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.

Clinical Focus

  • 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
  • Blepharoplasty
  • Cosmetic Surgery & Treatments
  • Pediatric Oculoplastics
  • Ophthalmic Plastic and Reconstructive Surgery

Academic Appointments

Administrative Appointments

  • 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)

Professional Education

  • 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

    Partnering Organization(s)

    Virtue Foundation

    Populations Served




    Ongoing Project


    Opportunities for Student Involvement


  • Ophthalmology Outreach in Tanzania, Morogoro, Tanzania



    Populations Served




    Ongoing Project


    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.

2023-24 Courses

Stanford Advisees

All Publications

  • An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome. Nature communications Liu, S., Ezran, C., Wang, M. F., Li, Z., Awayan, K., Long, J. Z., De Vlaminck, I., Wang, S., Epelbaum, J., Kuo, C. S., Terrien, J., Krasnow, M. A., Ferrell, J. E. 2024; 15 (1): 2188


    Hormones mediate long-range cell communication and play vital roles in physiology, metabolism, and health. Traditionally, endocrinologists have focused on one hormone or organ system at a time. Yet, hormone signaling by its very nature connects cells of different organs and involves crosstalk of different hormones. Here, we leverage the organism-wide single cell transcriptional atlas of a non-human primate, the mouse lemur (Microcebus murinus), to systematically map source and target cells for 84 classes of hormones. This work uncovers previously-uncharacterized sites of hormone regulation, and shows that the hormonal signaling network is densely connected, decentralized, and rich in feedback loops. Evolutionary comparisons of hormonal genes and their expression patterns show that mouse lemur better models human hormonal signaling than mouse, at both the genomic and transcriptomic levels, and reveal primate-specific rewiring of hormone-producing/target cells. This work complements the scale and resolution of classical endocrine studies and sheds light on primate hormone regulation.

    View details for DOI 10.1038/s41467-024-46070-9

    View details for PubMedID 38467625

    View details for PubMedCentralID 1540572

  • Functional Oculofacial Abstracts. Ophthalmic plastic and reconstructive surgery Ali, M. J., Bernardini, F. P., Savar, A., Wu, A. Y., Tawfik, H. A. 2024; 40 (2): 233-234

    View details for DOI 10.1097/IOP.0000000000002612

    View details for PubMedID 38427839

  • Research productivity and gender of research award recipients in international ophthalmology societies. BMJ open ophthalmology Nguyen, A. X., Venkatesh, D. S., Biyani, A., Ratan, S., Youn, G. M., Wu, A. Y. 2024; 9 (1)


    The purpose of this study is to assess the research productivity and gender of award recipients of ophthalmology research awards in international societies.This is a retrospective, observational study. The study population included award recipients of research awards from 36 ophthalmologic societies (listed on the International Council of Ophthalmology database) in 99 years (1922-2021). A gender-specific pronoun and a photograph of each award recipient were extracted from professional websites to assign their gender. Research productivity levels were retrieved from the Elsevier Scopus author database. The main outcome measures were gender distribution of award recipients per year, mean h-index per year, mean m-quotient per year, mean h-index by society, and mean m-quotient by society.Out of 2506 recipients for 122 awards, 1897 (75.7%) were men and 609 (24.3%) were women. The proportion of woman recipients increased from 0% in 1922 to 41.0% in 2021. Compared with 2000-2010 (19.8%, 109 of 550), women received a greater proportion of awards (48.4%, 459 of 949) in the last decade, from 2011 to 2021. Furthermore, men more often had greater h-index scores and m-quotient scores.Women received awards (24.3%) at a lower rate than men (75.7%) while also exhibiting lower productivity, supporting the existence of a gender disparity. Our study found that women are under-represented in research awards, and further investigation into award selection processes and gender membership data is recommended.

    View details for DOI 10.1136/bmjophth-2023-001323

    View details for PubMedID 38417914

    View details for PubMedCentralID PMC10900313

  • Functional Oculofacial Abstracts. Ophthalmic plastic and reconstructive surgery Ali, M. J., Bernardini, F. P., Savar, A., Wu, A. Y., Tawfik, H. A. 2024; 40 (1): 121-122

    View details for DOI 10.1097/IOP.0000000000002576

    View details for PubMedID 38241627

  • BDNF and cAMP are neuroprotective in a porcine model of traumatic optic neuropathy. JCI insight Heng, K., Young, B. K., Li, B., Nies, A. D., Xia, X., Wen, R. R., Dalal, R., Bramblett, G. T., Holt, A. W., Cleland, J. M., Harris, J. N., Wu, A. Y., Goldberg, J. L. 2024


    Traumatic optic neuropathy (TON) is a devastating condition that can occur after blunt or penetrating trauma to the head, leading to visual impairment or blindness. Despite these debilitating effects, no clinically available therapeutic targets neuroprotection or promotes axon regeneration in this or any optic neuropathy. Limited data in large animal models is a major obstacle to advancing treatments toward clinical therapeutics. To address this issue, we refined a surgical model of TON in Yucatan minipigs. First, we validated the model by demonstrating visual impairment by flash visual-evoked potential and retinal ganglion cell degeneration and death. Next, we developed and optimized a delivery method and non-toxic dosing of intravitreal brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP). Finally, we showed that intravitreal injection of BDNF and cAMP rescued visual function and protected against retinal ganglion cell death and optic nerve axon degeneration. Together these data in a pre-clinical large animal model advance our understanding of and ability to model TON and further identify and develop candidate clinical therapeutics.

    View details for DOI 10.1172/jci.insight.172935

    View details for PubMedID 38194296

  • Gender and research productivity of award recipients among Canadian national ophthalmology and affiliate subspecialty societies. Women's health (London, England) Nguyen, A. X., Zahedi-Niaki, G., Lando, L., Hutnik, C. M., Wu, A. Y. 2023; 19: 17455057231219613


    Although women remain historically underrepresented in medical achievement awards, gender distribution of award recipients in ophthalmology in Canada remain to be explored based on research productivity metrics.To characterize the gender distribution of award recipients among the main Canadian national ophthalmological societies and subspecialty affiliates based on research productivity, graduate degrees, affiliated institution, and award type.Retrospective, observational study.Award recipients were selected from the Canadian Ophthalmological Society (COS), Canadian Association of Paediatric Ophthalmology and Strabismus (CAPOS); Canadian Cornea, External Disease, and Refractive Surgery Society (CCEDRSS); Canadian Council of Ophthalmology Residents (CCOR) Research Proposal Award; and Canadian Glaucoma Society (CGS). The recipients' gender was determined by web search for the gender-specific pronoun, profile photograph check, or using Gender-API. Outcomes included gender distribution of recipients per award, society, year, and training level and differences in research productivity.Thirteen special awards were given to 255 recipients (215 individuals) from 1995 to 2022. In total, 31% of recipients were women, the majority being from Canada. Women had a significantly lower median h-index (2.0 (0-62) women versus 4.0 (0-81) men, p = 0.001) and number of published documents (3.0 (0-213) women versus 8.0 (0-447) men, p < 0.001). On stratified analyses by type of award (research or lifetime achievement) and level of training (trainee or ophthalmologist), significant differences were found for mean h-index and number of publications for awardees within the research category (p = 0.01 and p = 0.02, respectively) and trainee level (p = 0.01 and p = 0.02, respectively). Overall, women's proportion rates in awards did not reach parity in 27 out of the 28 years analyzed.Women were confirmed to be historically minored in proportion among the prominent society awards in Canada, with attested research disparity possibly explaining some of this bias. These findings require further confirmation in larger cohorts accounting for additional educational, institutional, and provincial factors.Not applicable.

    View details for DOI 10.1177/17455057231219613

    View details for PubMedID 38130083

    View details for PubMedCentralID PMC10748528

  • Regenerated Corneal Epithelium Expresses More βIII-Tubulin After Chemical Injuries Compared to Mechanical Injuries. Translational vision science & technology Shadmani, A., Ercal, O., Uzun, S., Swarup, A., Wu, A. Y. 2023; 12 (12): 12


    Defining the regenerative response following various types of corneal chemical and mechanical injuries is important for understanding the pathophysiology of the injury and evaluating the effectiveness of the therapies. This study characterizes corneal epithelial healing in a murine chemical and mechanical injury model.Four groups of 10 mice each received complete corneolimbal injuries by AlgerBrush, AlgerBrush/thermal, NaOH (0.5 N), or ethanol. Slit-lamp and optical coherence tomography examinations were performed daily for 14 days. Corneal opacity (CO) and neovascularization (NV) were evaluated. The origin of the regenerated epithelium was illustrated by anti-cytokeratin 12 (K12) and anti-K13. The height of regenerated corneal epithelium and intraepithelial free nerve endings (FNEs) stained with anti-βIII-tubulin were measured. The amount of fibrosis was measured by anti-α-smooth muscle actin (α-SMA) monoclonal antibody in the different groups. Statistical analysis was performed by ANOVA and t-test.Corneal opacity and neovascularization were markedly higher in the NaOH and AlgerBrush/thermal groups. Molecular studies revealed the following: Regenerated corneal epithelium thickness was less than normal in all groups, the AlgerBrush group had the shortest height of the regenerated epithelium, βIII-tubulin was expressed in the entire height of corneal epithelium in all groups except in the AlgerBrush group, and K12 was replaced by K13 in all groups.Corneal wound healing is more effective following chemical injuries in terms of epithelial thickness. Inflammation may play an important role in the outcome.Inflammation following different injuries may be redirected to be more effective in corneal regeneration and clarity.

    View details for DOI 10.1167/tvst.12.12.12

    View details for PubMedID 38085248

  • Single-cell transcriptomic analysis of corneal organoids during development. Stem cell reports Swarup, A., Phansalkar, R., Morri, M., Agarwal, A., Subramaniam, V., Li, B., Wu, A. Y. 2023


    Corneal organoids are useful tools for disease modeling and tissue transplantation; however, they have not yet been well studied during maturation. We characterized human iPSC-derived corneal organoids at 1, 2, 3, and 4 months of development using single-cell RNA sequencing to determine the cellular heterogeneity at each stage. We found pluripotent cell clusters committed to epithelial cell lineage at 1 month; early corneal epithelial, endothelial, and stromal cell markers at 2 months; keratocytes as the largest cell population at 3 months; and a large epithelial cell population at 4 months. We compared organoid to fetal corneal development at different stages and found that 4-month organoids closely resemble the corneal cellular complexity of the fetal (16 post conception week) and adult cornea. Using RNA velocity trajectory analysis, we found that less differentiated cells appear to give rise to corneal epithelial cells during development.

    View details for DOI 10.1016/j.stemcr.2023.10.022

    View details for PubMedID 38039970

  • Evaluation of the Algerbrush II rotating burr as a tool for inducing ocular surface failure in a mouse model MOLECULAR VISION Shadmani, A., Jarin, T., Meng, X., Rajaendran, Y., Uzun, S., Wu, A. Y. 2023; 29: 256-265
  • Evaluation of the Algerbrush II rotating burr as a tool for inducing ocular surface failure in a mouse model. Molecular vision Shadmani, A., Jarin, T., Meng, X. Q., Rajaendran, Y., Uzun, S., Wu, A. Y. 2023; 29: 256-265


    The Algerbrush II has been widely used to induce corneal and limbal injuries in animal models. The extent of injury varies with the duration of exposure, pressure from the placement of the burr, and the size of the burr. However, no study has explored the correlation between the duration of exposure and the severity of injury in mouse model with corneal and limbal stem cell deficiency (LSCD) induced using the Algerbrush II. Therefore, this study aimed to evaluate the variations in the severity of corneal and limbal injury with different durations of the Algerbrush II application.The entire cornea and limbus of C57BL/6 mice were injured for 30-45 s, 60-75 s, 90-120 s, and 3-4 min. Photography and slit-lamp examination was performed on days 0, 2, 4, and 7, followed by hematoxylin & eosin, periodic acid-Schiff, and immunohistochemical staining. Statistical analysis was performed using one way ANOVA analysis.A duration of 30-45 s of injury was found to be sufficient to induce superficial corneal and limbal epithelial debridement and re-epithelialization was completed in all eyes by day 7; however, clinical signs of LSCD were not observed in all mice. Increasing the exposure time to 90-120 s resulted in central 2+ corneal opacity with limbal and paracentral corneal neovascularization. All eyes injured for 3-4 min displayed clinical signs of LSCD, such as persistent epithelial defects on day 7 after the injury, central corneal neovascularization, and 2.2+ diffuse corneal opacity. Histological signs of LSCD, including goblet cell metaplasia and K13 expression on the corneal surface, were observed in all injured eyes.Our findings suggest that the duration of injury is an important factor influencing the severity of LSCD in a murine model of injury. A 1-mm rotating burr was found to be more effective for keratectomy and pigment release, whereas a 0.5-mm burr was more suitable for corneal epithelial debridement.

    View details for PubMedID 38222449

    View details for PubMedCentralID PMC10784216

  • Functional Oculofacial Abstracts. Ophthalmic plastic and reconstructive surgery Ali, M. J., Bernardini, F. P., Savar, A., Wu, A. Y., Tawfik, H. A. 2023; 39 (6): 653-654

    View details for DOI 10.1097/IOP.0000000000002534

    View details for PubMedID 37922050

  • Demographic and socioeconomic disparities in receipt of ophthalmology consultation for facial trauma. BMJ open ophthalmology Gervasio, K. A., Camarena, J., Hampton, J., Chopra, N., Kalosza, B., Shumate, L., Wu, A. Y. 2023; 8 (1)


    OBJECTIVE: Functional outcomes following facial and ocular trauma are time-sensitive and require prompt evaluation to minimise long-term vision loss, yet few studies have systematically evaluated disparities in the management of these cases. This study investigates whether a patient's race/ethnicity, primary language, insurance status, gender or age affects receipt of ophthalmology consultation for facial trauma.METHODS AND ANALYSIS: This study was a retrospective cohort analysis of patients from the Elmhurst City Hospital Trauma Registry in Queens, New York who were seen for facial trauma including open globe injuries and orbital fractures between January 2014 and May 2016.RESULTS: Of the 264 patients included, 43% reported as Hispanic, 23% white, 11% Asian, 8% black and 15% other/unknown. After controlling for confounding variables by multivariable logistic regression, neither race/ethnicity, gender, nor primary language were significantly associated with the likelihood of receiving an ophthalmology consult. However, patients with private insurance had 2.57 times greater odds of receiving an ophthalmology consultation than those with Medicaid or state corrections insurance (95%CI 1.37 to 4.95). As age increased, the likelihood of receiving an ophthalmology consultation decreased (p=0.009); patients 60 years of age and older had one-third the odds of ophthalmology consultation as younger patients (OR 0.33; 95%CI 0.16 to 0.68).CONCLUSIONS: This study highlights that lack of ophthalmology consultation in patients with facial trauma is linked to age and underinsurance. Extra attention must be paid during primary assessments to ensure elderly patients and those with public insurance have equitable access to timely and appropriate care for facial trauma.

    View details for DOI 10.1136/bmjophth-2023-001259

    View details for PubMedID 37797981

  • Ocular Symptoms in Adolescents and Young Adults With Electronic Cigarette, Cigarette, and Dual Use. JAMA ophthalmology Nguyen, A. X., Gaiha, S. M., Chung, S., Halpern-Felsher, B., Wu, A. Y. 2023


    Despite increasing use of cigarettes and electronic cigarettes (e-cigarettes) and related health effects among youth, few studies have reported their effects on eyes.To examine the frequency and severity of ocular symptoms (ocular discomfort, pain, burning, itching, redness, dryness, glare, blurriness, strain, and headaches) in young e-cigarette and cigarette users.In an observational cross-sectional study, a survey conducted in May 6 to 14, 2020, asked participants about use (ever, past 30 days, and past 7 days) of e-cigarettes and cigarettes. The participants included US individuals aged 13 to 24 years.Associations between vision-related outcomes (general vision, severity/frequency of ocular symptoms) and tobacco use were analyzed using weighted multivariable logistic regressions, adjusting for sociodemographic factors, contact lens use, and other combustible use.There were 2168 never users, 2183 ever users, 1092 past 30-day users, and 919 past 7-day users of e-cigarettes; 55.9% of e-cigarette ever users also used cigarettes (dual users). Of the 4351 respondents, 63.8% identified as female, and mean (SD) age was 19.1 (2.9) years. Between 1.1% and 3.9% of ever dual users reported severe to very severe ocular symptoms; between 0.9% and 4.3% reported daily symptoms, which was higher than the proportion of symptoms in e-cigarette- or cigarette-only users. Past 7-day dual users had more severe itching (adjusted odds ratio [AOR], 2.37; 95% CI, 1.36-4.13; P = .002), redness (AOR, 2.58; 95% CI, 1.50-4.46; P = .001), dryness (AOR, 2.89; 95% CI, 1.64-5.08; P < .001), glare (AOR, 2.56; 95% CI, 1.50-4.35; P = .001), blurriness (AOR, 2.47; 95% CI, 1.36-4.50; P = .003), headaches (AOR, 2.31; 95% CI, 1.34-4.00; P = .003); and more frequent pain (AOR, 3.45; 95% CI, 2.09-5.68; P < .001), burning (AOR, 3.08; 95% CI, 1.86-5.09; P < .001), and redness (AOR, 2.72; 95% CI, 1.69-4.36; P < .001) than all other participants. Past 30-day dual users had more severe dryness (AOR, 2.65; 95% CI, 1.61-4.36; P < .001) and more frequent pain (AOR, 3.33; 95% CI, 2.12-5.21; P < .001) than all other participants. Ever dual users experienced more severe dryness (AOR, 1.60; 95% CI, 1.05-2.43; P = .03) and blurriness (AOR, 1.79; 95% CI, 1.21-2.64; P = .003) and more frequent pain (AOR, 1.69; 95% CI, 1.13-2.53; P = .01) and blurriness (AOR, 1.63; 95% CI, 1.13-2.36; P = .009) than never users.In this cross-sectional US study, adolescents and young adult users of both e-cigarettes and cigarettes had a higher likelihood of experiencing severe and frequent ocular symptoms, with past 7-day users reporting more symptoms than past 30-day users or ever users. These findings provide additional reasons for users of e-cigarettes and cigarettes to reduce their tobacco use to possibly prevent or minimize ocular symptoms.

    View details for DOI 10.1001/jamaophthalmol.2023.3852

    View details for PubMedID 37651129

  • Corneal and Limbal Alkali Injury Induction Using a Punch-Trephine Technique in a Mouse Model. Journal of visualized experiments : JoVE Shadmani, A., Dhowre, H. S., Ercal, O., Meng, X. Q., Wu, A. Y. 2023


    The cornea is critical for vision, and corneal healing after trauma is fundamental in maintaining its transparency and function. Through the study of corneal injury models, researchers aim to enhance their understanding of how the cornea heals and develop strategies to prevent and manage corneal opacities. Chemical injury is one of the most popular injury models that has extensively been studied on mice. Most previous investigators have used a flat paper soaked in sodium hydroxide to induce corneal injury. However, inducing corneal and limbal injury using flat filter paper is unreliable, since the mouse cornea is highly curved. Here, we present a new instrument, a modified biopsy punch, that enables the researchers to create a well-circumscribed, localized, and evenly distributed alkali injury to the murine cornea and limbus. This punch-trephine method enables researchers to induce an accurate and reproducible chemical burn to the entire murine cornea and limbus while leaving other structures, such as the eyelids, unaffected by the chemical. Moreover, this study introduces an enucleation technique that preserves the medial caruncle as a landmark for identifying the nasal side of the globe. The bulbar and palpebral conjunctiva, and lacrimal gland are also kept intact using this technique. Ophthalmologic examinations were performed via slit lamp biomicroscope and fluorescein staining on days 0, 1, 2, 6, 8, and 14 post-injury. Clinical, histological, and immunohistochemical findings confirmed limbal stem cell deficiency and ocular surface regeneration failure in all experimental mice. The presented alkali corneal injury model is ideal for studying limbal stem cell deficiency, corneal inflammation, and fibrosis. This method is also suitable for investigating pre-clinical and clinical efficacies of topical ophthalmologic medications on the murine corneal surface.

    View details for DOI 10.3791/65609

    View details for PubMedID 37590514

  • American Academy of Ophthalmology Clinical Practice Guidelines and Financial Disclosures-Where Is the Money Going?-Reply. JAMA ophthalmology Nguyen, A. X., Joly-Chevrier, M., Wu, A. Y. 2023

    View details for DOI 10.1001/jamaophthalmol.2023.3110

    View details for PubMedID 37471067

  • Accuracy of Digital Image Analysis for Diagnosing IgG4 Related Ophthalmic Disease Charoenkijkajorn, C., Gill, H., Glory, B., Shi, W., Homer, N., Men, C., Kossler, A., Wu, A., Lin, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • Quantitative Characterization of Mechanical and Chemical-Induced Corneal Injury and Lacrimal Gland Response in Mouse Model Shadmani, A., Wu, A., Ercal, O. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • Orbital floor fractures in Taiwan: A 10-year nationwide population-based study. Taiwan journal of ophthalmology Lin, Y. C., Yim, C. K., Wu, A. Y., Hwang, D. K. 2023; 13 (2): 203-209


    To characterize the epidemiology, associated complications, and risk factors of orbital floor fractures in a nationwide longitudinal health insurance database.Claims data from a million randomly selected registered residents from the Taiwan National Health Insurance Research Database were analyzed between 2001 and 2011 as part of a retrospective cohort review. Patients were identified using the International Classification of Disease-9 diagnosis codes for orbital floor fracture (closed: 802.6; open: 802.7). The cases were categorized as surgical or nonsurgical based on the procedure codes and compared statistically.From 2001 to 2011, 663 patients were diagnosed with orbital floor fractures out of a total population at risk of 9,836,431 person-years (average incidence: 6.78 persons/100,000/year) with overall increasing incidence. Surgical treatments were performed in 213 (32%) patients. Patients who received surgical treatment were younger than those who did not (mean age 25.3 ± 13.6 years vs. 34.2 ± 18.6 years, P < 0.001). The diagnosis with diplopia was a significantly associated factor for surgical treatment (2.2% in nonsurgery group vs. 6.6% in surgery group, P = 0.007). Male gender (adjusted hazard ratios [aHR] = 2.1, 95% confidence interval [CI]: 1.79-2.49) and low monthly income (aHR = 1.76, 95% CI: 1.16-2.67) were the risk factors for orbital floor fracture.The incidence of orbital floor fractures increased in the Taiwanese population between 2001 and 2011. Men and low income patients were at increased risk of orbital floor fracture. More research is necessary to clarify what factors are driving the escalating incidence of orbital fractures in this national population.

    View details for DOI 10.4103/tjo.TJO-D-23-00005

    View details for PubMedID 37484620

    View details for PubMedCentralID PMC10361428

  • Challenges Assessing Disparities in Patients Discharged After Firearm-Associated Ocular Injury. JAMA ophthalmology Wu, A. Y., Nguyen, A. X. 2023

    View details for DOI 10.1001/jamaophthalmol.2023.1739

    View details for PubMedID 37166808

  • Single-cell transcriptomics of the ocular anterior segment: a comprehensive review. Eye (London, England) Ahsanuddin, S., Wu, A. Y. 2023


    Elucidating the cellular and genetic composition of ocular tissues is essential for uncovering the pathophysiology of ocular diseases. Since the introduction of single-cell RNA sequencing (scRNA-seq) in 2009, vision researchers have performed extensive single-cell analyses to better understand transcriptome complexity and heterogeneity of ocular structures. This technology has revolutionized our ability to identify rare cell populations and to make cross-species comparisons of gene expression in both steady state and disease conditions. Importantly, single-cell transcriptomic analyses have enabled the identification of cell-type specific gene markers and signalling pathways between ocular cell populations. While most scRNA-seq studies have been conducted on retinal tissues, large-scale transcriptomic atlases pertaining to the ocular anterior segment have also been constructed in the past three years. This timely review provides vision researchers with an overview of scRNA-seq experimental design, technical limitations, and clinical applications in a variety of anterior segment-related ocular pathologies. We review open-access anterior segment-related scRNA-seq datasets and illustrate how scRNA-seq can be an indispensable tool for the development of targeted therapeutics.

    View details for DOI 10.1038/s41433-023-02539-3

    View details for PubMedID 37138096

    View details for PubMedCentralID 6421592

  • Epidemiologic Pattern and Injury Mechanism of Intimate Partner Violence-Related Ocular Trauma in the US. JAMA ophthalmology Alik, M., Malik, M., Ashrafi, R., Wu, A. Y. 2023


    Intimate partner violence (IPV) is an important cause of death and disability worldwide. The literature estimates that 45% of IPV injuries involve the eyes. Many medical fields have increased IPV-related research; however, ophthalmology IPV research remains rare.To evaluate the epidemiologic pattern and injury mechanism of IPV related to ocular trauma.This study was a retrospective cross-sectional analysis with deidentified data using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) codes from the National Trauma Data Bank (NTDB), which is a data set collected by the American College of Surgeons. The NTDB is the largest US hospitalized trauma case database with submissions from more than 900 US facilities. Included in this analysis were the IPV-related ocular injuries of patients hospitalized between 2017 and 2019. Study data were analyzed from April 20 to October 15, 2022.IPV-related ocular injuries.Ocular injuries and adult IPV trauma survivors were identified with the ICD-10-CM codes. The following demographic data were collected: sex, age, race and ethnicity, health insurance plan, substance misuse screening results, trauma level of hospital, the emergency department disposition, the total Glasgow Coma Scale score, the abbreviated injury scale, and caregiver at discharge.A total of 2598 of the recorded ocular injuries were associated with IPV. Patients had a mean (SD) age of 45.2 (18.4) years, and 1618 were female (62.3%). Most patients in the population sample (1195 [46.0%]) were aged 18 to 39 years. The race and ethnicity distribution was as follows: 629 Black (24.2%), 296 Hispanic (11.4%), 1358 White (52.3%), 229 other (8.8%), and 86 missing (3.3%). Insurance statuses were Medicaid (847 [32.6%]), Medicare (524 [20.2%]), private insurance (524 [20.2%]), and self-pay (488 [18.8%]). Women had greater odds of testing positive during alcohol screening (odds ratio [OR], 1.42; 95% CI, 1.21-1.67; P < .001). Black patients were most likely to have Medicaid (OR, 1.64; 95% CI, 1.35-1.99; P < .001), Hispanic patients were most likely to self-pay (OR, 1.96, 95% CI, 1.48-2.58; P < .001), and White patients were most likely to use Medicare (OR, 2.94, 95% CI, 2.33-3.73; P < .001).Social determinants of health were identified as key risk factors for IPV-related ocular injuries. Study findings highlight identifiable risk factors associated with IPV and ocular trauma that can contribute to IPV awareness among ophthalmologists.

    View details for DOI 10.1001/jamaophthalmol.2023.0578

    View details for PubMedID 36995733

    View details for PubMedCentralID PMC10064286

  • Financial Disclosures Reported by Industry Among Authors of the American Academy of Ophthalmology Clinical Practice Guidelines. JAMA ophthalmology Nguyen, A. X., Joly-Chevrier, M., Nguyen, D. D., Wu, A. Y. 2023


    Recommendations of clinical guidelines affect physicians' care delivery. Potential bias and undeclared conflicts of interests (COIs) among guideline authors can impact clinical practice decisions.To assess financial disclosures reported by physician authors of the American Academy of Ophthalmology (AAO) Practice Pattern Guidelines compared with those reported by industry to evaluate the disclosures' accuracy.In this cross-sectional study, all clinical guidelines in the AAO Preferred Practice Patterns (PPP) since 2013 (first year with publicly available industry payment reports) were reviewed on May 1, 2022. Guideline physician authors' name and their reported COI disclosure were extracted from the guideline publication. Payments to physician authors reported by industry were retrieved from the US Centers for Medicare & Medicaid Open Payments database. Physician authors serving on the AAO guideline committee were included.The primary outcome measure was the accuracy of authors' COIs disclosure. Secondary outcome measures were payments to physician authors reported by industry, the types of payments, and authors' gender.A total of 24 AAO guidelines released between 2016 and 2020 were included. Per guideline, there was a mean (SD) of 7.83 (2.24) physician authors. After removing 14 nonphysician authors, 188 physician author names remained, including 83 names assigned as women (44.1%) and 105 names assigned as men (55.9%). Authors could be counted multiple times in these 188 names. According to the Open Payments database, industry reported that 112 of 188 physician authors (59.6%) had at least received 1 payment while serving on the guideline committee, with a payment mean (SD) of $29 849.35 ($54 131.56). According to AAO guidelines, 149 authors (79.3%) had no financial disclosures while serving on the guideline committee. Among these 149 authors, most authors (81 [54.4%]) had payments reported by industry on the Open Payments database not disclosed within the guideline reports. Women physicians were paid significantly more than men for total payments (median [IQR] payments, $15 265 [$598.47-$41 104.67] vs $301.48 [$218.85-$14 615.09]; difference, $14 963.52; P = .003).Industry reported physician guideline authors to have received significant industry payments, some of which were not disclosed within information of the guidelines. To strengthen author transparency regarding these reported disclosures, the authors may want to review and resolve such potential discrepancies during the review and subsequent publication of guidelines.

    View details for DOI 10.1001/jamaophthalmol.2023.0267

    View details for PubMedID 36928457

  • Influence of Age, Gender, and Wait-Times On Public Online Ratings of Glaucoma Physicians in the United States. Journal of glaucoma Kim, J. Y., Francisco, R., Wang, J., Liu, J. J., Stephenson, N. J., Khalil, C. B., Kim, D. H., Nguyen, A. X., Youn, G. M., Sun, Y., Wu, A. Y. 2023


    PRCIS: Glaucoma surgeons are highly rated by the general public. Physicians with shorter wait times and who are younger are more likely to have higher ratings. Women glaucoma physicians are less likely to have higher ratings.PURPOSE: Find what characteristics of glaucoma physicians are associated with higher online ratings.PATENTS AND METHODS: All American members of the American Glaucoma Society (AGS) were queried on Healthgrades, Vitals, and Yelp. Ratings, medical school ranking, region of practice, gender, age, and wait times were recorded.RESULTS: 1106 (78.2%) of AGS members had at least one review across the three platforms. The average score among glaucoma surgeons was 4.160 (0.898 standard deviation, SD). Women physicians were associated with lower online ratings (adjusted odds ratio [aOR] 0.536 [95% CI 0.354-0.808). Physicians with less than 30 minutes of wait time had higher ratings: 15-30 minutes wait time (aOR 2.273 [95% CI 1.430-3.636]) and <15-minute wait time (aOR 3.102 [95% CI 1.888-5.146]). Older physicians had lower ratings (aOR 0.384 [95% CI 0.255-0.572]).CONCLUSIONS: Public online ratings of glaucoma specialists in the United States appear to favour those of younger age, men, and those with shorter wait times.

    View details for DOI 10.1097/IJG.0000000000002189

    View details for PubMedID 36795534

  • Characterization of Primary Cilia Formation in Human ESC-Derived Retinal Organoids. Stem cells international Ning, K., Luo, Z., Kowal, T. J., Tran, M., Majumder, R., Jarin, T. M., Wu, A. Y., Goldberg, J. L., Sun, Y. 2023; 2023: 6494486


    Objectives: Primary cilia are conserved organelles found in polarized mammalian cells that regulate neuronal growth, migration, and differentiation. Proper cilia formation is essential during eye development. Our previous reports found that both amacrine and retinal ganglion cells (RGCs) contain primary cilia in primate and rodent retinas. However, whether primary cilia are present in the inner retina of human retinal organoids remains unknown. The purpose of this study is to characterize the primary cilia distribution in human embryonic stem cell (hESC-derived retinal organoid development.Materials and Methods: Retinal organoids were differentiated from a hESC line, harvested at various developmental timepoints (day 44-day 266), and immunostained with antibodies for primary cilia, including Arl13b (for the axoneme), AC3, and Centrin3 (for the basal body). AP2alpha, Prox1, GAD67, Calretinin, GFAP, PKCalpha, and Chx10 antibodies as well as Brn3b-promoted tdTomato expression were used to visualize retinal cell types.Results: A group of ciliated cells were present in the inner aspects of retinal organoids from day 44 to day 266 in culture. Ciliated Chx10-positive retinal progenitor cells, GFAP-positive astrocytes, and PKCalpha-positive rod-bipolar cells were detected later during development (day 176 to day 266). Ciliation persisted during all stages of retinal developmental in AP2alpha-positive amacrine cells, but it was decreased in Brn3b-positive retinal ganglion cells (RGCs) at later time points. Additionally, AC3-positive astrocytes significantly decreased during the later stages of organoid formation.Conclusions: Amacrine cells in retinal organoids retain cilia throughout development, whereas RGC ciliation gradually and progressively decreases with organoid maturation.

    View details for DOI 10.1155/2023/6494486

    View details for PubMedID 36684387

  • Pathway of care for visual and vestibular rehabilitation after mild traumatic brain injury: a critical review. Brain injury Xiang, L., Bansal, S., Wu, A. Y., Roberts, T. L. 2022: 1-10


    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 Youn, G. M., Case, A. G., Jarin, T., Li, B., Swarup, A., Naranjo, A., Bou-Khalil, C., Yao, J., Zhou, Q., Hom, M. E., Rosenthal, E. L., Wu, A. Y. 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 Jarin, T., Ning, K., Luo, Z., Kowal, T., Li, B., Hu, Y., Wu, A. Y., Goldberg, J. L., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Association between heavy metals and diabetic retinopathy in the National Health and Nutrition Examination Surveys (NHANES) Nguyen, A., Lando, L., Trinh, X., Kurian, J., Trinh, V., Wu, A. Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • BDNF and cAMP promote retinal ganglion cell survival and function in a porcine model of traumatic optic neuropathy Heng, K., Li, B., Xia, X., Wen, R., Nies, A., Wu, A. Y., Goldberg, J. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans. Science (New York, N.Y.) Jones, R. C., Karkanias, J., Krasnow, M. A., Pisco, A. O., Quake, S. R., Salzman, J., Yosef, N., Bulthaup, B., Brown, P., Harper, W., Hemenez, M., Ponnusamy, R., Salehi, A., Sanagavarapu, B. A., Spallino, E., Aaron, K. A., Concepcion, W., Gardner, J. M., Kelly, B., Neidlinger, N., Wang, Z., Crasta, S., Kolluru, S., Morri, M., Pisco, A. O., Tan, S. Y., Travaglini, K. J., Xu, C., Alcántara-Hernández, M., Almanzar, N., Antony, J., Beyersdorf, B., Burhan, D., Calcuttawala, K., Carter, M. M., Chan, C. K., Chang, C. A., Chang, S., Colville, A., Crasta, S., Culver, R. N., Cvijović, I., D'Amato, G., Ezran, C., Galdos, F. X., Gillich, A., Goodyer, W. R., Hang, Y., Hayashi, A., Houshdaran, S., Huang, X., Irwin, J. C., Jang, S., Juanico, J. V., Kershner, A. M., Kim, S., Kiss, B., Kolluru, S., Kong, W., Kumar, M. E., Kuo, A. H., Leylek, R., Li, B., Loeb, G. B., Lu, W. J., Mantri, S., Markovic, M., McAlpine, P. L., de Morree, A., Morri, M., Mrouj, K., Mukherjee, S., Muser, T., Neuhöfer, P., Nguyen, T. D., Perez, K., Phansalkar, R., Pisco, A. O., Puluca, N., Qi, Z., Rao, P., Raquer-McKay, H., Schaum, N., Scott, B., Seddighzadeh, B., Segal, J., Sen, S., Sikandar, S., Spencer, S. P., Steffes, L. C., Subramaniam, V. R., Swarup, A., Swift, M., Travaglini, K. J., Van Treuren, W., Trimm, E., Veizades, S., Vijayakumar, S., Vo, K. C., Vorperian, S. K., Wang, W., Weinstein, H. N., Winkler, J., Wu, T. T., Xie, J., Yung, A. R., Zhang, Y., Detweiler, A. M., Mekonen, H., Neff, N. F., Sit, R. V., Tan, M., Yan, J., Bean, G. R., Charu, V., Forgó, E., Martin, B. A., Ozawa, M. G., Silva, O., Tan, S. Y., Toland, A., Vemuri, V. N., Afik, S., Awayan, K., Botvinnik, O. B., Byrne, A., Chen, M., Dehghannasiri, R., Detweiler, A. M., Gayoso, A., Granados, A. A., Li, Q., Mahmoudabadi, G., McGeever, A., de Morree, A., Olivieri, J. E., Park, M., Pisco, A. O., Ravikumar, N., Salzman, J., Stanley, G., Swift, M., Tan, M., Tan, W., Tarashansky, A. J., Vanheusden, R., Vorperian, S. K., Wang, P., Wang, S., Xing, G., Xu, C., Yosef, N., Alcántara-Hernández, M., Antony, J., Chan, C. K., Chang, C. A., Colville, A., Crasta, S., Culver, R., Dethlefsen, L., Ezran, C., Gillich, A., Hang, Y., Ho, P. Y., Irwin, J. C., Jang, S., Kershner, A. M., Kong, W., Kumar, M. E., Kuo, A. H., Leylek, R., Liu, S., Loeb, G. B., Lu, W. J., Maltzman, J. S., Metzger, R. J., de Morree, A., Neuhöfer, P., Perez, K., Phansalkar, R., Qi, Z., Rao, P., Raquer-McKay, H., Sasagawa, K., Scott, B., Sinha, R., Song, H., Spencer, S. P., Swarup, A., Swift, M., Travaglini, K. J., Trimm, E., Veizades, S., Vijayakumar, S., Wang, B., Wang, W., Winkler, J., Xie, J., Yung, A. R., Artandi, S. E., Beachy, P. A., Clarke, M. F., Giudice, L. C., Huang, F. W., Huang, K. C., Idoyaga, J., Kim, S. K., Krasnow, M., Kuo, C. S., Nguyen, P., Quake, S. R., Rando, T. A., Red-Horse, K., Reiter, J., Relman, D. A., Sonnenburg, J. L., Wang, B., Wu, A., Wu, S. M., Wyss-Coray, T. 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 Vorperian, S. K., Moufarrej, M. N., Tabula Sapiens Consortium, Quake, S. R., Jones, R. C., Karkanias, J., Krasnow, M., Pisco, A. O., Quake, S. R., Salzman, J., Yosef, N., Bulthaup, B., Brown, P., Harper, W., Hemenez, M., Ponnusamy, R., Salehi, A., Sanagavarapu, B. A., Spallino, E., Aaron, K. A., Concepcion, W., Gardner, J. M., Kelly, B., Neidlinger, N., Wang, Z., Crasta, S., Kolluru, S., Morri, M., Tan, S. Y., Travaglini, K. J., Xu, C., Alcantara-Hernandez, M., Almanzar, N., Antony, J., Beyersdorf, B., Burhan, D., Calcuttawala, K., Carter, M. M., Chan, C. K., Chang, C. A., Chang, S., Colville, A., Culver, R. N., Cvijovic, I., D'Amato, G., Ezran, C., Galdos, F. X., Gillich, A., Goodyer, W. R., Hang, Y., Hayashi, A., Houshdaran, S., Huang, X., Irwin, J. C., Jang, S., Juanico, J. V., Kershner, A. M., Kim, S., Kiss, B., Kong, W., Kumar, M. E., Kuo, A. H., Leylek, R., Li, B., Loeb, G. B., Lu, W., Mantri, S., Markovic, M., McAlpine, P. L., de Morree, A., Mrouj, K., Mukherjee, S., Muser, T., Neuhofer, P., Nguyen, T. D., Perez, K., Phansalkar, R., Puluca, N., Qi, Z., Rao, P., Raquer-McKay, H., Schaum, N., Scott, B., Seddighzadeh, B., Segal, J., Sen, S., Sikandar, S., Spencer, S. P., Steffes, L., Subramaniam, V. R., Swarup, A., Swift, M., Van Treuren, W., Trimm, E., Veizades, S., Vijayakumar, S., Vo, K. C., Vorperian, S. K., Wang, W., Weinstein, H. N., Winkler, J., Wu, T. T., Xie, J., Yung, A. R., Zhang, Y., Detweiler, A. M., Mekonen, H., Neff, N. F., Sit, R. V., Tan, M., Yan, J., Bean, G. R., Charu, V., Forgo, E., Martin, B. A., Ozawa, M. G., Silva, O., Toland, A., Vemuri, V. N., Afik, S., Awayan, K., Bierman, R., Botvinnik, O. B., Byrne, A., Chen, M., Dehghannasiri, R., Gayoso, A., Granados, A. A., Li, Q., Mahmoudabadi, G., McGeever, A., Olivieri, J. E., Park, M., Ravikumar, N., Stanley, G., Tan, W., Tarashansky, A. J., Vanheusden, R., Wang, P., Wang, S., Xing, G., Xu, C., Yosef, N., Culver, R., Dethlefsen, L., Ho, P., Liu, S., Maltzman, J. S., Metzger, R. J., Sasagawa, K., Sinha, R., Song, H., Wang, B., Artandi, S. E., Beachy, P. A., Clarke, M. F., Giudice, L. C., Huang, F. W., Huang, K. C., Idoyaga, J., Kim, S. K., Kuo, C. S., Nguyen, P., Rando, T. A., Red-Horse, K., Reiter, J., Relman, D. A., Sonnenburg, J. L., Wu, A., Wu, S. M., Wyss-Coray, T. 2022

    View details for DOI 10.1038/s41587-022-01293-3

    View details for PubMedID 35347330

  • Sentiment Analysis Surrounding Blepharoplasty in Online Health Forums PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN Lu, T. J., Nguyen, A., Trinh, X., Wu, A. Y. 2022; 10 (3)
  • Sentiment Analysis Surrounding Blepharoplasty in Online Health Forums. Plastic and reconstructive surgery. Global open Lu, T. J., Nguyen, A. X., Trinh, X. V., Wu, A. Y. 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. Nature biotechnology Vorperian, S. K., Moufarrej, M. N., Tabula Sapiens Consortium, Quake, S. R., Jones, R. C., Karkanias, J., Krasnow, M., Pisco, A. O., Quake, S. R., Salzman, J., Yosef, N., Bulthaup, B., Brown, P., Harper, W., Hemenez, M., Ponnusamy, R., Salehi, A., Sanagavarapu, B. A., Spallino, E., Aaron, K. A., Concepcion, W., Gardner, J. M., Kelly, B., Neidlinger, N., Wang, Z., Crasta, S., Kolluru, S., Morri, M., Tan, S. Y., Travaglini, K. J., Xu, C., Alcantara-Hernandez, M., Almanzar, N., Antony, J., Beyersdorf, B., Burhan, D., Calcuttawala, K., Carter, M. M., Chan, C. K., Chang, C. A., Chang, S., Colville, A., Culver, R. N., Cvijovic, I., D'Amato, G., Ezran, C., Galdos, F. X., Gillich, A., Goodyer, W. R., Hang, Y., Hayashi, A., Houshdaran, S., Huang, X., Irwin, J. C., Jang, S., Juanico, J. V., Kershner, A. M., Kim, S., Kiss, B., Kong, W., Kumar, M. E., Kuo, A. H., Leylek, R., Li, B., Loeb, G. B., Lu, W., Mantri, S., Markovic, M., McAlpine, P. L., de Morree, A., Mrouj, K., Mukherjee, S., Muser, T., Neuhofer, P., Nguyen, T. D., Perez, K., Phansalkar, R., Puluca, N., Qi, Z., Rao, P., Raquer-McKay, H., Schaum, N., Scott, B., Seddighzadeh, B., Segal, J., Sen, S., Sikandar, S., Spencer, S. P., Steffes, L., Subramaniam, V. R., Swarup, A., Swift, M., Van Treuren, W., Trimm, E., Veizades, S., Vijayakumar, S., Vo, K. C., Vorperian, S. K., Wang, W., Weinstein, H. N., Winkler, J., Wu, T. T., Xie, J., Yung, A. R., Zhang, Y., Detweiler, A. M., Mekonen, H., Neff, N. F., Sit, R. V., Tan, M., Yan, J., Bean, G. R., Charu, V., Forgo, E., Martin, B. A., Ozawa, M. G., Silva, O., Toland, A., Vemuri, V. N., Afik, S., Awayan, K., Bierman, R., Botvinnik, O. B., Byrne, A., Chen, M., Dehghannasiri, R., Gayoso, A., Granados, A. A., Li, Q., Mahmoudabadi, G., McGeever, A., Olivieri, J. E., Park, M., Ravikumar, N., Stanley, G., Tan, W., Tarashansky, A. J., Vanheusden, R., Wang, P., Wang, S., Xing, G., Xu, C., Yosef, N., Culver, R., Dethlefsen, L., Ho, P., Liu, S., Maltzman, J. S., Metzger, R. J., Sasagawa, K., Sinha, R., Song, H., Wang, B., Artandi, S. E., Beachy, P. A., Clarke, M. F., Giudice, L. C., Huang, F. W., Huang, K. C., Idoyaga, J., Kim, S. K., Kuo, C. S., Nguyen, P., Rando, T. A., Red-Horse, K., Reiter, J., Relman, D. A., Sonnenburg, J. L., Wu, A., Wu, S. M., Wyss-Coray, T. 2022


    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 Swarup, A., Grosskopf, A. K., Stapleton, L. M., Subramaniam, V. R., Li, B., Weissman, I. L., Appel, E. A., Wu, A. Y. 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) Radell, J. E., Tatum, J. N., Lin, C., Davidson, R. S., Pell, J., Sieja, A., Wu, A. Y. 2021


    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 Olivieri, J., Dehghannasiri, R., Wang, P. L., Jang, S., de Morree, A., Tan, S. Y., Ming, J., Wu, A., Consortium, T., Quake, S. R., Krasnow, M. A., Salzman, J. 2021; 10
  • Gender Gap in Neurology Research Authorship (1946-2020) FRONTIERS IN NEUROLOGY Nguyen, A. X., Yoffe, L., Li, A., Trinh, X., Kurian, J., Moss, H. E., Wu, A. Y. 2021; 12
  • Gender Gap in Neurology Research Authorship (1946-2020). Frontiers in neurology Nguyen, A. X., Yoffe, L., Li, A., Trinh, X. V., Kurian, J., Moss, H. E., Wu, A. Y. 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

  • Gender Gap in the Award Recipients of the Association for Research in Vision and Ophthalmology Ratan, S., Anne Xuan-Lan Nguyen, Biyani, A., Trinh, X., Sun, Y., Saleh, S., Wu, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Determination of Patient Sentiment and Emotion in Ophthalmology: Infoveillance Tutorial on Web-Based Health Forum Discussions. Journal of medical Internet research Nguyen, A. X., Trinh, X., Wang, S. Y., Wu, A. Y. 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 Swarup, A., Ta, C. N., Wu, A. Y. 2021


    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 Swarup, A., Wu, A. Y. 2021; 36 (4): 425

    View details for DOI 10.1097/IOP.0000000000001658

    View details for PubMedID 33877060

  • Longitudinal Gender Authorship Trends in Neurology Research Anne Xuan-Lan Nguyen, Yoffe, L., Li, A., Xuan-Vi Trinh, Kurian, J., Wu, A. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • 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 Nguyen, A. X., Trinh, X., Kurian, J., Wu, A. Y. 2021


    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 Gervasio, K. A., Sklar, B. A., Nguyen, A. X., Wu, A. Y. 2021


    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 Nguyen, A. X., Ratan, S., Biyani, A., Trinh, X. V., Saleh, S., Sun, Y., Wu, A. Y. 2021


    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 Nguyen, A. X., Gervasio, K. A., Wu, A. Y. 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 Nguyen, A. X., Wu, A. Y. 2020: 1–6


    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 Nguyen, A. X., Gervasio, K. A., Wu, A. Y. 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) Uhr, J. H., Governatori, N. J., Zhang, Q. E., Hamershock, R. n., Radell, J. E., Lee, J. Y., Tatum, J. n., Wu, A. Y. 2020


    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 Garcia, G. A., Veerappan, M. n., Bair, H. n., Charlson, E. S., Wu, A. Y. 2020

    View details for DOI 10.1016/j.jcjo.2020.07.016

    View details for PubMedID 32818428

  • Management and outcomes of proteasome inhibitor associated chalazia and blepharitis: a case series. BMC ophthalmology Sklar, B. A., Gervasio, K. A., Leng, S., Ghosh, A., Chari, A., Wu, A. Y. 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 Nguyen, A. X., Wu, A. Y. 2019


    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. Genes Wang, S. F., Kowal, T. J., Ning, K., Koo, E. B., Wu, A. Y., Mahajan, V. B., Sun, Y. 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 Wang, S. F., Kowal, T. J., Ning, K., Koo, E. B., Wu, A. Y., Mahajan, V. B., Sun, Y. 2018; 9 (12)
  • Orbital Metastasis From Urothelial Carcinoma: A Comprehensive Literature Review. Ophthalmic plastic and reconstructive surgery Sklar, B. A., Gervasio, K. A., Karmazin, K., Wu, A. Y. 2018


    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



    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 Sklar, B., Gervasio, K. A., Kaur, K., Sivak, M., Wu, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Surgical loupe usage among oculoplastic surgeons in North America CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE Wei, C., Wu, A. Y. 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? Acta ophthalmologica Wu, A. Y., Gervasio, K. A., Gergoudis, K. N., Wei, C. n., Oestreicher, J. H., Harvey, J. T. 2018


    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 ( 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) Chopra, N., Gervasio, K. A., Kalosza, B., Wu, A. Y. 2017


    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 Wu, A. Y., Baldwin, T. J., Patel, B. C., Clymer, J. W., Lewis, R. D. 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 Brown, S. E., Friedman, A. H., Phelps, R. G., Bleiweiss, I. J., Wu, A. Y. 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 Daniel, M. G., Wu, A. Y. 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 JAMA OPHTHALMOLOGY Uhr, J. H., Mishra, K., Wei, C., Wu, A. Y. 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 MOLECULAR VISION Selver, O. B., Durak, I., Gurdal, M., Baysal, K., Ates, H., Ozbek, Z., Wang, Z., Wu, A., Wolosin, J. M. 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 Gervasio, K. A., Weinstock, B. M., Wu, A. Y. 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 Gervasio, K. A., Wu, A. Y. 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 OPHTHALMOLOGY Tang, S. X., Lim, R. P., Al-Dahmash, S., Blaydon, S. M., Cho, R. I., Choe, C. H., Connor, M. A., Durairaj, V. D., Eckstein, L. A., Hayek, B., Langer, P. D., Lelli, G. J., Mancini, R., Rabinovich, A., Servat, J., Shore, J. W., Sokol, J. A., Tsirbas, A., Wladis, E. J., Wu, A. Y., Shields, J. A., Shields, C., Shinder, R. 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) Zheng, C., Wu, A. Y. 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 Wu, A. Y., Kugathasan, K., Harvey, J. T. 2012; 47 (5): e28-9

    View details for DOI 10.1016/j.jcjo.2012.03.012

    View details for PubMedID 23036560

  • A case of orbital involvement in IgG4-related disease. Orbit (Amsterdam, Netherlands) Teichman, J. C., Wu, A. Y., El-Shinnawy, I., Harvey, J. T. 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 Rootman, D., DeAngelis, D., Tucker, N., Wu, A., Hurwitz, J. 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 Wu, A. Y., Oestreicher, J. H. 2011; 46 (6): 556-557

    View details for DOI 10.1016/j.jcio.2011.10.002

    View details for Web of Science ID 000299017600027

    View details for PubMedID 22153651

  • Bicanalicular Laceration Repair Via an Endoscopic Retrograde Approach OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Wu, A. Y., Tucker, N. A. 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 Wu, A. Y., Chapman, W. B., Witterick, I. J., DeAngelis, D. D. 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 Wu, A. Y., Jebodhsingh, K., Le, T., Law, C., Tucker, N. A., DeAngelis, D. D., Oestreicher, J. H., Harvey, J. T. 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) Wu, A. Y., Vagefi, M. R., Georgescu, D., Burroughs, J. R., Anderson, R. L. 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 Wu, A. Y., Thakker, M. M., Wladis, E. J., Weinberg, D. A. 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 Wu, A. Y., Vagefi, M. R., Georgescu, D., McCann, J. D., Anderson, R. L. 2008; 24 (5): 429-429

    View details for Web of Science ID 000259652900028

    View details for PubMedID 18806679

  • Molecular determinants for cyclic nucleotide binding to the regulatory domains of phosphodiesterase 2A JOURNAL OF BIOLOGICAL CHEMISTRY Wu, A. Y., Tang, X. B., Martinez, S. E., Ikeda, K., Beavo, J. A. 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 Martinez, S. E., Wu, A. Y., Glavas, N. A., Tang, X. B., Turley, S., Hol, W. G., Beavo, J. A. 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 CIRCULATION RESEARCH Peterson, T. E., Poppa, V., Ueba, H., Wu, A., Yan, C., Berk, B. C. 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 MOLECULAR PHARMACOLOGY Kovoor, A., Celver, J. P., Wu, A., Chavkin, C. 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