ASSOCIATION OF METFORMIN USE WITH RISK OF NEWLY ONSET NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEVELOPMENT.

PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD). METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed. RESULTS: Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g. CONCLUSION: Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.

FULL-THICKNESS MACULAR HOLE CLOSURE WITH TOPICAL MEDICAL THERAPY.

PURPOSE: To examine the efficacy and clinical characteristics of successful full-thickness macular hole closure with topical therapy. METHODS: Retrospective case series of full-thickness macular holes managed by a single retinal physician (DS) diagnosed and treated from 2017 to 22. RESULTS: Of 168 patients with full-thickness macular holes, 71 patients were started on steroid, carbonic anhydrase inhibitor, and nonsteroidal antiinflammatory (NSAID) drops. 49 patients (mean 67 years, 59% women) were included in the analysis, and 22 patients were excluded for poor follow-up. In total, 7/49 were secondary post-PPV holes and 42/49 were idiopathic. In addition, 18/49 eyes (36.7%) achieved closure on topical therapy, of which 13 were idiopathic. Hole size was directly correlated with odds of closure: for every 10 µm decrease in size and odds of closure increased by 1.2× ( P = 0.001, CI 1.1-1.4). Average time to closure was 107.2 days (range 20-512 days) and was not correlated with hole size ( P = 0.217, CI -0.478 to +1.938). The presence of VMT was found to be inversely related to successful closure (OR 6.1, P = 0.029, CI 1.2-31.3). There was no significant difference in final best-corrected visual acuity for eyes undergoing primary pars plana vitrectomy versus those trialing drops before undergoing pars plana vitrectomy ( P = 0.318, CI -0.094 to +0.112). CONCLUSION: In the first study to date to report the overall efficacy and clinical characteristics of successful macular hole closure with topical therapy, drops achieved an overall closure rate of 36.7%, with higher efficacy in smaller holes and those without VMT. Rates of MH narrowing and reduction in central foveal thickness acted as predictors of effectiveness of drop therapy.

INTERACTIONS OF METFORMIN AND OTHER MEDICATIONS IN REDUCING THE ODDS OF AGE-RELATED MACULAR DEGENERATION IN A COHORT OF PATIENTS WITH DIABETES.

PURPOSE: A previous study from our group demonstrated protective effects of the use of metformin in the odds of developing age-related macular degeneration (AMD). This is a subgroup analysis in a cohort of patients with diabetes to assess the interaction of metformin and other medications in protecting diabetic patients against developing AMD. METHODS: This is a case-control analysis using data from the Merative MarketScan Commercial and Medicare databases. Patients were 55 years and older with newly diagnosed AMD and matched to controls. We performed multivariable conditional logistic regressions, which adjusted for known risk factors of AMD and tested multiple interaction effects between metformin and 1) insulin, 2) sulfonylureas, 3) glitazones, 4) meglitinides, and 5) statins. RESULTS: The authors identified 81,262 diabetic cases and 79,497 diabetic controls. Metformin, insulin, and sulfonylureas demonstrated independent protective effects against AMD development. Sulfonylureas in combination with metformin demonstrated further decreased odds of AMD development compared with metformin alone. The other medication group (exenatide, sitagliptin, and pramlintide) slightly increased the odds of developing AMD when taken alone, but the combination with metformin alleviated this effect. CONCLUSION: The authors believe that their results bring them one step closer to finding an optimal effective hypoglycemic regimen that also protects against AMD development in diabetic patients.

Central Serous Chorioretinopathy: An Update on the Current State of Management.

Central serous chorioretinopathy (CSCR) is a relatively common retinal disorder that leads to central vision impairment, often with a high recurrence rate. The exact etiology and pathogenetic mechanisms have not been fully elucidated but are likely to be associated with hyperpermeability of the choroidal capillaries and failure of the retinal pigment epithelium (RPE), leading to serous detachment of the neurosensory retina. Multimodal imaging plays a critical role in the diagnostic approach and monitoring of CSCR. Fortunately, the natural course of the disease is usually self-limiting, with spontaneous resolution and total fluid reabsorption. However, some patients may exhibit recurrences or persistent subretinal fluid (chronic CSCR), leading to progressive and irreversible RPE atrophy or photoreceptor damage. Thus, to prevent permanent visual loss, individualized treatment should be considered. Recent developments in the diagnostic and therapeutic approach have contributed to better outcomes in patients with CSCR. More studies are required to improve our understanding of epidemiology, pathogenesis, diagnosis, and treatment, with a significant impact on the management of this challenging clinical entity. The purpose of this review is to summarize the current knowledge about the clinical features, diagnostic workup, and therapeutic approach of CSCR.

Association of metformin use with risk of newly onset neovascular age-related macular degeneration development.

PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD). METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched controls using the Merative™ Marketscan® Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic controls was also performed. RESULTS: Metformin use was associated with reduced odds ratio (OR) of developing nAMD (OR 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy (DR) -an effect that persisted after Bonferroni correction. In the diabetic cohort without DR, reduced OR was observed at 24-month cumulative doses of 1 to 300g, 301 to 630g, and 631 to 1080g. CONCLUSIONS: Metformin use was associated with reduced OR of nAMD, particularly in patients without DR. The protective effect was noted for 24-month cumulative doses below 1080g. Metformin may be a novel preventive strategy for nAMD.

Gonioscopy-assisted transluminal trabeculotomy in neovascular glaucoma: Salvaging the conventional outflow pathway.

Purpose: To report a case of acute neovascular glaucoma with partial synechial angle closure secondary to central retinal vein occlusion that underwent gonioscopy-assisted transluminal trabeculotomy as well as near-monthly anti-vascular endothelial growth factor (VEGF) injections and panretinal photocoagulation (PRP) treatments. Observations: Nine months after GATT, the patient had achieved intraocular pressure control on no medications. However, she was lost to follow up for 4 months and received no anti-VEGF or PRP during that time; she re-presented with acute NVG and complete synechial closure, and ultimately underwent aqueous shunt implantation. Conclusions and Importance: To our knowledge, this is the first reported attempt of an ab interno angle surgery to successfully restore aqueous outflow through the conventional outflow pathway in an eye with acute NVG and partial synechial angle closure. We posit that this can be an effective approach to achieve IOP control in NVG with at least partially open angles, as long as sufficient anti-neovascular treatments are administered until the underlying neovascular drive achieves quiescence.

Neovascular Glaucoma from Ocular Ischemic Syndrome Treated with Serial Monthly Intravitreal Bevacizumab and Panretinal Photocoagulation: A Case Report.

Purpose: To describe a case of open-angle neovascular glaucoma (NVG) secondary to ocular ischemic syndrome (OIS) treated with a planned series of 6 monthly anti-VEGF injections with interspersed panretinal photocoagulation (PRP) sessions. We term this treatment protocol the Salvaging Conventional Outflow Pathway in Neovascular Glaucoma (SCOPING) Protocol, and this is our (MQ and DS) standard of care for all NVG patients presenting with partially or completely open angles. Case: A 66-year-old man's right eye had a visual acuity of 20/50, intraocular pressure (IOP) of 42 mmHg on 0 IOP-lowering medications, and neovascularization of the iris and angle with no peripheral anterior synechiae. Fundoscopy revealed midperipheral dot-blot hemorrhages without diabetic retinopathy or vein occlusion. Fluorescein angiography revealed peripheral retinal nonperfusion in both eyes. The patient was diagnosed with open-angle NVG secondary to OIS and treated with 6 serial monthly anti-VEGF injections interspersed with 4 PRP sessions, after which his anterior segment neovascularization regressed and IOP normalized on 0 medications. Ten weeks after the last injection, the anterior segment neovascularization and elevated IOP recurred, so he underwent 4 more monthly anti-VEGF injections and 4 PRP sessions, after which his anterior segment neovascularization regressed and his IOP normalized on 0 medications. However, 6 weeks after the last injection, the anterior segment neovascularization and elevated IOP again recurred, so he was resumed on a third course of lifetime monthly anti-VEGF injections, which may be continued in perpetuity. Conclusion: The patient's NVG was quiescent while under the protection of serial anti-VEGF injections with interspersed PRP; however, the disease recurred each time injections were stopped. Therefore, in patients with open-angle NVG secondary to OIS, serial monthly anti-VEGF injections may be necessary combined with PRP to suppress underlying neovascular drive and regress anterior segment neovascularization, maintain physiologic IOP, and prevent synechial angle closure.

Use of OCT Angiography to Diagnose and Manage Atypical Presentations of Macular Telangiectasia Type 2.

Macular telangiectasia Type 2 (MacTel) is a bilateral acquired retinal disease characterized by both vascular changes and atrophy of the retina. The purpose of this case series is to highlight the use of optical coherence tomography angiography (OCTA) as a non-invasive imaging modality to distinguish atypical MacTel from other macular conditions with similar presentations. We performed a retrospective review of patients referred to our academic retinal practice with unconfirmed or misdiagnosed MacTel between July 2017 and July 2021. Patients' OCTA imaging findings were reviewed to guide the appropriate diagnosis and management of atypical MacTel. Fifteen eyes from eight patients were included in this study. Six patients were referred with previous diagnoses of either full-thickness macular hole, lamellar hole, vitreomacular traction (VMT), postoperative cystoid macular edema (CME), or diabetic macular edema (DME). Two patients were referred to us to confirm the diagnosis of MacTel. OCTA revealed telangiectatic vessels in the temporal parafovea of all 15 eyes. OCTA also highlighted previously undiagnosed subretinal neovascularization (SRNV) in seven eyes. OCTA imaging is a valuable imaging modality to distinguish MacTel from other macular conditions, whose treatment courses vary substantially. Due to its ease of use, it holds immense potential in the future as treatments for non-proliferative MacTel emerge.

Metformin and retinal diseases in preclinical and clinical studies: Insights and review of literature.

Metformin is one of the most prescribed drugs in the world giving potential health benefits beyond that of type 2 diabetes (T2DM). Emerging evidence suggests that it may have protective effects for retinal/posterior segment diseases including diabetic retinopathy (DR), age-related macular degeneration (AMD), inherited retinal degeneration such as retinitis pigmentosa (RP), primary open angle glaucoma (POAG), retinal vein occlusion (RVO), and uveitis. Metformin exerts potent anti-inflammatory, antiangiogenic, and antioxidative effects on the retina in response to pathologic stressors. In this review, we highlight the broad mechanism of action of metformin through key preclinical studies on animal models and cell lines used to simulate human retinal disease. We then explore the sparse but promising retrospective clinical data on metformin's potential protective role in DR, AMD, POAG, and uveitis. Prospective clinical data is needed to clarify metformin's role in management of posterior segment disorders. However, given metformin's proven broad biochemical effects, favorable safety profile, relatively low cost, and promising data to date, it may represent a new therapeutic preventive and strategy for retinal diseases.

Quantitative Optical Coherence Tomography Angiography (OCTA) Parameters in a Black Diabetic Population and Correlations with Systemic Diseases.

This is a cross-sectional, prospective study of a population of black diabetic participants without diabetic retinopathy aimed to investigate optical coherence tomography angiography (OCTA) characteristics and correlations with systemic diseases in this population. These parameters could serve as novel biomarkers for microvascular complications; especially in black populations which are more vulnerable to diabetic microvascular complications. Linear mixed models were used to obtain OCTA mean values ± standard deviation and analyze statistical correlations to systemic diseases. Variables showing significance on univariate mixed model analysis were further analyzed with multivariate mixed models. 92 eyes of 52 black adult subjects were included. After multivariate analysis; signal strength intensity (SSI) and heart disease had statistical correlations to superficial capillary plexus vessel density in our population. SSI and smoking status had statistical correlations to deep capillary plexus vessel density in a univariate analysis that persisted in part of the imaging subset in a multivariate analysis. Hyperlipidemia; hypertension; smoking status and pack-years; diabetes duration; creatinine; glomerular filtration rate; total cholesterol; hemoglobin A1C; and albumin-to-creatinine ratio were not significantly associated with any OCTA measurement in multivariate analysis. Our findings suggest that OCTA measures may serve as valuable biomarkers to track systemic vascular functioning in diabetes mellitus in black patients.

Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema.

INTRODUCTION: Non-exudative (dry) age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss worldwide. Besides age-related eye disease study (AREDS) vitamin supplements, there are no efficacious pharmaceutical interventions for dry AMD available. While numerous pharmacologics are available to treat diabetic macular edema (DME), many patients respond suboptimally to existing therapies. Risuteganib is a novel anti-integrin peptide that targets the multiple integrin heterodimers involved in the pathophysiology of dry AMD and DME. Inhibiting these selected integrin heterodimers may benefit patients with these conditions. AREAS COVERED: This article offers a brief overview of current pharmaceuticals available for dry AMD and DME. The proposed role of integrins in AMD and DME is reviewed and later, risuteganib, a novel anti-integrin peptide is introduced. The data from initial Phase 1 and Phase 2 risuteganib clinical trials are discussed in the latter part of the paper. EXPERT OPINION: While there are currently limited treatment options for dry AMD, more data are needed before we can truly evaluate the benefits of adopting risuteganib into the clinic. Conversely, several effective treatment options exist for DME; hence, risuteganib must show that it can add to these results, especially in those with refractory disease, before retina specialists adopt risuteganib into their treatment regimens.

Repair of Superior Chorioretinal Coloboma-Associated Retinal Detachments: Case Report and Literature Review.

Purpose: This case report discusses the management of a patient with a superior chorioretinal coloboma-associated retinal detachment (RD), including surgical management, along with a review of the literature. Methods: A case report is presented. Results: A 58-year-old man presented with a chronic RD of the right eye that was symptomatic for approximately 1 year prior to presentation. On examination, he was found to have a macula-off RD associated with superior chorioretinal coloboma. He underwent 23-gauge pars plana vitrectomy with membrane peel, endolaser, and perfluoropropane (14%) gas tamponade. Three months after his surgery, his best-corrected visual acuity in his right eye was 20/250 distance and 20/80 near, and his retina remained attached. Conclusions: This case report describes surgical management of a superior chorioretinal coloboma-associated RD.