Faculty Bibliography

Age-related macular degeneration (AMD) is a global health concern and the leading cause of vision loss in the developed world. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of neovascular AMD, but there are still challenges with delivery of care and treatment burden with currently available medications. Brolucizumab is a single-chain antibody fragment inhibitor of all isoforms of VEGF-A. Its small molecular weight allows for high solubility and tissue penetration. Brolucizumab has most recently been evaluated in 2 parallel phase 3 randomized controlled trials which demonstrated its safety and efficacy in an extended dosing regimen. The present review summarizes the safety, visual and anatomic outcomes, and durability of brolucizumab in the treatment of neovascular AMD and discusses some of the extended dosing regimens explored with currently approved medications and other therapies still under clinical investigation.

PURPOSE: To describe the multimodal imaging findings of transient subretinal deposits occurring in multiple evanescent white dot syndrome (MEWDS). METHODS: The multimodal imaging characteristics of transient subretinal deposits occurring in MEWDS were investigated with ultra-widefield color and fundus autofluorescence, cross-sectional and en-face optical coherence tomography (OCT), en face OCT-angiography, and quantitative autofluorescence. RESULTS: A 28-year-old woman presented with photopsia and temporal visual field loss in her right eye. Her best-corrected visual acuity was 20/20 in her right eye and 20/25 in her left eye. Funduscopic examination showed characteristic peripapillary hyperautofluorescent white dots of MEWDS corresponding to ellipsoid zone disruption on OCT. These lesions became confluent throughout the posterior fundus over the next 4 weeks. As the patient's symptoms were resolving, a second type of transient hyperautofluorescent lesion was noted which corresponded to hyperreflective subretinal deposits on cross-sectional and en face structural OCT. These subretinal deposits were most evident at 10-week follow-up and had nearly resolved at 14-week follow-up. Quantitative autofluorescence showed that, unlike the acute MEWDS lesions, the hyperautoflurescence of the subretinal deposits persisted after photobleaching. At multiple time points over 14 weeks of follow-up, OCT angiography showed no evidence of retinal or choroidal flow abnormalities. CONCLUSION: Transient subretinal deposits may develop during MEWDS in areas of previous diffuse outer retinal disruption. As these deposits remain hyperautoflurescent on quantitative autofluorescence after photobleaching, they may represent accumulations of debris originating from damaged photoreceptor outer segments.

Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch's membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

Importance/UNASSIGNED:Analysis of collateral vessel formation following retinal vein occlusion may advance our understanding of the venous outflow anatomy in the macula. Objective/UNASSIGNED:To determine the location of collateral vessels with optical coherence tomography (OCT) angiography imaging. Design, Setting, and Participants/UNASSIGNED:Observational retrospective cohort study. Collateral vessel formation was studied with OCT angiography (OCTA) in patients with retinal vein occlusion (RVO). The study took place at 2 retinal practices (Vitreous Retina Macula Consultants of New York and Stein Eye Institute, University of California, Los Angeles), with patient records retrieved from March 2015 to August 2017. Data analysis was completed in November 2017. Exposures/UNASSIGNED:Collaterals identified with fundus photography and/or fluorescein angiography were analyzed with OCTA to determine their course through the superficial vascular plexus (SVP) and the deep vascular complex (DVC). Main Outcomes and Measures/UNASSIGNED:Collateral vessel pathways through the SVP and DVC were analyzed with cross-sectional and en face OCT and OCTA segmentation and color-coded volume renderings prepared from raw OCTA voxel data. Results/UNASSIGNED:From 23 eyes (22 branch and 1 hemispheric retinal vein occlusion ) of 23 patients (mean [SD] age, 73 [11] years), 101 collateral vessels were identified and analyzed (mean [SD], 4.4 [2.0]; range, 2-9 collateral per eye). On OCTA, the collaterals appeared as curvilinear dilated flow signals that connected veins across the horizontal raphe or veins on opposite sides of an occluded venous segment within the same retinal hemisphere. Of the 101 collaterals analyzed, all showed greater flow signal in the DVC, and all had some portion of their course identified within the DVC. No collaterals were found exclusively in the SVP. Volume renderings for 3 cases confirmed qualitatively that retinal collateral vessels course through the retina predominantly at the level of the DVC. Conclusions and Relevance/UNASSIGNED:Based on a limited number of cases, all collateral vessels associated with retinal vein occlusion were found to course through the DVC. The absence of collaterals isolated to the SVP supports a serial arrangement of the SVP and DVC, with venous drainage predominantly coursing through the DVC.

PURPOSE/OBJECTIVE:To analyze the spectrum of ischemia associated with paracentral acute middle maculopathy (PAMM) in eyes with acute retinal vascular occlusion and to describe an ischemic cascade. DESIGN/METHODS:A retrospective observational case series. METHODS:Patients presenting with PAMM secondary to acute retinal vascular occlusion were identified. Analysis of multimodal imaging was performed at baseline and at follow up visits to elucidate the patterns and progression of ischemia within the retinal layers. RESULTS:Multimodal retinal imaging from 16 eyes of 16 patients with acute retinal vascular occlusion associated with PAMM was studied. Analysis of en face OCT segmentation of the inner nuclear layer (INL) identified distinct patterns of PAMM correlating with the severity of ischemia and not the type of occlusion. A perivenular fern-like PAMM pattern was associated with better visual outcomes (average final visual acuity was 20/25). This pattern was noted to sequentially progress in 2 cases to a diffuse globular PAMM pattern in the INL, or to a pattern of ischemia involving both the middle and inner retinal layers with commensurate vision loss. Globular patterns of PAMM or ischemia involving both the middle and inner retina correlated with poorer visual outcomes (average final visual acuity was counting fingers at 5.5 ft). These various patterns of ischemia developed in eyes with retinal vascular occlusions in which blood flow through the retinal capillary plexuses was present but was significantly reduced and delayed. CONCLUSIONS:This study describes OCT findings suggestive of an ischemic cascade in eyes with retinal vascular occlusion. The middle retina at the level of the deep capillary plexus, especially at the venular pole, may be more vulnerable to ischemic injury.