Dr. Wu is a board-certified ophthalmologist and a fellowship-trained specialist in oculoplastic and orbital surgery. This specialty is dedicated to care of the eyelid and other structures around the eye. It is also called ophthalmic plastic and reconstructive surgery.
Dr. Wu focuses his expertise on saving people’s vision. He provides comprehensive, compassionate care for both adults and children with sight-threatening diseases and injuries of the eye and surrounding area. He treats tearing, eyelid drooping, thyroid eye disease, eyelid tumors, and other facial disorders. He also performs facial rejuvenation as well as reconstructive and aesthetic surgery procedures.
Dr. Wu is a national leader in advancing the use of stem cell therapy to treat conditions involving the eye and face. His research explores how stem cells can regenerate a patient’s own tissues for potential transplant. His goal is to make regenerative medicine an accepted treatment for people worldwide suffering from diseases of the eye.
The National Eye Institute funded Dr. Wu’s research to develop stem cell therapies to treat corneal blindness and regenerate the surface of the eye. He leads the Stanford Ophthalmic Stem Cell and Regenerative Medicine Laboratory and is developing leading-edge treatments for vision loss and eye disease.
He also has participated as a principal investigator in research projects including “The Human Eye Cell Atlas.” The goal of this project is to create a reference atlas of all cell types in the human eye. Dr. Wu is also helping to lead a groundbreaking study of a strategy for reconstruction of the surface of the eye. These projects are among more than a dozen involving Dr. Wu that have explored innovations in medication and surgical technique for eye disorders.
He has co-authored articles on his research discoveries in JAMA Ophthalmology, Ophthalmic Plastic & Reconstructive Surgery, Clinical and Experimental Ophthalmology, Retina, Medical Research and Innovations, and many other peer-reviewed publications. He is an article reviewer for publications including the American Journal of Ophthalmology, Ophthalmic Plastic and Reconstructive Surgery, and Human Gene Therapy.
He also has contributed to chapters in the textbooks Ophthalmology and Ophthalmologic Oncology: Mount Sinai Expert Guides.
Dr. Wu has presented the findings of his research at numerous international, national, and local conferences. They include meetings of the North American Society of Academic Oculoplastic Surgeons, Endocrine Society, American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS), and others. Topics have included the stem cells and other approaches to perform regeneration procedures on the eye.
Dr. Wu has earned honors for his clinical, research, and academic achievements. He has won awards from the National Institutes of Health, American Society of Ophthalmic Plastic and Reconstructive Surgery, Icahn School of Medicine at Mount Sinai, the University of Washington, and Yale University.
- Ophthalmic Reconstructive & Facial Plastic Surgery
- Orbital Oncology
- Mohs Reconstruction & Eyelid Surgery
- Facial Nerve Palsy
- Thyroid Eye Disease
- Lacrimal and Tear Duct Surgery
- Eyelid Surgery and Reconstruction
- Ptosis Repair
- Ocular Surface Reconstruction
- Cosmetic Surgery & Treatments
- Pediatric Oculoplastics
Director of Oculoplastics Research, Department of Ophthalmology, Stanford School of Medicine (2017 - Present)
Honors & Awards
Dr. Solomon Silver Award in Clinical Medicine, Icahn School of Medicine at Mount Sinai (2016)
Excellence in Teaching Award, Icahn School of Medicine at Mount Sinai (2015)
Faculty Council Award for Academic Excellence, Icahn School of Medicine at Mount Sinai (2015)
Honorary Member, Romanian Association of Plastic Surgery (2015)
Alpha Omega Alpha Honor Medical Society, Icahn School of Medicine at Mount Sinai (2013)
ASOPRS Fellowship, American Society of Ophthalmic Plastic and Reconstructive Surgery (2009)
Young Investigator Award, 1st International Conference on cGMP (2003)
Biology of Aging Fellowship, National Institute of Health (1998)
Parrett Scholarship, University of Washington (1998)
Poncin Award, University of Washington (1998)
Medical Scientist Training Program, National Institute of Health (1995)
Richter Fellowship, Yale University (1994)
Boards, Advisory Committees, Professional Organizations
Fellow, American College of Surgeons (2016 - Present)
Scientific Review Committee, Asia-Pacific Academy of Ophthalmology Congress (2016 - 2016)
Information Technology Committee, American Society of Ophthalmic Plastic and Reconstructive Surgery (2015 - Present)
Scientific Review Committee, Fight for Sight (2015 - Present)
Education Committee, American Society of Ophthalmic Plastic and Reconstructive Surgery (2014 - Present)
Advocacy and Public Outreach Committee, Association for Research in Vision and Ophthalmology (2013 - Present)
Fellow, American Society of Ophthalmic Plastic and Reconstructive Surgery (2013 - Present)
Residency: University of Utah Ophthalmology Residency (2009) UT
Board Certification: American Board of Ophthalmology, Ophthalmology (2013)
Fellowship: Toronto University Ocuplastic and Orbital Surgery Fellowship (2011) Canada
Internship: University of Utah Internal Medicine Residency (2006) UT
Medical Education: University of Washington School of Medicine (2005) WA
PhD, University of Washington, Molecular and Cellular Biology
BS, Yale University, Molecular Biophysics and Biochemistry
Community and International Work
Virtue Foundation Humanitarian Surgical Mission, Khovd, Mongolia
Surgical mission for patients in need
Opportunities for Student Involvement
Ophthalmology Outreach in Tanzania, Morogoro, Tanzania
Opportunities for Student Involvement
Current Research and Scholarly Interests
My goal is to perform translational research, bringing breakthroughs in stem cell biology and tissue engineering to clinical ophthalmology and reconstructive surgery. Over 6 million people worldwide are afflicted with corneal blindness, usually caused by chemical and thermal burns, ocular cicatricial pemphigoid, Stevens-Johnson syndrome, microbial infections, or chronic inflammation. These injuries often result in corneal vascularization, conjunctivalization, scarring, and opacification from limbal epithelial stem cell (LSC) deficiency (LSCD), for which there is currently no durable treatment. Bilateral LSCD is particular devastating not only because of lost quality of life and social productivity, but because unlike most retinal diseases that affect the aged, LSCD largely affects the relatively young. The most promising cure for bilateral LSCD is finding an autologous source of limbal epithelial cells for transplantation. Utilizing recent advances in the field of induced pluripotent stem cells (iPSC), my research aims to create a reliable and renewable source of limbal epithelial cells for potential use in treating human eye diseases. These cells will be grown on resorbable biomatrices to generate stable transplantable corneal tissue. These studies will serve as the basis for human clinical trials and make regenerative medicine a reality for those with sight-threatening disease. On a broader level, this experimental approach could serve as a paradigm for the creation of other transplantable tissue for use throughout the body. Stem cell biology has the potential to influence every field of medicine and will revolutionize the way we perform surgery.
Pathway of care for visual and vestibular rehabilitation after mild traumatic brain injury: a critical review.
To review the pathway to care for treatment and management of patients receiving visual and vestibular rehabilitation after mild traumatic brain injury (mTBI).English scientific peer-reviewed articles from PubMed, CINAHL, Embase, and PsycINFO between 2000 and 2020 were first screened by title and abstract, then those selected underwent full-text review and analysis.The database search yielded 1640 results and after title and abstract review, 75 articles were selected for full-text screening, from which 8 were included in the qualitative synthesis. Current evidence includes a limited number of retrospective cohort studies and case studies.Many patients with visual and vestibular deficits following mTBI do not receive rehabilitation services until months following their injury as there is no standardized pathway to care for patients for visual and vestibular rehabilitation. Barriers to establishing a standardized pathway are the lack of natural history data for visual and vestibular function following mTBI and the lack of randomized clinical trials establishing the efficacy of rehabilitation in patients following mTBI.
View details for DOI 10.1080/02699052.2022.2105399
View details for PubMedID 35918848
The Use of Panitumumab-IRDye800CW in a Novel Murine Model for Conjunctival Squamous Cell Carcinoma.
Translational vision science & technology
2022; 11 (7): 23
Purpose: Conjunctival squamous cell carcinoma (SCC) is a sight-threatening ocular surface malignancy with the primary treatment modality being surgical resection. To evaluate surgical imaging modalities to improve surgical resection, we established a novel murine model for conjunctival SCC to demonstrate the utility of panitumumab-IRDye800, a fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibody.Methods: NOD-scid IL2Rgammanull (NSG) mice received subconjunctival injection of UM-SCC-1 or SCC-9, head and neck SCC cell lines. On tumor growth, mice were injected with Panitumumab-IRDye800CW, and imaged with a small animal imaging system and optical coherence tomography (OCT). Immunohistochemistry for SCC markers were used to confirm tumor origin.Results: Seventy-five percent (N = 4) of the UM-SCC-1 group developed aggressive, rapidly growing tumors that were P40 and EGFR positive within two weeks of inoculation. The SCC-9 tumors failed to demonstrate any growth (N = 4). Ocular tumors demonstrated high fluorescence levels with a tumor to background ratio of 3.8.Conclusions: Subconjunctival injections are an appropriate technique to create in vivo models for assessing treatment modalities and novel therapies in conjunctival SCC.Translational Relevance: This model demonstrates Panitumumab-IRDye800CW's utility in the ophthalmic setting and suggests that clinical trials may be warranted.
View details for DOI 10.1167/tvst.11.7.23
View details for PubMedID 35895055
Distribution Of Primary Cilia In hESC-Derived Retinal Organoid
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844437004144
Association between heavy metals and diabetic retinopathy in the National Health and Nutrition Examination Surveys (NHANES)
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844401301220
BDNF and cAMP promote retinal ganglion cell survival and function in a porcine model of traumatic optic neuropathy
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
View details for Web of Science ID 000844401302299
The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans.
Science (New York, N.Y.)
2022; 376 (6594): eabl4896
Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.
View details for DOI 10.1126/science.abl4896
View details for PubMedID 35549404
- Publisher Correction: Cell types of origin of the cell-free transcriptome. Nature biotechnology 2022
- Sentiment Analysis Surrounding Blepharoplasty in Online Health Forums PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2022; 10 (3)
Sentiment Analysis Surrounding Blepharoplasty in Online Health Forums.
Plastic and reconstructive surgery. Global open
2022; 10 (3): e4213
Upper and lower blepharoplasty are among the most common procedures in aesthetic surgery and are often emotionally laden due to the subjective nature of outcomes and implications with beauty and self-identity. This article capitalizes on the increasing wealth of patient-provided health information online and is the first to analyze the emotions surrounding blepharoplasty discussions in an open internet health forum, MedHelp.We used Python to scrape MedHelp for threads that contained "blepharoplasty" and then used IBM Watson Natural Language Understanding to perform sentiment analyses, calculating a general sentiment score (-1 to +1) as well as emotion scores for anger, sadness, joy, fear, and disgust (0 to 1) for posts and keywords contained within the posts. Keywords were then manually grouped into five distinct clinical categories: symptoms, doctor, treatment, medication, and body.We collected 52 threads containing "blepharoplasty," yielding 154 posts and 1365 keywords. The average sentiment score was negative among all posts (-0.15) and keywords (-0.30). Among all posts and keywords, sadness had the highest score and disgust had the lowest score.Fear and sadness are the predominant emotions for blepharoplasty patients online, and the most negative symptoms cited are not ones that surgeons typically expect.
View details for DOI 10.1097/GOX.0000000000004213
View details for PubMedID 35492229
View details for PubMedCentralID PMC9038503
Cell types of origin of the cell-free transcriptome.
Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases.
View details for DOI 10.1038/s41587-021-01188-9
View details for PubMedID 35132263
PNP Hydrogel Prevents Formation of Symblephara in Mice After Ocular Alkali Injury.
Translational vision science & technology
2022; 11 (2): 31
Purpose: To create an alkali injury symblephara mouse model to study conjunctival fibrosis pathophysiology and test polymer nanoparticle (PNP) hydrogel as a preventative therapeutic.Methods: Mice were injured using NaOH-soaked filter paper to determine the optimal NaOH concentration to induce the formation of symblephara. Injured mice were observed for 7 days to detect the formation of symblephara. Forniceal shortening observed on hematoxylin and eosin (H&E)-stained tissue sections was used as a symblephara marker. Alpha-smooth muscle actin (alpha-SMA) expression, Masson's trichrome assay, and periodic acid-Schiff (PAS) staining were used to determine myofibroblast expression, collagen deposition, and goblet cell integrity. PNP hydrogel, with multivalent, noncovalent interactions between modified biopolymers and nanoparticles, was applied immediately after alkali injury to determine its ability to prevent the formation of symblephara.Results: Forniceal shortening was observed in H&E images with 1N NaOH for 2 minutes after 7 days without globe destruction. PNP hydrogel prevented forniceal shortening after alkali injury as observed by H&E histology. alpha-SMA expression and collagen deposition in eye tissue sections were increased in the fornix after injury with 1N NaOH compared with uninjured controls. PNP hydrogel treatment immediately after injury reduced alpha-SMA expression and collagen deposition in the forniceal region. Mucin-secreting goblet cells stained with PAS were significantly lower in alkali-injured and PNP hydrogel-treated conjunctivas than in uninjured control conjunctivas.Conclusions: We observed that 1N NaOH for 2 minutes induced maximal forniceal shortening and symblephara in mice. PNP hydrogel prevented forniceal shortening and conjunctival fibrosis after injury. This first murine model for symblephara will be useful to study fibrosis pathophysiology after conjunctival injury and to determine therapeutic targets for cicatrizing diseases.Translational Relevance: This mouse model of symblephara can be useful for studying conjunctival scarring disease pathophysiology and preventative therapeutics. We tested PNP hydrogel, which prevented the formation of symblephara after injury.
View details for DOI 10.1167/tvst.11.2.31
View details for PubMedID 35191963
Risks and rewards of increasing patient access to medical records in clinical ophthalmology using OpenNotes.
Eye (London, England)
BACKGROUND: The implementation of OpenNotes and corresponding increase in patient access to medical records requires thorough assessment ofthe risks and benefitsof note-sharing. Ophthalmology notes are unique among medical records in that they extensively utilize non-standardized abbreviations and drawings; they are often indecipherable even to highly-educated clinicians outside of ophthalmology. No studies to date have assessed ophthalmologist perceptions of OpenNotes.METHODS: A cross-sectional study was conducted from 4/28 to 5/12/2016. A survey was distributed to 30 clinicians (25 ophthalmologists, three optometrists, two nurses) in the University of Colorado's Department of Ophthalmology to evaluate provider attitudes towards granting patients access to online medical records.RESULTS: Many clinicians felt patients would have difficulty understanding their records and may be unnecessarily alarmed or offended by them. Some clinicians worried their workload would increase and feared having to change the way they document. Perceived benefits of OpenNotes included improving patient understanding of their medical conditions, strengthening patient-physician trust, and enhancing patient care. Many perceived risks and benefits of note-sharing were associated with conceptions of the ideal clinician-patient relationship.CONCLUSIONS: Clinicians in ophthalmology perceived both benefits and consequences of increasing patient access to ophthalmic records, and there were significant correlations between these perceptions and their conceptions of the clinician-patient relationship. This is the first study to assess potential ophthalmology provider attitudes toward sharing ophthalmic records. Although limited in sample size and power, this study demonstrates some ways patient-accessible ophthalmic records can affect the clinical practice of ophthalmology and emphasizes the unique challenges of OpenNotes in ophthalmology.
View details for DOI 10.1038/s41433-021-01775-9
View details for PubMedID 34611314
- RNA splicing programs define tissue compartments and cell types at single-cell resolution ELIFE 2021; 10
- Gender Gap in Neurology Research Authorship (1946-2020) FRONTIERS IN NEUROLOGY 2021; 12
Gender Gap in Neurology Research Authorship (1946-2020).
Frontiers in neurology
2021; 12: 715428
Gender disparity in the field of neurology impedes scientific advancements and innovations. In 2018, 45.0% of neurology and neurological subspecialty residents were women. Despite a notable rise in the proportion of women neurologists over the past decades, inequalities regarding publication proportions between men and women persist in the field. This cohort study examines authorship trends in articles published in 155 international neurology journals, identified as those listed in the annual Journal Citation Reports' "Clinical Neurology" section. Authors' names, authorship positions and countries of affiliation were extracted from PubMed for indexed articles published from 1946 to 2020. Gender-API (a validated and highly accurate application program interface) assigned binary genders to authors. Author gender proportions were compared across subspecialties, authorship position and years. In 303,385 unique articles, 1,663,036 total authors were identified of which 34.1% were women. Neuroradiology demonstrated the lowest proportion of women authors (21.3%), while neurogenetics displayed the highest (44.5%). In articles with multiple authors, both men and women last authors were more likely to publish with a male first author, though this was significantly more pronounced for men last authors (1.86 vs. 1.08; p < 0.001). From 2002 to 2020, women remained in the minority of last (24.6%), first (36.2%), and middle author positions (35.8%). The authorship gender distribution in neurological journals neither reflects the gender proportion of neurologists in the field overall nor in any subspecialty examined. We also find a tendency for senior and junior authors of the same gender to publish together which perpetuates authorship inequity. Further work is needed to identify underlying causes so that interventions might be developed to improve authorship diversity.
View details for DOI 10.3389/fneur.2021.715428
View details for PubMedID 34497579
View details for PubMedCentralID PMC8419229
Intravitreal delivery of AAV2 transduces porcine retinal ganglion cells
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690761100290
Gender Gap in the Award Recipients of the Association for Research in Vision and Ophthalmology
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
View details for Web of Science ID 000690760500066
Determination of Patient Sentiment and Emotion in Ophthalmology: Infoveillance Tutorial on Web-Based Health Forum Discussions.
Journal of medical Internet research
2021; 23 (5): e20803
BACKGROUND: Clinical data in social media are an underused source of information with great potential to allow for a deeper understanding of patient values, attitudes, and preferences.OBJECTIVE: This tutorial aims to describe a novel, robust, and modular method for the sentiment analysis and emotion detection of free text from web-based forums and the factors to consider during its application.METHODS: We mined the discussion and user information of all posts containing search terms related to a medical subspecialty (oculoplastics) from MedHelp, the largest web-based platform for patient health forums. We used data cleaning and processing tools to define the relevant subset of results and prepare them for sentiment analysis. We executed sentiment and emotion analyses by using IBM Watson Natural Language Understanding to generate sentiment and emotion scores for the posts and their associated keywords. The keywords were aggregated using natural language processing tools.RESULTS: Overall, 39 oculoplastic-related search terms resulted in 46,381 eligible posts within 14,329 threads. Posts were written by 18,319 users (117 doctors; 18,202 patients) and included 201,611 associated keywords. Keywords that occurred ≥500 times in the corpus were used to identify the most prominent topics, including specific symptoms, medication, and complications. The sentiment and emotion scores of these keywords and eligible posts were analyzed to provide concrete examples of the potential of this methodology to allow for a better understanding of patients' attitudes. The overall sentiment score reflects a positive, neutral, or negative sentiment, whereas the emotion scores (anger, disgust, fear, joy, and sadness) represent the likelihood of the presence of the emotion. In keyword grouping analyses, medical signs, symptoms, and diseases had the lowest overall sentiment scores (-0.598). Complications were highly associated with sadness (0.485). Forum posts mentioning body parts were related to sadness (0.416) and fear (0.321). Administration was the category with the highest anger score (0.146). The top 6 forum subgroups had an overall negative sentiment score; the most negative one was the Neurology forum, with a score of -0.438. The Undiagnosed Symptoms forum had the highest sadness score (0.448). The least likely fearful posts were those from the Eye Care forum, with a score of 0.260. The overall sentiment score was much more negative before the doctor replied. The anger, disgust, fear, and sadness emotion scores decreased in likelihood, whereas joy was slightly more likely to be expressed after doctors replied.CONCLUSIONS: This report allows physicians and researchers to efficiently mine and perform sentiment analysis on social media to better understand patients' perspectives and promote patient-centric care. Important factors to be considered during its application include evaluating the scope of the search; selecting search terms and understanding their linguistic usages; and establishing selection, filtering, and processing criteria for posts and keywords tailored to the desired results.
View details for DOI 10.2196/20803
View details for PubMedID 33999001
Molecular mechanisms and treatments for ocular symblephara.
Survey of ophthalmology
There are currently no effective methods to prevent or durably treat ocular symblephara, the adhesions between the palpebral and bulbar conjunctiva. How symblephara form at the molecular level is largely unknown. We present here an overview of current clinical symblephara treatments and describe potential molecular mechanisms behind conjunctival adhesion formation that may inform future symblephara treatment and prevention options. Understanding how symblephara form at the molecular level will facilitate treatment development. Preventative therapies may be possible by targeting symblephara progenitor cells immediately after injuries, while novel therapeutics should be aimed at modulating TGF-beta pathways and effector cells in conjunctival scarring to treat symblephara formation more effectively.
View details for DOI 10.1016/j.survophthal.2021.04.008
View details for PubMedID 33932469
- Orbital Fractures: Principles, Concepts and Management. Ophthalmic plastic and reconstructive surgery 2021; 36 (4): 425
Longitudinal Gender Authorship Trends in Neurology Research
LIPPINCOTT WILLIAMS & WILKINS. 2021
View details for Web of Science ID 000729283603087
Impact of COVID-19 on longitudinal ophthalmology authorship gender trends.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
BACKGROUND: The COVID-19 pandemic increased the gender gap in academic publishing. This study assesses COVID-19's impact on ophthalmology gender authorship distribution and compares the gender authorship proportion of COVID-19 ophthalmology-related articles to previous ophthalmology articles.METHODS: This cohort study includes authors listed in all publications related to ophthalmology in the COVID-19 Open Research Dataset and CDC COVID-19 research database. Articles from 65 ophthalmology journals from January to July 2020 were selected. All previous articles published in the same journals were extracted from PubMed. Gender-API determined authors' gender.RESULTS: Out of 119,457 COVID-19-related articles, we analyzed 528 ophthalmology-related articles written by 2518 authors. Women did not exceed 40% in any authorship positions and were most likely to be middle, first, and finally, last authors. The proportions of women in all authorship positions from the 2020 COVID-19 group (29.6% first, 31.5% middle, 22.1% last) are significantly lower compared to the predicted 2020 data points (37.4% first, 37.0% middle, 27.6% last) (p<.01). The gap between the proportion of female authors in COVID-19 ophthalmology research and the 2020 ophthalmology-predicted proportion (based on 2002-2019 data) is 6.1% for overall authors, 7.8% for first authors, and 5.5% for last and middle authors. The 2020 COVID-19 authorship group (1925 authors) was also compared to the 2019 group (33,049 authors) based on journal category (clinical/basic science research, general/subspecialty ophthalmology, journal impact factor).CONCLUSIONS: COVID-19 amplified the authorship gender gap in ophthalmology. When compared to previous years, there was a greater decrease in women's than men's academic productivity.
View details for DOI 10.1007/s00417-021-05085-4
View details for PubMedID 33537883
Gender Authorship Trends in the Ophthalmic Plastic and Reconstructive Surgery Literature.
Ophthalmic plastic and reconstructive surgery
Despite increasing numbers of women oculoplastic surgeons, they remain underrepresented within the subspecialty. The purpose of this study was to analyze trends in gender authorship within the field of ophthalmic plastic and reconstructive surgery.This retrospective observational study sampled articles published in Ophthalmic Plastic and Reconstructive Surgery (OPRS) and Orbit during the years 1985, 1995, 2005, 2015, and 2020. Data reviewed included article type, total number of authors, and the gender of each article's first and senior author.Nine hundred ninety-nine articles were analyzed, including 701 in OPRS and 298 in Orbit. Of 3,716 total authors, 1,151 (31%) were women, including 297 (29.7%) first authors, and 191 (21.5%) senior authors. Women authorship in OPRS in 1985 (first, 3.9%; senior, 3.3%; all, 3.2%) significantly increased by 2020 (first, 44.6%; senior, 27.9%; all, 42%). Women authorship in Orbit in 1985 (first, 0%; senior, 4.5%; all, 7.4%) also significantly increased by 2020 (first, 43.3%; senior, 34%; all, 42.9%). In a subanalysis of OPRS original investigations alone, women first authorship increased from 3.1% in 1985 to 35.8% in 2020 (p < 0.001) and women senior authorship increased from 4.3% in 1985 to 25% in 2020 (p = 0.001). In a subanalysis of Orbit original investigations alone, women first authorship increased from 0% in 1985 to 65.4% in 2020 (p < 0.001) and women senior authorship increased from 5.3% in 1985 to 42.3% in 2020 (p < 0.001).Despite a significant increase in women authorship over the past several decades, women remain underrepresented within the oculoplastic literature, particularly in regard to senior authorship. When considering original investigations alone, there has been a significant increase in women first and senior authorship in both OPRS and Orbit.
View details for DOI 10.1097/IOP.0000000000002013
View details for PubMedID 34293783
Gender of Award Recipients in Major Ophthalmology Societies.
American journal of ophthalmology
To assess the gender distribution of major ophthalmology society awards.Retrospective, observational study.The study population included award recipients from nine ophthalmological societies: American Academy of Ophthalmology (AAO), American Association for Pediatric Ophthalmology and Strabismus (AAPOS), American Glaucoma Society (AGS), American Society of Cataract and Refractive Surgery (ASCRS), American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS), American Society of Retina Specialists (ASRS), American Uveitis Society (AUS), Cornea Society, and North American Neuro-Ophthalmology Society (NANOS). A gender-specific pronoun and photograph of each award recipient were extracted from professional websites to assign their gender. Main outcome measures were gender distribution by award society, year (1970-2020), type (lectureship or not), category (achievement, education, research contribution, research item, international member achievement, public service - global health, service to society), and training level.Out of 2,150 recipients for 78 awards, 1,606 (74.7%) were men and 544 (25.3%) were women. The proportion of women recipients increased from 0% in 1970 to 33.2% in 2020 (P<0.001). Women representation varied within each society (P<0.01), with ASCRS having the highest percentage (40.8%). Women received 11.0% of awards accompanied by a lecture. Women received significantly greater research-related awards than achievement or service awards. Awards for trainees and early-career ophthalmologists had a greater proportion of women (39.8%) than the rest of the awards (21.5%) (P<0.001).Overall women received awards (25.3%) at a higher prevalence than the average 1970-2020 American gender distributions of ophthalmologists. However, women are still underrepresented in many award categories and subspecialties.
View details for DOI 10.1016/j.ajo.2021.05.021
View details for PubMedID 34102152
COVID-19 Recommendations From Ophthalmic and Plastic Reconstructive Surgery Societies Worldwide.
Ophthalmic plastic and reconstructive surgery
2020; 36 (4): 334–45
PURPOSE: The COVID-19 pandemic has brought unprecedented challenges for oculoplastic surgeons worldwide, in terms of care delivery, medical equipment and at-risk patient management. To date, there are no centralized or compiled international COVID-19 guidelines for oculoplastic surgeons.METHODS: We examined COVID-19 guidelines published by oculoplastic societies worldwide. All countries around the world were initially considered in this study, but only 9 oculoplastic societies met the inclusion criteria: (1) publicly available guidelines displayed on the oculoplastic society's website, or (2) guidelines received from the oculoplastic society after contacting them twice using the contact information on their website.RESULTS: The 9 oculoplastic societies examined include: the American Society of Ophthalmic Plastic and Reconstructive Surgery, the British Oculoplastic Surgery Society, the Canadian Society of Oculoplastic Surgery, the European Society of Ophthalmic Plastic and Reconstructive Surgery, la Sociedad Espanola de Cirugia Plastica Ocular y Orbitaria, la Asociacion Colombiana de Cirugia Plastica Ocular, the Asia Pacific Society of Ophthalmic Plastic & Reconstructive Surgery, the Oculoplastics Association of India, and the Philippine Society of Ophthalmic Plastic and Reconstructive Surgery. They all agree that urgent procedures should not be delayed, while non-necessary procedures (including all elective clinic services) should be postponed. When adequate protective equipment is available, oculoplastic surgeons must treat urgent cases. Eight out of 9 societies have provided recommendations on personal protective equipment use in order to prevent the spread of COVID-19 and to adequately protect mucous membranes. Other recommendations provided by certain societies are related to shelter in place measures, hand hygiene and surface disinfection protocols, patient triage, and thyroid eye disease management.CONCLUSIONS: All 9 societies with published recommendations have provided valuable recommendations to their members, regarding urgency of care and infection control solutions (personal protective equipment, hand hygiene, telemedicine, and social isolation).
View details for DOI 10.1097/IOP.0000000000001776
View details for PubMedID 32658132
Cannabis and the Cornea.
Ocular immunology and inflammation
Purpose: While cannabis has the potential to reduce corneal pain, cannabinoids might induce side effects. This review article examines the effects of cannabinoids on the cornea. As more states and countries consider the legalization of adult cannabis use, health-care providers will need to identify ocular effects of cannabis consumption.Methods: Studies included in this review examined the connection between cannabis and the cornea, more specifically anti-nociceptive and anti-inflammatory actions of cannabinoids. NCBI Databases from 1781 up to December 2019 were consulted.Results: Five studies examined corneal dysfunctions caused by cannabis consumption (opacification, decreased endothelial cell density). Twelve studies observed a reduction in corneal pain and inflammation (less lymphocytes, decreased corneal neovascularization, increased cell proliferation and migration).Conclusion: More than half of the studies examined the therapeutic effects of cannabinoids on the cornea. As the field is still young, more studies should be conducted to develop safe cannabinoid treatments for corneal diseases.
View details for DOI 10.1080/09273948.2020.1726969
View details for PubMedID 32159404
Differences in SARS-CoV-2 recommendations from major ophthalmology societies worldwide.
BMJ open ophthalmology
2020; 5 (1): e000525
Objective: Since the WHO declared the COVID-19 outbreak as a public health emergency, medical societies around the world published COVID-19 recommendations to physicians to ensure patient care and physician safety. During this pandemic, ophthalmologists around the world adapted their clinical and surgical practice following such guidelines. This original research examines all publicly available COVID-19 recommendations from twelve major ophthalmology societies around the world.Methods and analysis: Twelve ophthalmology societies recognised by the International Council of Ophthalmology were included in this study. One society per each WHO region was included: the society selected was the one who had the highest number of national COVID-19 confirmed cases on 11 May 2020. In addition to these countries, the major ophthalmology society in each G7 country was included.Results: Ten out of 12 major international ophthalmology societies from countries covering all six WHO regions have given recommendations regarding urgent patient care, social distancing, telemedicine and personal protective equipment when caring for ophthalmic patients during the COVID-19 pandemic. While all guidelines emphasise the importance of postponing non-urgent care and taking necessary safety measures, specific recommendations differ between countries.Conclusions: As there is no clear consensus on ophthalmology guidelines across countries, this paper highlights the differences in international ophthalmic care recommendations during the COVID-19 pandemic. Knowledge of the differences in ophthalmic management plans will allow ophthalmologists and all eye care providers to consider the variety of international approaches and apply best practices following evidence-based recommendations during pandemics.
View details for DOI 10.1136/bmjophth-2020-000525
View details for PubMedID 32656359
Training in and comfort with diagnosis and management of ophthalmic emergencies among emergency medicine physicians in the United States.
Eye (London, England)
Patients with ophthalmic emergencies often present to emergency rooms. Emergency medicine (EM) physicians should feel comfortable encountering these conditions. We assessed EM physicians' comfort working up, diagnosing, and managing ophthalmic emergencies.329 EM physicians participated in this cross-sectional multicentre survey. Questions inquired about the amount, type, and self-perceived adequacy of ophthalmic training. Likert scales were used to assess confidence and comfort working up, diagnosing, and managing ophthalmic emergencies.Participants recall receiving a median of 5 and 10 h of ophthalmic training in medical school and residency, respectively. Few feel this prepared them for residency (16.5%) or practice (52.0%). Only 50.6% feel confident with their ophthalmic exam. Most (75.0%) feel confident in their ability to identify an ophthalmic emergency, but 58.8% feel well prepared to work them up. Responders feel more comfortable diagnosing acute retrobulbar hematoma (72.5%), retinal detachment (69.8%), and acute angle closure glaucoma (78.0%) than central retinal artery occlusion (28.9%) or giant cell arteritis (53.2%). Only 60.2% feel comfortable determining if canthotomy and cantholysis is necessary in the setting of acute retrobulbar hematoma, and 40.3% feel comfortable performing the procedure. There was a trend towards attending physicians and providers in urban and academic settings feeling more comfortable diagnosing and managing ophthalmic emergencies compared to trainees, non-urban, and non-academic physicians.Many participants do not feel comfortable using ophthalmic equipment, performing an eye exam, making vision or potentially life-saving diagnoses, or performing vision-saving procedures, suggesting the need to increase ophthalmic training in EM curricula.
View details for DOI 10.1038/s41433-020-0889-x
View details for PubMedID 32350451
- "Percussive" orbital trauma from wooden drumstick. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 2020
Management and outcomes of proteasome inhibitor associated chalazia and blepharitis: a case series.
2019; 19 (1): 110
BACKGROUND: The purpose of this case series was to further characterize proteasome inhibitor associated chalazia and blepharitis, to investigate outcomes of different management strategies, and to propose a treatment algorithm for eyelid complications in this patient population.METHODS: This retrospective case series included sixteen patients found to have chalazia and/or blepharitis while receiving proteasome inhibitors for plasma cell disorders at Mount Sinai Hospital in New York, NY from January 2010 through January 2017. Main outcomes were complete resolution of eyelid complications and time to resolution. Student's t-test was used to compare average values and Fisher's exact test was used to compare proportions.RESULTS: Fourteen patients had chalazia and 10 had blepharitis. Chalazia averaged 5.4mm, and 11 patients with chalazia experienced two or more lesions. Median follow-up time was 17months. Average time from bortezomib exposure to onset of first eyelid complication was 3.4months. Chalazia episodes were more likely to completely resolve than blepharitis episodes (p=0.03). Ocular therapy alone was trialed for an average of 1.8months before proceeding to bortezomib omission. Average time to eyelid complication resolution using ocular therapy alone was 1.8months versus 3.1months after bortezomib omission. In this series, the combination of ocular therapy and bortezomib omission led to complete resolution of eyelid complications more often than ocular therapy alone.CONCLUSION: Proteasome inhibitor associated eyelid complications were identified in sixteen patients with plasma cell disorders. Eyelid complications may be treated with a 2-month trial of conservative ocular therapies alone, followed by continuation of ocular therapy in combination with bortezomib omission if eyelid signs persist.
View details for DOI 10.1186/s12886-019-1118-x
View details for PubMedID 31088416
Association between cannabis and the eyelids: A comprehensive review.
Clinical & experimental ophthalmology
Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients. There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug. These include: ptosis induction, an "eyelid tremor" appearance and blepharospasm attenuation. Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors. Fourteen articles report eyelid tremors in intoxicated drivers and ptosis as a secondary effect in cannabinoid animal experimental models. The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear. Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/ceo.13687
View details for PubMedID 31747112
Review of Ocular Manifestations of Joubert Syndrome.
2018; 9 (12)
Joubert syndrome is a group of rare disorders that stem from defects in a sensory organelle, the primary cilia. Affected patients often present with disorders involving multiple organ systems, including the brain, eyes, and kidneys. Common symptoms include breathing abnormalities, mental developmental delays, loss of voluntary muscle coordination, and abnormal eye movements, with a diagnostic "molar tooth" sign observed by magnetic resonance imaging (MRI) of the midbrain. We reviewed the ocular phenotypes that can be found in patients with Joubert syndrome. Ocular motor apraxia is the most frequent (80% of patients), followed by strabismus (74%) and nystagmus (72%). A minority of patients also present with ptosis (43%), chorioretinal coloboma (30%), and optic nerve atrophy (22%). Although mutations in 34 genes have been found to be associated with Joubert syndrome, retinal degeneration has been reported in only 38% of patients. Mutations in AHI1 and CEP290, genes critical to primary cilia function, have been linked to retinal degeneration. In conclusion, Joubert syndrome is a rare pleiotropic group of disorders with variable ocular presentations.
View details for PubMedID 30518138
- Review of Ocular Manifestations of Joubert Syndrome GENES 2018; 9 (12)
Orbital Metastasis From Urothelial Carcinoma: A Comprehensive Literature Review.
Ophthalmic plastic and reconstructive surgery
PURPOSE: To review the clinical features of orbital and choroidal metastases from urothelial carcinomas of the urinary tract among cases reported in the literature, and to describe a case of orbital metastasis from bladder cancer presenting as apparent internuclear ophthalmoplegia.METHODS: Case reports of orbital and choroidal metastases from urothelial carcinomas published in the literature from 1965 to 2018 were reviewed. Data collected included patient demographics, cancer stage and primary site, time to onset of ocular symptoms, length of presenting ocular symptoms, types of primary ocular symptoms, diagnostic imaging, histology, systemic and ocular treatments, and survival time.RESULTS: Twenty-eight cases of urothelial carcinoma with metastasis to the orbit or choroid were reviewed. Men were significantly more likely to suffer from this condition than women (p = 0.011). The average age of presentation with orbital symptoms was 63 years, with an average time of 19 months between primary cancer diagnosis and onset of orbital symptoms. Twenty-two patients had metastasis to the orbit and 6 to the choroid. In 4 cases, ocular deficits secondary to orbital and/or choroidal metastases were the initial presenting symptoms in patients with previously undiagnosed urothelial carcinoma. The most commonly noted primary ocular symptoms and signs consisted of decreased visual acuity, decreased ocular motility, proptosis, and diplopia. Average survival from onset of ocular symptoms was 4.67 months.CONCLUSIONS: Urothelial carcinoma may metastasize to the orbit or choroid; furthermore, its presentation may mimic internuclear ophthalmoplegia. It is recommended that any patient with visual symptoms and known urothelial cancer should undergo expedited workup for metastatic disease.
View details for DOI 10.1097/IOP.0000000000001256
View details for PubMedID 30489454
RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNEA AND THE PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2018; 38 (11): 2197–2206
To evaluate the relationship between obstructive sleep apnea (OSA) and the presence and severity of diabetic retinopathy (DR).Three hundred seventeen patients with International Classification of Diseases diagnoses of both DR and OSA were evaluated retrospectively. Diabetic retinopathy severity and diabetic macular edema status were determined by diagnostic coding and medical records. Obstructive sleep apnea severity and additional sleep measures were obtained from overnight polysomnography. Analysis was performed using multivariable logistic regression.After adjustment, an association was seen between DR and severe OSA (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.14-4.18, P = 0.019). Proliferative DR was associated with severe OSA versus no DR (OR: 2.40, 95% CI: 1.12-5.14, P = 0.024) and mild nonproliferative DR (OR: 2.87, 95% CI: 1.26-6.55, P = 0.012). Comparing all nonproliferative DR with proliferative DR, proliferative DR and severe OSA were associated (OR: 2.20, 95% CI: 1.03-4.70, P = 0.043), as well as diabetic macular edema and severe OSA (OR: 2.89, 95% CI: 1.58-5.27, P = 0.001). No association was seen between DR/diabetic macular edema and secondary sleep measures.The findings suggest an increased risk of DR, proliferative DR, and diabetic macular edema in patients with severe OSA. Ophthalmologists following these patients should be aware of this association to better manage ocular sequelae of diabetes.
View details for DOI 10.1097/IAE.0000000000001848
View details for Web of Science ID 000454007400012
View details for PubMedID 28937527
Multi-electrode recording as a novel technique in electromyography of the orbicularis oculi muscle
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
View details for Web of Science ID 000442912500290
Surgical loupe usage among oculoplastic surgeons in North America
CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
2018; 53 (2): 139–44
To study the patterns of usage and perception among U.S. oculoplastic surgeons regarding surgical loupes.An anonymous 20-question survey was emailed out to the American Society of Ophthalmic Plastic and Reconstructive Surgery listserv. Data were compiled in Google Forms. SPSS was used for statistical analyses. This study was approved by the institutional review board.Of the 609 members contacted, 239 (39%) completed the survey; 95% of respondents owned loupes and 78% regularly used them. No association was observed between frequency of loupe usage and sex or years in practice. The most common magnification and brand were 2.5× and Designs for Vision, respectively. The most common problems associated with loupes were limited vision (33%) and lack of comfort (24%), with 11% citing neck and cervical spinal disorders. The most common benefits were magnification (93%) and increased visual accuracy (68%). Of the respondents, 56% believed improved patient care to be a benefit and 76% believed that loupes enhance surgical outcome. With regard to training, 67% supported incorporating loupes into residency, 35% believed in mandating loupe purchase, and 25% wanted residencies to provide loupes at no cost. Respondent support for the use of loupes in practice and training was directly correlated with how frequently they used loupes.The vast majority of respondents owned loupes. Although most loupe owners used loupes regularly, a sizable proportion operated with limited vision and lack of comfort. Overall, just over half of respondents believed that loupes improve patient care and should be integrated into residency.
View details for PubMedID 29631825
Conservative therapy for chalazia: is it really effective?
To assess the within-treatment efficacy of hot compresses (HC), HC plus tobramycin (Tobrex) and HC plus tobramycin/dexamethasone (Tobradex) for chalazia treatment.Design: Multicentre, randomized clinical trial (ClinicalTrials.gov identifier, NCT01230593).Two clinical sites in New York and two clinical sites in Ontario.A total of 149 patients with one or more chalazia on separate eyelids randomly assigned to receive HC (n = 50), HC plus tobramycin (n = 50) or HC plus tobramycin/dexamethasone (n = 49).4-6 weeks of assigned treatment. Patients were measured for chalazion horizontal width and surveyed for pain and treatment satisfaction levels.Primary outcome was complete resolution (100% size reduction). Secondary outcomes were size change in millimetres and patient reported pre- and post-treatment pain and satisfaction levels.In the intention-to-treat (ITT) population, complete resolution occurred in 36 (18%) lesions total, 13 (21%) treated with HC, 12 (16%) with HC plus tobramycin and 11 (18%) with HC plus tobramycin/dexamethasone, with no significant difference between them (p = .78). Individually by paired t-test, there were statistically significant post-treatment mean size differences: HC 1.20 mm (p < 0.001), HC plus tobramycin 1.69 mm (p < .001) and HC plus tobramycin/dexamethasone 1.54 mm (p < 0.001), but no significant difference between them (p = .61). Lesions that completely resolved had a statistically significant lower pretreatment duration (1.5 months) compared to lesions that did not completely resolve (2.2 months) (p = .04).Hot compresses (HC) alone or in combination with tobramycin or tobramycin/dexamethasone drops and ointment are all effective first-line treatment options for chalazia. However, physicians may consider moving directly to the use of more invasive therapies, such as incision and curettage or steroid injections, for chalazia that have been present for more than 2 months, as older lesions are less likely to resolve with conservative therapies alone.
View details for PubMedID 29338124
Gun trauma and ophthalmic outcomes.
Eye (London, England)
PurposeThis retrospective cohort study assesses the visual outcomes of patients who survive gunshot wounds to the head.MethodsThe Elmhurst City Hospital Trauma Registry and Mount Sinai Data Warehouse were queried for gun trauma resulting in ocular injury over a 16-year period. Thirty-one patients over 16 years of age were found who suffered a gunshot wound to the head and resultant ocular trauma: orbital fracture, ruptured globe, foreign body, or optic nerve injury. Gun types included all firearms and air guns. Nine patients were excluded due to incorrect coding or unavailable charts. Statistical analysis was performed using a simple bivariate analysis (χ2).ResultsOf the 915 victims of gun trauma to the head, 27 (3.0%) sustained ocular injuries. Of the 22 patients whose records were accessible, 18 survived. Eight of the 18 surviving patients (44%) suffered long-term visual damage, defined as permanent loss of vision in at least one eye to the level of counting fingers or worse. Neither location of injury (P=0.243), nor type of gun used (P=0.296), nor cause of gun trauma (P=0.348) predicted visual loss outcome. The Glasgow Coma Scale eye response score on arrival to the hospital also did not predict visual loss outcome (P=0.793).ConclusionThere has been a dearth of research into gun trauma and even less research on the visual outcomes following gun trauma. Our study finds that survivors of gun trauma to the head suffer long-term visual damage 44% of the time after injury.Eye advance online publication, 22 December 2017; doi:10.1038/eye.2017.249.
View details for DOI 10.1038/eye.2017.249
View details for PubMedID 29271420
Healing comparison of porcine cutaneous incisions made with cold steel scalpel, standard electrosurgical blade, and a novel tissue dissector.
Medical research and innovations
2017; 1 (5)
Standard electrosurgery provides superior hemostasis compared to a cold steel scalpel, but inferior tissue healing. A novel electrosurgical blade with an advanced waveform, the MEGADYNE ACE BLADE™ 700 Soft Tissue Dissector (ACE), was designed to provide both excellent hemostasis and wound healing. This study compared ACE to scalpel and standard electrosurgery in a porcine model of wound healing.Skin incisions from six pigs were evaluated at time points of 0, 1, 2, 3 and 6 weeks after application of the three devices. Histopathology was performed on samples from each time point. For each non-initial time point, the healing incisions were photographed for later evaluation by expert graders, and excised for wound strength testing.Time 0 photomicrographs showed a gradient of thermal tissue damage by initial incision, ranging from no damage made by the scalpel, minimal damage made by ACE, and twice the ACE damage made by a nonstick PTFE-coated electrosurgical blade. Histopathologic analysis at 6 weeks showed comparable dermal scar width measurements for scalpel and ACE incisions. Scars were wider for incisions made by standard electrosurgical blade. Wound strength was greater for scalpel and ACE than for standard electrosurgery. Cosmetic results at 6 weeks were not significantly different between scalpel and ACE incisions, while standard electrosurgical blade incisions were significantly inferior to ACE (odds ratio: 53.4, p<0.001).The MEGADYNE ACE BLADE™ 700 Soft Tissue Dissector represents a significant improvement in electrosurgical technology for skin incisions and dispels the traditional concerns of delayed healing and poor cosmetic result that have been attributed to using conventional electrosurgical blades for skin incisions.
View details for DOI 10.15761/MRI.1000124
View details for PubMedID 33073169
View details for PubMedCentralID PMC7561048
Novel Hormone Receptors Present in Apocrine Cystadenoma of the Eyelid
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
2017; 33 (1): E20-E21
A 53-year-old woman presented with an apocrine cystadenoma of the right upper eyelid. Histologic examination revealed proliferating epithelial cells with apocrine snouts and occasional mitotic figures. Immunohistochemical analysis revealed a Ki-67 index of 15% and positive staining for synaptophysin, chromogranin, estrogen receptor, progesterone receptor, gross cystic disease fluid protein (GCDFP)-15, and mammoglobin. The complement of positive immunomarkers in this case reinforces the importance of total excision and careful histologic assessment.
View details for DOI 10.1097/IOP.0000000000000416
View details for Web of Science ID 000392250400028
View details for PubMedID 25719370
Applications of stem cell biology to oculoplastic surgery
CURRENT OPINION IN OPHTHALMOLOGY
2016; 27 (5): 428-432
The review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery.The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in-vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte-derived stem cells offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery.The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through induced pluripotent stem cells differentiation, permitting their use in transplants for oculoplastic surgery.
View details for DOI 10.1097/ICU.0000000000000288
View details for Web of Science ID 000382560300011
View details for PubMedID 27206262
Awareness and Knowledge of Emergent Ophthalmic Disease Among Patients in an Internal Medicine Clinic
2016; 134 (4): 424-431
Emergent ophthalmic disease can lead to permanent visual impairment or blindness if medical attention is delayed. Awareness and knowledge of emergent ophthalmic disease may be important for early medical presentation and maximization of visual prognosis in some cases.To assess public awareness and knowledge of 4 emergent ophthalmic diseases.This cross-sectional study was conducted from June 1 to July 30, 2015, in the waiting rooms of the outpatient internal medicine resident clinic at Mount Sinai Hospital. A written survey was administered to evaluate awareness and knowledge of retinal detachment, acute angle-closure glaucoma, giant cell arteritis, and central retinal artery occlusion. Awareness of each disease was assessed by whether participants knew what the diseases were (yes or no). Knowledge was evaluated by responses to 3 questions for each disease, including 1 question about basic pathophysiologic features, 1 question about basic symptoms, and 1 question about basic treatment options. All English-speaking patients who were physically and cognitively able to fill out the survey without assistance were considered eligible and offered the opportunity to participate during times of survey distribution; 237 completed the survey. Demographic information, including age, sex, race, income, and educational level, was collected. Data were assessed from August 1 to 7, 2015.Awareness of each ophthalmic disease was determined by the proportion of respondents who answered yes, and knowledge was determined by the proportion of aware respondents who answered the knowledge questions correctly.Two hundred thirty-seven patients (of 227 who gave complete demographic information, 76 men [33.5%], 151 women [66.5%], and mean [SD] age, 51.3 [16.8] years) completed the survey. Awareness of each of the diseases studied was low; 61 of 220 respondents (27.7%; 95% CI, 21.8%-33.6%) were aware of retinal detachment; 32 of 219 respondents (14.6%; 95% CI, 9.9%-19.3%), acute angle-closure glaucoma; 11 of 216 respondents (5.1%; 95% CI, 2.2%-8.0%), giant cell arteritis; and 10 of 218 respondents (4.6%; 95% CI, 1.8%-7.4%), central retinal artery occlusion. Respondents who were aware and knowledgeable ranged from 29 of 199 (14.6%) for the pathophysiologic features of retinal detachment, 1 of 208 (0.5%) for the symptoms and 2 of 203 (1.0%) for treatment of giant cell arteritis, and 1 of 193 (0.5%) for the pathophysiologic features of central retinal artery occlusion.Levels of awareness and knowledge of emergent ophthalmic diseases are low. These results indicate a need to educate the public about these acutely vision-threatening entities to ensure early medical presentation, to achieve the best possible visual prognosis, and to preserve quality of life.
View details for DOI 10.1001/jamaophthalmol.2015.6212
View details for Web of Science ID 000373988900019
View details for PubMedID 26892039
Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants
2016; 22: 138-149
To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model.Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compared with histology, immunochemistry for p63 and Krt3, ABCG2-dependent dye exclusion, and capacity for outgrowths in explant culture.Immunohistology and western blot of the outgrowths for p63 and Krt3 indicated no differences in expression between the primary and tertiary outgrowths for these two markers of growth and differentiation. Clinically, all rabbits treated with amniotic membrane alone developed severe LSCD. Most rabbits grafted with cell outgrowths from all three outgrowth generations achieved stable (>6 months) recovery of the ocular surface. There were partial failures of grafts performed with two secondary and tertiary outgrowths. However, Kruskal-Wallis statistical analysis of the clinical scores yielded no significant difference between the three groups (p=0.524). Histology showed full anatomic recovery of grafts made with primary and tertiary outgrowths. Krt3 and p63 expression throughout the whole limbal corneal epithelium with primary or tertiary outgrowths was not distinguishable from each other. The percentage of dye-excluding cells present within this zone and the capacity of the explant epithelial outgrowth of the regenerated peripheral corneal zone were also on par with those of the donor corneas. The Krt3-negative cells that characterize the basal epithelial layer of the normal limbus could not be found in any regenerated cornea from the primary to tertiary outgrowths.Our results demonstrate that in rabbits post-primary explant outgrowths retain the capacity for LSCD recovery found in primary explants.
View details for Web of Science ID 000369699800001
View details for PubMedID 26937166
View details for PubMedCentralID PMC4757454
Prognostic Value of Ocular Trauma Scores in Patients With Combined Open Globe Injuries and Facial Fractures
AMERICAN JOURNAL OF OPHTHALMOLOGY
2015; 160 (5): 882-888
To assess the prognostic value of the Ocular Trauma Score in patients with combined open globe injuries and facial fractures.Retrospective cohort study.A comprehensive chart review was conducted on 25 patients (28 eyes) identified from the Elmhurst City Hospital Trauma Registry between January 1, 2000 and June 30, 2012. Elmhurst City Hospital is a level 1 trauma center located in Elmhurst, New York, USA.Average age was 52 (range 18-88) and patients were predominantly male (84%). The majority of patients had an Ocular Trauma Score of 1 (87.5%), and of these patients, 76% and 14% had final visual acuities of no light perception (NLP) and light perception/hand motion (LP/HM), respectively. These corresponded to 74% and 15% predicted by the original Ocular Trauma Score guidelines (100% sensitive and 100% specific). Ocular Trauma Score of 1 was associated with zone 3 eye wound location (P = .02). Independent of Ocular Trauma Score, initial visual acuity and frontal bone fractures were predictive of NLP (P = .006 and P = .047). Nonblindness was associated with nasal bone fractures (P = .047).This study validates the use of the Ocular Trauma Score in patients with combined facial fracture and open globe injury. The presence of facial fractures does not appear to influence visual prognosis for open globe injuries with an Ocular Trauma Score of 1. In the absence of data to calculate a full Ocular Trauma Score, initial visual acuity was the strongest predictor of final visual outcome.
View details for DOI 10.1016/j.ajo.2015.08.007
View details for Web of Science ID 000363914800006
View details for PubMedID 26275473
Diagnostic Delay and Amniotic Membrane Transplantation in a Child With Atypical Stevens-Johnson Syndrome.
Journal of pediatric ophthalmology & strabismus
2015; 52 Online: e41-4
A 4-year-old boy presented with a 6-day history of severe non-limbic-sparing conjunctivitis. Atypical Stevens-Johnson syndrome with a possible cause of Mycoplasma pneumoniae was suspected as the precipitant of the clinical symptoms. The patient recovered with amniotic membrane transplantation and intravenous immunoglobulin therapy despite an initial delay in diagnosis.
View details for DOI 10.3928/01913913-20150811-01
View details for PubMedID 26301401
Bilateral Lacrimal Gland Disease Clinical Features of 97 Cases
2014; 121 (10): 2040-?
Bilateral lacrimal gland (LG) disease is a unique presentation that can result from varied causes. We reviewed the diagnoses, clinical features, and outcomes of 97 patients with this entity.Case series.Ninety-seven patients with bilateral LG disease.Retrospective review and statistical analysis using analysis of variance and the Fisher exact test.Patient demographics, clinical features, diagnostic testing, diagnosis, and treatment.Patient age ranging from 8 to 84 years (mean, 46 years). The predominant gender was female (77%), and race included black (49%), white (38%), and Hispanic (12%) patients. Diagnoses fell into 4 categories: inflammatory (n = 51; 53%), structural (n = 20; 21%), lymphoproliferative (n = 19; 20%), and uncommon (n = 7; 7%) entities. The most common diagnoses included idiopathic orbital inflammation (IOI; n = 29; 30%), sarcoidosis (n = 19; 20%), prolapsed LG (n = 15; 15%), lymphoma (n = 11; 11%), lymphoid hyperplasia (n = 8; 8%), and dacryops (n = 5; 5%). Inflammatory conditions were more likely in younger patients (P<0.05) and in those with pain (P<0.001) and mechanical blepharoptosis (P<0.01) at presentation, whereas lymphoma was more common in older patients (P<0.001) without active signs of inflammation at presentation. Black patients were more likely to have sarcoidosis (P<0.01). Laboratory results showed high angiotensin converting enzyme level being significantly more likely in patients with sarcoidosis (P<0.05). However, sensitivity was limited to 45%, with 25% of patients diagnosed with IOI also demonstrating positive results. Corticosteroid therapy was the treatment of choice in 38 cases, corresponding to resolution of symptoms in 29% and improvement in an additional 32%. Overall, chronic underlying disease was found in 71% of patients, among whom 26% achieved a disease-free state, whereas 3% succumbed to their underlying disease.The cause of bilateral lacrimal gland disease most commonly was inflammatory, followed by structural and lymphoproliferative. Patient characteristics and clinical presentations were key features distinguishing between competing possibilities. Despite local control with corticosteroids or radiotherapy, underlying disease continued in 71% of patients and led to death in 3%.
View details for DOI 10.1016/j.ophtha.2014.04.018
View details for Web of Science ID 000342697300036
View details for PubMedID 24907059
Enucleation versus evisceration in ocular trauma: a retrospective review and study of current literature.
Orbit (Amsterdam, Netherlands)
2013; 32 (6): 356-361
To compare variables and outcomes from ocular trauma leading to either enucleation or evisceration to better inform surgical decision making.Retrospective chart review.We reviewed 441 patients between 2001 and 2012 presenting with ocular trauma to a Level 1 trauma center in Queens, New York; of these, there were 16 enucleations and 6 eviscerations. Retrospective chart review noted age, gender, mechanism of injury, initial and final visual acuity, time to surgery, length of follow-up, pain, degree of motility, and complications. A review of literature in the context of our study was performed.20 patients were male and 2 patients were female; average age was 44 (SD: 20.0, range 18-91). 9/16 patients were enucleated to prevent sympathetic ophthalmia, whereas only 1/5 patient was eviscerated for this indication (p = 0.1619). No cases of sympathetic ophthalmia were reported over an average follow-up of 316 days. Average length of follow-up varied significantly between the two groups, with an average of 370.4 days (SD: 566.9, range 0-1870) for enucleated eyes and 172.7 days (SD: 146.3, range 0-422) for eviscerated eyes (p = 0.42). Medpor implants were preferred in eviscerations (5/6 eviscerations), whereas hydroxyapatite implants were preferred in enucleations (10/16 enucleations, p = 0.04).Surgical decision-making in ocular trauma is largely based on surgeon preference and experience, with minimal evidence in the literature to support either enucleation or evisceration. We recommend evisceration over enucleation in cases of reliable patient follow-up due to the low incidence of sympathetic ophthalmia.
View details for DOI 10.3109/01676830.2013.764452
View details for PubMedID 23909276
- Idiopathic recurrent subconjunctival hemorrhage. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 2012; 47 (5): e28-9
A case of orbital involvement in IgG4-related disease.
Orbit (Amsterdam, Netherlands)
2012; 31 (5): 327-329
A 46-year-old male was referred to the Ophthalmology Service for a 7-year history of bilateral proptosis and a presumptive diagnosis of thyroid eye disease. Past medical history was only significant for autoimmune pancreatitis. All laboratory testing including tests of thyroid function were within normal limits. The patient underwent orbital biopsy and was found to have plasma cells containing mainly IgG4 immunoglobulin that was consistent with IgG4-related disease. The patient was treated with oral prednisone and the proptosis resolved within 3 weeks.
View details for DOI 10.3109/01676830.2011.616618
View details for PubMedID 22712681
Cadaveric Anatomical Comparison of the Lateral Nasal Wall After External and Endonasal Dacryocystorhinostomy
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
2012; 28 (2): 149-153
Much literature has accumulated espousing the relative merits of endonasal and external dacryocystorhinostomy (DCR). However, there is comparatively little information on the relative anatomic differences between these 2 approaches. The purpose of this study is to investigate the anatomic relationships of the lateral nasal wall for endonasal and external DCR.Ten cadaver half heads were used in this study. Half were subject to endonasal and half to external DCR procedures. The lateral nasal wall was then dissected and measurements were taken of ostium and anastomosis size and position relative to other landmarks on the lateral nasal wall. Relationships were compared between the 2 procedures.The dimensions and area of the ostium and the anastomosis were similar between the 2 procedures. The lower portion of the ostium was located more inferiorly in endonasal DCR. Additionally, the ostium was more likely to be found lateral to the axilla of the middle turbinate in endonasal DCR, when compared with anterior for external. External DCR was also more likely to involve opening the anterior ethmoid air cells than endonasal approach.Endonasal and external DCR osteomies appear to be of similar size, with the endonasal opening being located slightly lower and more posterior on the lateral nasal wall.
View details for DOI 10.1097/IOP.0b013e318248e687
View details for Web of Science ID 000301974000025
View details for PubMedID 22410664
- Endogenous bacterial endophthalmitis after routine colonoscopy CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE 2011; 46 (6): 556-557
Bicanalicular Laceration Repair Via an Endoscopic Retrograde Approach
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
2011; 27 (6): E165-E167
A 31-year-old man presented 5 days after a left bicanalicular laceration from trauma. Identification of the medial cut ends under direct visualization was unsuccessful. A retrograde endoscopic approach was used to identify the common canaliculus or one of the medial cut ends of the canaliculi by injecting the lacrimal sac with saline and observing fluid egress from the wound. Both canaliculi were stented with a silicone tube and both ends of the tube were passed through the identified medial opening in the lacrimal sac. The tubes were retrieved from the nose and tied, and then left for 6 months before removal. The patient did not complain of epiphora and demonstrated bicanalicular patency on irrigation. This is the first description of using an endoscopic retrograde approach to identify the medial ends of a bicanalicular laceration.
View details for DOI 10.1097/IOP.0b013e31820c6e3f
View details for Web of Science ID 000296865200012
View details for PubMedID 21346667
Bifocal Orbital and Nasopharyngeal Amyloidomas Presenting as Graves Disease
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
2011; 27 (5): E132-E134
A 72-year-old man presented with a slowly progressive left hyperglobus, left infraduction deficit, bilateral lower eyelid retraction, and dysphagia. He had a notable chin-down head position, diplopia in primary position, and 3 mm of left proptosis. He had been diagnosed with Graves disease 3 years before presentation. CT scans showed enlargement of the left inferior and medial rectus muscles with associated stranding of the retrobulbar fat and a low-density heterogeneous mass in the left aspect of the neck protruding in the nasopharynx. Biopsies of the orbit and nasopharynx revealed focal areas of amyloid. This represents the first report of bifocal amyloidomas of the orbit and nasopharynx.
View details for DOI 10.1097/IOP.0b013e31820367ca
View details for Web of Science ID 000294711700012
View details for PubMedID 21178798
Indications for Orbital Imaging by the Oculoplastic Surgeon
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
2011; 27 (4): 260-262
To determine the indications for ordering orbital imaging and the indications for ordering CT versus MRI by oculoplastic surgeons and to assess the correlation between surgeon's clinical indications for imaging and the radiologist's diagnosis.Retrospective review of imaging requisitions and radiology reports.Patients of 4 oculoplastic surgeons who required CT or MRI scans.Imaging requisitions and radiology reports of patients from 4 oculoplastic surgeons were reviewed to determine the indication for ordering a CT or MRI scan between March 2006 and March 2009. The indications were then compared with the radiologist's diagnosis.A total of 735 patients were included: 449 (61.1%) female and 286 (38.9%) male, with an average age of 50.1 years and an age range of 7 months to 93 years. Of these patients, a total of 632 CT and 223 MRI scans were ordered, 135 of which were follow-up scans.The most common indication for CT scan was thyroid disease, followed by orbital tumors and then inflammatory disease, while the most common indication for MRI scan was orbital tumors, followed by inflammatory disease and then thyroid disease. CT scans were more commonly ordered than MRI, largely for trauma and to rule out orbital foreign body.
View details for DOI 10.1097/IOP.0b013e31820b0365
View details for Web of Science ID 000292633700022
View details for PubMedID 21326128
Enduragen patch grafts for exposed orbital implants.
Orbit (Amsterdam, Netherlands)
2011; 30 (2): 92-95
To present a new technique using the recently introduced Enduragen(®) material (Tissue Science Laboratories) as a patch graft for exposed ocular implants.A retrospective, interventional, non-comparative case series of 3 patients who had Enduragen patch grafts for the closure of Tenon's capsule and conjunctiva over exposed ocular implants. Medical records were reviewed and the following parameters were collected: age, gender, indication for surgery, type of surgery, laterality, type of orbital implant, complications after repair and length of follow-up.Three patients were identified, 2 males and 1 female. One patient had a secondary quad-motility implant with supertemporal exposure. The second patient had a secondary implant with a fistula at the lateral aspect of the socket. The third patient had a centrally exposed primary hydroxyapatite implant. All patients received Enduragen patch grafts to cover the implant. Follow up ranged from 40 to 43 months (mean, 41.3 months; SD, ± 1.5). None of the 3 patients had any signs of implant re-exposure at the time of the last post-operative visit. There were no intra-operative or early complications observed.This consecutive case series suggests that Enduragen could be used as a safe and effective patch graft for exposed ocular implants. However, a larger prospective study with longer follow-up would be useful in further defining the indications and limitations of the Enduragen patch graft for the treatment of exposed orbital implants.
View details for DOI 10.3109/01676830.2011.558974
View details for PubMedID 21438730
Eyelash Resection Procedure for Severe, Recurrent, or Segmental Cicatricial Entropion
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
2010; 26 (2): 112-116
To study the safety, efficacy, and cosmetic outcome of the eyelash resection procedure for treatment of severe, recurrent, or segmental cicatricial entropion.Retrospective consecutive case series of patients with severe, recurrent, or segmental cicatricial entropion treated with eyelash resection at the Moran Eye Center and the University of Vermont. Investigators performed chart reviews of these patients and evaluated effectiveness of the treatment and outcome data, including age, gender, diagnoses, method of repair, recurrence of trichiasis, and cosmetic satisfaction. There were no exclusionary characteristics specified in the study.A total of 26 eyelids were operated on in 5 male and 11 female patients. The mean age was 74 years, with the following diagnoses: idiopathic (6), ocular cicatricial pemphigoid (2), postoperative (2), ocular pseudopemphigoid (drug related) (1), graft-versus-host disease (1), Stevens-Johnson syndrome (1), trachoma (1), linear IgA bullous dermatosis (1), and trauma (1). Mean postoperative follow-up was 13 months. The functional success rate was 90.5%, and the cosmetic success rate was 100%.The eyelash resection procedure is a safe, effective, and cosmetically acceptable procedure for treatment of severe, recurrent, or segmental cicatricial entropion.
View details for DOI 10.1097/IOP.0b013e3181b8c900
View details for Web of Science ID 000276129300011
View details for PubMedID 20305511
- Low-cost headlamps for facial and oculoplastic surgery OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY 2008; 24 (5): 429-429
Molecular determinants for cyclic nucleotide binding to the regulatory domains of phosphodiesterase 2A
JOURNAL OF BIOLOGICAL CHEMISTRY
2004; 279 (36): 37928-37938
Binding of cGMP to the GAF-B domain of phosphodiesterase 2A allosterically activates catalytic activity. We report here a series of mutagenesis studies on the GAF-B domain of PDE2A that support a novel mechanism for molecular recognition of cGMP. Alanine mutations of Phe-438, Asp-439, and Thr-488, amino acids that interact with the pyrimidine ring, decrease cGMP affinity slightly but increase cAMP affinity by up to 8-fold. Each interaction is required to provide for cAMP/cGMP specificity. Mutations of any of the residues that interact with the phosphate-ribose moiety or the imidazole ring abolish cGMP binding. Thus, residues that interact with the pyrimidine ring collectively control cAMP/cGMP specificity, whereas residues that bind the phosphate-ribose moiety and imidazole ring are critical for high affinity binding. Similar decreases in binding were found for mutations made in a bacterially expressed GAF-A/B plus catalytic domain construct. Because these constructs had very high catalytic activity, it appears that these mutations did not cause a global denaturation. The affinities of cAMP and cGMP for wild-type GAF-B alone were approximately 4-fold greater than for the holoenzyme, suggesting that the presence of neighboring domains alters the conformation of GAF-B. More importantly, the PDE2A GAF-B, GAF-A/B, GAF-A/B+C domains, and holoenzyme all bind cGMP with much higher affinity than has previously been reported. This high affinity suggests that cGMP binding to PDE2 GAF-B activates the enzyme rapidly, stoichiometrically, and in an all or none fashion, rather than variably over a large range of cyclic nucleotide concentrations.
View details for DOI 10.1074/jbc.M404287200
View details for Web of Science ID 000223554600086
View details for PubMedID 15210692
The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2002; 99 (20): 13260-13265
Cyclic nucleotide phosphodiesterases (PDEs) regulate all pathways that use cGMP or cAMP as a second messenger. Five of the 11 PDE families have regulatory segments containing GAF domains, 3 of which are known to bind cGMP. In PDE2 binding of cGMP to the GAF domain causes an activation of the catalytic activity by a mechanism that apparently is shared even in the adenylyl cyclase of Anabaena, an organism separated from mouse by 2 billion years of evolution. The 2.9-A crystal structure of the mouse PDE2A regulatory segment reported in this paper reveals that the GAF A domain functions as a dimerization locus. The GAF B domain shows a deeply buried cGMP displaying a new cGMP-binding motif and is the first atomic structure of a physiological cGMP receptor with bound cGMP. Moreover, this cGMP site is located well away from the region predicted by previous mutagenesis and structural genomic approaches.
View details for DOI 10.1073/pnas.192374899
View details for Web of Science ID 000178391700137
View details for PubMedID 12271124
View details for PubMedCentralID PMC130621
Opposing effects of reactive oxygen species and cholesterol on endothelial nitric oxide synthase and endothelial cell caveolae
1999; 85 (1): 29-37
Synthesis of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) is critical for normal vascular homeostasis. eNOS function is rapidly regulated by agonists and blood flow and chronically by factors that regulate mRNA stability and gene transcription. Recently, localization of eNOS to specialized plasma membrane invaginations termed caveolae has been proposed to be required for maximal eNOS activity. Because caveolae are highly enriched in cholesterol, and hypercholesterolemia is associated with increased NO production, we first studied the effects of cholesterol loading on eNOS localization and NO production in cultured bovine aortic endothelial cells (BAECs). Caveolae-enriched fractions were prepared by OptiPrep gradient density centrifugation. Treatment of BAECs with 30 microgram/mL cholesterol for 24 hours stimulated significant increases in total eNOS protein expression (1.50-fold), eNOS associated with caveolae-enriched membranes (2.23-fold), and calcium ionophore-stimulated NO production (1.56-fold). Because reactive oxygen species (ROS) contribute to endothelial dysfunction in hypercholesterolemia, we next studied the effects of ROS on eNOS localization and caveolae number. Treatment of BAECs for 24 hours with 1 micromol/L LY83583, a superoxide-generating napthoquinolinedione, decreased caveolae number measured by electron microscopy and prevented the cholesterol-mediated increases in eNOS expression. In vitro exposure of caveolae-enriched membranes to ROS (xanthine plus xanthine oxidase) dissociated caveolin more readily than eNOS from the membranes. These results show that cholesterol treatment increases eNOS expression, whereas ROS treatment decreases eNOS expression and the association of eNOS with caveolin in caveolae-enriched membranes. Our data suggest that oxidative stress modulates endothelial function by regulating caveolae formation, eNOS expression, and eNOS-caveolin interactions.
View details for Web of Science ID 000081424900006
View details for PubMedID 10400908
Agonist induced homologous desensitization of mu-opioid receptors mediated by G protein-coupled receptor kinases is dependent on agonist efficacy
1998; 54 (4): 704-711
Using Xenopus laevis oocytes coexpressing mammalian mu-opioid receptors (MORs), beta-adrenergic receptor kinase 2 (beta-ARK2) [also called G protein-coupled receptor kinase (GRK3)], and beta-arrestin 2 (beta-arr 2), we compared the rates of beta-ARK2 (GRK3)- and beta-arr 2-mediated homologous receptor desensitization produced by treatment with opioid agonists of different efficacies. The response to MOR activation was measured using two-electrode voltage clamp as an increase in the conductance of the coexpressed G protein-coupled inwardly rectifying potassium (heteromultimer of KIR3.1 and KIR3.4) channels. Treatment with opioids of high efficacy, either [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin, fentanyl, or sufentanyl, produced a GRK3- and beta-arr 2-dependent reduction in response in <20 min, whereas treatment with the partial agonist morphine produced receptor desensitization at a significantly slower rate. Because GRK3 requires activation and membrane targeting by free G protein betagamma subunits released after agonist-mediated activation of G proteins, a low efficacy agonist such as morphine may produce weak receptor desensitization as a consequence of poor GRK3 activation. To address this hypothesis, we substituted GRK5, a GRK that does not require activation by G protein betagamma. In oocytes expressing GRK5 instead of GRK3, both [D-Ala2,N-MePhe4, Gly-ol5]enkephalin and fentanyl, but not morphine, produced desensitization of MOR-activated potassium conductance. Thus, mu-opioid agonists produced significant receptor desensitization, mediated by either GRK3 or GRK5, at a rate dependent on agonist efficacy.
View details for Web of Science ID 000076485500014
View details for PubMedID 9765514