Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.

Background Non-paraneoplastic autoimmune retinopathy (npAIR) is a rare autoimmune disease that primarily affects retinal photoreceptor function and results in profound and often times permanent vision loss. Delay in diagnosis and treatment initiation may contribute to the poor visual prognosis. Methods A retrospective chart review of all patients diagnosed with autoimmune retinopathy at the University of Wisconsin-Madison Eye Clinics between January 2012 and January 2017 was performed. Twenty eyes of 15 patients had evidence of any form of autoimmune retinopathy through a combination of symptoms, ocular findings, visual fields, optical coherence tomography, fundus autofluorescence, full-field and multifocal electroretinography, and serum anti-retinal antibodies. Clinical records were also analyzed for demographic data, systemic comorbidities, visual acuity, treatment employed, and disease progression. Results We identified 18 eyes from 13 patients who fit the criteria for non-paraneoplastic autoimmune retinopathy. Sixty-nine percent of patients were female with a mean age of symptom onset of 56.9 ± 20.3 years. Sixty-seven percent of eyes had an associated autoimmune condition, most commonly hypothyroidism. Serum testing revealed a preponderance of antibodies against carbonic anhydrase II, while imaging revealed characteristic changes. Fundus autofluorescence most commonly showed hyperautofluorescence around the macula. The delayed diagnosis led to a larger reduction in the horizontal extent of ellipsoid zone in 1-mm perifoveal area on optical coherence tomography with resulting visual decline. There was no difference in the change of visual acuity when stratifying for patients with autoimmune conditions ( p = 0.52) or treatment status ( p = 0.50). None of the patients who received treatment developed contralateral eye involvement or experienced disease progression based on visual acuity or symptoms. Conclusion Non-paraneoplastic autoimmune retinopathy has a wide and often challenging to diagnose spectrum of clinical symptoms and imaging findings. Immunosuppressive therapy can be considered empiric in the face of a suggestive presentation and can be initiated after an evaluation of clinical findings and multimodal testing, though treatment does not appear to affect regeneration of the ellipsoid zone on OCT or impact visual acuity. Treatment should be primarily used to prevent disease progression and contralateral eye involvement. Trial registration N/A

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.

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