Faculty Bibliography

PURPOSE/OBJECTIVE:To report a case of Vogt-Koyanagi-Harada (VKH)-like uveitis followed by melanoma-associated retinopathy (MAR) with focal chorioretinal atrophy and subsequent choroidal neovascularization (CNV) in a patient with metastatic cutaneous melanoma. OBSERVATION/METHODS:A 68-year-old man with a history cutaneous melanoma presented with VKH-like uveitis. Work up revealed a pelvic mass, which was excised and found to be metastatic melanoma. Two years later, the patient developed MAR with focal chorioretinal atrophy and adjacent CNV. CONCLUSION/CONCLUSIONS:and Importance: Patients with metastatic cutaneous melanoma can develop distinct and sequential paraneoplastic ocular complications. Onset of a VKH-like uveitis may be a good prognostic factor for survival in patients with metastatic cutaneous melanoma.

Vitelliform lesions (VLs) are associated with a wide array of macular disorders but are the result of one common pathway: retinal pigment epithelium (RPE) impairment and phagocytic dysfunction. VLs are defined by the accumulation of yellowish subretinal material. In the era of multimodal advanced retinal imaging, VLs can be further characterized by subretinal hyperreflectivity with optical coherence tomography and hyperautofluorescence with fundus autofluorescence. VLs can be the result of genetic or acquired retinal diseases. In younger patients, VLs usually occur in the setting of Best disease. Additional genetic causes of VL include pattern dystrophy or adult-onset vitelliform macular dystrophy. In older patients, acquired VLs can be associated with a broad spectrum of etiologies, including tractional, paraneoplastic, toxic, and degenerative disorders. The main cause of visual morbidity in eyes with VLs is the onset of macular atrophy and macular neovascularization. Histopathological studies have provided new insights into the location, nature, and lifecycle of the vitelliform material comprised of melanosomes, lipofuscin, melanolipofuscin, and outer segment debris located between the RPE and photoreceptor layer. Impaired phagocytosis by the RPE cells is the unifying pathway leading to VL development. We discuss and summarize the nature, pathogenesis, multimodal imaging characteristics, etiologies, and natural course of vitelliform maculopathies.

PURPOSE:The purpose of this study was to identify a precise location of deep capillary plexus (DCP) injury in acute macular neuroretinopathy (AMN) lesions using multimodal imaging. METHODS:En face structural optical coherence tomography (OCT) images were manually segmented to delineate outer retinal AMN lesions involving the ellipsoid zone and interdigitation zone. AMN lesion centroid was calculated, and image distortion was applied to correct for Henle fiber layer (HFL) length and orientation. The resulting image was registered with the corresponding en face OCT angiography (OCTA) image segmented at the DCP and structural OCT volume before grading for vascular and structural features, respectively. RESULTS:Thirty-nine AMN lesions from 16 eyes (11 female patients, mean age 34 ± 4 years) were analyzed. After correcting for HFL anatomy, in 62% of AMN lesions, the centroid co-localized with a capillary vortex (pattern 1); flow defects were detected in 33% of lesions (pattern 2); and in 5% of lesions no specific pattern could be identified (pattern 3). The detection of a specific pattern increased after correcting the projection of AMN lesion for HFL anatomy (28% vs. 5%, P = 0.04). Outer nuclear layer thickness was lower in the centroid area in 10 (29%) AMN lesions from 6 patients, all corresponding to lesions fitting pattern 2 (r = 0.78, P < 0.001). CONCLUSIONS:AMN lesions might be a result of DCP impairment at the level of the capillary vortex or draining venule. In eyes with AMN, the location of outer retinal changes associated with DCP ischemia appears to be influenced by the length and orientation of HFL.

PURPOSE/OBJECTIVE:To characterize and distinguish non-neovascular deep retinal age-related microvascular anomalies (DRAMA) from type 3 macular neovascularization (MNV) using volume rendering of optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN/METHODS:Retrospective, consecutive case series. SUBJECTS/METHODS:Consecutive patients with age-related macular degeneration (AMD) exhibiting de novo non-neovascular abnormalities within the deep vascular plexus (DCP) on high-resolution (High-Res) spectral domain and swept-source OCT/OCTA. Patients with retinal vascular alterations attributable to other disease entities were excluded. METHODS:Complete ophthalmologic examination and multimodal imaging including confocal fundus photography (CFP), spectral domain OCT (SD-OCT), High-Res SD-OCT and OCTA, and volume-averaged swept-source OCTA (SS-OCTA). Volume rendering of High-Res OCTA and averaged SS-OCTA were used to analyze capillary abnormalities and inflow/outflow connectivity pathways. MAIN OUTCOME MEASURES/METHODS:The primary outcomes were the characteristics of capillary abnormalities (number, size, shape, reflectivity, and location) and inflow/outflow connectivity pathways. Secondary outcomes were nearby changes in CFP and structural OCT (hyperreflective foci, outer retinal atrophy, and retinal pigment epithelium (RPE) atrophy). RESULTS:From 8 eyes of 8 patients, 2 DRAMA subtypes were identified: small diameter perifoveal capillary dilations with hyperreflective walls within the inner nuclear layer (type 1, n=4) and vascular outpouchings, typically multiple, extending posteriorly into Henle's fiber layer with reflectivity similar to adjacent normal retinal capillaries (type 2, n=10). Four eyes had both DRAMA subtypes. Three-dimensional visualization of OCTA data demonstrated DRAMA corresponding to dilations of DCP capillaries without direct inflow or outflow connections to the superficial plexus. Fundus photographs showed circular red dots in 3 eyes, all corresponding to type 1 DRAMA. DRAMA co-localized with hyperreflective foci in all cases. No lesions were found anterior to areas of retinal pigment epithelium or outer retina atrophy. Asymptomatic intraretinal exudation varied through a follow-up of up to 6 years, with no lesions progressing to type 3 MNV. CONCLUSIONS:In eyes with non-neovascular AMD, DRAMA includes two types of capillary dilations occurring without remodeling of the surrounding vascular network. DRAMA can resemble microvascular changes due to other causes and can masquerade as type 3 MNV. Mild intraretinal exudation can vary during follow up without progression to type 3 MNV.

Background/aims Demonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs). Methods Cross-sectional study. Two hundred AMD subjects (aged 51-100 years; 121 women, 79 men) were recruited. Spectral domain optical coherence tomography, autofluorescence and near-infrared reflectance imaging, and lipid profiles were obtained. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (eg, aortic stenosis), myocardial defect (eg, myocardial infarction) and stroke/transient ischaemic attack. Masked readers assigned subjects into two groups: SDD (with or without drusen) and drusen (only). Univariate testing was performed by χ 2 test. We built multivariate regression models to test relationships of coexistent HRVD to SDD status, lipid levels and other covariates. Results The prevalence of HRVD was 41.2% (40/97) and 6.8% (7/103) in the SDD and non-SDD groups, respectively (correlation of SDD with HRVD, p=9×10 -9, OR 9.62, 95% CI 4.04 to 22.91). Multivariate regressions: only SDDs and high-density lipoprotein (HDL) in the first two HDL quartiles remained significant for HRVD (p=9.8×10 -5, 0.021, respectively). Multivariate regression model: SDDs and an HDL in Q1 or Q2 identified the presence of HRVD with the accuracy of 78.5%, 95% CI 72.2% to 84.0%. Conclusions High-risk cardiovascular and neurovascular diseases were accurately identified in an AMD cohort from SDDs and HDL levels. The SDDs may be related to inadequate ocular perfusion resulting from the systemic vasculopathies. Further research with this paradigm is warranted and might reduce mortality and morbidity from vascular disease.

PURPOSE/OBJECTIVE:To report a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) associated with primary Epstein-Barr virus (EBV) infection. METHODS:Multimodal imaging including color fundus photography, spectral domain optical coherence tomography (SD-OCT), blue light fundus autofluorescence (FAF), fluorescein angiography (FA) and indocyanine green angiography (ICGA). RESULTS:A 24-year-old otherwise healthy woman presented with an acute bilateral visual disturbance associated with cervical lymphadenopathy. SD-OCT showed bilateral foveal serous retinal detachment (SRD) with thickening of the ellipsoid zone (EZ) throughout the posterior pole corresponding to hyperautofluorescence on FAF, faint diffuse hyperfluorescence on FA without leakage, and mild late hyperfluorescence on ICGA. Systemic workup revealed an acute EBV infection. Within several weeks, multifocal SRDs developed in the macula and paramacula. The SRDs then became increasingly hyperautofluorescent with SD-OCT showing subretinal hyperreflective material. This vitelliform material then slowly resolved while the thickness of the surrounding EZ normalized. The FA and ICGA appeared normal at month 8. Visual acuity was 20/20 in both eyes at all times. No treatment was initiated. CONCLUSION/CONCLUSIONS:AEPVM may be associated with an acute EBV-infection. Acutely, multimodal imaging revealed findings consistent with RPE dysfunction and reduced photopigment density. Subsequent accumulation of vitelliform material gradually resolved over an 8 month follow up.

The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor axons intermingled with outer Müller cell processes. The photoreceptor axons extend from the cell bodies located in the outer nuclear layer and radially project toward the outer plexiform layer, the inner third of which includes the synaptic junctional complexes and the outer two-thirds of which includes the HFL. The oblique path of the HFL provides unique structural and reflectance properties and this radial anatomy is highlighted in many macular disorders including those with macular star exudation and HFL hemorrhage. Recent investigations using multimodal imaging techniques, especially cross sectional and en face optical coherence tomography (OCT), have provided new perspectives regarding HFL disruption in retinal diseases. The aim of this review is to highlight the pathoanatomy and multimodal imaging, especially OCT, associated with HFL disruption that is present in various macular diseases. After describing the current knowledge of the embryology, anatomy, and physiology of the HFL, we review the existing imaging modalities that allow in vivo visualization of the HFL in the healthy and diseased retina. Finally, we report the clinical and imaging findings of acute HFL alteration in various macular disorders, including degenerative, inflammatory, and vascular conditions. Also, we propose a novel and signature OCT biomarker indicative of acute photoreceptor disruption involving the HFL, termed the "angular sign of HFL hyperreflectivity" (ASHH) of macular disease, to unify the pathoanatomy common to these various macular disorders and to provide clarity regarding the underlying pathogenesis.

PURPOSE/OBJECTIVE:To describe the multimodal imaging findings of extensive choroidal caverns within a choroidal nevus in an eye with pachychoroid spectrum disease. METHODS:A 69 year-old woman was referred with a known history of branch retinal vein occlusion (BRVO) in the right eye and choroidal nevus in the left eye. Fundus examination of both eyes (OU) revealed subretinal yellow deposits, suggestive of pachydrusen. Retinal venous collaterals were noted in the temporal macular of the right eye. A lightly pigmented choroidal lesion with nearly confluent overlying drusen and retinal pigment epithelial (RPE) alterations, consistent with chronic choroidal nevus, was noted in the macula of the left eye. RESULTS:Optical coherence tomography B-scans revealed thickened choroid (pachychoroid) with subfoveal choroidal thickness of 504 and 580 µm with large hyporeflective spaces suggestive of pachyvessels OU. In the region of the choroidal nevus, the choroidal vascular spaces appeared comparatively large and were classified as "caverns", measuring up to 480 µm in diameter. OCT angiography (OCTA) and indocyanine green angiography (ICGA) demonstrated absence of flow within the caverns. ICGA further illustrated choroidal vascular hyperpermeability with patchy hyperfluorescent areas OU. Widefield swept source OCT showed mild posterior scleral bowing, a feature occasionally documented with choroidal nevus, and highlighted greater hyporeflectivity and hypertransmission on OCT within the caverns compared to the non-cavernous choroidal vessels. CONCLUSION/CONCLUSIONS:Choroidal caverns can occur within choroidal nevus in the setting of pachychoroid disease.

AIMS/OBJECTIVE:(1) To assess the morphology and 3-dimensional (3D) displacements of the eye globe and optic nerve (ON) in adduction/abduction using MRI. (2) To assess differences between healthy emmetropic and highly myopic (HM) subjects. METHODS:MRI volumes of both eyes from 18 controls and 20 HM subjects in primary gaze, abduction and adduction (15°) were postprocessed. All ONs were manually segmented and fitted to a 3D curve to assess ON tortuosity. ON displacements were evaluated in four quasicoronal planes which were perpendicular to the ON in primary gaze and were 3 mm apart. RESULTS:Axial length was higher in the HM group (28.62±2.60 vs 22.84±0.89 mm; p<0.0001). Adjusted ON tortuosities (ie, ON tortuosities estimated before myopia onset) were lower in HM eyes (0.9063±0.0591) versus controls (1.0152±0.02981) in primary gaze, adduction (0.9023±0.05538 vs 1.0137±0.0299) and abduction (0.9100±0.0594 vs 1.0182±0.0316); p<0.0001 for all cases. In all eyes, ON displacements in adduction were significantly different from those in abduction in the naso-temporal direction (p<0.0001 in all planes) but not in the supero-inferior direction. ON displacements in the posterior segments of the ON were smaller in the HM group in both gaze directions and were larger in the anterior-most ON segment in adduction only. CONCLUSION/CONCLUSIONS:The adjusted tortuosity of the ON was significantly lower in HM eyes, suggesting that eyes destined towards HM exhibited higher ON traction forces during eye movements before the onset of myopia. Our ON metrics may be valuable to explore a potential link between eye movements and axial elongation.