A case of accommodation-induced lens subluxation with iris displacement causing intermittent angle closure.

Purpose: To present an uncommon cause of intermittent angle closure in a young adult patient presenting with intermittent headache and blurry vision exacerbated by accommodation. Observations: A 37-year-old man reported experiencing intermittent blurry vision, headache, and pain in both eyes associated with prolonged periods of reading beginning at age 17. Serial intraocular pressure (IOP) measurements showed an increase in IOP from 14 to 32 mmHg in the right eye and from 9 to 37 mmHg in the left eye after 145 minutes of sustained accommodation while sitting up. IOP did not normalize after laser peripheral iridotomy but did normalize after clear lens extraction. Conclusions and importance: This case characterized a rare presentation of accommodation-induced IOP elevation in a young adult male that resolved only after clear lens extraction. The clinical takeaway was the importance of considering accommodation-associated angle closure in patients presenting with high intraocular pressures, eye strain, and/or headache with accommodative activities. Notable symptoms that should raise suspicion for this syndrome include halos, changes in visual acuity, and headache with accommodation. We suggested that patients presenting with these symptoms be followed closely, with a full glaucoma evaluation including gonioscopy and possible ultrasound biomicroscopy to assess for pediatric eversional angle closure with headache, plateau iris, angle closure glaucoma, and lens-induced angle closure.

Diverse Research Teams and Underrepresented Groups in Clinical Studies.

Importance: Several ophthalmic diseases disproportionately affect racial and ethnic minority patients, yet most clinical trials struggle to enroll cohorts that are demographically representative of disease burden; some barriers to recruitment include time and transportation, language and cultural differences, and fear and mistrust of research due to historical abuses. Incorporating diversity within the research team has been proposed as a method to increase trust and improve engagement among potential study participants. Objective: To examine how demographic factors of potential research participants and personnel may be associated with patient consent rates to participate in prospective ophthalmic clinical studies. Design, Setting, and Participants: This retrospective cohort study included patients from an urban, academic hospital who were approached for consent to participate in prospective ophthalmic clinical studies conducted between January 2015 and December 2021. Main Outcomes and Measures: Multivariable logistic regression assessing associations between patient and research personnel demographics and rates of affirmative consent to participate was used. Results: In total, 1380 patients (mean [SD] age, 58.6 [14.9] years; 50.3% male) who were approached for consent to participate in 10 prospective ophthalmic clinical studies were included. Of prospective patients, 566 (43.5%) were Black; 327 (25.1%), Hispanic or Latino; 373 (28.6%), White; 36 (2.8%), other race and ethnicity; and 78 (5.8%) declined to answer. Black patients (odds ratio [OR], 0.32; 95% CI, 0.24-0.44; P < .001) and Hispanic or Latino patients (OR, 0.31; 95% CI, 0.20-0.47; P < .001) were less likely to consent compared with White patients. Patients with lower socioeconomic status were less likely to consent than patients with higher socioeconomic status (OR, 0.43; 95% CI, 0.33-0.53; P < .001). Concordance between patient and research staff race and ethnicity was associated with increased odds of affirmative consent (OR, 2.72; 95% CI, 1.99-3.73; P < .001). Conclusions and Relevance: In this cohort study, patients from underrepresented racial and ethnic groups and those with lower socioeconomic status were less likely to participate in ophthalmic clinical studies. Concordance of race and ethnicity between patients and research staff was associated with improved participant enrollment. These findings underscore the importance of increasing diversity in clinical research teams to improve racial and ethnic representation in clinical studies.

Race and ethnic representation among clinical trials for diabetic retinopathy and diabetic macular edema within the United States: A review.

PURPOSE: Evaluate racial and ethnic representation in clinical trials compared to the disease burden for diabetic retinopathy (DR) and diabetic macular edema (DME) within the United States (US). Diabetic retinopathy (DR) is currently the leading cause of blindness in American adults, affecting over 7.7 million individuals and disproportionately affecting Black Americans. Black patients represent 38.3 ± 16.5% of DME within the US population while White patients represented 44.6 ± 18.3% of the DME population in the US. METHODS: All completed interventional clinical trials involving the conditions "Macular Edema" or "Diabetic Retinopathy" between 2001 and 2020. Excluded studies had fewer than 50 participants, terminated early, did not have published results, or involved locations outside the US. RESULTS: Twenty-five clinical trials were included in this review. In National Institute of Health (NIH) and industry-sponsored clinical trials for DME, the proportion of Black patients was 12.6 ± 3.3% (p < 0.05) and 8.6 ± 2.9% (p < 0.05), respectively. White patients' representation in NIH and industry-sponsored trials was significantly greater at 69.5 ± 4.4% (p < 0.05) and 80.0 ± 2.2% (p < 0.05), respectively. For DR trials, the proportion of Black patients in NIH and industry was 23.3 ± 11.7% and 11.2 ± 2.2%, respectively. CONCLUSIONS: Black patients are under-represented by a 3.0-fold disparity in NIH trials and 4.5-fold disparity in industry trials for DME, while White patients are overrepresented. In industry-funded DR trials, there is a 2.1-fold disparity compared to disease burden. Clinical trials for diabetic eye disease should aim to recruit patients based on the disease burden, which enables measurements of treatment outcomes by race and promotes health equity.

Extracellular Soluble Membranes from Retinal Pigment Epithelial Cells Mediate Apoptosis in Macrophages.

A central characterization of retinal immunobiology is the prevention of proinflammatory activity by macrophages. The retinal pigment epithelial cells (RPEs) are a major source of soluble anti-inflammatory factors. This includes a soluble factor that induces macrophage apoptosis when the activity of the immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) is neutralized. In this manuscript, isolated extracellular soluble membranes (ESMs) from primary RPE were assayed to see if they could be the soluble mediator of apoptosis. Our results demonstrated that RPE ESMs mediated the induction of macrophage apoptosis that was suppressed by α-MSH. In contrast, the RPE line ARPE-19, cultured under conditions that induce similar anti-inflammatory activity to primary RPEs, did not activate apoptosis in the macrophages. Moreover, only the ESMs from primary RPE cultures, and not those from the ARPE-19 cell cultures, expressed mFasL. The results demonstrate that RPE ESMs are a soluble mediator of apoptosis and that this may be a mechanism by which the RPEs select for the survival of α-MSH-induced suppressor cells.

The Impact of Race on Short-term Treatment Response to Bevacizumab in Diabetic Macular Edema.

PURPOSE: To determine the impact of race and ethnicity on efficacy of intravitreal bevacizumab for diabetic macular edema in anti-vascular endothelial growth factor (VEGF) treatment-naive patients. DESIGN: Retrospective cohort study. METHODS: Setting: Urban-based academic institution with affiliated private offices. STUDY POPULATION: Intravitreal anti-VEGF naïve patients seen between 2010 and 2019 of White (W) race, Black (B) race, or Hispanic (H) ethnicity aged 18 years and older with diabetic macular edema who received intravitreal injections of bevacizumab. Exclusion criteria were prior intravitreal anti-VEGF treatment, invasive ophthalmologic interventions, and laser treatments within 3 months prior to first injection through the duration of the study. Exposures: Intravitreal bevacizumab. MAIN OUTCOMES MEASURES: Percentage of patients with visual acuity (VA) improvement and mean percentage reduction in central macular thickness (CMT). RESULTS: Percentage with VA improvement was 27% vs 39% vs 50% after 1 injection (n = 314), and 34% vs 55% vs 59% after 3 injections (n = 150) for B, H, and W cohorts, respectively. Black patients experienced lower odds of VA improvement compared with White and Hispanic patients after 1 injection (odds of 0.480, CI 0.284-0.814, P = .006) and 3 injections (odds of 0.342, CI 0.149-0.782, P = .008) while controlling for age, sex, baseline glycated hemoglobin (HbA1c), baseline CMT, baseline VA, laser history, injection time course, and follow-up delay. CONCLUSIONS: Black patients had a significantly lower likelihood of visual acuity improvement following intravitreal bevacizumab treatment compared with White and Hispanic patients. Further research is warranted to understand the effect of race and ethnicity on anti-VEGF efficacy to ensure optimal treatment for each individual.