Objective To evaluate the association of subretinal hyper-reflective material (SHRM) with visual acuity (VA), geographic atrophy (GA) and scar in the Comparison of Age related Macular Degeneration Treatments Trials (CATT) Design Prospective cohort study within a randomized clinical trial. Participants The 1185 participants in CATT. Methods Participants were randomly assigned to ranibizumab or bevacizumab treatment monthly or as-needed. Masked readers graded scar and GA on fundus photography and fluorescein angiography images, SHRM on time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1mm2, or outside the center 1mm2 were obtained on SD-OCT images at 56 (n=76) and 104 (n=66) weeks. VA was measured by certified examiners. Main Outcome Measures SHRM presence, location and size, and associations with VA, scar, and GA. Results Among all CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than eyes with SHRM that resolved (64% vs. 31%; p<0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n=76) and 104 (n=66), mean [SE] VA letter score was 73.5 [2.8], 73.1 [3.4], 65.3 [3.5], and 63.9 [3.7] when SHRM was absent, present outside the central 1mm2, present within the central 1mm2 but not the foveal center, or present at the foveal center (p=0.02). SHRM was present at the foveal center in 43 (30%), within the central 1mm2 in 21 (15%) and outside the central 1mm2 in 19 (13%). When SHRM was present, the median maximum height in microns under the fovea, within the central 1 mm2 including the fovea and anywhere within the scan was 86; 120; and 122, respectively. VA was decreased with greater SHRM height and width (p<0.05). Conclusions SHRM is common in eyes with NVAMD and often persists after anti-VEGF treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM height and width were associated with worse VA. SHRM is an important morphological biomarker in eyes with NVAMD.

Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition.

Purpose To establish adaptive optics scanning laser ophthalmoscopy (AOSLO) as a method to detect and characterize microscopic signs of diabetic retinopathy, in capillaries and cone photoreceptors in the parafovea. Methods Recently, AOSLO has enabled noninvasive assessment of photoreceptors, capillaries, and leukocytes in the retinas of live human subjects. Repeated application of AOSLO imaging along with comparison to fluorescein angiography was used to track individual capillaries near the foveal avascular zone (FAZ) from one eye affected with severe non-proliferative diabetic retinopathy. Fluorescein angiography was used to identify clinical signs of diabetic retinopathy, such as microaneurysms and intra-retinal microvascular abnormalities (IRMAs), and corresponding regions were imaged and assessed using the AOSLO. In addition, the structural integrity of photoreceptors and the spatial distribution of leukocytes around the parafoveal capillary network were quantitatively assessed. Results Capillaries and cone photoreceptors were visualized using the AOSLO, without the use of injected contrast agents. Although the majority of capillaries were stable over a period of 16 months, one capillary at the edge of the FAZ dropped out, leading to a small, but significant increase in FAZ size. Longitudinal assessment of the capillaries also showed microaneurysm formation and disappearance, as well as the formation of tiny capillary bends similar in appearance to IRMAs. The leukocytes in the capillary network were found to preferentially travel through the same routes in all four visits, suggesting that these channels are robust against small changes to the surrounding capillaries. In this eye, cone photoreceptor spacing was increased in the fovea when compared to normal data, but stable across all visits. Conclusions AOSLO imaging can be used to longitudinally track capillaries, leukocytes and photoreceptors in diabetic retinopathy. Capillary changes that can be detected include dropout of individual capillaries, as well as formation and disappearance of microaneurysms.

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