Faculty Bibliography

PURPOSE/OBJECTIVE:The purpose of this study was to report the findings of a hyperreflective nodular epiretinal gliosis observed with optical coherence tomography presumed to be due to subclinical hyaloidal traction causing Mϋller cell cone gliosis. METHODS:Retrospective, observational case series. RESULTS:Six eyes of six patients (mean age: 57 years, range 35-81 years) presented with a nodular epiretinal gliosis and had an average follow-up interval of 26 months (range 1-82 months). The mean baseline best-corrected visual acuity was 0.25 ± 0.17 (Snellen equivalent 20/38.3 ± 16.9). Fundus photography demonstrated a yellowish lesion overlying the fovea. Optical coherence tomography imaging revealed a hyperreflective preretinal lesion with a mean vertical length of 267 μ m (range 185-497) and a mean greatest linear diameter of 312 µ m (range 124-640). There was no vitreoretinal abnormality including vitreomacular traction or epiretinal membrane noted in any eye, and two of six eyes displayed a definitive posterior vitreous detachment. These nodules may have occurred before and persisted even after a posterior vitreous detachment or may have been acquired after the posterior vitreous detachment. The nodules typically remained stable with minimal change although in one eye, a posterior vitreous detachment occurred 6 months after initial presentation and lifted the gliosis off of the retinal surface where it remained attached to the posterior hyaloid. CONCLUSION/CONCLUSIONS:Foveal nodular epiretinal gliosis may occur due to subclinical hyaloidal traction on the Müller cell cone even without obvious vitreoretinal interface abnormality on optical coherence tomography.

Age-related macular degeneration (AMD) is the leading cause of severe loss of central vision among people over 50. The pathophysiology of the disease is multifactorial and can be attributed to genetics, aging, inflammation, environmental factors, and lifestyle factors including smoking, diet, obesity, and alcohol consumption. While there is no treatment for dry AMD, the current standard treatment for wet AMD is an intraocular injection of anti-vascular endothelial growth factor-an effective, yet expensive, therapy that requires ongoing treatment. As the aging population continues to grow, and AMD diagnoses continue to rise, new treatments should be explored to reduce vision complications and decrease treatment burdens. Many systemic conditions have progressive pathological changes that may affect AMD, particularly those affecting systemic vasculature like diabetes and cardiovascular status. Consequently, systemic drugs used to treat coexistent systemic diseases may influence some of the pathogenic mechanisms of AMD and lead its progression or delay. In this review we explore the current literature to summarize the findings of the reported effects of antihypertensive, immunosuppressants, cholesterol lowering agents, nonsteroidal anti-inflammatory drugs, dopamine precursors, hypoglycemic agents, and anticoagulants on AMD.

We describe the clinical characteristics of treatment-naïve polypoidal choroidal vasculopathy (PCV) in three tertiary clinic settings in 2 cities (Chicago in the USA and Nishinomiya in Japan). This cohort study was a retrospective, multicenter, consecutive case series. A total of 126 patients with treatment-naïve PCV-46 in Chicago and 80 in Nishinomiya-were identified. The proportion of PCV in patients with neovascular age-related macular degeneration was lower in Chicago (10.8% vs. 36.9%). Patients in Chicago had a significantly higher prevalence of soft drusen (50.0% vs 25.0%, p = 0.006) and intra-retinal cyst (37.0% vs 15.0%, p = 0.008), and a significantly lower prevalence of pachyvessels (41.3% vs 62.5%, p = 0.03). At baseline, presenting vision for patients in Chicago was worse than in Nishinomiya (mean log MAR: 0.609 vs. 0.312, p < 0.001). Ninety-five eyes were followed for more than one year. The Nishinomiya group received a higher rate of combination therapy (61.0%) compared to the Chicago group (5.3%). Vision and central foveal thickness at month 12 were significantly improved from baseline in both Chicago (p = 0.009 and p = 0.01) and Nishinomiya groups (both p < 0.001). Our study highlights interesting differences in the proportion of PCV, clinical findings and treatment responses of PCV, that need to be further evaluated in larger, epidemiologic cohorts.

Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy. More recently, the gut microbiome has emerged as an influential player in various ocular pathologies. As mediators of metabolism and immune regulation, perturbations in gut microbiota may impart significant effects distally on the neuroretina and its adjacent tissues, termed the gut-retina axis. In this review, key studies over the past several decades are summarized, both in humans and in animal models, which shed insight on the relationships between the gut microbiome and retinal biology and their implications for AMD. The literature linking gut dysbiosis with AMD is examined, along with preclinical animal models and techniques apt for studying the role of gut microbiota in AMD pathogenesis, which include interactions with systemic inflammation, immune regulation, chorioretinal gene expression, and diet. As understanding of the gut-retina axis continues to advance, so too will the possibility for more accessible and effective prevention and therapy of this vision-threatening condition.

PURPOSE:Proliferative vitreoretinopathy (PVR) is the dreaded cause of failure following retinal detachment repair; however, no cures or preventative therapies exist to date. The purpose of this study was to use bioinformatics tools to identify drugs or compounds that interact with biomarkers and pathways involved in PVR pathogenesis that could be eligible for further testing for the prevention and treatment of PVR. METHODS:We queried PubMed to compile a comprehensive list of genes described in PVR to date from human studies, animal models, and genomic studies found in the National Center for Biotechnology Information database. Gene enrichment analysis was performed using ToppGene on PVR-related genes against drug-gene interaction databases to construct a pharmacome and estimate the statistical significance of overrepresented compounds. Compounds with no clinical indications were filtered out from the resulting drug lists. RESULTS:Our query identified 34 unique genes associated with PVR. Out of 77,146 candidate drugs or compounds in the drug databases, our analysis revealed multiple drugs and compounds that have significant interactions with genes involved in PVR, including antiproliferatives, corticosteroids, cardiovascular agents, antioxidants, statins, and micronutrients. Top compounds, including curcumin, statins, and cardiovascular agents such as carvedilol and enalapril, have well-established safety profiles and potentially could be readily repurposed for PVR. Other significant compounds such as prednisone and methotrexate have shown promising results in ongoing clinical trials for PVR. CONCLUSIONS:This bioinformatics approach of studying drug-gene interactions can identify drugs that may affect genes and pathways implicated in PVR. Predicted bioinformatics studies require further validation by preclinical or clinical studies; however, this unbiased approach could identify potential candidates among existing drugs and compounds that could be repurposed for PVR and guide future investigations. TRANSLATIONAL RELEVANCE:Novel repurposable drug therapies for PVR can be found using advanced bioinformatics models.

OBJECTIVE:To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). DESIGN:Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1-2) and case-control analysis in the Merative MarketScan Research Databases (#3). PARTICIPANTS:Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). METHODS:Eyes were divided into 2 groups (#1-2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100-300 mg, and approximately > 300 mg per day, #3). MAIN OUTCOME MEASURES:Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2-3) after adjusting for AMD risk factors. RESULTS:In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N = 84 088 control vs. 530 L-DOPA eyes, P = 0.006). In eyes with nonneovascular AMD (N = 42 081-203 155 control vs. 314-1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P = 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P = 0.024). In the MarketScan databases (N = 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75-0.97) and 23% (OR, 0.77; 95% CI, 0.67-0.87), respectively. CONCLUSIONS:Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.