Faculty Bibliography

PURPOSE/OBJECTIVE:To investigate the macular changes over time in eyes containing subretinal drusenoid deposits (also known as pseudodrusen) with no drusen >63 µm. METHODS:A consecutive series of patients were examined with color fundus photography, optical coherence tomography, and autofluorescence imaging with fluorescein angiography used as necessary. Exclusionary criteria included macular neovascularization, history of retinal surgery, pseudoxanthoma elasticum, and drusen >63 µm. RESULTS:There were 85 eyes of 54 patients. The mean age at baseline was 83.6 (±7.8) years, and there were 17 men. The mean follow-up was 5.0 (±2.9) years. At initial optical coherence tomography examination, 12 eyes had extrafoveal atrophy and 17 eyes had vitelliform deposits, which were yellowish white subretinal collections that showed intense hyperautofluorescence. During follow-up, 11 eyes lost vitelliform material. After the disappearance of small deposits, focal hyperpigmentation remained. Loss of larger deposits was associated with noteworthy sequela; six developed subfoveal atrophy and one macular neovascularization close to regressing vitelliform material. Subfoveal geographic atrophy developed in four other eyes without vitelliform material by extension from areas of extrafoveal atrophy. Macular neovascularization developed in seven eyes over follow-up. The CFH Y402H and ARMS2 A69S allele frequencies were 57% and 48.9%, respectively, which is similar to a group of age-related macular degeneration controls. One patient had a novel PRPH2 mutation, but did not have a vitelliform deposit; the remainder had a normal PRPH2 and BEST1 coding sequences. CONCLUSION/CONCLUSIONS:Eyes with subretinal drusenoid deposits and no drusen >63 mm have significant risk for the development of both neovascularization and geographic atrophy, the fundamental components of late age-related macular degeneration. An intermediate step in some eyes was the development of a vitelliform deposit, an entity not traditionally associated with age-related macular degeneration, but in these patients, the material seemed to be an important component of the disease pathophysiology. This vitelliform deposit was not associated with genetic markers for pattern dystrophy or Best disease.

PURPOSE: To demonstrate longitudinal multimodal imaging findings in a case of neovascular age-related macular degeneration presenting with multiple retinal pigment epithelium (RPE) tears showing progressive RPE restoration. METHODS: Observational clinical case report. RESULTS: A 79-year-old woman diagnosed with neovascular age-related macular degeneration developed 3 consecutive RPE tears in her right eye during the course of treatment with intravitreal anti-vascular endothelial growth factor therapy. The RPE tears initially appeared hypoautofluorescent on fundus autofluorescence. Spectral domain optical coherence tomography showed contractile folds of the RPE with adjacent subretinal fluid and overlying ellipsoid zone disruption. Over an 8-year follow-up period, the RPE defects progressively resolved with a return of patchy fundus autofluorescence. Eye-tracked spectral domain optical coherence tomography showed gradual restoration of the RPE band defects over an enlarging Type 1 neovascular lesion. CONCLUSION: Some RPE tears may show observable remodeling and restoration over time. These changes may be followed longitudinally with multimodal imaging, including eye-tracked spectral domain optical coherence tomography and fundus autofluorescence.

Pachychoroid is a relatively novel concept describing a phenotype characterized by attenuation of the choriocapillaris overlying dilated choroidal veins, and associated with progressive retinal pigment epithelium dysfunction and neovascularization. The emphasis in defining pachychoroid-related disorders has shifted away from simply an abnormally thick choroid (pachychoroid) toward a detailed morphological definition of a pathologic state (pachychoroid disease) with functional implications, which will be discussed in this review. Several clinical manifestations have been described to reside within the pachychoroid disease spectrum, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome. These conditions all exhibit the characteristic choroidal alterations and are believed to represent different manifestations of a common pathogenic process. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical and imaging features, management considerations, as well as current understanding of pathogenesis of these disorders within the context of the recent findings related to pachychoroid disease.

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.

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 report a case of "posterior scleral melanocytosis," a pigmented lesion of the posterior sclera that clinically resembles a flat choroidal nevus. METHODS: Case report of a patient with posterior scleral melanocytosis. Multimodal imaging, including swept source optical coherence tomography, was used to demonstrate the scleral location of the pigmented lesion and to distinguish its features from a typical choroidal nevus present in the same eye. RESULTS: An 86-year-old woman was seen for regular follow-up for neovascular age-related macular degeneration in her right eye and 2 pigmented lesions in her left eye, both presumed to be choroidal nevi. Anterior segment examination showed no evidence of ocular or dermal melanocytosis. Optical coherence tomography of the pigmented lesion in the left eye showed two distinct patterns. One lesion showed hyperreflectivity within the choroidal tissue associated with posterior shadowing, whereas the second lesion showed normal choroidal reflectivity with hyperreflectivity confined to the inner sclera associated with marked posterior shadowing. CONCLUSION: To the authors' knowledge, this is the first report of posterior scleral melanocytosis, a pigmented fundus lesion confined to the inner sclera. The need for high-penetrance optical coherence tomography to differentiate these lesions from a typical choroidal nevus may explain why this entity has not been previously described. The true nature of this entity will ultimately require histopathologic study.