Wound Modulations in Glaucoma Surgery: A Systematic Review.

Excessive fibrosis and resultant poor control of intraocular pressure (IOP) reduce the efficacy of glaucoma surgeries. Historically, corticosteroids and anti-fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), have been used to mitigate post-surgical fibrosis, but these have unpredictable outcomes. Therefore, there is a need to develop novel treatments which provide increased effectiveness and specificity. This review aims to provide insight into the pathophysiology behind wound healing in glaucoma surgery, as well as the current and promising future wound healing agents that are less toxic and may provide better IOP control.

Exploring Underrepresentation: The Role of Diversity Statements in Ophthalmology Residency Programs.

INTRODUCTION: The underrepresentation of underrepresented minorities (URMs) in the medical field, particularly in ophthalmology, poses a critical challenge to achieving diversity and equity. While URMs constitute 19% of medical school attendees, their presence is markedly lower in ophthalmology residency programs and among practicing ophthalmologists. This study seeks to investigate the prevalence of diversity statements on ophthalmology residency program websites and their role in the underrepresentation of URMs within the field. METHODS: This observational, cross-sectional study analyzed the websites of 126 ophthalmology residency programs listed on the San Francisco (SF) Match website. Diversity statements were categorized based on their inclusion of specific underrepresented groups (race or ethnicity, gender, sexual orientation, and disability) and analyzed for correlation with program characteristics. Descriptive statistics and Chi-squared tests were utilized to assess the prevalence of diversity statements and their association with program size, ranking, geographical location, and institutional nature. RESULTS: Of the 126 programs analyzed, 21 (16.7%) had diversity statements specific to the ophthalmology residency program, and 115 (91.3%) featured institutional-level diversity statements. Race or ethnicity was the most commonly addressed category in diversity statements (75.3%), followed by gender (65.9%), sexual orientation (61.1%), and disability (53.2%). Statistical analyses revealed no significant correlation between program size and the presence of diversity statements. However, higher-ranked programs were more likely to mention sexual orientation and disability. Significant differences were observed at the institutional level, with public institutions more likely to include specific diversity categories. CONCLUSION: The study highlights a significant disparity in the presence and focus of diversity statements across ophthalmology residency programs. Despite a high prevalence of institutional-level diversity statements, program-specific initiatives are lacking, particularly in addressing disability inclusion. The findings suggest a need for a more comprehensive and targeted effort to address underrepresentation in ophthalmology.

Associations between depression and diabetic retinopathy in the National Health and Nutrition Examination Survey, 2011 to 2018.

Introduction: Diabetic retinopathy (DR) is a vision-threatening complication of diabetes mellitus (DM). The relationship between depression and DR is unclear, and prior studies are limited by small sample sizes at single centers. This retrospective, cross-sectional study assessed the prevalence of and associations between depression and DR in the US using the National Health and Nutrition Examination Survey for 2011 to 2018. Methods: We collected information on the demographic characteristics, medical conditions, and examination data of NHANES participants with DM. We performed weighted analysis to estimate national prevalence and multivariate analysis to assess the relationship between depression and DR. Results: Of the 22,618 participants included, the prevalence of DM and DR were 3146 (13.9%) and 664 (2.9%). The prevalence of depression was 14.2% in DM only and 19.3% in DR (P = 0.006) with greater severity in the DR group (P < 0.001). After adjusting for comorbidities, DR was no longer significantly associated with depression. Depression was not associated with differences in disease management, although participants with depression had poorer self-perceived health status (P < 0.001). Conclusions: Depression is more prevalent in individuals with DR than those with DM only. The relationship between depression and DR may be mediated by additional medical comorbidities, but further studies are needed.

The impact of the COVID-19 pandemic on early termination of ophthalmology clinical trials: A cross-sectional analysis of ClinicalTrials.gov.

Objective: To study the effect of the COVID-19 pandemic on the early termination of ophthalmology clinical trials. Methods: On June 10, 2022, we searched ClinicalTrials.gov and identified clinical trials pertaining to eye diseases. We included trials last updated between January 1, 2020 and June 8, 2022, as ones possibly impacted by the pandemic. We selected all interventional trials in any stage and country that were "recruiting," "active, not recruiting," "enrolling by invitation," "suspended," "terminated," "completed," or "withdrawn" and excluded trials that had been completed or discontinued before 2020, had incomplete data, trials in which the eye was not the primary focus of the trial (e.g., Chediak-Higashi syndrome, myasthenia gravis). The following trial-level characteristics were collected: location, trial status, enrollment count, ocular condition, sponsors, intervention purpose, trial phase (I-IV), randomization, number of arms, and reasons for discontinuation. In addition to calculating descriptive statistics, we assessed whether trial characteristics differed between ophthalmology clinical trials canceled due to COVID-19 and those canceled for other reasons. Results: Following the screening, 2280/12,679 (18%) ophthalmology clinical trials were retained. Of these, 142 (6.2%) were discontinued between January 1, 2020 and June 8, 2022. Moreover, 34 out of 142 (23.9%) ophthalmology clinical trials were discontinued due to COVID-19. These trials were more likely to be sponsored by academic medical centers (26/34, 76.5% vs 57/108, 52.8%, p = 0.03) and were not assigned to a specific study phase, indicating they were not investigational new drugs (22/34, 64.7% vs 46/108 42.6%, p = 0.003). Conclusions: COVID-19-related trial discontinuations were more likely to be reported by academic medical centers and associated with trials investigating fully approved drugs, medical devices, procedures, diagnostic imaging, and behavioral changes. Further investigation of these characteristics may lead to a more robust and resilient understanding of the causes of early termination of these clinical trials.

Healthcare lobbying and campaign finance activities of vision-related professional societies, 2015 to 2022.

Purpose: To compare the lobbying expenditures and political action committee (PAC) campaign finance activities of the American Academy of Ophthalmology (AAO), American Society of Cataract and Refractive Surgery (ASCRS), and American Optometric Association (AOA) from 2015 to 2022. Methods: Financial data were collected from the Federal Election Commission and OpenSecrets database. Analysis was performed to characterize and compare financial activity among the organizations. P < 0.05 was considered significant and all analyses were two-sided. Results: From 2015 to 2022, the AAO, ASCRS, and AOA spent $6,745,000, $5,354,406, and $13,335,000 on lobbying, respectively. The AOA's annual lobbying expenditure (median, $1,725,000) was significantly greater than AAO's ($842,500, P = 0.03) and ASCRS's ($694,289, P < 0.001). In PAC donations, OPHTHPAC, affiliated with AAO, received $3,221,737 from 2079 donors (median, $900); eyePAC, affiliated with ASCRS, received $506,255 from 349 donors ($500); and AOA-PAC received $6,642,588 from 3641 donors ($825). Compared to eyePAC, median donations to OPHTHPAC (P = 0.01) and AOA-PAC (P = 0.04) were significantly higher. In campaign spending, OPHTHPAC contributed $2,728,500 to 326 campaigns (median, $5000), eyePAC contributed $293,500 to 58 campaigns ($3000), and AOA-PAC contributed $5,128,673 to 617 campaigns ($5500). eyePAC's median campaign contribution was significantly lower than the AOA's (P < 0.001) and AAO's (P = 0.007). Every PAC directed most of its contributions toward Republican campaigns; eyePAC donated the highest proportion (64.9%). Conclusions: AOA was more assertive in shaping policy by increasing lobbying expenditures, fundraising, and donating to a greater number of election campaigns.

Quantification of vascular morphology in optical coherence tomography angiography in primary open angle glaucoma.

Purpose: To quantitatively measure and compare the vascular morphology in healthy eyes and eyes with primary open-angle glaucoma (POAG) using optical coherence tomography angiography (OCTA) scans. Methods: This is a retrospective and cross-sectional study which include healthy individuals and individuals with POAG that underwent OCTA imaging at an academic center's glaucoma clinic. We analyzed OCTA scans of the macula and optic nerve head (ONH) of one eye from each subject to quantitatively measure vessel density (VD), vessel length density (VLD), and branchpoint density (BPD). We compared these 3 parameters between the healthy and POAG groups and used logistic regression classification models to determine their diagnostic value in differentiating healthy and glaucomatous eyes. Results: We included 49 healthy subjects and 49 subjects with POAG. After age-adjusted analysis, the parameters of VD, VLD, and BPD were significantly reduced in eyes with POAG (P â€‹< â€‹0.001) in all scan layers and most significantly around the ONH. The parameter with the best performances were radial peripapillary capillary (RPC) VD [AUC (areas under the curve): 0.939 (0.891, 0.987)] which had statistically higher performances (P â€‹< â€‹0.05) than parameters in the superficial or deep layers. All 3 parameters in the RPC layer had statistically similar performances. Conclusions: We found that VD, VLD, and BPD were reduced in glaucomatous eyes. The morphologic parameters of VLD and BPD had similar performances to the traditional parameter of VD in RPC layers. Our results suggest that vascular morphology parameters may provide additional value in the diagnosis and evaluation of glaucoma.

Residency Program Characteristics Associated with Higher Cataract Surgery Volume.

PURPOSE: Prior research has shown that ophthalmology residents improve their cataract surgery competency as they perform additional surgeries beyond the 86 minimum cases mandated by the Accreditation Council for Graduate Medical Education (ACGME). Therefore, cataract surgery volume is an important benchmark for ophthalmology programs. Understanding the possible influence of residency program characteristics on resident cataract surgery volume may help educators in identifying areas for improvement and aid applicants in choosing between programs. The aim of this study was to assess residency program characteristics associated with higher mean cataract surgery volume for ophthalmology residents. METHODS: We conducted a retrospective, cross-sectional analysis of the San Francisco Match Program Profile Database to assess various program characteristics from the 113 listed ophthalmology residency programs. The associations between program characteristics and the mean cataract surgery volume per graduating resident (CSV/GR) over years 2018-2021 were analyzed using multiple linear regression. RESULTS: Out of 113 listed residency programs, 109 (96.5%) were included in our study. Across all programs, the mean (SD) CSV/GR was 195.9 (56.9) cases with a range of 86 to 365 cases. In multiple linear regression analysis, the presence of a Veteran Affairs (VA) training site (ß = 38.8, P = .005) and the number of approved fellows per year (ß = 2.9, P = .026) were positively correlated with higher mean CSV/GR. The 85 (78.0%) programs with VA training sites had a higher mean (SD) CSV/GR of 204.1 (55.7) cases compared to 166.7 (52.7) cases in the 24 (22.0%) programs without VA sites (P = .004). The mean CSV/GR increased by 2.9 cases for each additional fellow slot after adjusting for other factors. The number of approved residents per year, affiliation with a medical school, and the number of faculty were not significantly associated with CSV/GR. CONCLUSION: All ophthalmology residency programs included in this study currently meet or exceed the ACGME requirements for cataract surgery case numbers. The presence of a VA training site and a higher number of fellowship positions were associated with higher mean resident cataract surgery volumes. Residency programs may consider further investing in these areas when seeking to improve resident surgical education. Additionally, residency applicants prioritizing cataract surgery volume may consider these factors when evaluating programs.

Prevalence and risk factors of retinal vein occlusion in the United States: The National Health and Nutrition Examination Survey, 2005 to 2008.

Retinal vein occlusion (RVO) is a rare, vision-threatening vascular disorder. Due to limited recovery associated with RVO, prevention is essential. There is a significant discrepancy in previously reported epidemiological studies in the United States on the prevalence and risk factors of RVO. The purpose of this retrospective, cross-sectional study was to determine the prevalence and risk factors of RVO in adults ≥40 years of age in the US using the National Health and Nutrition Examination Survey (NHANES) 2005-2008. We collected information on the demographic characteristics, medical conditions, and ocular pathology of NHANES participants. We performed weighted analysis to estimate national prevalence rates and multivariate analysis to examine associated risk factors. The main outcome measures were the prevalence of RVO and the odds ratios of associated risk factors. We included 5559 participants and found 33 cases of RVO. The overall prevalence of RVO in the US was 0.50%. Age, per 10-year increase (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.31-2.92) and elevated diastolic blood pressure, per 10 mm Hg increase (OR 1.47; 95% CI, 1.10-2.12) were significant risk factors for RVO. Race, sex, glaucoma, elevated cholesterol, and self-reported history of diabetes, stroke, and heart disease were not significant risk factors. RVO is significantly associated with older age and elevated diastolic blood pressure. Our findings should alert clinicians to identify individuals at risk for RVO.

Trends and Characteristics of Industry Payments for Ophthalmology Research From 2014 to 2020.

Importance: Characterizing industry-ophthalmology collaborations in research can highlight current areas of focus, improve transparency, and identify potential sources for conflicts of interest. Objective: To assess the trends and characteristics in research payments reported from industry to ophthalmologists from 2014 to 2020. Design, Setting, and Participants: This cross-sectional study used data from the Centers of Medicare & Medicaid Services' Open Payments database (OPD), which contains public records of payments between industry and physicians, to identify all ophthalmologists who received industry payments for research purposes between 2014 and 2020. Industry funding was compared with public research funding by the National Eye Institute. Main Outcomes and Measures: The value and distribution of payments, sponsoring manufacturers, and research products were assessed. Changes in aggregate and per individual-level funding were characterized using formal trend analysis. Results: From 2014 to 2020, 2102 ophthalmologists were reported to have received $825 417 233 in industry research payments. Industry funding increased 203% from $62 924 525 in 2014 to $190 714 508 in 2020 (P = .01). Comparatively, total National Eye Institute research funding during the same period was $5 003 407 764 and increased 6.6% from $701 313 262 in 2014 to $747 929 556 in 2020 (P = .04). The share of all medical research funding from industry directed specifically toward ophthalmology research increased from 1.2% in 2014 to 3.2% in 2020 (P = .04). The distribution of industry payments was skewed, with the top 15 of 108 manufacturers accounting for 93.9% of funding. The top 10% of ophthalmologists (210) were reported to have received 65.7% of all research dollars ($542 299 121). The highest funded research products were anti-vascular endothelial growth factor agents, glaucoma treatments, and intraocular lenses. Conclusions and Relevance: Although unequal in distribution, industry-funded research in ophthalmology is extensive and increasing in scope. Industry funding for research is less than that of public funding; however, industry funding increased faster between 2014 and 2020. Results of this study highlight the increasing importance of industry funding in ophthalmology research, but it may also present ethical challenges for clinicians collaborating with industry.

Glaucoma Diagnosis Through the Integration of Optical Coherence Tomography/Angiography and Machine Learning Diagnostic Models.

Purpose: To establish optical coherence tomography (OCT)/angiography (OCTA) parameter ranges for healthy eyes (HE) and glaucomatous eyes (GE) for a North Texas based population; to develop a machine learning (ML) tool and to identify the most accurate diagnostic parameters for clinical glaucoma diagnosis. Patients and Methods: In this retrospective cross-sectional study, we included 1371 eligible eyes, 462 HE and 909 GE (377 ocular hypertension, 160 mild, 156 moderate, 216 severe), from 735 subjects. Demographic data and full OCTA parameters were collected. A Kruskal-Wallis test was used to produce the normative database. Models were trained to solve a two-class problem (HE vs GE) and four-class problem (HE vs mild vs moderate vs severe GE). A rigorous nested, stratified, group, 5×10 fold cross-validation strategy was applied to partition the data. Six ML algorithms were compared using classical and deep learning approaches. Over 2500 ML models were optimized using random search, with performance compared using mean validation accuracy. Final performance was reported on held-out test data using accuracy and F1 score. Decision trees and feature importance were produced for the final model. Results: We found differences across glaucoma severities for age, gender, hypertension, Black and Asian race, and all OCTA parameters, except foveal avascular zone area and perimeter (p<0.05). The XGBoost algorithm achieved the highest test performance for both the two-class (F1 score 83.8%; accuracy 83.9%; standard deviation 0.03%) and four-class (F1 score 62.4%; accuracy 71.3%; standard deviation 0.013%) problem. A set of interpretable decision trees provided the most important predictors of the final model; inferior temporal and inferior hemisphere vessel density and peripapillary retinal nerve fiber layer thickness were identified as key diagnostic parameters. Conclusion: This study established a normative database for our North Texas based population and created ML tools utilizing OCT/A that may aid clinicians in glaucoma management.

Predictors of Early Onset Glaucoma.

Purpose/Relevance: To determine the influence of hypertension (HTN), type 2 diabetes (DM2), migraine, and obstructive sleep apnea (OSA) on the onset of primary open-angle glaucoma (POAG) to enhance predictive accuracy. Methods: In this cross-sectional study, data for 389 eligible patients with POAG were collected through medical records review and phone surveys. All data were assessed collectively using stepwise multiple regression analysis to determine the relative contribution to age at POAG diagnosis. We used the following groups, based on age at diagnosis, HTN for patients with or without DM2 (model 1), HTN for patients with DM2 (model 2), DM2 for patients with or without HTN (model 3), and DM2 for patients with HTN (model 4). Results: In model 1, age at HTN diagnosis was associated with age at POAG diagnosis (ß = 0.14; 95% CI, 0.01-0.26, p = 0.04). In model 2, age at HTN diagnosis was not associated with age at POAG diagnosis (p > 0.05). In model 3, age at DM2 diagnosis was associated with age at POAG diagnosis (ß = 0.37; 95% CI 0.16-0.58, p = 0.001). In model 4, age at DM2 diagnosis was associated with age at POAG diagnosis (ß = 0.40; 95% CI 0.00-0.15, p = 0.003). Asian race/ethnicity was associated with early onset of POAG in model 3 (ß = -6.44; 95% CI -12.34-0.54, p = 0.033). OSA and migraine did not influence the onset of POAG. Conclusion: Our study found that the diagnosis of DM2 and HTN at an earlier age is associated with the early onset of POAG.

Nail-Patella Syndrome: Optical Coherence Tomography Angiography Findings.

We describe a 51-year-old Hispanic female with nail-patella syndrome (NPS), a rare genetic disease with a wide range of systemic features such as nail dysplasia and finger abnormalities, elbow webbing, iliac horn, patellar subluxation, and proteinuria. Some patients additionally have a history of glaucoma and other ocular features such as thick central corneal thickness, Lester's sign, prominent iris processes, and optic nerve cupping. Our patient had a history of glaucoma suspicion, prominent iris processes, increased cup to disc ratios, tilted optic discs, and tigroid fundi. In addition, we report optical coherence tomography angiography (OCTA) findings of focal areas of poor vessel densities in the macular and circumpapillary regions of both eyes, suggesting early compromised vascular supplies to these areas. Our OCTA findings (which include both structural and vascular details of retina and optic nerve) lend support to the use of this technology in patients with NPS.

Lifestyle Counseling for Medication Adherence in Glaucoma.

BACKGROUND: Medication adherence in glaucoma patients remains sub-par despite proven benefits of regular administration. The objective was to analyze medication adherence before and after lifestyle counseling in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) (mild, moderate, severe). METHODS: Prospective cohort study from May to July 2018 at a single academic center. From 391 consecutive records, 247 were excluded based on exclusion criteria with 28 patients not meeting inclusion criteria resulting in the final sample of 116 patients (33 had OHT, 83 had POAG - 28 mild, 39 moderate, 16 severe). Scripted lifestyle counseling focusing on diet, exercise, vitamin intake, stress management, and medication adherence was administered by a team of trained medical students. Primary outcome measure was self-reported medication adherence, defined as not missing an eye drop administration in the past month. A 2-3 week follow-up with scripted telephone survey assessing medication adherence, diet, and exercise was collected. RESULTS: At baseline, in 116 patients, 59.5% were adherent to their medication with a breakdown of 42.4% OHT, 64.3% mild, 66.7% moderate, and 68.7% severe and an increasing trend in medication adherence was found across increasing disease severity (p=0.055). Of the 76 (65.5%) patients reached for follow-up, 17 (22.4%) became adherent following lifestyle counseling (p=0.02) increasing overall adherence to 78.9% from 62.5%. CONCLUSION: In our study, comprehensive lifestyle counseling succeeded in increasing medication adherence in patients with OHT and POAG.

Investigational Rho Kinase Inhibitors for the Treatment of Glaucoma.

This review provides a comprehensive update on emerging ROCK inhibitors as an innovative treatment option for lowering intraocular pressure (IOP) in glaucoma and aims to describe the structure, mechanism of action, pharmaceutical characteristics, desirable ocular effects, including side effects for each agent. A literature review was conducted using PubMed, Scopus, clinicaltrials.gov, ARVO journals, Cochrane library and Selleckchem. Databases were searched using "investigational Rho kinase inhibitors," and "glaucoma" as keywords. In addition to this building block strategy, successive fractions were employed to further refine the results. Of the several ROCK inhibitors discovered, only two drugs are currently approved for glaucoma treatment; Netarsudil in the USA and Ripasudil in Japan and China. We identified and reviewed 15 agents currently in laboratory or clinical trials. These agents lower IOP mainly by decreasing outflow resistance through pharmacologic relaxation of the trabecular meshwork (TM) cells and reducing episcleral venous pressure. They have an optimistic safety profile; however, conjunctival hyperemia, conjunctival hemorrhage, pain on instillation, and corneal verticillata are common. Other properties such as neuroprotection (enhancing optic nerve blood flow and promoting axonal regeneration), anti-fibrotic activity, and endothelial cell proliferation may improve the visual prognosis and surgical outcomes in glaucoma. In addition, these agents have the potential to work synergistically with other topical glaucoma medications.

Polymicrobial infection confined to Ahmed glaucoma shunt.

PURPOSE: To present a case of a unique complication of an Ahmed glaucoma shunt. The pathological and immunohistochemical findings will also be discussed. OBSERVATIONS: A 58-year-old woman with glaucoma secondary to Marfan syndrome and cataract surgery developed exposure of an Ahmed glaucoma tube, intraluminal white inflammatory material, and low-grade endophthalmitis five years after insertion. The patient was treated with topical and oral antibiotics and successfully underwent removal and replacement of the shunt. Pathologic analysis of the intraluminal contents revealed a bacterial infiltrate of mixed morphology. CONCLUSIONS AND IMPORTANCE: Concurrent tube exposure, intraluminal exudates, and endophthalmitis is a rare but potentially serious complication of glaucoma drainage device surgery. When this complication is encountered, prompt medical and surgical intervention is necessary to prevent significant vision loss. Ultimately, the glaucoma shunt may be revised, replaced, or removed altogether from the eye.

Acute Bilateral Uveitis, Hypotony, and Cataracts Associated with Ipilimumab and Nivolumab Therapy: Optical Coherence Tomography Angiography Findings.

Immune checkpoint inhibitors are increasingly being used for the treatment of several malignancies. In rare cases, patients develop disabling ophthalmic side effects such as dry eyes, episcleritis, keratitis, uveitis, inflammatory orbitopathy, myasthenia gravis, macular edema, and serous retinal detachment. We present a case of acute bilateral anterior uveitis, prolonged hypotony, and cataracts following the use of dual therapy ipilimumab and nivolumab. Physicians should be aware of these immune-mediated ocular adverse events and should have a management plan to deal with these side effects that range from mild to vision threatening.