinal membranes were peeled but the normal appearing internal limiting membrane was not routinely stripped. Outcome measures included final Snellen visual acuity, rate of macular hole closure, complications, and number of supplemental procedures performed.Closed at one month, were 110 of 121 (91%) macular holes, including two that underwent repeat fluid/gas exchange and laser within the first two weeks after surgery. At the time of final follow-up (mean: 10.9 months), 110 of 121 (91%) macular holes were closed. This included 8 of 9 eyes that had reopening of the macular hole between one and 21 months successfully treated by repeat fluid-gas exchange and 2 eyes that underwent a second successful pars plana vitrectomy, membrane peeling, and repeat fluid-gas exchange. Overall, 98 of 121 eyes overall (81%) were successfully treated by a single surgery; 94 of 121 (78%) achieved two lines or greater of visual improvement; 83 of 121 (69%) achieved 20/70 or better vision; and 47 eyes (39%) achieved 20/40 or better vision. Complications in this series included infectious endophthalmitis (1 eye), intraoperative retinal break (2 eyes), late retinal detachment (5 eyes), transient mild intraocular pressure elevation (46 eyes), inflammatory response (six eyes), epiretinal membrane (6 eyes), intraretinal hemorrhages (1 eye), and cataract (33 of 99 phakic eyes underwent cataract extraction during the follow-up).A combination of intravitreal perfluorocarbon gas and autologous plasma-thrombin mixture (tissue glue) was well tolerated in most patients and did not result in any specific long-term complications. The use of supplemental fluid-gas exchange when necessary improved the final success rate. Further well-controlled and randomized studies will be required to determine the efficacy of this as an adjunct or alternative to other methods of treatment for macular holes.

    View details for Web of Science ID 000168620300003

    View details for PubMedID 11371086

  • Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: Two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2 AMERICAN JOURNAL OF OPHTHALMOLOGY Arnold, J., Kilmartin, D., Olson, J., Neville, S., Robinson, K., Laird, A., Richmond, C., Farrow, A., McKay, S., McKechnie, R., Evans, G., AABERG, T. M., Brower, J., Waldron, R., Loupe, D., Gillman, J., Myles, B., Saperstein, D. A., Schachat, A. P., Bressler, N. M., Bressler, S. B., Nesbitt, P., Porter, T., Hawse, P., Harnett, M., Eager, A., Belt, J., Cain, D., Emmert, D., George, T., Herring, M., McDonald, J., Mones, J., Corcostegui, B., Gilbert, M., Duran, N., Sisquella, M., Nolla, A., Margalef, A., Miller, J. W., Gragoudas, E. S., Lane, A. M., Emmanuel, N., Holbrook, A., Evans, C., Lord, U. S., Walsh, D. K., Callahan, C. D., Dubois, J. L., Moy, J., Kenney, A. G., Milde, I., Platz, E. S., Lewis, H., Kaiser, P. K., Holody, L. J., Lesak, E., LICHTERMAN, S., Siegel, H., Fattori, A., Ambrose, G., Fecko, T., Ross, D., Burke, S., Conway, J., Singerman, L., Zegarra, H., Novak, M., Bartel, M., Tilocco-DuBois, K., Ilc, M., Schura, S., Joyce, S., Tanner, V., Rowe, P., Smith-Brewer, S., Greanoff, G., Daley, G., Dubois, J., Lehnhardt, D., Kukula, D., Fish, G. E., Jost, B. F., Anand, R., Callanan, D., Arceneaux, S., Arnwine, J., Ellenich, P., KING, J., AGUADO, H., Rollins, R., ANDERSON, T., NORK, C., Duignan, K., Boleman, B., Jurklies, B., Pauleikhoff, D., Hintzmann, A., Fischer, M., Sowa, C., Behne, E., Pournaras, C. J., Donati, G., Kapetanios, A. D., Cavaliere, K., Guney-Wagner, S., Gerber, N., Sickenberg, M., Sickenberg, V., Gans, A., Hosner, B., Sbressa, A., Kozma, C., Curchod, M., Ardoni, S., Harding, S., Yang, Y. C., Briggs, M., Briggs, S., Phil, E. B., Tompkin, V., Jackson, R., Pearson, S., Natha, S., Sharp, J., Tompkin, A., Lim, J. I., Flaxel, C., Padilla, M., Levin, L., Walonker, F., CISNEROS, L., Nichols, T., Schmidt-Erfurth, U., Barbazetto, I., Laqua, H., Kupfer, R., Bulow, R., Glisovic, B., Bredfeldt, T., Elsner, H., Wintzer, V., Bahlmann, D., Michels, S., Gordes, R., Neppert, B., Grote, M., Honnicke, K., Blumenkranz, M. S., Little, H. L., Jack, R., Espiritu, L. M., Unyi, L., Regan, J., Lamborn, L., Silvestri, C., Rosa, R. H., Rosenfeld, P. J., Lewis, M. L., Rodriguez, B., Torres, A., MUNOZ, N., Contreras, T., Galvez, M., Hess, D., Cubillas, T., Rams, I., Slakter, J. S., Sorenson, J. A., Bruschi, P. A., Burke, K., Schnipper, E., Maranan, L., Scolaro, M., Riff, M., Agresta, E., Napoli, J., Johansson, I., Dedorsson, I., Stenkula, S., Hvarfner, C., Carlsson, T., Liljedahl, A. M., Fallstrom, S., Jacobsson, E., Hendeberg, K., Soubrane, G., Kuhn, D., Oubraham, H., Benelhani, A., Kunsch, A., Delhoste, B., Ziverec, G., Lasnier, M., Debibie, C., Lobes, L. A., OLSEN, K., Bahr, B. J., Worstell, N. T., Wilcox, L. A., Wellman, L. A., VAGSTAD, G., STEINBERG, D., Campbell, A., Ma, C., Dreyer, R., Williamson, B., Johnson, M., Crider, H., Anderson, H., Brown, T., Jelinek, K., Graves, D., POPE, S., Boone, R., Beaumont, W., MARGHERIO, R. R., WILLIAMS, G. A., Zajechowski, M., Stanley, C., Kulak, M., STREASICK, P., Szdlowski, L., Falk, R., Shoichet, S., Regan, G., MANATREY, P., CUMMING, K., Fadel, R., Mitchel, B., Vandell, L., Yesestrepsky, D., Medina, T., Bridges, C., Huston, G., Koenig, F., Benchaboune, M., Mezmate, K., Fontanay, S., Meredith, T., Binning, J., Gualdoni, J., Boyd, L., Ort, E., Barts, B., Allen, R., Dahl, J., Holle, T., Harvey, P. T., Kaus, L., Leuschner, D., Bolychuk, S., Hewitt, I., Voyce, J., Menchini, U., Bandello, F., Virgili, G., Lanzetta, P., Ambesi, M., Pirracchio, A., Tedeschi, M., Potter, M. J., Sahota, B., Hall, L., Le, G., Rai, S., Johnson, D., Stur, M., Lukas, J., Tittl, M., Docker, S., Vogl, K., Bressler, S. B., Bressler, N. M., Pieramici, D. J., Manos, K. S., Cooper, R., Denbow, R. L., Lowery, E. R., Phillips, D. A., Thibeault, S. K., Tian, Y., Alexander, J., Harnett, M., Hawse, P., Orr, P. R., Black, N., Escartin, P., Hartley, D., Haworth, P., Hecker, T., Hiscock, D., Jamali, F., Maradan, N., North, J., Norton, B., Stapleton-Hayes, T., Taylor, R., Huber, G., Deslandes, J. Y., Fsadni, M., Hess, I., de Pommerol, H., Bobillier, A., Reaves, A., Banasik, S., Birch, R., Koester, J., Stickles, R., Truett, K., McAlister, L., Parker, F., Strong, H. A., Azab, M., Buskard, N., Gray, T., Manjuris, U., Hao, Y., Su, X. Y., Mason, M., Taylor, R., Hynes, L., Arnold, J., Barbezetto, I., Birngruber, R., Bressler, N. M., Bressler, S. B., Donati, G., Fish, G. E., Flaxel, C. J., Gragoudas, E. S., Harvey, P., Kaiser, P. K., Koester, J. M., Lewis, H., Lim, J. I., Ma, C., MEREDITH, T. A., Miller, J. W., Mones, J., Murphy, S. A., Pieramici, D. J., Potter, M. J., Reaves, A., Rosenfeld, P. J., Schachat, A. P., Schmidt-Erfurth, U., Singerman, L., Strong, A., Stur, M., WILLIAMS, G. A., Bressler, N. M., Ulrike, M., Reaves, A., Strong, A., Beck, R. W., Bird, A. C., Coscas, G., Deutman, A., Jampol, L., Klein, R., Maguire, M., Bressler, N. M., Bressler, S. B., Deslandes, J. Y., Huber, G., Manjuris, U., Miller, J. W., Sickenberg, M., Schmidt-Erfurth, U., Strong, A., Reaves, A., Rosenfeld, P., Stur, M., Acreneaux, S., Margherio, R. P., Staflin, P., Bressler, N. M., Lim, J. I., Potter, M. J., Mones, J. M., Rosenfeld, P. J., Gragoudas, E. S., Miller, J. W., Schmidt-Erfurth, U. 2001; 131 (5): 541-560

    Abstract

    To determine if photodynamic therapy with verteporfin (Visudyne; Novartis AG, Bülach, Switzerland), termed verteporfin therapy, can safely reduce the risk of vision loss compared with a placebo (with sham treatment) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization, or with presumed early onset classic choroidal neovascularization with good visual acuity letter score.This was a double-masked, placebo-controlled (sham treatment), randomized, multicenter clinical trial involving 28 ophthalmology practices in Europe and North America. The study population was patients with age-related macular degeneration, with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1) occult with no classic choroidal neovascularization, best-corrected visual acuity score of at least 50 (Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent disease progression; or 2) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 (better than a Snellen equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) was administered by means of intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The main outcome measure was at least moderate vision loss, that is, a loss of at least 15 letters (approximately 3 lines), adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data.Two hundred ten (93%) and 193 (86%) of the 225 patients in the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in the placebo group completed the month 12 and 24 examinations, respectively. On average, verteporfin-treated patients received five treatments over the 24 months of follow-up. The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination, although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group. Between the month 12 and 24 examinations, the treatment benefit grew so that by the month 24 examination, the verteporfin-treated eyes were less likely to have moderate or severe vision loss. Of the 225 verteporfin-treated patients, 121 (54%) compared with 76 (67%) of 114 placebo-treated patients lost at least 15 letters (P =.023). Likewise, 67 of the verteporfin-treated patients (30%) compared with 54 of the placebo-treated patients (47%) lost at least 30 letters (P =.001). Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization. This subgroup included 166 of the 225 verteporfin-treated patients (74%) and 92 of the 114 placebo-treated patients (81%). In these patients, 91 of the verteporfin-treated group (55%) compared with 63 of the placebo-treated group (68%) lost at least 15 letters (P =.032), whereas 48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group (47%) lost at least 30 letters (P =.004). Other secondary outcomes, including visual acuity letter score worse than 34 (approximate Snellen equivalent of 20/200 or worse), mean change in visual acuity letter score, development of classic choroidal neovascularization, progression of classic choroidal neovascularization and size of lesion, favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline. Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions (4 disc areas or less) or lower levels of visual acuity (letter score less than 65, an approximate Snellen equivalent of 20/50(-1) or worse) at baseline. Prospectively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit. (ABSTRACT TRUNCATED)

    View details for Web of Science ID 000168609900001

    View details for PubMedID 11336929

  • Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin - 1-year results of a randomized clinical trial - VIP report no. 1 OPHTHALMOLOGY Arnold, J., Kilmartin, D., Olson, J., Neville, S., Robinson, K., Laird, A., Richmond, C., Farrow, A., McKay, S., Saperstein, D. A., AABERG, T. M., Johnson, J. B., Waldron, R., Loupe, D., Gillman, J., Myles, B., Schachat, A. P., Bressler, N. M., Bressler, S. B., Nesbitt, P., Porter, T., Hawse, P., Hartnett, M., Eager, A., Belt, J., Cain, D., Emmert, D., George, T., Herring, M., McDonald, J., Mones, J., Corcostegui, B., Gilbert, M., Duran, N., Sisquella, M., Nolla, A., Margalef, A., Miller, J. W., Gragoudas, E. S., Lane, A. M., Emmanuel, N., Holbrook, A., Evans, C., Lord, U. S., Walsh, D. K., Callahan, C. D., Dubois, J. L., Lewis, H., Kaiser, P. K., Holody, L. J., Lesak, E., LICHTERMAN, S., Siegel, H., Fattori, A., Ambrose, G., Fecko, T., Ross, D., Burke, S., Singerman, L., Zegarra, H., Novak, M., Bartel, M., Tilocco-DuBois, K., Iic, M., Schura, S., Mayes, S. J., Tanner, V., Rowe, P., Smith-Brewer, S., Kukula, D., Greanoff, G., Daley, G., Dubois, J., Lehnhardt, D., Fish, G. E., Jost, B. F., Anand, R., Callanan, D., Arceneaux, S., Arnwine, J., Ellenich, P., KING, J., AGUADO, H., Rollins, R., Jurklies, B., Pauleikhoff, D., Hintzmann, A., Fischer, M., Sowa, C., Behne, E., Pournaras, C. J., Donati, G., Kapetanios, A. D., Cavaliere, K., Guney-Wagner, S., Gerber, N., Sickenberg, M., Sickenberg, V., Gans, A., Hosner, B., Sbressa, A., Kozma, C., Curchod, M., Cancelli, S. A., Harding, S., Yang, Y. C., Briggs, M., Briggs, S., Tompkin, V., Jackson, R., Pearson, S., Natha, S., Sharp, J., Lim, J. I., Flaxel, C., Padilla, M., Levin, L., Walonker, F., CISNEROS, L., Nichols, T., Schmidt-Erfurth, U., Barbazetto, I., Laqua, H., Kupfer, R., Bulow, R., Glisovic, B., Bredfeldt, T., Elsner, H., Wintzer, V., Bahlmann, D., Michels, S., Blumenkranz, M. S., Little, H. L., Jack, R., Espiritu, L. M., Unyi, L., Regan, J., Lamborn, L., Silvestri, C., Rosa, R. H., Rosenfeld, P. J., Lewis, M. L., Rodriguez, B., Torres, A., MUNOZ, N., Contreras, T., Galvez, M., Hess, D., Cubillas, T., Rams, I., Slakter, J. S., Sorenson, J. A., Bruschi, P. A., Burke, K., Schnipper, E., Maranan, L., Scolaro, M., Riff, M., Agresta, E., Johansson, I., Dedorsson, I., Stenkula, S., Hvarfner, C., Carlsson, T., Liljedahl, A. M., Fallstrom, S., Jacobsson, E., Soubrane, G., Kuhn, D., Oubraham, H., Benelhani, A., Kunsch, A., Delhoste, B., Ziverec, G., Lasnier, M., Lobes, L. A., OLSEN, K., Bahr, B. J., Worstell, N. T., Wilcox, L. A., Wellman, L. A., VAGSTAD, G., STEINBERG, D., Campbell, A., Dreyer, R., Williamson, B., Johnson, M., Crider, H., MARGHERIO, R. R., WILLIAMS, G. A., Zajechowski, M., Stanley, C., Kulak, M., STREASICK, P., Szdlowski, L., Falk, R., Shoichet, S., Regan, G., MANATREY, P., CUMMING, K., Koenig, F., Benchaboune, M., Mezmate, K., Fontanay, S., Meredith, T., Binning, J., Gualdoni, J., Boyd, L., Ort, E., Barts, B., Allen, R., Dahl, J., Holle, T., Harvey, P. T., Kaus, L., Leuschner, D., Bolychuk, S., Hewitt, I., Menchini, U., Bandello, F., Virgili, G., Lanzetta, P., Ambesi, M., Pirracchio, A., Tedeschi, M., Potter, M. J., Sahota, B., Hall, L., Stur, M., Lukas, J., Tittl, M., Docker, S., Vogl, K., Bressler, S. B., Bressler, N. M., Pieramici, D. J., Manos, K. S., Cooper, R., Denbow, R. L., Lowery, E. R., Phillips, D. A., Thibeault, S. K., Tian, Y., Harnett, M., Hawse, P., Black, N., Escartin, P., Hartley, D., Haworth, P., Hecker, T., Hiscock, D., Jamali, F., Maradan, N., North, J., Norton, B., Stapleton-Hayes, T., Taylor, R., Huber, G., Deslandes, J. Y., Fsadni, M., Hess, I., de Pommerol, H., Bobillier, A., Reaves, A., Banasik, S., Koester, J., Gray, T., Truett, K., Baker, J., McAlister, L., Birch, R., Strong, A., Azab, M., Buskard, N., Manjuris, U., Hao, Y., Mason, M., McCurry, U., Barbazetto, I., Birngruber, R., Bressler, S. B., Bressler, N. M., Donati, G., Fish, G. E., Gragoudas, E. S., Harvey, P., Kaiser, P. K., Koester, J. M., Lewis, H., Lim, J. I., Ma, C., Miller, J. W., Mones, J., Murphy, S. A., Pieramici, D. J., Potter, M. J., Pournaras, C. J., Schachat, A. P., Schmidt-Erfurth, U., Singerman, L., Slakter, J. S., Soubrane, S., Strong, H. A., van den Berg, H., WILLIAMS, G. A., Bressler, N. M., Manjuris, U., Strong, H. A., Beck, R. W., Bird, A. C., Coscas, G., Deutman, A., Jampol, L., Klein, R., Maguire, M., Deslandes, J. Y., Huber, G., Miller, J. W., Sickenberg, M., Rosenfeld, P., Stur, M., Arceneaux, S., Margherio, R. P., Staflin, P. 2001; 108 (5): 841-852

    Abstract

    To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (<8 letter loss) safely in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia.Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North AMERICA:One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 microM and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better.Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water; n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000, microM larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present.The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis.At baseline, more than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least five letters (>/=1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01). Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment.Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients.

    View details for Web of Science ID 000168315500020

    View details for PubMedID 11320011

  • Evaluation of toxicity in vitreoretinal application of the Pulsed Electron Avalanche Knife (PEAK). Sanislo, S. R., Palanker, D. V., Miller, J., Marmor, M. F., Huie, P., Vankov, A., Branco, A., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2001: S429–S429
  • Photodynamic angiography: A new technique utilizing Lutex. Branco, A., Blumenkranz, M., Miller, J., Slakter, J., Sanislo, S., Woodburn, K., ROWE, T., Simpson, G. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2001: S512–S512
  • Immediate bacterial contamination of the aqueous humor in intraocular surgery. Braun, M., de Kaspar, H., Ta, C. N., Egbert, P., Singh, K., Blumenkranz, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2001: S256–S256
  • Antibiotic susceptibility pattern of coagulase-negative staphylococci in patients undergoing intraocular surgery. Ta, C. N., de Kaspar, H., Egbert, P., Singh, K., Blumenkranz, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2001: S254–S254
  • Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin - Two-year results of 2 randomized clinical trials - TAP report 2 ARCHIVES OF OPHTHALMOLOGY Blumenkranz, M. S., Bressler, N. M., Potter, M. J., Bressler, S. B., Mones, J. M., Harvey, P., Singerman, L. J., Gragoudas, E. S., Miller, J. W., Schmidt-Erfurth, U. 2001; 119 (2): 198-207

    Abstract

    To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD).Two multicenter, double-masked, placebo-controlled, randomized clinical trials.Twenty-two ophthalmology practices in Europe and North America.Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension on the retina measuring 5400 micrometer or less, with evidence of classic CNV and best-corrected visual acuity (approximate Snellen equivalent) between 20/40 and 20/200.The methods were similar to those described in our 1-year results, with follow-up examinations beyond 1 year continuing every 3 months (except for Photograph Reading Center evaluations, which occurred only at month 18 and month 24 examinations). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. The primary outcome was the proportion of eyes with fewer than 15 letters (approximately 3 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis. The last observation was carried forward to impute for any missing data.Three hundred fifty-one (87%) of 402 patients in the verteporfin group compared with 178 (86%) of 207 patients in the placebo group completed the month 24 examination. Beneficial outcomes with respect to visual acuity and contrast sensitivity noted at the month 12 examination in verteporfin-treated patients were sustained through the month 24 examination. At the month 24 examination for the primary outcome, 213 (53%) of 402 verteporfin-treated patients compared with 78 (38%) of 207 placebo-treated patients lost fewer than 15 letters (P<.001). In subgroup analyses for predominantly classic lesions (in which the area of classic CNV makes up at least 50% of the area of the entire lesion) at baseline, 94 (59%) of 159 verteporfin-treated patients compared with 26 (31%) of 83 placebo-treated patients lost fewer than 15 letters at the month 24 examination (P<.001). For minimally classic lesions (in which the area of classic CNV makes up <50% but >0% of the area of the entire lesion) at baseline, no statistically significant differences in visual acuity were noted. Few additional photosensitivity adverse reactions and injection site adverse events were associated with verteporfin therapy in the second year of follow-up.The visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years, providing more compelling evidence to use verteporfin therapy for these cases. For AMD patients with subfoveal lesions that are minimally classic, there is insufficient evidence to warrant routine use of verteporfin therapy.

    View details for Web of Science ID 000166866300004

    View details for PubMedID 11176980

  • Transient improvement in visual acuity and macular edema in central retinal vein occlusion accompanied by inflammatory features after pulse steroid and anti-inflammatory therapy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Shaikh, S., Blumenkranz, M. S. 2001; 21 (2): 176-178

    View details for Web of Science ID 000168148600013

    View details for PubMedID 11321147

  • Presumed acquired ocular toxoplasmosis in deer hunters RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Ross, R. D., Stec, L. A., Werner, J. C., Blumenkranz, M. S., Glazer, L., WILLIAMS, G. A. 2001; 21 (3): 226-229

    Abstract

    To describe acquired ocular toxoplasmosis in deer hunters.The authors describe five young men presenting with flu-like symptoms followed by visual loss due to a unilateral, focal necrotizing retinitis. All five men gave a history of ingesting undercooked or uncooked venison. All five had elevated toxoplasma serology, and all five improved clinically with an antitoxoplasma regimen.In previously healthy young men, flu-like symptoms associated with visual loss and retinitis should prompt questioning about hunting and raw game meat ingestion, especially when toxoplasmosis is suspected.

    View details for Web of Science ID 000169241600005

    View details for PubMedID 11421011

  • Fluorescein angiographic findings in ocular siderosis AMERICAN JOURNAL OF OPHTHALMOLOGY Shaikh, S., Blumenkranz, M. S. 2001; 131 (1): 136-138

    Abstract

    To report a case of siderosis from a retained intraocular iron foreign body manifesting localized retinal capillary nonperfusion documented by fluorescein angiography.Case Report. In a 35-year-old man with decreased vision in the left eye, studies included fundus photography, fluorescein angiography, visual field testing, and electrophysiology. Surgical foreign body extraction and histopathologic examination were performed.Preoperatively, in the left eye, humphrey visual fields and electrophysiology testing revealed marked depression. Fluorescein angiography demonstrated nasal capillary nonperfusion with occlusion of the second- and third-order arterioles extending along a gradient from the foreign body. Microscopic examination of the lens capsule confirmed the diagnosis of siderosis secondary to a retained iron foreign body.Extensive capillary nonperfusion may be associated with a retained iron intraocular foreign body, as documented by fluorescein angiography.

    View details for Web of Science ID 000166429600024

    View details for PubMedID 11162994

  • Lutetium texaphyrin (lu-tex): A potential new agent for ocular fundus angiography and photodynamic therapy AMERICAN JOURNAL OF OPHTHALMOLOGY Blumenkranz, M. S., Woodburn, K. W., Qing, F., Verdooner, S., Kessel, D., Miller, R. 2000; 129 (3): 353-362

    Abstract

    To investigate the suitability of lutetium texaphyrin (lu-tex) as a fluorescence imaging agent in the delineation of retinal vascular and choroidal vascular diseases. The utilization of an efficient fluorescent molecule that is also a photosensitizer represents a unique opportunity to couple diagnosis and therapy.Fundus fluorescence angiography comparing lu-tex (motexafin lutetium, Optrin, Pharmacyclics Inc, Sunnyvale, California) with the conventional angiographic dyes, sodium fluorescein, and indocynanine green (ICG), was performed on the eyes of normal and laser-injured New Zealand white rabbits. Plasma pharmacokinetic data and plasma protein binding were assessed in addition to light microscopy of the retina in both imaged and laser-injured eyes.Normal retinal and choroidal vasculature was well delineated by lu-tex angiography. Experimentally induced choroidal and retinal vascular lesions were enhanced by lu-tex and demonstrated different staining patterns than fluorescein or ICG, particularly at the margins of the lesions. Lu-tex cleared rapidly from the plasma, with 39.7% bound to the high-density lipoprotein (HDL) fraction while 15.8% was bound to the low-density lipoprotein (LDL) fraction. No evidence of retinal toxicity after dye administration was observed by either ophthalmoscopy and fundus photography or by light microscopy.Lu-tex angiography is a potentially valuable method for retinal vascular and choroidal vascular evaluation, and it has advantages over fluorescein and ICG angiography. The same agent could conceivably be used for both the identification of abnormal vasculature and subsequent photodynamic treatment.

    View details for Web of Science ID 000085807500013

    View details for PubMedID 10704552

  • Fluorescein angiographic changes in acute toxic retinopathy associated with polypharmacy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Shaikh, S., Shaikh, N., Blumenkranz, M. S. 2000; 20 (6): 685-688

    View details for Web of Science ID 000167054900025

    View details for PubMedID 11131433

  • The role of digital fundus photography in diabetic retinopathy screening. Digital Diabetic Screening Group (DDSG). Diabetes technology & therapeutics Lin, D. Y., Blumenkranz, M. S., Brothers, R. 1999; 1 (4): 477-487

    Abstract

    The role of digital monochromatic nonmydriatic fundus photography as an adjunct in the diagnosis of diabetic retinopathy is evaluated.197 patients were sequentially evaluated by three different techniques: dilated ophthalmoscopy by an experienced ophthalmologist, performance of 7 standard color mydriatic stereo fields, and a single digital monochromatic nonmydriatic image incorporating the disc and macula. Stereo color photographs served as the reference standard and were compared to either ophthalmoscopy performed by a physician, or a single digital photograph transmitted electronically to a reading site and evaluated by a trained non-physician grader. Sensitivity and specificity of the three methods were compared. The decision as to whether or not to refer to an ophthalmologist for potential treatment (Kaiser modified ETDRS level > 21) was then chosen for analysis.A single nonmydriatic monochromatic digital photograph appeared equivalent to standard color photography and more sensitive than mydriatic ophthalmoscopy in the detection of diabetic retinopathy in this patient population. Sensitivity of digital photography compared with color photography was 78%, and the specificity 86% contrasted with comparable ratios of 34% and 100% for ophthalmoscopy versus color photography. No patient identified by ophthalmoscopy alone for referral based on retinopathy level of > 21 would have been missed by a single digital monochromatic photographic image.A single nonmydriatic monochromatic wide field digital photograph of the disc and macula in diabetic patients is a sensitive and cost-effective means for detecting diabetic retinopathy in high-risk populations.

    View details for PubMedID 11484714

  • Management of submacular hemorrhage associated with retinal arterial macroaneurysms AMERICAN JOURNAL OF OPHTHALMOLOGY Humayun, M., Lewis, H., Flynn, H. W., Sternberg, P., Blumenkranz, M. S. 1998; 126 (3): 358-361

    Abstract

    Experience is reported with intraoperative pharmacologic lysis of recent submacular hemorrhage with tissue plasminogen activator followed by surgical drainage of the unclotted blood in patients with retinal arterial macroaneurysms.Nine eyes (nine patients) with a recent (< or = 7 days old) submacular hemorrhage involving the center of the fovea secondary to retinal arterial macroaneurysm that were managed with recombinant tissue plasminogen activator-assisted subretinal hemorrhage evacuation, including subretinal injection of tissue plasminogen activator and removal of the liquefied blood. Patients were followed for a mean 18 +/- 7 months (range, 7 to 30 months).All nine eyes had improved final corrected visual acuity after surgery, and eight eyes (89%) attained a corrected visual acuity of 20/60 or better (mean, 20/40; range, 20/20 to 20/200). Final corrected visual acuity was limited to 20/200 in one eye. Two eyes developed a cataract that required surgery.Submacular surgery with tissue plasminogen activator-assisted thrombolysis achieved improved best-corrected visual acuity in eyes with recent submacular hemorrhage involving the center of the fovea associated with retinal arterial macroaneurysm.

    View details for Web of Science ID 000075858500003

    View details for PubMedID 9744368

  • Treatment of reopened macular hole after vitrectomy by laser and outpatient fluid-gas exchange OPHTHALMOLOGY Ohana, E., Blumenkranz, M. S. 1998; 105 (8): 1398-1403

    Abstract

    This study aimed to assess a new nonsurgical treatment for patients who have previously undergone vitrectomy for macular hole with either persistent or reopened holes.A prospective, noncomparative, consecutive case series.Fifteen patients (15 eyes) were studied.Patients were treated by an outpatient method consisting of laser photocoagulation to the foveal pigment epithelium followed by fluid-gas exchange with 20% perfluoropropane gas and prone positioning. Patients without known allergy were treated with two doses of oral Diamox (250 mg) and ciprofloxacin (500 mg).Visual acuity, intraocular pressure, anatomic status of the macular hole, and cataract were the principal outcome measures studied.Thirteen of 15 macular holes were closed successfully with 1 or more procedures. All patients with macular hole closure achieved two lines or greater of vision improvement on Snellen testing. Three patients (20%) achieved 20/40 and nine (60%) achieved 20/80 or better. Three patients required more than one procedure. Four patients developed mild transient ocular hypertension.The combination of office-based outpatient fluid-gas exchange and laser appears to be a safe and cost-effective alternative to repeat surgery in selected patients with persistent or reopened macular holes after vitrectomy, in whom there are no visible epiretinal membranes, or in whom return to the operating room is undesirable for medical or personal reasons.

    View details for Web of Science ID 000075231500019

    View details for PubMedID 9709749

  • Exudative retinal detachment in X-linked retinoschisis OPHTHALMIC SURGERY AND LASERS Fong, D. S., Frederick, A. R., Blumenkranz, M. S., Walton, D. S. 1998; 29 (4): 332-335

    Abstract

    X-linked retinoschisis is a vitreoretinal dystrophy characterized by foveal and peripheral retinoschisis in the nerve fiber layer. Although many associated peripheral retinal findings have been reported, few reports have described massive exudative retinal detachments in patients with X-linked retinoschisis. The authors report the unusual occurrence of Coats'-like exudative retinopathy in two patients with X-linked retinoschisis. Both patients had peripheral massive exudative retinal detachments.

    View details for Web of Science ID 000073026800012

    View details for PubMedID 9571668

  • Laser treatment in eyes with large drusen - Short-term effects seen in a pilot randomized clinical trial Annual Meeting of the American-Academy-of-Ophthalmology Sternberg, P., Capone, A., AABERG, T. M., Hyatt, M., Gilman, J., SWORDS, R., Singerman, L., Rice, T. A., Zegarra, H., Novak, M. A., LICHTERMAN, S., Knight, D., Tilocco, K., Elk, M., Daley, G., Greanoff, G., Dubois, J., Lyon, A., Jampol, L., Weinberg, D., Chiapetta, B., Strugala, Z., Richine, L., Fish, G. E., Callanan, D., ANDERSON, T., Arceneaux, S., AGUADO, H., NORK, C., Boleman, B., Avery, P., Solomon, S., Orth, D., MacLeod, C., Morrison, C., Lluen-Johnson, K., Bryant, D., Doherty, D., Folk, J., Boldt, C., Fountain, C., Griffin, M., Heffron, E., Vogel, C., Ward, B., Northway, R., Sabates, F., Schuchard, R., Sabates, N., Poulose, A., Crosser, V., Matta, C., Gallimore, G., Holt, E. R., Wood, W., Wolfe, J., Hawkins, L., Taul, Y., Oldroyd, M., Cornett, L., Van Arsdall, J., SLADE, E., Harris, M., Chandra, S., Stevens, T., Meyers, F., Olsen, T., Walker, W., Knutson, G., Harrison, R., Neider, M., Wabers, H., Little, H., Blumenkranz, M., Showman, J., Hahn, T., JIMENEZ, L., Mattio, P., Gitter, K., Cohen, G., Newell, K., Ross, R., Schomaker, K., Fine, S. L., Brucker, A., Ho, A. C., Maguire, A., GRUNWALD, J., Dupont, J., Kirschner, J., Sterling, E., Sheehan, M., Nyberg, B., Weeney, L., Reynolds, J., Elkins, D., Klein, M., Wilson, D., Nolte, S., Evans, M., Wallace, P., MARGHERIO, R. R., TRESE, M. T., Hassan, T. S., CUMMING, K., Mitchell, B., STREASICK, P., Bridges, C., Huston, G., Szydlowski, L., Medina, T., McDonald, H. R., SCHATZ, H., Johnson, R., Ai, E., Wood, P., Di Angelo, M., Stolarczuk, M., Rosenfeld, I., Wild, S., Uy, J., Maguire, M. G., Brightwell-Arnold, M., Stanford, N. N., Dallas, V., Reich, A., Fatula, E., Ho, A. C., Javornik, N. B., FINKELSTEIN, D., Hawkins, B. S. ELSEVIER SCIENCE INC. 1998: 11–23
  • Tissue plasminogen activator in treatment of infectious endophthalmitis: A pilot study Sanislo, S. R., Lim, S. Y., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 1997: 5178–78
  • Subretinal hemorrhages in proliferative diabetic retinopathy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Morse, L. S., Chapman, C. B., Eliott, D., Benner, J. D., Blumenkranz, M. S., MCCUEN, B. W. 1997; 17 (2): 87-93

    Abstract

    To describe the clinical features of patients with advanced proliferative diabetic retinopathy who underwent vitrectomy and were found to have subretinal hemorrhages.The authors conducted a retrospective study of 49 patients with complications of proliferative diabetic retinopathy requiring pars plana vitrectomy and demonstrating the presence of subretinal hemorrhage. Preoperative, intraoperative, and postoperative clinical characteristics were evaluated. Patients were observed for a minimum of 6 months.The location, size, and clearance of subretinal hemorrhages revealed wide variation. Forty-two patients had focal subretinal hemorrhages, and 14 patients within this group had submacular hemorrhages. A retinal break was observed in 15 patients (31%). Only one patient required drainage of the subretinal hemorrhage to achieve retinal reattachment. Vitreous surgery resulted in 59% of patients achieving a visual acuity > or = 5/200. Seventy-nine percent had stable or improved vision, whereas 20% had worse vision after surgery.Subretinal hemorrhages appear to be an uncommon feature associated with long-term, advanced proliferative diabetic retinopathy and portend a guarded visual prognosis. These hemorrhages may occur spontaneously in previously untreated eyes and are often unsuspected until observed at the time of vitreous surgery. In general, removal of subretinal hemorrhages was not necessary to achieve macular anatomic attachment, and most patients experienced improved visual function after surgery. Diabetic subretinal hemorrhages may indicate a retinal break, and, therefore, careful ophthalmic inspection should be performed in these patients.

    View details for Web of Science ID A1997WW83100001

    View details for PubMedID 9143034

  • Microbiologic factors and visual outcome in the endophthalmitis vitrectomy study AMERICAN JOURNAL OF OPHTHALMOLOGY Han, D. P., Vine, A. K., Blodi, B. A., Elner, S. G., Johnson, M. W., Jessup, L. M., Khanderia, S., Pierson, C. L., Willis, J., McIver, F., Stanley, S., Sneed, S. R., Capone, A., AABERG, T. M., Lim, J. I., Sternberg, P., COFFMAN, D. S., Moore, C. N., Gardner, S. K., Nolte, F. S., FREMSTAD, A., Gibbs, D., Gilman, J., SWORDS, R., Aguilar, H. E., MEREDITH, T. A., LAKHANPAL, V., CHRISTIAN, F. D., Hood, M. A., Schwalbe, R. S., BILLINGS, E. E., Buie, W., MALLONEE, J. J., Millar, M. A., Verbeek, S., Campochiaro, P. A., PALARDY, C. B., Reynolds, L., Dick, J. D., Cain, D., DAMICO, D. J., Frederick, A. R., Morley, M. G., Pesavento, R. D., Puliafito, C. A., Topping, T. M., Finn, S. M., Raymond, L. A., Baker, A. S., Paton, B., Evans, C., Napoli, J., Kiernan, C., Makris, K., MCINNES, T., REIDY, W. T., White, R., Garfinkel, R. A., Pilkerton, A. R., Frantz, R. A., Abernathy, G. B., BARBACCIA, J. G., ENSEY, H. R., ORMES, C. A., Park, C. H., Caplan, J., Russel, K., Toma, R., Packo, K. H., DEBUSTROS, S., Flood, T. P., Glazer, L., DEALBA, M., Evanich, E., MONTWILL, M. A., ROTHMAN, J. J., Ruderman, G., Beard, M., Landau, W., Shen, M. H., Gordon, M., Graff, S., Kwiatkowski, K., Pappas, L., Bryant, D., Doherty, D., Morini, F., Arredondo, L., Garretson, B. R., GERENA, C., Hunt, M., KINNAIRD, S. M., Neri, T., Rice, T. A., Novak, M. A., Rwe, P. S., Jamieson, S., Newberry, D., RECH, G. R., Dul, M. J., KINSER, L., Strozewski, K., CLARKRATH, S., DELISIO, M., Dempsey, D. L., Kukula, D., PINTERSMITH, A., Rowe, P. S., SMITHBREWER, S., Ludwig, T., Chambers, R. B., Davidorf, F. H., Taylor, C. S., HALE, K. N., BUESCHING, W. J., Chaudhuri, C., COVER, N. J., SHORTLIDGE, G. R., Keating, M. J., Savage, S. J., ANDRZEJEWSKA, P., CORNETET, S., MILLIRON, J. D., Richmond, R., Schneider, L., Weisenberger, D., CANTRILL, H. L., RAMSAY, R. C., BRALLIER, A. B., Johnson, T. P., ROSSING, E. E., KNAUTH, K. A., MONAHAN, M. M., OESTREICH, N. W., CLARK, K. F., GLENNEN, A. M., Yarian, D. L., Green, S. N., Leff, S. R., MASCIULLI, L., Lucido, M. M., Ludwig, E. J., MARANO, C. L., Peters, L., Joho, K., VOLKERT, D. C., Andersen, F., Coffey, D., Schlosser, A., HONEYWELL, A., Mames, R. N., Driebe, W. T., Stern, G. A., Francis, A., Zam, Z. S., Cooper, R., Gaskins, D., SHAMIS, D. J., Willingham, M., Barker, K., Rosa, H., Friedman, S. M., Gardner, T. W., BLANKENSHIP, G. W., COYLE, C. J., BERO, C. J., HALAS, C., Schick, S., Walker, J., Cunningham, D., Lambert, H. M., CLOGSTON, P. S., FRADY, P. M., Gardner, S. N., Osato, M. S., CARR, L., Shigley, J., Lopez, P. F., Chong, L. P., Frambach, D. A., CISNEROS, L., Padilla, M., YEE, E. M., Nakamura, T., WALONKER, A. F., Morales, R., Nichols, T., HUETE, M. E., LIGGETT, P. E., Ober, R. R., QUILLENTHOMAS, B., Williams, M., BARR, C. C., Bloom, S. M., Greene, P. J., WHITTINGTON, G. K., Martin, M. E., Watson, G., JENKINSCURRY, B., GILKEY, L. A., HUELSMAN, S., Burton, T. C., MIELER, W. F., Pulido, J. S., REESER, F. H., Newman, J. L., WERNER, K. A., PISARZEWICZ, P. J., REINERIO, N. A., WALLOCH, M. L., WILMER, Z., Laabs, J., PICCHIOTTINO, R., Phillips, J., WIPPLINGER, W., ABRAMS, G. W., JURKIEWICZ, D. T., LEET, M. L., Mandel, P., Metzger, K., SUCHLA, L., Zarling, D., BALLES, M. W., Ryan, E. H., KNOBLOCH, W. H., Cook, S. M., LUKE, D. G., Ferrieri, P., SCHIMINSKY, N. M., GENIA, A., PHILIPH, D. A., STINSON, E. K., Wright, L. M., McMichael, W. C., MIELKE, S. J., PONWITH, L. J., Pavan, P. R., Pautler, S. E., COATS, M. L., KIRK, N. M., Millard, S. M., CASTELLANO, F. C., Edwards, C. R., Marquardt, A., McCormack, A. J., McCormick, M. T., RENSHAW, B., Restuccia, A., Campbell, M., Christopher, N., Garrett, L. S., HALKIAS, D. G., HOTHERSALL, K., Mickler, K., MINNICK, T. S., Burr, C., Saxon, W., ARCACHA, M. A., Carlton, S., EDISON, S. K., Mallis, M. J., SAYERS, T. L., SUDDS, T. W., TIBERIA, R. J., WOLABAUGH, S., Bradford, R. H., Parke, D. W., Wolf, T. C., Shofner, J. M., TOBEY, L. E., Jensen, H. G., Sanchez, D., Shofner, J., Burris, R., Drake, K. K., GRISSOM, K. R., Rowsey, J. J., WILKINSON, C. P., Brown, G. C., BENSON, W. E., FEDERMAN, J. L., LUCIER, A. C., Maguire, J. I., SARIN, L. K., Shakin, E. P., Sivalingam, A., Tasman, W., Vander, J. F., Ward, N., WEISBECKER, C. A., Agnew, C. L., Lambert, R., TOMER, T., Carlson, K., Franchine, G., SERFASS, M. S., Doft, B. H., Bergren, R. L., Lobes, L. A., OLSEN, K. R., RINKOFF, J. S., Metz, D. J., Leonard, M. N., Karenchak, L. M., Kowalski, R. P., Wellman, L. A., Wilcox, L. A., CAMPBELL, A. F., Steinberg, D. R., VAGSTAD, G. L., FLOOK, K. A., GOOD, M. M., KEENEN, B. J., MELLINGER, K. A., MARGHERIO, R. R., COX, M. S., MURPHY, P. L., TRESE, M. T., Werner, J. C., WILLIAMS, G. A., MANATREY, P. E., Prote, J. L., LUCAROTTI, R., Martin, S., Band, J., Bostic, G., CUMMING, K., Mitchell, B., REGAN, V. S., Bridges, C., Cox, S., Houston, G., Johnson, J., STREASIK, P., Wood, B., Blumenkranz, M. S., Cayo, L., Kaye, V., VALENZUELA, C. L., ORGEL, I. K., Poliner, L. S., Tornambe, P. E., CANNON, S. V., Nielsen, J. L., Carlson, A., Chan, P., DRAKE, L., Grim, M., Peterson, C., BORG, L. A., GILLYATT, J., Beyer, C., Hammer, M. E., Grizzard, W. S., SHANNON, T. L., TRAYNOM, J. R., COLLADO, M. J., MCMANUS, D. W., Sweeney, D. E., Adams, D. H., Watson, T. T., ANTWORTH, M. V., ARAOS, J. G., Greenwald, M. A., Habib, M., MYERS, S. K., OCKERS, K. M., THIBODEAU, J. A., Watkins, B., NELSEN, P. T., Rosenthal, J. G., MINTZ, F. V., BIEDENBACH, M., Leonardy, N. J., LAWNICZAK, S. M., Bork, C., HAGEAGE, G., Hunter, E. B., Marshall, M. J., Roman, P., Hill, R., Hofbauer, T., LEMANOWICZ, J., Cupples, H. P., Guzman, G. I., BRODEUR, R. J., Yee, D., DELAHA, E. C., GEYER, S. L., SLOVIS, S., Shields, W. J., Lauber, S., Michelitsch, K., Barza, M., Kassoff, A., WATLING, S., Wilson, L. A., Buehler, J. C., McVay, J., Kelsey, S. F., Wisniewski, S. R., Podobinski, G. K., Sillett, R. L., GROER, S., Avery, B., Belle, S. H., Boles, J., Henry, L., Shema, S. J., TITUSERNSTOFF, L., Davis, M., Magli, Y. L., HUBBARD, L., Thomas, S., Everett, D. F., MOWERY, R., Davis, K., Azen, S., COVEY, P., McCuen, B., Packer, A., Robbin, J. 1996; 122 (6): 830-846

    Abstract

    To evaluate the relationship between microbiologic factors, effect of treatment, and visual outcome in the Endophthalmitis Vitrectomy Study.Four hundred twenty patients were enrolled in the Endophthalmitis Vitrectomy Study between February 1990 and January 1994. Of these, 394 completed 9 to 12 months of follow-up. Patients presented with features of bacterial endophthalmitis within 6 weeks of cataract extraction or secondary intraocular lens implantation. The relations between visual outcome and the identity of infecting species, gram stain results, antibiotic susceptibilities, and presence of vitrectomy cassette growth were examined.Rates of achieving final visual acuity of 20/100 or better for the more common isolates were as follows: gram-positive, coagulase-negative micrococci, 84%; Staphylococcus aureus, 50%; streptococci, 30%; enterococci, 14%; and gram-negative organisms, 56%. A positive gram stain or infection with species other than gram-positive, coagulase-negative micrococci were significantly associated with poorer visual outcome (P < .001 for species group comparisons). However, presenting visual acuity was more powerful than microbiologic factors in predicting visual outcome and favorable response to vitrectomy. Bacterial growth from the vitrectomy cassette specimen had prognostic significance equivalent to growth from other intraocular sources.Visual prognosis was strongly associated with the type of infecting organism and gram stain positivity. However, visual acuity at initial presentation appeared to be more useful than microbiologic factors in predicting visual outcome and judging the value of immediate vitrectomy in acute bacterial endophthalmitis after cataract surgery.

    View details for Web of Science ID A1996VW75800009

    View details for PubMedID 8956638

  • Multicenter clinical experience using an Erbium:YAG laser for vitreoretinal surgery Annual Meeting of American-Academy-of-Ophthalmology DAMICO, D. J., Blumenkranz, M. S., Lavin, M. J., QUIROZMERCADO, H., Pallikaris, I. G., Marcellino, G. R., Brooks, G. E. LIPPINCOTT-RAVEN PUBL. 1996: 1575–85

    Abstract

    To evaluate the advantages, disadvantages, safety, complications, and surgical applicability of an erbium:YAG laser system for maneuvers in vitreoretinal surgery.A prospective, consecutive trial of 68 eyes in 66 patients undergoing vitreoretinal surgery in which an erbium:YAG laser with graduated output from 0.2 to 5.0 mJ per pulse, repetition rate of 2 to 30 Hz, and equipped with a flexible fiber optic and interchangeable 20-gauge intraocular fiber optic endoprobes was used to perform specific maneuvers, including transection, incision, and ablation of membranes, retinotomy, vessel coagulation, iridectomy, and lens tissue ablation. The patients were treated in five centers in contemporary vitreoretinal surgical settings for surgical indications, including proliferative diabetic retinopathy, proliferative vitreoretinopathy, epiretinal membrane, and retinopathy of prematurity.One hundred seventy-four maneuvers were performed with an overall surgical efficacy rating of excellent or good in 84% of maneuvers, ranging from a high of 100% for subretinal membrane transection to a low of 25% for coagulation of blood vessels. Complications included retinal break or photocoagulative injury in 5% of epiretinal membrane incisions, minor bleeding from transected retinal vessels during 29% of retinotomies, and intraocular lens damage during two posterior capsulotomies. The most significant limitation was the cautious pace used during maneuvers near the retinal surface.The erbium:YAG laser is capable of versatile new approaches offering precise tissue cutting and ablation in vitreoretinal surgical maneuvers with a high degree of safety. The main limitation encountered was the slow speed of certain critical maneuvers near the retina.

    View details for Web of Science ID A1996VN52800021

    View details for PubMedID 8874429

  • The selective effect of micropulse diode laser upon the retina Kim, S. Y., Sanislo, S. R., Dalal, R., Kelsoe, W. E., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 1996: 3584–84
  • RESULTS OF THE ENDOPHTHALMITIS VITRECTOMY STUDY - A RANDOMIZED TRIAL OF IMMEDIATE VITRECTOMY AND OF INTRAVENOUS ANTIBIOTICS FOR THE TREATMENT OF POSTOPERATIVE BACTERIAL ENDOPHTHALMITIS ARCHIVES OF OPHTHALMOLOGY Vine, A. K., Blodi, B. A., Elner, S. G., Johnson, M. W., Jessup, L. M., Pierson, C. L., Willis, J., McIver, F., Stanley, S., Sneed, S. R., Capone, A., AABERG, T. M., Lim, J. I., Sternberg, P., COFFMAN, D. S., Moore, C. N., Gardner, S. K., Nolte, F. S., FREMSTAD, A., Gibbs, D., Gilman, J., SWORDS, R., Aguilar, H. E., MEREDITH, T. A., LAKHANPAL, V., CHRISTIAN, F. D., Hood, M. A., Schwalbe, R. S., BILLINGS, E. E., Buie, W., MALLONEE, J. J., Millar, M. A., Verbeek, S., Campochiaro, P. A., PALARDY, C. B., Reynolds, L., Dick, J. D., Cain, D., DAMICO, D. J., Frederick, A. R., Morley, M. G., Pesavento, R. D., Puliafito, C. A., Topping, T. M., Finn, S. M., Raymond, L. A., Baker, A. S., Paton, B., Evans, C., Napoli, J., KIEMAN, C., Makris, K., REIDY, W. T., White, R., Garfinkel, R. A., Pilkerton, A. R., Frantz, R. A., Abernathy, G. B., BARBACCIA, J. G., ENSEY, H. R., ORMES, C. A., Park, C. H., Caplan, J., Russell, K., Toma, R., Packo, K. H., DEBUSTROS, S., Flood, T. P., Glazer, L., DEALBA, M., Evanich, E., MONTWILL, M. A., ROTHMAN, J. J., Ruderman, G., Beard, M., Landau, W., Shen, M. H., Gordon, M., Graff, S., Kwiatkowski, K., Pappas, L., Bryant, D., Doherty, D., Morini, F., Arredondo, L., Garretson, B. R., GERENA, C., Hunt, M., KINNAIRD, S. M., Rice, T. A., Novak, M. A., Rowe, P. S., Jamieson, S., Newbery, D., RECH, G. R., Dul, M. J., KINSER, L., Strozewski, K., CLARKRATH, S., DELISIO, M., Dempsey, D. L., Kukula, D., PINTERSMITH, A., SMITHBREWER, S., Ludwig, T., Chambers, R. B., Davidorf, F. H., Taylor, C. S., HALE, K. N., BUESCHING, W. J., Chaudhuri, C., SHORTLIDGE, G. R., COVER, N. J., Keating, M. J., Savage, S. J., ANDRZEJEWSKA, P., CORNETET, S., MILLIRON, J. D., Richmond, R., Schneider, L., Weisenberger, D., CANTRILL, H. L., RAMSAY, R. C., BRALLIER, A. B., Johnson, T. P., ROSSING, E. E., KNAUTH, K. A., MONAHAN, M. M., OESTREICH, N. W., CLARK, K. F., GLENNEN, A. M., Yarian, D. L., Green, S. N., Leff, S. R., MASCIULLI, L., Lucido, M. M., Ludwig, E. J., MARANO, C. L., Peters, L., Joho, K., VOLKERT, D. C., Andersen, F., Coffey, D., Schlosser, A., HONEYWELL, A., Mames, R. N., Driebe, W. T., Stern, G. A., Francis, A., Zam, Z. S., Cooper, R., Gaskins, D., SHAMIS, D. J., Willingham, M., Barker, K., Rosa, H., Friedman, S. M., Gardner, T. W., BLANKENSHIP, G. W., COYLE, C. J., BERO, C. J., HALAS, C., Schick, S., Walker, J., Cunningham, D., Lambert, H. M., CLOGSTON, P. S., Gardner, S. N., Osato, M. S., FRADY, P. M., CARR, L., Shigley, J., Lopez, P. F., Chong, L. P., CISNEROS, L., Padilla, M., YEE, E. M., Nakamura, T., WALONKER, A. F., Nichols, T., HUETE, M. E., LIGGETT, P. E., Ober, R. R., QUILLENTHOMAS, B., Williams, M., BARR, C. C., Bloom, S. M., Greene, P. J., WHITTINGTON, G. K., Martin, M. E., Watson, G., JENKINSCURRY, B., GILKEY, L. A., HUELSMAN, S., Han, D. P., Burton, T. C., MIELER, W. F., Pulido, J. S., REESER, F. H., Newman, J. L., WERNER, K. A., PISARZEWICZ, P. J., REINERIO, N. A., WALLOCH, M. L., WILMER, Z., Laabs, J., Phillips, J., PICCHIOTTINO, R., WIPPLINGER, W., ABRAMS, G. W., JURKIEWICZ, D. T., LEET, M. L., Mandel, P., Metzger, K., SUCHLA, L., Zarling, D., BALLES, M. W., Ryan, E. H., KNOBLOCH, W. H., Cook, S. M., LUKE, D. G., Ferrieri, P., SCHIMINSKY, N. M., GENIA, A., PHILIPH, D. A., STINSON, E. K., Wright, L. M., MCMICHAEL, M. C., MIELKE, S. J., PONWITH, L. J., Pavan, P. R., Pautler, S. E., COATS, M. L., KIRK, N. M., Millard, S. M., CASTELLANO, F. C., Edwards, C. R., Marquardt, A., McCormack, A. J., McCormick, M. T., RENSHAW, B., Restuccia, A., Campbell, M., Christopher, N., Garrett, L. S., HALKIAS, D. G., HOTHERSALL, K., Mickler, K., MINNICK, T. S., Burr, C., Saxon, W., ARCACHA, M. A., Carlton, S., EDISON, S. K., Mallis, M. J., SAYERS, T. L., SUDDS, T. W., TIBERIA, R. J., WOLABAUGH, S., Bradford, R. H., Parke, D. W., Wolf, T. C., SHOFNER, L. M., TOBEY, L. E., Jensen, H. G., Sanchez, D., Shofner, J., Burris, R., Drake, K. K., GRISSOM, K. R., Rowsey, J. J., WILKINSON, C. P., Brown, G. C., BENSON, W. E., FEDERMAN, J. L., LUCIER, A. C., Maguire, J. I., SARIN, L. K., Shakin, E. P., Sivalingam, A., Tasman, W., Vander, J. F., Ward, N., WEISBECKER, C. A., Agnew, C. L., Lambert, R., TOMER, T., Carlson, K., RANCHINE, G., SERFASS, M. S., Doft, B. H., Bergren, R. L., Lobes, L. A., OLSEN, K. R., RINKOFF, J. S., Metz, D. J., Leonard, M. N., Karenchak, L. M., Kowalski, R. P., Wellman, L. A., Wilcox, L. A., CAMPBELL, A. F., Steinberg, D. R., VAGSTAD, G. L., FLOOK, K. A., GOOD, M. M., KEENEN, B. J., MELLINGER, K. A., MARGHERIO, R. R., COX, M. S., MURPHY, P. L., LUCAROTTI, R., Martin, S., Band, J., Bostic, G., CUMMING, K., MANATREY, P. E., Mitchell, B., REGAN, V. S., Bridges, C., Cox, S., Houston, G., Johnson, J., STREASIK, P., Wood, B., Blumenkranz, M. S., Cayo, L., Kaye, V., VALENZUELA, C. L., ORGEL, I. K., Poliner, L. S., Tornambe, P. E., CANNON, S. V., Nielsen, J. L., Carlson, A., Chan, P., DRAKE, L., Grim, M., Peterson, C., BORG, L. A., GILLYATT, J., Beyer, C., Hammer, M. E., Grizzard, W. S., SHANNON, T. L., TRAYNOM, J. R., COLLADO, M. J., MCMANUS, D. W., Sweeney, D. E., Adams, D. H., Watson, T. T., ANTWORTH, M. V., ARAOS, J. G., Greenwald, M. A., Habib, M., MYERS, S. K., OCKERS, K. M., THIBODEAU, J. A., Watkins, B., Frambach, D. A., Morales, R., NELSEN, P. T., Rosenthal, J. G., MINTZ, F. V., BIEDENBACH, M., Leonardy, N. J., ORGER, I. K., LAWNICZAK, S. M., Bork, C., HAGEAGE, G., Hunter, E. B., Marshall, M. J., Roman, P., Hill, R., Hofbauer, T., LEMANOWICZ, J., Cupples, H. P., Guzman, G. I., BRODEUR, R. J., Yee, D., DELAHA, E. C., GEYER, S. L., SLOVIS, S., Shields, W., Lauber, S., Michelitsch, K. 1995; 113 (12): 1479-1496
  • COTTON-WOOL SPOTS AND THE EARLY DIAGNOSIS OF GIANT-CELL ARTERITIS OPHTHALMOLOGY MELBERG, N. S., Grand, M. G., Dieckert, J. P., Barney, N. P., Blumenkranz, M. S., Boone, D. E., Folk, J. C., STRANSKY, T. J. 1995; 102 (11): 1611-1614

    Abstract

    Giant cell arteritis is a common cause of severe visual loss in older individuals. Patients often present to the ophthalmologist having already lost vision in one eye. Detection of early ophthalmoscopic signs that precede irreversible visual loss in giant cell arteritis would allow preventative treatment in an otherwise frequently blinding disease.Case presentations.Seven patients with mild visual symptoms and results of an ophthalmologic examination significant for cotton-wool spots were found to have giant cell arteritis. On specific questioning, six of seven patients described constitutional symptoms consistent with giant cell arteritis. Six patients had an abnormally elevated Westergren erythrocyte sedimentation rate. Temporal artery biopsy confirmed giant cell arteritis in six patients. The seventh patient received a diagnosis of polymyalgia rheumatica. Prompt treatment with corticosteroids led to preservation of vision and uneventful resolution of the cotton-wool spots in all seven patients.Cotton-wool spots are an early ophthalmoscopic finding in giant cell arteritis and can precede severe visual loss. Recognition of the significance of cotton-wool spots, use of laboratory studies, and prompt treatment may preserve vision in an otherwise frequently blinding disease.

    View details for Web of Science ID A1995TD88300014

    View details for PubMedID 9098251

  • IMPROVED SURGICAL-TREATMENT OF FAMILIAL EXUDATIVE VITREORETINOPATHY IN CHILDREN AMERICAN JOURNAL OF OPHTHALMOLOGY GLAZER, L. C., MAGUIRE, A., BLUMERKRANZ, M. S., TRESE, M. T., GREEN, W. R. 1995; 120 (4): 471–79

    Abstract

    To evaluate current surgical results in patients with familial exudative vitreoretinopathy and study the histologic findings of epiretinal membranes obtained at the time of surgery.We performed phakic pars plana vitrectomy and membrane peeling on five patients (six eyes) with familial exudative vitreoretinopathy, who ranged in age from 18 months to 9 years and had traction retinal detachment. Membranes from two eyes (two patients) were analyzed by light and electron microscopy.The macula was reattached in all six eyes. Visual acuity improved after surgery in five of the six eyes, with two eyes improving from a preoperative visual acuity of 20/400 to a postoperative visual acuity of 20/25 and 20/60. Electron microscopic analysis of the membranes from two patients disclosed thick fibrocellular fragments with vascular elements and astrocytes.With current surgical techniques, there appears to be improvement in the anatomic reattachment rate and visual outcome in patients with familial exudative vitreoretinopathy. Amblyopia, reproliferation, and vitreous hemorrhage may limit long-term improvement in vision.

    View details for DOI 10.1016/S0002-9394(14)72661-3

    View details for Web of Science ID A1995RY82200007

    View details for PubMedID 7573305

  • TREATMENT OF MASSIVE SUBRETINAL HEMORRHAGE FROM COMPLICATIONS OF SCLERAL BUCKLING PROCEDURES AMERICAN JOURNAL OF OPHTHALMOLOGY Rubsamen, P. E., Flynn, H. W., Civantos, J. M., Smiddy, W. E., Murray, T. G., Nicholson, D. H., Blumenkranz, M. S. 1994; 118 (3): 299-303

    Abstract

    Vitrectomy techniques permit removal of subretinal hemorrhage, but the prognosis varies and depends principally on the cause of the hemorrhage. Nine consecutive patients undergoing pars plana vitrectomy with internal drainage of massive subretinal hemorrhage from complications of scleral buckling procedures were studied, to evaluate the long-term results. In all eyes, the final visual acuity was improved, compared with preoperative visual acuity, and was 20/80 or better in seven of nine cases. Recurrent retinal detachment secondary to proliferative vitreoretinopathy developed in two patients, but complete retinal reattachment was achieved after further procedures were performed. Patients with massive subretinal hemorrhage from complications of scleral buckling procedures comprise a subgroup of patients with subretinal hemorrhage in which internal drainage via pars plana vitrectomy is an acceptable alternative to observation only and may result in improved visual acuity outcomes.

    View details for Web of Science ID A1994PF31300002

    View details for PubMedID 8085585

  • EFFECTS OF SILICONE OIL REMOVAL - SILICONE STUDY REPORT-6 ARCHIVES OF OPHTHALMOLOGY HUTTON, W. L., AZEN, S. P., Blumenkranz, M. S., Lai, M. Y., MCCUEN, B. W., Han, D. P., Flynn, H. W., RAMSAY, R. C., RYAN, S. J. 1994; 112 (6): 778-785

    Abstract

    To evaluate the advisability of removing silicone oil from eyes after surgery for severe (with a classification of at least C-3) proliferative vitreoretinopathy.Subgroup analysis of the Silicone Study, a randomized, multicentered, surgical trial.Community- and university-based clinics.Two hundred twenty-two eyes with severe proliferative vitreoretinopathy followed up in the Silicone Study.Vitrectomy for proliferative vitreoretinopathy with silicone oil as the intraocular tamponade.Changes in visual acuity, recurrent retinal detachment, and incidence of complications.Ninety-nine (45%) of 222 eyes had surgery for silicone oil removal (oil-removed eyes). Compared with the eyes that did not undergo silicone oil removal (oil-retained eyes) evaluated at a comparable time after oil injection, oil-removed eyes at the examination prior to oil removal were more likely to be attached (85% vs 40%; P < .0001), have a visual acuity of 5/200 or greater (63% vs 35%; P < .0001), and not be hypotonous (5% vs 22%; P < .001). There was no association between the length of oil retention and incidence of recurrent retinal detachment after oil removal. Eyes with attached retinas at the time of oil removal generally improved in visual acuity at the last follow-up examination (P < .0001), which was not evident in eyes with detached retinas at the time of oil removal. In a matched-pair cohort analysis comparing both sets of eyes, there was an increased risk for recurrent retinal detachment at the last follow-up examination in the oil-removed eyes (odds ratio [OR], 2.1; P = .09). However, overall visual acuity improved for oil-removed eyes in 19 (29%) of 66 pairs and for oil-retained eyes in one (2%) of 66 pairs (OR, 19.0; P < .0001). Although nonsignificant, incidence rates of keratopathy (OR, 0.5) and hypotony (OR, 0.5) were lower in oil-removed eyes.Removal of silicone oil in anatomically successful eyes significantly increases the likelihood of improved visual acuity with a slight increase in the likelihood of recurrent retinal redetachment. There was a trend for a reduction in the incidence of complications in the oil-removed eyes.

    View details for Web of Science ID A1994NQ99400020

    View details for PubMedID 8002836

  • RELAXING RETINOTOMY WITH SILICONE OIL OR LONG-ACTING GAS IN EYES WITH SEVERE PROLIFERATIVE VITREORETINOPATHY SILICONE STUDY REPORT 5 AMERICAN JOURNAL OF OPHTHALMOLOGY Blumenkranz, M. S., AZEN, S. P., Aaberg, T., BOONE, D. C., Lewis, H., Radtke, N., RYAN, S. J. 1993; 116 (5): 557-564

    Abstract

    In the Silicone Study, 117 of 404 eyes (29%) with severe proliferative vitreoretinopathy (> or = C-3, full-thickness retinal folds in three or more quadrants) enrolled in the study were treated with vitrectomy, underwent a relaxing retinotomy, and were randomly assigned to treatment with long-acting gas or silicone oil. Forty-six eyes (20%) had undergone no previous vitrectomy (group 1); 71 eyes (42%) had undergone previous vitrectomy (group 2) with intraocular gas tamponade (P < .001). Group 1 eyes not undergoing retinotomy had better anatomic (six months) and visual (six and 24 months) outcomes and less hypotony (six months) than eyes that did regardless of tamponade (P < .05). For eyes undergoing retinotomy, silicone oil decreased the likelihood of hypotony (six months, P < .05). These differences were not found in group 2 eyes. We conclude that eyes undergoing a vitreous operation for the first time for the treatment of proliferative vitreoretinopathy can in most instances be successfully treated by conventional techniques without the need for relaxing retinotomy. Retinotomy may be required more often in patients undergoing repeat vitreous surgery for proliferative vitreoretinopathy, in which case both silicone oil and long-acting perflouropropane gas appear to be equally effective.

    View details for Web of Science ID A1993MF62400003

    View details for PubMedID 8238214

  • GIANT RETINAL-PIGMENT EPITHELIAL TEARS IN ACUTE RETINAL NECROSIS AMERICAN JOURNAL OF OPHTHALMOLOGY FOX, G. M., BLUMENKRANZ, M. 1993; 116 (3): 302–6

    Abstract

    We observed large peripheral tears of the retinal pigment epithelium in two patients, a 59-year-old man and a 15-year-old girl, who had acute retinal necrosis. These tears ranged from 90 to 180 degrees of the circumference of the peripheral retinal pigment epithelium and occurred in areas of previous retinal viral infection. Both patients had curled folds of tissue at the posterior edge of the retinal pigment epithelial tear. During vitrectomy at the time of fluid-air exchange, we noted the edge of these tears to sag posteriorly. Because of the area that was denuded of retinal pigment epithelium by the tears, we selected a more posterior location for argon laser endophotocoagulation in both patients. These large retinal pigment epithelial tears did not appear to have an adverse effect on the outcome of surgical treatment of the retinal detachments.

    View details for DOI 10.1016/S0002-9394(14)71347-9

    View details for Web of Science ID A1993LW15700005

    View details for PubMedID 8357054

  • A COMPARISON OF 5-FLUOROURIDINE AND 5-FLUOROURACIL IN AN EXPERIMENTAL-MODEL FOR THE TREATMENT OF VITREORETINAL SCARRING CURRENT EYE RESEARCH Ward, T., Hartzer, M., Blumenkranz, M., Lin, L. R. 1993; 12 (5): 397-401

    Abstract

    5-Fluorouridine (5-FUR), a ribonucleotide metabolite of 5-Fluorouracil (5-FU), is a more potent inhibitor of cellular proliferation and cell-mediated contraction in vitro than 5-FU. We compared the efficacy of these two drugs in a cell injection model of proliferative vitreoretinopathy using New Zealand albino rabbits. Forty-five eyes were divided into three groups and injected intravitreally with homologous fibroblasts. Eyes were examined at the time of injection and 7, 14, 21 and 28 days thereafter. By day 28, 70.5% (12 of 17) of 5-FUR treated eyes demonstrated no appreciable proliferative or tractional activity compared with 41.7% (5 of 12) of 5-FU treated eyes and 10% (1 of 10) of control eyes (p < 0.006). Medullary ray puckers developed in 29.4% (5 of 17) and 25% (3 of 12) of 5-FUR and 5-FU treated eyes respectively. No 5-FUR treated eye developed extensive tractional or combined tractional and rhegmatogenous retinal detachment compared with 33.3% (4 of 12) of 5-FU treated eyes and 80% (8 of 10) of control eyes (p < 0.001). These results suggest that 5-Fluorouridine may be more effective than 5-FU for the treatment of vitreoretinal scarring.

    View details for Web of Science ID A1993LH74700002

    View details for PubMedID 8344064

  • INTRAOCULAR EXTRACELLULAR CYCLIC-NUCLEOTIDE CONCENTRATIONS - THE INFLUENCE OF VITREOUS SURGERY GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY DALMAWEISZHAUZ, J., Blumenkranz, M., Hartzer, M., Hernandez, E. 1993; 231 (3): 184-186

    Abstract

    Levels of cAMP (23.1 pmol/ml) and cGMP (22.6 pmol/ml) are nearly equal in normal rabbit vitreous, although aqueous cAMP levels (29.9 pmol/ml) are 10 times higher than aqueous cGMP levels (2.6 pmol/ml) (P < 0.01). Intravitreal cAMP values decrease slightly 1 week after vitrectomy and lensectomy and return to normal whether the retina is attached, detached, or surgically removed. In contrast, intravitreal cGMP levels are profoundly depressed at 7 days (approximating normal aqueous levels) and are more than 50% lower than normal 30-42 days after surgery. The presence of these cyclic nucleotides in intraocular fluid and their responsiveness after surgery may signify a potential regulatory role in the physiologic responses of the eye to retinal detachment and its repair.

    View details for Web of Science ID A1993KP27400012

    View details for PubMedID 8385056

  • MICRORIPS OF THE RETINAL-PIGMENT EPITHELIUM ARCHIVES OF OPHTHALMOLOGY Ie, D., Yannuzzi, L. A., Spaide, R. F., WOODWARD, K. P., Singerman, L. J., Blumenkranz, M. S. 1992; 110 (10): 1443-1449

    Abstract

    We describe six patients with exudative age-related macular degeneration who had retinal pigment epithelial detachments with associated overlying neurosensory detachments. During fluorescein angiography, each patient demonstrated a solitary, intense, central serouslike leak at the edge of the retinal pigment epithelial detachment with passage of fluorescein into the subretinal space. In patients in whom the location of associated choroidal neovascularization was evident, the leakage site was remote to the area of neovascularization. Our observations suggest that these leaks result from small retinal epithelial rips, which we termed "microrips," that differ from conventionally described retinal pigment epithelial rips in clinical course and response to laser treatment. We hypothesize that the mechanisms and forces that generate these microrips are different from those producing conventionally described retinal pigment epithelial rips.

    View details for Web of Science ID A1992JT34900024

    View details for PubMedID 1384462

  • ACQUIRED-IMMUNODEFICIENCY-SYNDROME AND THE EYE DERMATOLOGIC CLINICS Blumenkranz, M. S., Penneys, N. S. 1992; 10 (4): 777-783

    Abstract

    Patients with AIDS or ARC may develop ocular manifestations falling in four broad categories: (1) conjunctival and periorbital disease, (2) neuro-ophthalmologic abnormalities, (3) retinal microangiopathy, and (4) opportunistic retinal and choroidal infections. Careful ophthalmologic examination generally permits identification and differentiation of these entities. Although ocular involvement is frequently a harbinger of an unfavorable systemic prognosis, specific drug therapy may be of some benefit in arresting disease in selected individuals. Further advances in the diagnosis and treatment of AIDS-related ocular tumors and infections may improve the quality of life for these patients.

    View details for Web of Science ID A1992JP72500011

    View details for PubMedID 1395158

  • RETINAL MANIFESTATIONS OF OCULAR LYMPHOMA (RETICULUM-CELL SARCOMA) OPHTHALMOLOGY RIDLEY, M. E., McDonald, H. R., Sternberg, P., Blumenkranz, M. S., Zarbin, M. A., Schachat, A. P. 1992; 99 (7): 1153-1160

    Abstract

    Diagnosis and treatment of ocular large cell lymphoma may lessen visual loss and prolong life. Although reports in the literature have described retinal infiltrates in eyes with large cell lymphoma, they have focused on the more prominent vitreous and subretinal pigment epithelial findings. Eyes with retinal infiltrates and hemorrhagic retinal necrosis are usually believed to harbor a microbial infection. The authors describe 5 patients, aged 57 to 85 years, with ocular lymphoma in whom the most prominent initial findings were in the retina.Patients presented with findings suggestive of an infectious retinal necrosis. When the initial therapy failed, investigators performed a vitreous biopsy. Two patients had a concomitant retinal biopsy. Radiation therapy was given to four patients.All five patients had vitreous cells. Three patients had prominent perivascular exudate. Four patients had grayish-white retinal infiltrates, and three patients had associated retinal hemorrhage. Three patients had subretinal small white spots. An edematous thickened retina developed in three patients, and hemorrhagic retinal necrosis developed in three patients. The initial diagnosis was believed to be acute retinal necrosis (ARN) in three patients, toxoplasmosis in one patient, and frosted branch angiitis in one patient. Vitreous biopsy was positive in two patients but negative in three patients. In two of these three patients, the diagnosis was established by retinal biopsy.Ocular lymphoma should be considered in the differential diagnosis of retinal vasculitis or necrotizing retinitis in a middle-aged or older patient. Retinal biopsy may be helpful in establishing the diagnosis.

    View details for Web of Science ID A1992JC54300036

    View details for PubMedID 1495797

  • VITRECTOMY WITH SILICONE OIL OR SULFUR-HEXAFLUORIDE GAS IN EYES WITH SEVERE PROLIFERATIVE VITREORETINOPATHY - RESULTS OF A RANDOMIZED CLINICAL-TRIAL - SILICONE STUDY REPORT .1. ARCHIVES OF OPHTHALMOLOGY AZEN, S. P., Barlow, W., BOONE, D. C., QUILLENTHOMAS, B., Chen, A., Lee, M. B., LINTON, K. L., Lai, M. Y., Lee, K., BOCHYNSKI, E., COX, M. S., Blumenkranz, M. S., MARGHERIO, R. R., MURPHY, P. L., TRESE, M. T., WILLIAMS, G. A., WITKOP, C., MANATREY, P., LICHTERMAN, S., CUMMING, K., MCCURLEY, S., SNYDER, V., Cox, S., BRIDGES, G., Johnson, J., SOBEL, J., STREASICK, P., VALENZUELA, C. L., FLYNN, H., BLANKENSHIP, G. W., CLARKSON, J., OLSEN, K., VANDENBROUCKE, R., ROBEY, M., ESPINAL, M., ATTAWAY, J., BUZNEGO, A., Carrico, D., DENBESTE, B., EUGENIDES, J., LEMKIN, P., KIPPENBROCK, R., MCCLINTOCH, M., Noda, N., OLIVA, O., Phillips, B., Hess, D., DURIA, E., MCCUEN, B. W., Anderson, B., DEJUAN, E., JAFFE, G. J., MACHEMER, R., STEFANSSON, E., TIEDEMAN, J. S., ANDERSON, M. M., SCHIRMER, R., BENETZ, B. A., AABERG, T. M., MEREDITH, T. A., KAPLAN, H. J., Sternberg, P., CURTIS, L., BOYLES, D., Moore, K., LASALLE, J., Gilman, J., Maio, M., SWORDS, R., FREEMAN, H. M., TOLENTINO, F. I., DORRIEN, K., BUSBY, A., RAPP, E., Anderson, S., Friedman, G., IMMERMAN, R., MORANDI, T., ODAY, T., ROSENBLUM, A., GLASER, B. M., DEBUSTROS, S., MICHELS, R., ALFORD, A., HUPP, J., NUNEZ, M. A., George, T., BURTON, T., HAN, D. A., MIELER, W. F., REKOW, S., PRESCOTT, A., RICHIE, M. N., WIPPLINGER, W., KREIGER, A., DIDDIE, K. R., SIDIKARO, J., YOSHIZUMI, M., EURE, J., ARMSTRONG, P., KILBURN, D., MARK, B., PETRUS, R., WELLS, P., GREENSPAN, J., THAYER, D., STERN, W. H., IRVINE, A. R., STONE, R. D., BALLESTEROS, F., Morris, B., NARAHARA, M., Wanner, M., LEAN, J. S., LIGGETT, P. E., RYAN, S. J., WALONKER, A. F., HOWARD, E., Clark, T., Delgado, S., Nichols, T., ROZIER, M. R., TETREAULT, G., FEDERMAN, J. L., Fischer, D., SARIN, L. K., TASMAN, W. S., REBER, R., Nichol, J., HUTTON, W. L., FULLER, D. G., JOST, B., SNYDER, W. R., SPENCER, W. B., VAISER, A., ANDERSON, T., Powell, D., DALRYMPLE, D., NORK, C., AGUADO, H., Evans, R., BARR, C. C., ISERNHAGEN, R. A., JAEGERS, K., RADTKE, N. D., WOOD, W. J., WAGNER, F., WHITTINGTON, G. K., CARPENTER, M., COONS, K., GILKEY, L. A., Rogers, C., SAUER, L., HUELSMAN, S., SLADE, E., RAMSAY, R. C., CANTRILL, H. L., KNOBLOCK, W. H., Ryan, E. H., COOK, S., MCDONOUGH, G., MONAHAN, M., PHILIP, D., PONWITH, L., STINSON, L., Anderson, K., OESTREICH, N., MCMICHAEL, B., VAGSTAD, G., IRVINE, A., Hilton, G., Lonn, L., Schwartz, A., Hoffman, J., HILLIS, A., AFIFI, A. A., FINKELSTEIN, D., MCLEAN, E. B., RUDISILL, A. S., WILKINSON, C. P., ABRAMS, G. W., Davis, M. D., MOWERY, R., DUDLEY, P., Goldberg, I., MCLAUGHLIN, J., RATHJEN, A., HUBBARD, L. 1992; 110 (6): 770-779

    Abstract

    Between September 1985 and September 1987, 101 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy but without prior vitrectomy were treated with vitrectomy and randomized to either a mixture of 20% sulfur hexafluoride gas and air or to 1000 centistokes of silicone oil. Between 50% and 60% of eyes that received silicone oil had visual acuity better than or equal to 5/200 compared with 30% to 40% of the eyes that received sulfur hexafluoride gas (P less than .05). Macula attachment was more frequent in eyes that received silicone oil than in those that received sulfur hexafluoride gas (80% vs 60%, P less than .05). Hypotony was more prevalent in eyes with a detached macula (40% to 50% for sulfur hexafluoride gas vs 25% to 30% for silicone oil) when compared with those with attached maculas (less than 5% for either modality). Keratopathy was more prevalent in eyes with detached maculas (about 55% to 60% for either modality) compared with eyes with attached maculas (25% to 30% for sulfur hexafluoride gas vs 10% to 15% for silicone oil). In a companion article, we show that these differences between a gas tamponade and silicone oil are not found for perfluoropropane gas.

    View details for Web of Science ID A1992HX94700016

    View details for PubMedID 1596224

  • VITRECTOMY WITH SILICONE OIL OR PERFLUOROPROPANE GAS IN EYES WITH SEVERE PROLIFERATIVE VITREORETINOPATHY - RESULTS OF A RANDOMIZED CLINICAL-TRIAL - SILICONE STUDY REPORT .2. ARCHIVES OF OPHTHALMOLOGY AZEN, S. P., Barlow, W., BOONE, D. C., QUILLENTHOMAS, B., Chen, A., Lee, M. B., LINTON, K. L., Lai, M. Y., Lee, K., BOCHYNSKI, E., LUNSFORD, M., COX, M. S., Blumenkranz, M. S., MARGHERIO, R. R., MURPHY, P. L., TRESE, M. T., WILLIAMS, G. A., WITKOP, C., MANATREY, P., LICHTERMAN, S., CUMMING, K., MCCURLEY, S., SNYDER, V., Cox, S., BRIDGES, G., Johnson, J., SOBEL, J., STREASICK, P., VALENZUELA, C. L., FLYNN, H., BLANKENSHIP, G. W., CLARKSON, J., OLSEN, K., VANDENBROUCKE, R., ROBEY, M., ESPINAL, M., ATTAWAY, J., BUZNEGO, A., Carrico, D., DENBESTE, B., EUGENIDES, J., LEMKIN, P., KIPPENBROCK, R., MCCLINTOCH, M., Noda, N., OLIVA, O., Phillips, B., Hess, D., DURIA, E., MCCUEN, B. W., Anderson, B., DEJUAN, E., JAFFE, G. J., MACHEMER, R., STEFANSSON, E., TIEDEMAN, J. S., ANDERSON, M. M., SCHIRMER, R., BENETZ, B. A., AABERG, T. M., MEREDITH, T. A., KAPLAN, H. J., Sternberg, P., CURTIS, L., BOYLES, D., Moore, K., LASALLE, J., Gilman, J., Maio, M., SWORDS, R., FREEMAN, H. M., TOLENTINO, F. I., DORRIEN, K., BUSBY, A., RAPP, E., Anderson, S., Friedman, G., IMMERMAN, R., MORANDI, T., ODAY, T., ROSENBLUM, A., GLASER, B. M., DEBUSTROS, S., MICHELS, R., ALFORD, A., HUPP, J., NUNEZ, M. A., George, T., BURTON, T., HAN, D. A., MIELER, W. F., REKOW, S., PRESCOTT, A., RICHIE, M. N., WIPPLINGER, W., KREIGER, A., DIDDIE, K. R., SIDIKARO, J., YOSHIZUMI, M., EURE, J., ARMSTRONG, P., KILBURN, D., MARK, B., PETRUS, R., WELLS, P., GREENSPAN, J., THAYER, D., STERN, W. H., IRVINE, A. R., STONE, R. D., BALLESTEROS, F., Morris, B., NARAHARA, M., Wanner, M., LEAN, J. S., LIGGETT, P. E., RYAN, S. J., WALONKER, A. F., HOWARD, E., Clark, T., Delgado, S., Nichols, T., ROZIER, M. R., TETREAULT, G., FEDERMAN, J. L., Fischer, D., SARIN, L. K., TASMAN, W. S., REBER, R., Nichol, J., HUTTON, W. L., FULLER, D. G., JOST, B., SNYDER, W. R., SPENCER, W. B., VAISER, A., ANDERSON, T., Powell, D., DALRYMPLE, D., NORK, C., AGUADO, H., Evans, R., BARR, C. C., ISERNHAGEN, R. A., JAEGERS, K., RADTKE, N. D., WOOD, W. J., WAGNER, F., WHITTINGTON, G. K., CARPENTER, M., COONS, K., GILKEY, L. A., Rogers, C., SAUER, L., HUELSMAN, S., SLADE, E., RAMSAY, R. C., CANTRILL, H. L., KNOBLOCK, W. H., Ryan, E. H., COOK, S., MCDONOUGH, G., MONAHAN, M., PHILIP, D., PONWITH, L., STINSON, L., Anderson, K., OESTREICH, N., MCMICHAEL, B., VAGSTAD, G., IRVINE, A., Hilton, G., Lonn, L., Schwartz, A., Hoffman, J., HILLIS, A., AFIFI, A. A., FINKELSTEIN, D., MCLEAN, E. B., RUDISILL, A. S., WILKINSON, C. P., ABRAMS, G. W., Davis, M. D., MOWERY, R., DUDLEY, P., Goldberg, I., MCLAUGHLIN, J., RATHJEN, A., HUBBARD, L. 1992; 110 (6): 780-792

    Abstract

    Between September 1987 and October 1990, 265 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy were treated with vitrectomy and randomized to treatment with perfluoropropane gas or silicone oil; 131 eyes had undergone no prior vitrectomy (group 1) while 134 eyes had undergone vitrectomy with intraocular gas tamponade (group 2). At the last examination, there were no differences between perfluoropropane gas and silicone oil in achieving visual acuity greater than or equal to 5/200 (43% vs 45% for group 1, 38% vs 33% for group 2) and complete posterior retinal reattachment (73% vs 64% for group 1, 73% vs 61% for group 2). For group 1 eyes followed up for at least 18 months, there was an advantage favoring perfluoropropane gas in achieving complete posterior retinal reattachment (83% vs 60% at 36 months, P = .045). The rates of reoperation and keratopathy were similar, while hypotony was more prevalent in eyes randomized to perfluoropropane gas (group 2). Regardless of tamponade, groups 1 and 2 had similar anatomic and visual success. However, hypotony was twice as prevalent in group 2 (perfluoropropane), and the prevalence of keratopathy increased with follow-up in group 2 (either tamponade). Either tamponade produced better results than those seen with sulfur hexafluoride gas (Silicone Study Report 1).

    View details for Web of Science ID A1992HX94700017

    View details for PubMedID 1596225

  • VITRECTOMY FOR DIABETIC MACULAR TRACTION AND EDEMA ASSOCIATED WITH POSTERIOR HYALOIDAL TRACTION 1991 ANNUAL MEETING OF THE AMERICAN ACADEMY OF OPHTHALMOLOGY Lewis, H., ABRAMS, G. W., Blumenkranz, M. S., Campo, R. V. ELSEVIER SCIENCE INC. 1992: 753–59

    Abstract

    Pars plana vitrectomy with separation of the posterior hyaloid was performed in 10 eyes with diabetic macular edema and traction associated with a thickened and taut premacular posterior hyaloid. Nine of the 10 eyes had previous macular photocoagulation. Preoperative fluorescein angiography showed a deep and diffuse pattern of leakage in the macula. Intraoperatively, the attached and thickened posterior hyaloid was lifted and separated from the retina. Postoperatively, vision improved in nine eyes. The macular traction and edema resolved in eight eyes and decreased in two. Complications included a vitreous hemorrhage, a rhegmatogenous retinal detachment, cataract formation, and a mild epimacular membrane, each occurring in one eye. Vitreous surgery can improve the visual prognosis of some eyes with diabetic macular traction and edema associated with a thickened and taut posterior hyaloid.

    View details for Web of Science ID A1992HU97500028

    View details for PubMedID 1594222

  • TREATMENT OF DISLOCATED CRYSTALLINE LENS AND RETINAL-DETACHMENT WITH PERFLUOROCARBON LIQUIDS RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Lewis, H., Blumenkranz, M. S., Chang, S. 1992; 12 (4): 299-304

    Abstract

    Removal of a crystalline lens dislocated into the vitreous cavity can be hazardous, particularly in the presence of a retinal detachment. Hard pieces of nuclear material may be difficult to extract and may repeatedly fall onto the retina when emulsification is attempted in the vitreous cavity. Cases involving four eyes with dislocated crystalline lens and rhegmatogenous retinal detachment, into which liquid perfluorocarbon was injected after vitrectomy to float the dislocated lens material off the retina and reattach the retina, are reported. The dislocated lens was removed while floating on the perfluorocarbon liquid, which also provided a cushion that prevented dropped fragments of lens from traumatizing the retina. In all four cases, surgery was not associated with complications and resulted in improvement in visual acuity and retinal reattachment.

    View details for Web of Science ID A1992KD14800002

    View details for PubMedID 1485014

  • AN OVERVIEW OF POTENTIAL APPLICATIONS OF HEPARIN IN VITREORETINAL SURGERY RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Blumenkranz, M. S., Hartzer, M. K., Iverson, D. 1992; 12 (3): S71-S74

    Abstract

    Heparin is a naturally occurring complex polysaccharide with properties that lend themselves to the potential treatment of proliferative ocular disorders. The biochemistry of heparin and its effects on the eye and cultured ocular cells under varied experimental conditions are discussed.

    View details for Web of Science ID A1992JP34200015

    View details for PubMedID 1455088

  • APPLICATIONS AND LIMITATIONS OF VITREORETINAL BIOPSY TECHNIQUES IN INTRAOCULAR LARGE CELL LYMPHOMA 3RD INTERNATIONAL CONGRESS ON VITREORETINAL SURGERY Blumenkranz, M. S., Ward, T., Murphy, S., Mieler, W., WILLIAMS, G. A., Long, J. LIPPINCOTT-RAVEN PUBL. 1992: S64–S70

    Abstract

    The cases of 4 patients with clinical signs of intraocular large cell lymphoma are described. Initial cytopathologic examination of vitrectomy specimens failed to establish the malignant character of the vitreous infiltrates. Three of the four patients eventually developed solid central nervous system tumors, intracranial biopsy samples of which revealed large cell lymphoma, 13 months to 42 months after initial examination. In one patient, transscleral retinochoroidal biopsy confirmed the diagnosis at the same time as negative vitreous cytologic examination. Results of cytopathologic examination alone of vitreous biopsy specimens may not be sufficient to make a diagnosis in certain cases of large cell lymphoma that are subsequently documented by CNS biopsy. Careful attention should be paid to the handling, processing, and interpretation of vitrectomy specimens from patients suspected of having intraocular large cell lymphoma. Consideration should be given to immunocytologic staining and interpretation by centers that are highly experienced in vitreous cytopathology.

    View details for Web of Science ID A1992JP34200014

    View details for PubMedID 1455086

  • SCLERAL LOOP FIXATION FOR POSTERIORLY DISLOCATED INTRAOCULAR LENSES - OPERATIVE TECHNIQUE AND LONG-TERM RESULTS ARCHIVES OF OPHTHALMOLOGY Maguire, A. M., Blumenkranz, M. S., WARD, T. G., Winkelman, J. Z. 1991; 109 (12): 1754-1758

    Abstract

    Surgical management of a posteriorly dislocated intraocular lens requires vitrectomy techniques to remove adherent vitreous and prevent traction on the retina. The lens implant may be repositioned in the posterior chamber by ciliary sulcus fixation or by transscleral or iris suture fixation. Previous suture fixation techniques require multiple needle penetrations through the sclera, cornea, or both. We described a simplified technique for repositioning a posteriorly dislocated intraocular lens in which sclerotomy incisions are utilized for fixation. Six patients are described, with long-term follow-up demonstrating stable anatomic status and favorable visual outcome.

    View details for Web of Science ID A1991HB56300039

    View details for PubMedID 1841589

  • LIPOSOME SUPPRESSION OF PROLIFERATIVE VITREORETINOPATHY - RABBIT MODEL USING ANTIMETABOLITE ENCAPSULATED LIPOSOMES INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Assil, K. K., Hartzer, M., Weinreb, R. N., NEHORAYAN, M., Ward, T., Blumenkranz, M. 1991; 32 (11): 2891-2897

    Abstract

    The effects of the antimetabolites, cytarabine (Ara-C) and 5-fluorouridine 5'-monophosphate (FUMP), encapsulated in multivesicular liposomes on formation of vitreous fibroproliferative membranes in New Zealand white (NZW) rabbits were studied. In pharmacokinetic studies, the drug half-life in the vitreous cavity was 124 hr after intravitreal administration of 1.0 mg of FUMP in liposomes. By contrast, the drug half-life after a single injection in nonliposome-treated controls was only 4.5 hr. In a heterologous dermal fibroblast model of proliferative vitreoretinopathy (PVR), there was a 92% decrease in frequency of tractional retinal detachments in rabbits receiving a single intravitreal injection of liposome-encapsulated 0.1 mg of FUMP compared with controls receiving liposomes without drug. A dose of 1 mg of Ara-C in liposome-treated rabbits was associated with only a 46% reduction in tractional detachment compared with controls. Multivesicular liposome-encapsulated FUMP may be useful for inhibiting formation of fibroproliferative membranes in the vitreous after vitreoretinal surgery.

    View details for Web of Science ID A1991GL40700006

    View details for PubMedID 1917392

  • INHIBITION OF INTRAOCULAR FIBRIN FORMATION FOLLOWING INFUSION OF LOW-MOLECULAR-WEIGHT HEPARIN DURING VITRECTOMY ARCHIVES OF OPHTHALMOLOGY IVERSON, D. A., Katsura, H., Hartzer, M. K., Blumenkranz, M. S. 1991; 109 (3): 405-409

    Abstract

    We studied the inhibition of intraocular fibrin formation following infusion of 5 IU/mL of low-molecular-weight heparin sodium (Fragmin, KabiVitrum AB, Stockholm, Sweden) during lensectomy, vitrectomy, and retinotomy in the rabbit model. Surgery was performed on 18 eyes, with nine receiving low-molecular-weight heparin and nine serving as controls. Masked postoperative examinations assessed fibrin quantity, corneal clarity, media clarity, and amount of vitreous hemorrhage. Five (56%) of nine eyes receiving low-molecular-weight heparin did not show fibrin exudation development, with the remainder demonstrating a minimal fibrin response. Eight (89%) of nine control eyes demonstrated prominent fibrin exudation, with five (56%) showing development of a fibrin clot that obscured two or more quadrants of the posterior chamber. No significant difference in the degree of vitreous hemorrhage was noted between groups. Corneal clarity was improved in the heparin-treated group.

    View details for Web of Science ID A1991FB46300044

    View details for PubMedID 2003803

  • INDICATIONS AND RESULTS OF RELAXING RETINOTOMY OPHTHALMOLOGY IVERSON, D. A., WARD, T. G., Blumenkranz, M. S. 1990; 97 (10): 1298-1304

    Abstract

    The authors report their results of a consecutive series of 40 eyes undergoing relaxing retinotomy during vitrectomy to achieve retinal reattachment for the following indications: proliferative vitreoretinopathy (PVR), 21 eyes (52%); trauma, 10 eyes (25%); diabetic retinopathy, 6 eyes (15%); and expulsive choroidal hemorrhage, 3 eyes (8%). Thirty eyes (75%) had undergone previous vitreoretinal procedures. Extended tamponade was achieved in all cases with either silicone oil (27 eyes, 68%) or long-acting gas (13 eyes, 32%). Retinotomy size ranged from 45 degrees to 360 degrees. Intraoperative retinal attachment was possible in all eyes with 33 (83%) achieving total or subtotal retinal attachment including the macula for 5 months or more. Twenty-seven eyes (68%) achieved 3/200 visual acuity or better and 10 (37%) achieved 20/400 or better. Thirteen eyes (32%) failed to achieve 3/200 visual acuity secondary to recurrent detachment (18%), corneal decompensation (8%), macular dysfunction (5%), and glaucoma (3%).

    View details for Web of Science ID A1990EC68200015

    View details for PubMedID 2243680

  • SUBRETINAL HEMORRHAGE MANAGEMENT BY PARS-PLANA VITRECTOMY AND INTERNAL DRAINAGE ARCHIVES OF OPHTHALMOLOGY WADE, E. C., Flynn, H. W., OLSEN, K. R., Blumenkranz, M. S., Nicholson, D. H. 1990; 108 (7): 973-978

    Abstract

    We reviewed 14 consecutive cases of subretinal hemorrhage involving the macula, in which surgery to remove the hemorrhage was performed by the authors between February 1984 and January 1989. All patients underwent pars plana vitrectomy and internal subretinal hemorrhage drainage. The causes of subretinal hemorrhages in group 1 were primary rhegmatogenous retinal detachments (three eyes), complications from scleral buckling procedures (three eyes), traumatic retinal detachments (two eyes), and sickle cell retinopathy associated with anticoagulation therapy after a pulmonary embolus (one eye). Group 2 consisted of five eyes with massive subretinal hemorrhage associated with age-related macular degeneration. In group 1, recurrent postoperative retinal detachment occurred in five eyes but reattachment was achieved in eight of the nine eyes, and final visual acuities were 20/400 or better in those eight eyes. In group 2, marked subretinal fibrosis occurred in two eyes. Although three eyes had improved visual acuities, final visual acuities were 5/200 or worse in all five eyes.

    View details for Web of Science ID A1990DP19200026

    View details for PubMedID 2369357

  • TISSUE PLASMINOGEN-ACTIVATOR AND PENETRATING KERATOPLASTY OPHTHALMIC SURGERY AND LASERS Heidemann, D. G., WILLIAMS, G. A., Blumenkranz, M. S. 1990; 21 (5): 364-365

    Abstract

    We report a patient who developed severe intraocular fibrin formation following penetrating keratoplasty and vitrectomy surgery. The fibrin response worsened despite aggressive treatment with topical steroids. On the second postoperative day, 25 micrograms of intracameral tissue plasminogen activator was administered, resulting in rapid resolution of the fibrin response. The graft remained clear. We believe tissue plasminogen activator may be useful in selected cases of severe, recalcitrant postkeratoplasy fibrin formation.

    View details for Web of Science ID A1990DK90800013

    View details for PubMedID 2116614

  • CHOROIDAL NEOVASCULAR MEMBRANE AND OTHER CHORIORETINAL COMPLICATIONS OF ACQUIRED SYPHILIS AMERICAN JOURNAL OF OPHTHALMOLOGY Halperin, L. S., Lewis, H., Blumenkranz, M. S., Gass, J. D., Olk, R. J., Fine, S. L. 1989; 108 (5): 554-562

    Abstract

    We reviewed ten patients who had posterior segment complications of acquired syphilis. Five of these patients had a neovascular membrane of the choroid associated with secondary or tertiary syphilis. Vision was stabilized after laser photocoagulation in one patient who had a choroidal neovascular membrane. Five additional patients had ocular manifestations including uveitis, optic neuritis, neuroretinitis, chorioretinitis, retinal hemorrhages, arterial and venous occlusion, vasculitis, and retinitis. Treatment of chorioretinal complications of syphilis with intravenous penicillin, if initiated early in the course of the disease, may result in excellent visual recovery.

    View details for Web of Science ID A1989AX85100011

    View details for PubMedID 2479270

  • SILICONE OIL FOR THE TREATMENT OF SEVERE PROLIFERATIVE DIABETIC-RETINOPATHY OPHTHALMOLOGY BROURMAN, N. D., Blumenkranz, M. S., COX, M. S., TRESE, M. T. 1989; 96 (6): 759-764

    Abstract

    Although silicone oil is being used with increasing frequency for proliferative vitreoretinopathy (PVR), few studies have reported on its use for severe forms of proliferative diabetic retinopathy (PDR). Vitreous microsurgery with silicone oil tamponade was performed on 34 patients (37 eyes) with refractory severe neovascular glaucoma and/or recurrent retinal detachment (RD) from PDR that failed to respond to conventional techniques including vitrectomy, membrane peeling, gas tamponade and photocoagulation. With all patients followed a minimum of 6 months (mean, 13 months), anatomic attachment was maintained in 26 (70%) of the eyes. At the last follow-up examination, a final visual acuity of at least 5/200 was found in 9 (24%) of 37 eyes and 9 (35%) of 26 anatomically successful cases. Regression of iris neovascularization occurred in 8 (36%) of 22 eyes with rubeosis and the silicone oil was removed in 3 (8%) eyes. Significant complications included band keratopathy in nine (24%) eyes, corneal decompensation in three (8%) eyes, and recurrent retinal detachment in seven (19%) eyes.

    View details for Web of Science ID A1989U938300005

    View details for PubMedID 2472586

  • SELECTION OF THERAPEUTIC AGENTS FOR INTRAOCULAR PROLIFERATIVE DISEASE .3. EFFECTS OF FLUOROPYRIMIDINES ON CELL-MEDIATED CONTRACTION OF HUMAN-FIBROBLASTS EXPERIMENTAL EYE RESEARCH Hartzer, M. K., Blumenkranz, M. S., HAJEK, A. S., Dailey, W. A., Cheng, M., Margherio, A. R. 1989; 48 (3): 321-328

    Abstract

    We evaluated the efficacy of 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUR) as anticontractile agents in an in vitro model that measures the ability of human and rabbit fibroblasts to contract a collagen gel. Human fibroblasts were more contractile than rabbit fibroblasts, required higher concentrations of 5-FUR for inhibition of contraction, and were able to tolerate higher doses of the drug. 5-FU failed to inhibit contraction of human fibroblasts at concentrations up to 1.5 mM (200 micrograms ml-1), but significantly inhibited rabbit fibroblast contraction, although to a lesser degree than 5-FUR under similar conditions. 5-Fluorouridine (100 microM, 26 micrograms ml-1) inhibited contraction of human fibroblasts by more than 80%, whereas only 10 microM (2.6 micrograms ml-1) 5-FUR was required for 90% inhibition of rabbit fibroblast contraction. 5-FUR was cytotoxic to rabbit fibroblasts at concentrations of 200 microM (52 micrograms ml-1) or greater, but 800 microM was non-toxic to human fibroblasts after 96 hr exposure. At concentrations of 1.5 mM, 5-FU had no significant effects on the viability of either human or rabbit fibroblasts. These results suggest that 5-FUR may prove useful for the treatment of human ocular proliferative disorders in which contraction of fibrocellular elements is thought to play a part. They also suggest that fluoropyrimidine dosages found to be effective in a rabbit model of proliferative vitreoretinopathy may be less effective in humans and that 5-FUR levels shown to be toxic to rabbit-derived cells may be tolerated by humans cells.

    View details for Web of Science ID A1989T547600001

    View details for PubMedID 2924816

  • VISUAL RESULTS AND COMPLICATIONS AFTER RETINAL REATTACHMENT IN THE ACUTE RETINAL NECROSIS SYNDROME - THE INFLUENCE OF OPERATIVE TECHNIQUE RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Blumenkranz, M., CLARKSON, J., Culbertson, W. W., Flynn, H. W., Lewis, M. L., Young, G. M. 1989; 9 (3): 170-174

    Abstract

    The authors compare the complications and visual results encountered in a consecutive series of 16 eyes undergoing retinal reattachment surgery for retinal detachment associated with the acute retinal necrosis syndrome. Eight eyes were treated with scleral buckling, vitrectomy, and cryotherapy with or without gas injection. Eight consecutive eyes (with one exception) were treated by the combination of vitrectomy, gas injection and laser photocoagulation with or without primary lensectomy and not subjected to scleral buckling as a primary procedure. The final reattachment rate was 93.8% (15 of 16 eyes) with no significant difference between the primary scleral buckle group (87.5%) and the non-buckle group (100%). Retinal reoperation and complication rates were higher in the primary buckle group and final visual acuities better in the non-buckle group despite comparable preoperative characteristics.

    View details for Web of Science ID A1989AU77800002

    View details for PubMedID 2595108

  • ACUTE MULTIFOCAL HEMORRHAGIC RETINAL VASCULITIS OPHTHALMOLOGY Blumenkranz, M. S., KAPLAN, H. J., Clarkson, J. G., Culbertson, W. W., WILLIAMS, G. A., Kleiner, R. C., MEISSNER, R. H. 1988; 95 (12): 1663-1672

    Abstract

    The authors present a series of seven patients with acute visual loss associated with mild anterior uveitis, multifocal retinal vasculitis, retinal capillary nonperfusion, retinal hemorrhage, disc swelling, and vitreitis. Oral prednisone was of some benefit in these patients and oral acyclovir was generally ineffective. Neovascular complications including retinal, disc, choroidal, and iris new vessels were common, requiring photocoagulation in five patients. Horseshoe tears developed in two patients in zones of uninvolved retina but retinal detachment did not occur. The etiology remains unknown, although it may represent either a localized ocular form of Behçet's disease or other systemic syndrome, infection with a herpes group virus other than zoster varicella virus, or a manifestation of an undefined infectious agent.

    View details for Web of Science ID A1988R231700011

    View details for PubMedID 3266000

  • VITRECTOMY FOR RETINAL-DETACHMENT ASSOCIATED WITH ACUTE RETINAL NECROSIS AMERICAN JOURNAL OF OPHTHALMOLOGY Blumenkranz, M., CLARKSON, J., Culbertson, W. W., Flynn, H. W., Lewis, M. L., YOUNG, G. A. 1988; 106 (4): 426-429

    Abstract

    Six patients with retinal detachment associated with the acute retinal necrosis syndrome were treated by the combination of vitrectomy, gas injection, and laser photocoagulation. The retinas were successfully reattached in each patient with one operation. Five of the patients achieved a visual acuity of 20/200 or better, and three had a visual acuity of 20/40 or better.

    View details for Web of Science ID A1988Q346000008

    View details for PubMedID 3177560

  • FLUOROURACIL THERAPY OF INTRAOCULAR GREENE MELANOMA IN THE RABBIT ARCHIVES OF OPHTHALMOLOGY OLSEN, K. R., Blumenkranz, M., Hernandez, E., Hajek, A., Hartzer, M. 1988; 106 (6): 812-815

    Abstract

    We evaluated the efficacy of intraocular and periocular fluorouracil treatment in an experimental iris tumor of the rabbit (Greene amelanotic melanoma). Four consecutive intravitreal injections of 1 mg of fluorouracil given twice weekly completely suppressed tumor growth in all treated eyes for six weeks if treatment was initiated 24 hours after tumor implantation. In contrast, all control eyes implanted with an equal number of Greene melanoma cells but treated with intravitreal saline developed massive tumor invasion of the iris within two weeks. Additional subconjunctival therapy following intravitreal therapy for two weeks was only slightly more effective than intravitreal therapy alone. If therapy was delayed for one week, the iris tumors became macroscopically visible and subsequent treatment with intravitreal and subconjunctival fluorouracil was of limited value in suppressing growth.

    View details for Web of Science ID A1988N653100041

    View details for PubMedID 3370010

  • UPTAKE AND CLEARANCE OF 5-FLUOROURIDINE FOLLOWING SUB-CONJUNCTIVAL AND INTRAVITREAL INJECTION RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES HUANG, D. S., Blumenkranz, M. S., Hernandez, E., Hartzer, M. 1988; 8 (3): 205-209

    Abstract

    Described are some pharmacokinetic parameters for 5-fluorouridine, a potentially useful intermediate metabolite of 5-fluorouracil (5-FU), following subconjunctival and intravitreal injection in the pigmented rabbit. Immediately following a 500 microgram intravitreal injection of 3H-5-fluorouridine, a peak ipsilateral vitreous concentration of 308 micrograms/ml was measured. This decreased to 199 micrograms/ml at 2 hours, 33 micrograms/ml at 12 hours and 4.4 micrograms/ml at 24 hours, indicating that 5-fluorouridine is cleared from the vitreous at a rate similar to 5-fluorouracil. Aqueous concentrations in the ipsilateral eye reached a maximum at 6 hours (9.6 micrograms/ml) and decreased to 0.8 micrograms/ml at 24 hours. Following subconjunctival injection of 5 mg 3H-5-fluorouridine (0.5 ml), peak ipsilateral anterior chamber concentration of 10.7 micrograms/ml was measured 1 hour after injection and decreased to 2.4 micrograms/ml after 12 hours. Maximum vitreal concentrations of 1.7 micrograms/ml were measured 12 hours after injection.

    View details for Web of Science ID A1988Q391400011

    View details for PubMedID 3231913

  • ASSOCIATION OF VARICELLA ZOSTER DERMATITIS WITH ACUTE RETINAL NECROSIS SYNDROME OPHTHALMOLOGY Browning, D. J., Blumenkranz, M. S., Culbertson, W. W., Clarkson, J. D., Tardif, Y., GOURDEAU, A., Minturn, J. 1987; 94 (6): 602-606

    Abstract

    The authors report seven patients in whom the acute retinal necrosis (ARN) syndrome developed shortly after cutaneous varicella zoster infection. The length of time between the skin infection and ARN varied from 5 days to 3 months. Both eyes were affected in one of seven cases. The ophthalmic branch of cranial nerve V ipsilateral to an affected eye was involved by the zoster dermatitis in only two of the seven cases. The association lends further support to the proposal that herpes zoster virus is a major cause of ARN. A history of recent zoster dermatitis should be sought in patients with ARN.

    View details for Web of Science ID A1987H877500004

    View details for PubMedID 3498140

  • INTRUSION OF RETINAL TACKS AMERICAN JOURNAL OF OPHTHALMOLOGY Lewis, H., AABERG, T. M., Packo, K. H., RICHMOND, P. P., Blumenkranz, M. S., BLANKENSHIP, G. W. 1987; 103 (5): 672-680

    Abstract

    We examined nine patients in whom retinal tacks intruded into the eye and lodged in the subretinal space, preretinal space, vitreous cavity, or anterior chamber. Complications included retinal pigment epithelium atrophy; retinal phlebitis; vitreous hemorrhage; focal corneal, iris, and retinal injury; and corneal edema. The intrusion of the retinal tacks did not apparently cause, but was associated with retinal redetachment in five patients. Factors associated with intrusion of the retinal tacks included absence of a barb at the end of the tack to anchor it to the sclera, absence of a groove in the tack, a short shaft, incomplete penetration of the retina, choroid, and sclera by the tack, self-inflicted trauma to the eye, placing a scleral buckle after inserting the tacks, and reproliferation of periretinal membranes. In four patients the intruded tacks did not cause any complications. In four patients the intruded tacks were removed without complications and in the remaining five patients, they were left in the eye.

    View details for Web of Science ID A1987H204600009

    View details for PubMedID 3578464

  • GEOMETRIC ALTERATIONS PRODUCED BY ENCIRCLING SCLERAL BUCKLES - BIOMETRIC AND CLINICAL CONSIDERATIONS RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES HARRIS, M. J., Blumenkranz, M. S., Wittpenn, J., Levada, A., Brown, R., FRAZIERBYRNE, S. 1987; 7 (1): 14-19

    Abstract

    The geometric alterations induced in the human globe by the application of an encircling scleral buckle using an in vitro model are described. Both a thin, solid silicone band, and a thicker, oval element produces an encircling buckling effect of predictable height and width. With thin elements, height and width are a linear function of horizontal shortening of the band. A scleral buckle produced by horizontal shortening, irrespective of exoplant material, results in axial lengthening. In contrast, the scleral buckling effect produced by mattress suture invagination of oval or round thicker silicone exoplants results in axial shortening, provided there is no concomitant horizontal shortening. The amount of axial shortening can be increased by using two sutures per quadrant. Since axial lengthening is associated with the potential undesirable complication of radial retinal and scleral folds, and axial shortening is not, buckles created by invagination of broad encircling elements may have certain theoretical advantages.

    View details for Web of Science ID A1987H249200003

    View details for PubMedID 3602601

  • SELECTION OF THERAPEUTIC AGENTS FOR INTRAOCULAR PROLIFERATIVE DISEASE .2. DIFFERING ANTIPROLIFERATIVE ACTIVITY OF THE FLUOROPYRIMIDINES ARCHIVES OF OPHTHALMOLOGY Blumenkranz, M. S., Hartzer, M. K., HAJEK, A. S. 1987; 105 (3): 396-399

    Abstract

    We confirm the potent antiproliferative effects of the fluoropyrimidines on cellular proliferation in vitro in three different nonmalignant cell types. All fluoropyrimidines tested, except for fluorocytosine, decrease proliferation of human dermal fibroblasts, bovine aortic vascular endothelial cells, and human retinal pigment epithelial cells in vitro. Fluorouridine, an intracellular metabolite of fluorouracil, is nearly 100-fold more potent than fluorouracil and its deoxymetabolite. Human dermal fibroblasts are more sensitive to the inhibitory effects of deoxymetabolites than the cells of either human retinal pigment epithelium or bovine aortic vascular endothelium. Fluorouridine and other fluoropyrimidines may prove to be valuable second-generation drugs in the treatment of intraocular proliferative disorders.

    View details for Web of Science ID A1987G247000033

    View details for PubMedID 2950847

  • VARICELLA ZOSTER VIRUS IS A CAUSE OF THE ACUTE RETINAL NECROSIS SYNDROME OPHTHALMOLOGY Culbertson, W. W., Blumenkranz, M. S., Pepose, J. S., Stewart, J. A., Curtin, V. T. 1986; 93 (5): 559-569

    Abstract

    We studied two blind eyes enucleated during the active phase of the acute retinal necrosis syndrome. Both eyes showed similar histopathologic findings of necrotizing retinitis, retinal arteritis, and optic neuropathy. A virus morphologically consistent with a herpes group virus was found on electron microscopy and immunocytopathologic stains showed this virus to be varicella zoster in both cases. Varicella zoster virus was cultured from the vitreous of one of the eyes. We conclude that varicella zoster virus retinal infection is a cause of the acute retinal necrosis syndrome.

    View details for Web of Science ID A1986C720200003

    View details for PubMedID 3014414

  • RISK-FACTORS IN AGE-RELATED MACULOPATHY COMPLICATED BY CHOROIDAL NEOVASCULARIZATION OPHTHALMOLOGY Blumenkranz, M. S., Russell, S. R., ROBEY, M. G., KOTTBLUMENKRANZ, R., Penneys, N. 1986; 93 (5): 552-558

    Abstract

    We evaluated previously reported and hypothesized risk factors for the development of age-related maculopathy (ARM) in a case-control study. We compared 26 patients with documented disciform scarring or choroidal neovascularization with 23 age- and sex-matched controls. Systolic and diastolic blood pressure, smoking history, glucose, lipoprotein profiles, and serum levels of vitamins A, C, and E did not differ significantly between the two groups. Statistically significant associations (P less than 0.05) identified by univariate analysis include degree of dermal elastotic degeneration in sun-exposed and sun-protected skin, white blood count, increasing age and small posterior lenticular opacities. Using an interactive multivariate model, only extent of elastosis in sun protected dermis, age and white blood count were predictive (Mult R = 0.652, P less than .001). Our data support the concept of a multifactorial etiology of ARM but suggest that generalized increased susceptibility of elastic fibers to photic or other degenerative stimuli is a new and important risk factor for choroidal neovascularization.

    View details for Web of Science ID A1986C720200002

    View details for PubMedID 2425325

  • TREATMENT OF THE ACUTE RETINAL NECROSIS SYNDROME WITH INTRAVENOUS ACYCLOVIR OPHTHALMOLOGY Blumenkranz, M. S., Culbertson, W. W., Clarkson, J. G., Dix, R. 1986; 93 (3): 296-300

    Abstract

    We treated 13 eyes of 12 patients with the acute retinal necrosis syndrome (ARN) with intravenous acyclovir (1500 mg/M2/day) for an average of 10.9 days. All patients were also treated with oral aspirin or Coumadin. in an attempt to prevent thrombotic complications and nine of twelve patients were treated with oral prednisone after intravenous acyclovir had been initiated. Regression of retinal lesions was first seen on average 3.9 days after initiation of therapy and required 32.5 days on average for completion. No eye developed new retinal lesions or progressive optic nerve involvement 48 hours or more after initiation of therapy, although progression within the first 48 hours was occasionally seen. Treatment did not ameliorate vitritis or prevent retinal detachment, which occurred in 11 of 13 eyes, an average of 59 days after the initiation of therapy. There were no evident ocular or systemic complications of therapy. Our data suggest the need for a prospective randomized clinical trial to evaluate the efficacy of intravenous or oral acyclovir in the treatment of the acute retinal necrosis syndrome.

    View details for Web of Science ID A1986A700000005

    View details for PubMedID 3703498

  • FLUID-GAS EXCHANGE AND PHOTOCOAGULATION AFTER VITRECTOMY - INDICATIONS, TECHNIQUE, AND RESULTS ARCHIVES OF OPHTHALMOLOGY Blumenkranz, M., Gardner, T., Blankenship, G. 1986; 104 (2): 291-296

    Abstract

    We describe the indications, complications, and results of postvitrectomy fluid-gas exchange and laser photocoagulation for management of complicated vitreoretinal disease. Indications include proliferative vitreoretinopathy, vitreous opacities associated with proliferative diabetic retinopathy, giant retinal tear, recurrent rhegmatogenous retinal detachment, and trauma. Eyes treated with 50% sulfur hexafluoride gas rather than sterile air demonstrated a higher intraocular pressure on the first postexchange day, which was not a significant source of disease. There was no statistically significant difference in retinal reattachment between eyes treated with gas and those treated with air. Fluid-gas exchange in eyes with partial or total retinal detachment resulted in total or partial retinal reattachment, with the macula attached in 82% of cases within the first 48 hours following exchange. Final reattachment rate, with a mean follow-up of 8.9 months (range, six to 36 months), was 55%. In eyes with proliferative vitreoretinopathy, the combination of postoperative argon or krypton laser photocoagulation with fluid-gas exchange was associated with a final reattachment rate of 75%. Postoperative fluid-gas exchange and photocoagulation appear to be safe and effective advances in the treatment of complicated vitreoretinal diseases requiring vitrectomy.

    View details for Web of Science ID A1986AYU9200034

    View details for PubMedID 3947306

  • CLEARANCE OF INTRAVITREAL FLUOROURACIL - NORMAL AND APHAKIC VITRECTOMIZED EYES OPHTHALMOLOGY Jarus, G., Blumenkranz, M., Hernandez, E., SOSSI, N. 1985; 92 (1): 91-96

    Abstract

    The ocular pharmacokinetics of 5-fluorouracil (5-FU) after intravitreal administration in the rabbit are described for the first time. Following a 1 mg intravitreal injection of C-14 labeled 5-FU in the phakic nonvitrectomized eye, a peak level of 664 micrograms/ml is achieved which declines to 7.8 micrograms/ml at 24 hours. For the aphakic vitrectomized eye comparable values are 669 micrograms/ml at 0.1 hour and 0.21 micrograms/ml at 24 hours. 5-FU is cleared more than two times more rapidly in aphakic vitrectomized eyes than normal eyes during the first 12 hours following injection. Following this, when the actual concentrations are relatively low, the rate of clearance appears relatively similar for both groups of eyes. Although it is difficult to extrapolate from previous in vitro results, potentially therapeutic vitreous concentrations are present in normal rabbit eyes for up to 72 hours following a single intravitreal injection.

    View details for Web of Science ID A1985ABA7200014

    View details for PubMedID 3974999

  • RETINAL-DETACHMENT FOLLOWING THE ACUTE RETINAL NECROSIS SYNDROME OPHTHALMOLOGY Clarkson, J. G., Blumenkranz, M. S., Culbertson, W. W., Flynn, H. W., Lewis, M. L. 1984; 91 (12): 1665-1668

    Abstract

    Twenty-six patients with the acute retinal necrosis involving 32 eyes have been followed at the Bascom Palmer Eye Institute. Sixteen eyes developed retinal detachment and surgical repair was attempted in thirteen. Ten eyes were successfully reattached. Vitreous surgery was necessary in ten eyes and was performed in eight of the ten successful eyes. The clinical characteristics of the retinal detachments as well as the surgical procedures and results are presented.

    View details for Web of Science ID A1984TZ66100034

    View details for PubMedID 6151638

  • THE LENS CAPSULE AND RUBEOSIS IRIDIS - AN ANGIOGRAPHIC STUDY CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE Moffat, K., Blumenkranz, M. S., Hernandez, E. 1984; 19 (3): 130-133

    Abstract

    In 15 pigmented rabbits a pars plana lensectomy, vitrectomy and giant retinal tear with bullous retinal detachment were produced with maintenance of an intact anterior lens capsule. The incidence of subsequent rubeosis iridis, as detected angiographically, was compared with that in a control group of animals in whom the anterior lens capsule was not preserved but whose management was identical in all other respects. The rubeosis in the rabbits was angiographically identical to that seen in humans following vitrectomy, with immediate formation of a mossy hyperfluorescent surface membrane that leaked fluorescein extensively into the anterior chamber in the late phase of the angiography. It was possible to distinguish true neovascularization from breakdown of the blood-ocular barrier by the time and extent of the fluorescein leakage. Preservation of an intact anterior lens capsule reduced the incidence of unequivocal (florid) rubeosis from 73% to 33% (p less than 0.05).

    View details for Web of Science ID A1984SU88300008

    View details for PubMedID 6203631

  • SELECTION OF THERAPEUTIC AGENTS FOR INTRAOCULAR PROLIFERATIVE DISEASE - CELL-CULTURE EVALUATION ARCHIVES OF OPHTHALMOLOGY Blumenkranz, M. S., CLAFLIN, A., HAJEK, A. S. 1984; 102 (4): 598-604

    Abstract

    A variety of antimetabolites, steroids, and nonsteroidal anti-inflammatory agents were tested for their ability to inhibit rabbit dermal and conjunctival fibroblast proliferation in cell culture. Doxorubicin hydrochloride and fluorouracil produced notable inhibition in concentrations of less than 1 mg/L. Meclofenamate sodium and indomethacin produced notable inhibition at concentrations of 11 and 40 mg/L, respectively. Dexamethasone sodium phosphate and triamcinolone acetonide produced inhibition at 200 and 150 mg/L, respectively, but paradoxically increased proliferation almost two-fold at concentrations ranging from 1 to 30 mg/L under identical culture conditions. Methotrexate sodium demonstrated only limited effectiveness. This assay system may be a useful approach to drug selection in the treatment of a variety of ocular proliferative disorders. Fluorouracil may prove to be of significant value in the treatment of intraocular proliferative disorders.

    View details for Web of Science ID A1984SK33600028

    View details for PubMedID 6704019

  • 5-FLUOROURACIL - NEW APPLICATIONS IN COMPLICATED RETINAL-DETACHMENT FOR AN ESTABLISHED ANTIMETABOLITE OPHTHALMOLOGY Blumenkranz, M., Hernandez, E., Ophir, A., Norton, E. W., STERN, W. H. 1984; 91 (2): 122-130

    Abstract

    Long-term reattachment of the retina following the development of proliferative vitreoretinopathy is often prevented by the occurrence of cellular reproliferation. 5-fluorouracil, a synthetic pyrimidine analog, is a potent inhibitor of fibroblast proliferation in cell culture and an animal model of tractional retinal detachment. Doses of up to 1.0 mg, when administered intravitreally to rabbits, result in no demonstrable retinal toxicity by microscopic and electrophysiologic criteria. The first 22 consecutive patients with advanced forms of proliferative vitreoretinopathy were treated with a combination of periocular and intraocular 5-fluorouracil, in addition to scleral buckling and vitrectomy. Retinal reattachment was achieved in 60% of patients at 6 months postoperatively. No serious systemic or ocular complications were observed although delayed healing of corneal epithelial defects occurred in 18% of cases and subtle subepithelial scarring in 31.8%. In combination with standard vitrectomy techniques, post-operative fluid gas exchange, and photocoagulation, periocular and subconjunctival 5-fluorouracil appears to improve the prognosis for longterm retinal reattachment following the development of proliferative vitreoretinopathy.

    View details for Web of Science ID A1984SF45300003

    View details for PubMedID 6709326

  • MULTIFOCAL PIGMENT EPITHELIAL DETACHMENTS BY RETICULUM-CELL SARCOMA - A CHARACTERISTIC FUNDUSCOPIC PICTURE RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Gass, J. D., SEVER, R. J., Grizzard, W. S., Clarkson, J. G., Blumenkranz, M., WIND, C. A., SHUGARMAN, R. 1984; 4 (3): 135-143

    Abstract

    Patients with systemic reticulum cell sarcoma often develop evidence of ocular involvement months or several years prior to the onset of neurologic symptoms. This neoplasm appears to have proclivity of arising multicentrically within the subpigment epithelial space, as well as in the vitreous. When this occurs it may produce a peculiar ophthalmoscopic picture of multiple large, solid detachments of the pigment epithelium that is rarely duplicated by any other disease. Three patients illustrating this disease are presented.

    View details for Web of Science ID A1984TL89300001

    View details for PubMedID 6387833

  • THE ACUTE RETINAL NECROSIS SYNDROME .1. CLINICAL MANIFESTATIONS OPHTHALMOLOGY Fisher, J. P., Lewis, M. L., Blumenkranz, M., Culbertson, W. W., Flynn, H. W., Clarkson, J. G., Gass, J. D., Norton, E. W. 1982; 89 (12): 1309-1316

    Abstract

    The acute retinal necrosis syndrome is characterized by necrotizing retinitis, vitritis, and retinal vasculitis occurring in otherwise healthy patients. Experience with 11 cases and the review of 30 additional cases in the literature are presented. In this series, 50% of the affected eyes developed retinal detachments, and 64% had a final visual acuity of less than 20/200. The natural history, diagnosis, postulated etiology, and suggestions for management will be discussed.

    View details for Web of Science ID A1982PV90000005

    View details for PubMedID 7162777

  • THE ACUTE RETINAL NECROSIS SYNDROME .2. HISTOPATHOLOGY AND ETIOLOGY OPHTHALMOLOGY Culbertson, W. W., Blumenkranz, M. S., Haines, H., Gass, J. D., MITCHELL, K. B., Norton, E. W. 1982; 89 (12): 1317-1325

    Abstract

    The acute retinal necrosis syndrome is manifested by diffuse uveitis, vitritis, retinal vasculitis, and acute necrotizing retinitis (see Part 1). We studied the histopathology and electron microscopic findings of an eye enucleated from a 67-year-old man with typical acute retinal necrosis. Histology showed profound acute necrosis of the retina, retinal arteritis, and eosinophilic intranuclear inclusions in retinal cells. Electron microscopy demonstrated a herpes group virus in all layers of affected retina. The implications of these findings for antiviral and other treatments are discussed.

    View details for Web of Science ID A1982PV90000006

    View details for PubMedID 6298683

  • ATYPICAL SERPIGINOUS CHOROIDITIS ARCHIVES OF OPHTHALMOLOGY Blumenkranz, M. S., Gass, J. D., Clarkson, J. G. 1982; 100 (11): 1773-1775

    Abstract

    Patients with serpiginous choroiditis may demonstrate atypical features. In this series 14 (56%) of 53 patients demonstrated either active choroidal neovascularization (13%) or disciform macular scarring (13%). Despite a slight excess of male subjects, five of seven patients with active choroidal neovascularization were female. Three had bilateral disciform disease. All patients with this complication had visual acuity of 6/60 or less. None were able to be successfully treated by photocoagulation. One patient had secondary branch venous obstruction peripherally, associated with retinal neovascularization. Patients with serpiginous choroiditis are at risk of losing central vision from either an acute active lesion in the macula or choroidal neovascularization occurring at the margin of an inactive chorioretinal scar. Serial examination at regular intervals is recommended to rule out the development of possibly treatable choroidal neovascularization in patients with serpiginous choroiditis.

    View details for Web of Science ID A1982PP91000007

    View details for PubMedID 6182866

  • REGRESSION OF DIABETIC RUBEOSIS IRIDIS FOLLOWING SUCCESSFUL SURGICAL REATTACHMENT OF THE RETINA BY VITRECTOMY RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES SCUDERI, J. J., Blumenkranz, M. S., Blankenship, G. 1982; 2 (4): 193-196

    Abstract

    The relationship between successful surgical reattachment of the retina following diabetic vitrectomy and regression of preoperative rubeosis iridis was investigated. Seventy-nine (9.2%) of 850 diabetic cases undergoing vitrectomy had both preoperative iris rubeosis and retinal detachment. The iris could be adequately evaluated and the retina could be visualized after surgery in 36 cases. Regression of the rubeosis iridis occurred after surgery in 16 (76%) of 21 eyes in which the retina was reattached successfully. Only four (27%) of 15 eyes had regression of rubeosis iridis when the retina was not reattached completely. Retention of the lens also correlated with regression of rubeosis iridis. Regression occurred in 10 (55%) of 18 cases in which the lens was not removed, 13 (28.2%) of 46 eyes in which lensectomy was combined with vitrectomy, and none of eight previously aphakic eyes. Although the combination of preoperative retinal detachment and rubeosis iridis is associated with a worsened prognosis, successful reattachment of the retina and retention of the lens favorably influence later regression of preoperative rubeosis iridis.

    View details for Web of Science ID A1982PX67800001

    View details for PubMedID 6101125

  • FLUOROURACIL FOR THE TREATMENT OF MASSIVE PERIRETINAL PROLIFERATION AMERICAN JOURNAL OF OPHTHALMOLOGY Blumenkranz, M. S., Ophir, A., CLAFLIN, A. J., Hajek, A. 1982; 94 (4): 458-467

    Abstract

    A single intravitreal injection of fluorouracil was effective in the treatment of an experimental model of massive periretinal proliferation. When given with an intravitreal injection of 250,000 heterologous fibroblasts, fluorouracil decreased the rate of tractional retinal detachment from 36.8% in controls (seven of 19 eyes) to 5.2% in treated animals (one of 19 eyes) at one week, and from 73.6% in controls (14 of 19 eyes) to 31.5% in treated animals (six of 19 eyes) after four weeks (P less than .05). Intraocular neovascularization was reduced from 52.6% in controls (ten of 19 eyes) to 5.2% in treated animals (one of 19 eyes) after one week and 36.8% in controls (seven of 19 eyes) to 5.2% in treated animals (one of 19 eyes) after four weeks. When supplemented by repeated 10-mg subconjunctival injections of fluorouracil, or in combination with intravitreally administered indomethacin, this effect appeared to be enhanced. Intravitreal and subconjunctival injections of fluorouracil were well tolerated and may prove to be of significant value in the treatment of human disease.

    View details for Web of Science ID A1982PL08200003

    View details for PubMedID 6182799

  • EXPERIMENTAL INTRAOCULAR PROLIFERATION AND NEOVASCULARIZATION AMERICAN JOURNAL OF OPHTHALMOLOGY Ophir, A., Blumenkranz, M. S., CLAFLIN, A. J. 1982; 94 (4): 450-457

    Abstract

    An experimental model of massive periretinal proliferation and intraocular neovascularization, produced in rabbits by the intravitreal injection of 250,00 cultured heterologous fibroblasts, showed no significant difference in the detachment rate (69% to 100%) or neovascularization rate (45% to 88%) between the animals injected with autologous cells and those injected with heterologous cells. Dermal fibroblasts produced a slightly higher detachment rate than conjunctival fibroblasts and were equally effective after reconstitution and subculture from liquid nitrogen storage in 7% dimethyl sulfoxide. Heterologous cells produced no clinical or histologic evidence of rejection when compared with autologous cells in the same animal and had the following advantages: (1) elimination of several biopsies and extended cell culture time; (2) a ready source of cryopreserved cells is available; (3) multiple injections of many animals can be performed within a short time; (4) in vivo and in vitro drug testing can be correlated on the same cell line.

    View details for Web of Science ID A1982PL08200002

    View details for PubMedID 6182798