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/UNASSIGNED:To analyze the evolution of type 1 neovascularization associated with vascularized serous pigment epithelial detachment (vsPED) using three-dimensional, volumetric, en face optical coherence tomography angiography (OCTA). Methods/UNASSIGNED:This was a retrospective case series from four tertiary medical centers. OCTA images were analyzed at baseline and at the 3-, 6-, 12-, 18-, and 24-month follow-up visit when available. Visual acuity, number of injections, PED maximal height and PED area and volume, and choroidal neovascularization (CNV) flow area and progression were determined at each visit. Qualitative and quantitative analysis of CNV progression (including CNV/PED flow area) and final PED morphology was performed to determine anatomic outcomes. Results/UNASSIGNED:Twenty-four eyes in 22 patients were studied. Median follow-up was 20 months. Across all eyes, maximum PED height decreased from 395.5 to 369.5 μm while CNV/PED flow ratio increased from 27.3% to 40.2%. Median visual acuity was unchanged at 20/40. Final PED outcomes included filled fibrovascular versus persistent vsPED. Filled vsPEDs decreased in PED height and volume and displayed a multilayered morphology in contrast to persistent vsPEDs. Fibrovascular PEDs received on average seven less injections as compared to persistent vsPEDs. Conclusions/UNASSIGNED:Three-dimensional, volumetric, en face OCTA analysis of vsPED progression illustrated two anatomic outcomes: filled, typically multilayered fibrovascular PED versus persistent vsPED. The filled multilayered PED displayed a reduction in PED height and volume, greater CNV/PED flow ratio, and fewer anti-VEGF injections versus the persistent vsPED and may represent a more stable anatomic outcome while the persistent vsPED may indicate a more unstable morphology.

Purpose/UNASSIGNED:To explore patterns of disease progression in nonneovascular age-related macular degeneration (AMD) associated with hyperreflective crystalline deposits (HCDs) in the sub-retinal pigment epithelium-basal laminar space. Methods/UNASSIGNED:Retrospective review of medical records, multimodal imaging, and longitudinal eye-tracked near-infrared reflectance (NIR) and optical coherence tomography (OCT) spanning ≥2 years. NIR/OCT images were analyzed with ImageJ software to identify HCD morphology and location. Associated macular complications were reviewed from the time of HCD detection to the most recent follow-up, using NIR/OCT. Results/UNASSIGNED:Thirty-three eyes with HCDs from 33 patients (mean age: 72 ± 7.5 years) had 46.7 months (95% confidence limits: 33.7, 59.6) of serial eye-tracked NIR/OCT follow-up. Baseline best-corrected visual acuity (BCVA) was 0.44 logMAR (Snellen equivalent 20/55). At a mean of 11.3 months (3.1, 19.6) after HCD detection, 31/33 (93.9%) eyes had developed macular complications including de novo areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in 21/33 (64%) eyes, enlargement of preexisting cRORA in 4/33 (12%) eyes, and incident macular neovascularization in 3/33 (9%) eyes. Movement and clearance of HCDs in 9/33 (27%) eyes was associated with enlargement of preexisting cRORA (r = 0.44, P = 0.02). BCVA at the last follow-up visit had decreased to 0.72 logMAR (20/105). Conclusions/UNASSIGNED:Eyes with nonneovascular AMD demonstrating HCDs are at risk for vision loss due to macular complications, particularly when movement and clearance of these structures appear on multimodal imaging. HCD reflectivity and dynamism may be amenable to automated recognition and analysis to assess cellular activity related to drusen end-stages.

Central serous chorioretinopathy (CSC) is a common cause of central vision loss, primarily affecting men 20-60 years of age. To date, no consensus has been reached regarding the classification of CSC, and a wide variety of interventions have been proposed, reflecting the controversy associated with treating this disease. The recent publication of appropriately powered randomised controlled trials such as the PLACE trial, as well as large retrospective, non-randomised treatment studies regarding the treatment of CSC suggest the feasibility of a more evidence-based approach when considering treatment options. The aim of this review is to provide a comprehensive overview of the current rationale and evidence with respect to the variety of interventions available for treating CSC, including pharmacology, laser treatment, and photodynamic therapy. In addition, we describe the complexity of CSC, the challenges associated with treating CSC, and currently ongoing studies. Many treatment strategies such as photodynamic therapy using verteporfin, oral mineralocorticoid antagonists, and micropulse laser treatment have been reported as being effective. Currently, however, the available evidence suggests that half-dose (or half-fluence) photodynamic therapy should be the treatment of choice in chronic CSC, whereas observation may be the preferred approach in acute CSC. Nevertheless, exceptions can be considered based upon patient-specific characteristics.

Purpose/UNASSIGNED:To analyze "pseudoflow," a false positive flow-artifact observed with optical coherence tomography angiography (OCTA) of stationary hyperreflective structures corresponding to hard exudates and macular drusen. Methods/UNASSIGNED:Retrospective case series of patients with hard exudates (due to diabetic macular edema [DME] or retinal vein occlusion [RVO]) or macular drusen (due to nonneovascular, or dry, age-related macular degeneration [AMD]) studied with OCTA by using volume-based projection artifact removal (3D PAR). Results/UNASSIGNED:OCTA of 20 eyes (10 DME/10 RVO) with hard exudates were analyzed. All eyes exhibited pseudoflow corresponding to hard exudates. Seven eyes concurrently demonstrated hard exudates without pseudoflow that were noted in areas lacking vascular flow in the overlying retina. Eight eyes exhibited suspended scattering particles in motion. In 26 of 30 eyes with nonneovascular AMD, pseudoflow associated with macular drusen of any type was noted. Two of 11 eyes with small drusen, 16 of 17 eyes with medium or large drusen, 5 of 5 eyes with drusenoid pigment epithelial detachment, 12 of 16 eyes with ribbon-like subretinal drusenoid deposits, and 13 of 17 eyes with dot-like SDD exhibited pseudoflow. Conclusions/UNASSIGNED:Pseudoflow due to projection artifact is common in eyes with hard exudates or macular drusen. 3D PAR reduces but does not eliminate pseudoflow, and pseudoflow may be detected within the foveal avascular zone, indicating that other factors, such as Z-axis micromotion, may also contribute to pseudoflow. Translational Relevance/UNASSIGNED:This study provides insight into the etiology of pseudoflow noted on OCTA and will guide more accurate clinical interpretation and investigation of OCTA images.

Importance/UNASSIGNED:Incidence of conversion to neovascular age-related macular degeneration (nAMD) in untreated fellow eyes of patients who are treated for nAMD in 1 eye with anti-vascular endothelial growth factor agents provides important prognostic information to clinically manage patients. Objective/UNASSIGNED:To investigate the association of treatment assignment (intravitreal aflibercept vs ranibizumab) and baseline characteristics with fellow eye conversion to nAMD in the VEGF (Vascular Endothelial Growth Factor) Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies. Design, Setting, and Participants/UNASSIGNED:This post hoc analysis of the VIEW 1 and VIEW 2 studies (randomized, double-masked, active-controlled, multicenter, 96-week, phase 3 trials comparing the efficacy and safety of intravitreal aflibercept in 2457 patients with treatment-naive eyes with nAMD) analyzed a subgroup of participants treated for nAMD in 1 eye who had untreated fellow eyes without neovascularization at baseline. All participants in the VIEW studies were included in 1 of 4 groups: ranibizumab, 0.5 mg, every 4 weeks; aflibercept, 2 mg, every 4 weeks; aflibercept, 0.5 mg, every 4 weeks; or aflibercept, 2 mg, every 8 weeks after 3 injections at 4-week intervals. Data collection in the VIEW studies occurred from July 2007 to August 2011; the data analysis presented in this report took place from April 2016 to November 2018. Interventions/UNASSIGNED:Patients received no treatment in the fellow eyes unless after conversion to nAMD, when any treatment approved by heath authorities was given per the investigators' discretion. Main Outcomes and Measures/UNASSIGNED:Incidence of conversion to nAMD in patients with untreated fellow eyes that had not had clinical signs of neovascularization at baseline. Results/UNASSIGNED:A total of 1561 participants were included in this analysis. At 96 weeks, 375 patients (24.0%) experienced cases of conversion to neovascular disease in the fellow eye, including 107 of the 399 individuals who received ranibizumab, 0.5 mg, every 4 weeks; 93 of the 387 individuals who received aflibercept, 2 mg, every 4 weeks; 84 of the 387 individuals who received aflibercept, 0.5 mg, every 4 weeks; and 91 of the 388 individuals who received aflibercept, 2 mg, every 8 weeks after 3 doses at 4-week intervals. The rates were 18.1, 16.2, 14.7, and 16.0 per 100 patient-years at risk at week 96, respectively. On multivariate analysis, fellow eye conversion was associated with increasing patient age (per 10 years) at baseline (hazard ratio [HR], 1.20 [95% CI, 1.05-1.36]), female sex (HR, 1.32 [95% CI, 1.06-1.63]), intraretinal fluid in the study eye at baseline (HR, 1.28 [95% CI, 1.02-1.61]), and increasing choroidal neovascularization lesion size (per 10 mm2) in the study eye at baseline (HR, 1.29 [95% CI, 1.06-1.57]). Rates of fellow eye conversion were similar with either of the treatments. Conclusions and Relevance/UNASSIGNED:In this secondary analysis of randomized clinical trial data, patients with active nAMD in 1 eye appeared to have a high risk for fellow eye conversion. Such patients should be monitored closely.

This is a rare, multimodal imaging report spanning a decade of monitoring in a patient with chronic solar retinopathy showing the natural course of the disease. Spectral-domain optical coherence tomography (SD-OCT) showed mild widening of subfoveal loss of ellipsoid and interdigitation zones bilaterally, progressive retinal pigment epithelial thinning in the right eye, and hyperplasia in the left eye. Structural en face OCT showed subfoveal tissue loss bilaterally. There was no leakage on fluorescein angiography and OCT angiography (OCTA), and dense B-scan OCTA images were unremarkable. Microperimetry revealed bilateral decreased central sensitivity and eccentric fixation in the left eye. Vision remained stable throughout. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:388-392.].

PURPOSE/OBJECTIVE:To introduce a simple method for differentiating retinal veins from arteries on optical coherence tomography angiography (OCTA). DESIGN/METHODS:Cross-sectional pilot study. METHODS:Four default en face slabs including color depth encoded, greyscale full-thickness retina, superficial plexus, and deep capillary plexus (DCP) from 9 3x3 mm and 9 6x6 mm OCTA scans were exported and aligned. Nine ophthalmologists with minimum OCTA experience from 2 eye institutions were instructed to classify labeled vessels as arteries or veins in 3 stages. Classification was performed based on graders' own assessment at Stage 1. Graders were taught that a capillary-free zone was an anatomic feature of arteries at Stage 2 and were trained to identify veins originating from vortices within the DCP at Stage 3. Grading accuracy was analyzed and correlated with grading time and graders' years in practice. RESULTS:Overall grading accuracy in Stages 1, 2, and 3 was (50.4 ± 17.0) %, (75.4 ± 6.0) %, and (94.7 ± 2.6) %, respectively. Grading accuracy for 3x3 mm scans in Stages 1, 2, and 3 was (49.9 ± 16.3) %, (79.2 ± 9.6) %, and (96.9 ± 3.1) %, respectively. Accuracy for 6x6 mm scans in Stages 1, 2, and 3 was (51.4 ± 20.8) %, (72.3 ± 7.9) %, and (93.2 ± 3.3) %, respectively. Grading performance improved significantly at each stage (all P < .001). No significant correlation was found between accuracy and time spent grading or between accuracy and years in practice (r = -0.164 - 0.617, all P ≥ 0.077). CONCLUSIONS:We describe a simple method for accurately distinguishing retinal arteries from veins on OCTA which incorporates the use vortices in the DCP to identify venous origin.