Faculty Bibliography

PURPOSE: To describe atypical cases of multiple evanescent white dot syndrome (MEWDS) associated with foveal exudation, increased choroidal thickness, and secondary Type 2 (subretinal) neovascularization. METHODS: Four cases of atypical MEWDS were studied at a retina referral center. Patients underwent evaluation with multimodal retinal imaging, including fluorescein angiography, indocyanine green angiography, spectral-domain and enhanced depth imaging optical coherence tomography (OCT). Two patients were imaged with OCT angiography. RESULTS: Four patients (3 female, 1 male) with a median age of 23.5 years presented with acute onset, painless, decreased central vision. All cases demonstrated fundus findings consistent with MEWDS on color photography, indocyanine green angiography, fluorescein angiography, fundus autofluorescence, and structural OCT imaging. On structural OCT, all 4 patients were noted to have hyperreflective subretinal material and increased subfoveal choroidal thickness ranging from 307 mum to 515 mum. Type 2 neovascularization was diagnosed in all four patients using fluorescein angiography, indocyanine green angiography, and/or OCT angiography. Two patients had poor visual acuity at the last follow-up despite resolution of characteristic clinical findings of MEWDS. CONCLUSION: A subset of patients with atypical MEWDS may develop persistent poor vision due to subfoveal exudation and secondary Type 2 neovascularization. Patients showing increased choroidal thickness at presentation may be more susceptible to this unusual presentation.

PURPOSE: To describe two patients who showed full-thickness macular holes (FTMH) combined with pigment epithelial detachments (PED) and had contrasting outcomes to treatment. METHODS: A retrospective report of two cases. RESULTS: Case 1 was treated with intravitreal antivascular endothelial growth factor and photodynamic therapy, and the PED flattened. Subsequently, a vitrectomy was performed and the FTMH closed. Her visual acuity improved from 20/200 to 20/25. In Case 2, the same medical therapy, with less frequency compared with Case 1, did not affect the PED, and the FTMH failed to close with surgery. Later, a spontaneous collapse of the PED occurred but the FTMH was persistent with an associated poor visual acuity of 20/200. CONCLUSION: Full-thickness macular hole is rare, but can occur in association with large PEDs. Although the pathologic mechanism was uncertain, visual outcomes were dependent on response to treatments of the PED, as well as anatomical closure of the FTMH.

PURPOSE: To demonstrate unusual retinal findings in a patient with progressive renal failure due to idiopathic monoclonal immunoglobulin light chain deposition disease, using multimodal imaging. METHODS: Observational case report of a 43-year-old white man with renal failure due to light chain deposition disease. His course over 6 years was documented with multimodal imaging including fundus photography, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography. Additional evaluations included ocular ultrasound, electroretinography, positron emission tomography, serum protein electrophoreses, skeletal surveys to detect osteolytic lesions, and renal, liver, and rectal biopsies in search of amyloid. RESULTS: The patient's ocular course mirrored the severity of his renal dysfunction for which he required a renal transplant. Changes observed in the native kidney recurred in the transplant 2 years later, as evidenced by immunohistochemistry, revealing thick linear deposits of kappa chains, with no complement, overlying the glomerular basement membrane. The systemic workup was negative for amyloid but showed an overwhelming ratio of kappa to lambda light chains on serum protein electrophoreses and no clinical signs of plasma cell dyscrasias, all consistent with idiopathic light chain deposition disease. The patient presented with a generalized, bilateral "leopard-spot" fundus appearance on fundus autofluorescence, striking globular subretinal deposits on spectral domain optical coherence tomography, and subfoveal subretinal fluid without retinal pigment epithelium detachment or choroidal effusions. The subfoveal fluid did not respond to intravitreal injections of antiangiogenic agents or steroids but resolved after renal transplantation. A temporary posttransplant visual improvement was associated with lessening of the subretinal drusenoid deposits demonstrated by multimodal imaging. The terminal vision deterioration was associated with amorphous, vitelliform-like material deposition and atrophic changes. CONCLUSION: This case may illustrate a resemblance in the renal glomerulus basement membrane and retinal pigment epithelium-Bruch membrane complex, because the authors observed deposits of excess monoclonal kappa chains manifesting as extracellular, proteinaceous aggregates on the basement membrane of the glomerulus, and striking, globular subretinal deposits that overlay a thickened retinal pigment epithelium-Bruch membrane complex. The ocular lesions' refractoriness to intravitreal treatments could be attributed to the fact that they represent proteinaceous aggregates similar to those documented in the glomeruli. This is the first report of generalized, large, subretinal drusenoid deposits and their course, as documented through multimodal imaging, paralleling the chronology of systemic changes in a patient with light chain deposition disease.

PURPOSE/OBJECTIVE:The authors describe a woman diagnosed with hemophagocytic lymphohistiocytosis and found to have retinal examination findings consistent with Purtscher retinopathy. METHODS:A 52-year-old woman underwent multimodal imaging, including color fundus photography and spectral-domain optical coherence tomography, to confirm the diagnosis. RESULTS:The ophthalmic examination and imaging confirmed the findings of Purtscher retinopathy with significant inner retinal thickening on spectral-domain optical coherence tomography. Throughout a hospital course complicated by multi-organ failure, she continued to have profoundly limited visual acuity, likely resulting from inner retinal ischemia affecting the posterior pole of both eyes. CONCLUSION/CONCLUSIONS:The authors describe a patient with hemophagocytic lymphohistiocytosis, a disease characterized by disruption of normal natural killer cell activity with subsequent uncontrolled cytokine release, who presented with Purtscher retinopathy confirmed with spectral-domain optical coherence tomography.

PURPOSE: To evaluate the spectrum of macular chorioretinal lesions occurring in idiopathic multifocal choroiditis using optical coherence tomography angiography (OCTA) to evaluate those showing neovascular flow. METHODS: This was a descriptive, retrospective study of 18 eyes of 14 patients with multifocal choroiditis. Macular lesions were characterized as subretinal pigment epithelium, subretinal, or mixed and evaluated during active and presumed inactive states of multifocal choroiditis. Correlations between structural optical coherence tomography and OCTA were performed. In select cases, correlations between OCTA, fluorescein angiography, and fundus autofluorescence were evaluated. In 5 eyes, quantitative measurements of neovascular lesions were compared at baseline and following intravitreal anti-vascular endothelial growth factor therapy. RESULTS: Mean patient age was 48 years (SD: 13.8; 86% women). Optical coherence tomography angiography flow signatures consistent with neovascularization were identified in 83% of eyes, including in 0% of subretinal pigment epithelium, 91% of subretinal, and 100% of mixed lesions. Lesions that did not demonstrate definitive signs of fluorescein angiography leakage were frequently found to have neovascularization using OCTA. There was no change in quantitative measurements of neovascular lesions after anti-vascular endothelial growth factor therapy (all tested variables P > 0.05). CONCLUSION: Optical coherence tomography angiography may be a useful imaging modality for understanding the pathophysiology of multifocal choroiditis and monitoring its clinical course.

PURPOSE: To report the clinical features of bilateral Coats reaction in a patient with Bannayan-Zonana syndrome. METHODS: The clinical course and retinal manifestations of a 21-year-old patient with Bannayan-Zonana syndrome and bilateral Coats reaction were studied. Retinal manifestations were documented with clinical examination, ultrawide-field color imaging, and ultrawide-field fluorescein angiography. RESULTS: Best-corrected visual acuities were 20/25 OD and 20/25 OS. Anterior segment examinations were normal bilaterally. The inferotemporal quadrant of the left retina demonstrated retinal telangiectasias, exudation, and a neurosensory retinal detachment extending to the mid-periphery. Fluorescein angiography demonstrated bilateral peripheral nonperfusion and vascular staining. An epiretinal membrane also involved the left macula. CONCLUSION: Bannayan-Zonana syndrome is an autosomal-dominant, hamartomatous disease characterized by a mutation spectrum that involves genes responsible for vascular development. Retinal vascular abnormalities and exudation can be a manifestation of this syndrome.

Purpose: Perifoveal Exudative Vascular Anomalous Complex (PEVAC) is an uncommon disease recently described by our group as a unilateral, isolated, single, perifoveal, large aneurismal change. It generally affects otherwise healthy patients that do not show evidence of arterial hypertension, diabetes or any other vasculopathy. We reviewed the charts of patients with diagnosis of PEVAC to report their imaging features on optical coherence tomography angiography (OCT-A). Methods: All patients affected by PEVAC were identified from a pool of patients at 4 retina referral centers. The main exclusion criteria were the presence of retinal vascular diseases (e.g. diabetic retinopathy, hypertension retinopathy, retinal vein occlusion and retinal inflammatory diseases). All patients underwent a complete ophthalmologic examination including structural optical coherence tomography (OCT) and OCT-A (3x3 area). All OCT-A imagines were analyzed by two trained examiners (GQ and RS) to investigate the qualitative features of PEVAC. Results: A total of 12 eyes of 12 patients were included in the analysis. In 11 out of 12 cases, PEVAC was located inside 500 mum from the center of the fovea. In all cases, OCT-A showed an isolated large dilation in the retinal capillary plexuses, with a detectable flow inside the complex. Typically, PEVAC was characterized by a rarefaction of retinal capillaries surrounding the lesion. Three out of 12 cases were detected only in superficial retinal plexus, 2 out of 12 only in deep retinal plexus and 7 out of 12 in both superficial and deep retinal plexuses. In all cases there was no sign of flow in the avascular plexus and no sign of anastomosis between the retinal capillary plexuses and the choriocapillaris; a shadow effect was constantly present in the choriocapillaris segmentation. No other macular abnormalities were present on OCTA outside the area of the lesion. Conclusions: Optical coherence tomography angiography of PEVAC showed almost constantly a high-flow, isolated large dilation in the retinal vascularization associated with a surrounding rarefaction of normal retinal capillaries

PURPOSE: Drusenoid pigment epithelium detachment (DPED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histologic correlates for spectral-domain (SD) optical coherence tomography (OCT) signatures in DPED and determined the frequency and origin of these OCT signatures in a clinical cohort of DPED eyes. DESIGN: Laboratory imaging and histologic comparison, and retrospective, observational cohort study. PARTICIPANTS: Four donor eyes with histopathologic diagnosis of AMD (2 with nonneovascular DPED and 2 with neovascular pigment epithelium detachment [PED]) and 49 eyes of 33 clinic patients with nonneovascular DPED more than 2 mm in diameter. METHODS: Donor eyes underwent multimodal ex vivo imaging, including SD OCT, then processing for high-resolution histologic analysis. All clinic patients underwent SD OCT, near-infrared reflectance, and color photography. MAIN OUTCOME MEASURES: Histologic correlates for SD OCT signatures in DPED, estimate of coverage by different retinal pigment epithelium (RPE) phenotypes in the DPED surface; frequency and origin of histologically verified SD OCT signatures in a clinical cohort of DPED eyes, and comparisons of histologic features between neovascular PED and DPED resulting from AMD. RESULTS: Intraretinal and subretinal hyperreflective foci as seen on SD OCT correlated to RPE cells on histologic examination. Hypertransmission of light below the RPE-basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material resulting from acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared with PEDs associated with neovascular AMD, DPEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits. CONCLUSIONS: Multiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be followed and quantified reliably using eye-tracked serial SD OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic end points and response to therapy in AMD clinical trials.

Purpose: Histologic details of progression routes to geographic atrophy (GA) in AMD are becoming available through optical coherence tomography (OCT). We studied the origins and evolution of an OCT signature called plateau in eyes with GA and suggested a histologic correlate. Methods: Serial eye-tracked OCT scans and multimodal imaging were acquired from eight eyes of seven patients with GA and plateau signatures over a mean follow-up of 7.7 years (range, 3.7-11.6). The histology of unrelated donor eyes with AMD was reviewed. Results: Drusenoid pigment epithelial detachment (PED) on OCT imaging progressed into wide-based mound-like signatures with flattened apices characterized by a hyporeflective yet heterogeneous interior and an overlying hyperreflective exterior, similar to outer retinal corrugations previously ascribed to persistent basal laminar deposit (BLamD) but larger. These new signatures are described as "plateaus." An initial increase of the PED volume and hyporeflectivity of its contents was followed by a decrease in PED volume and thinning of an overlying hyperreflective band attributable to the loss of the overlying RPE leaving persistent BLamD. Both imaging and histology revealed persistent BLamD with defects through which gliotic Muller cell processes pass. Conclusions: Plateaus can be traced back to drusenoid PEDs on OCT imaging. We hypothesize that during progressive RPE atrophy, Muller cell extension through focal defects in the residual persistent BLamD may contribute to the heterogeneous internal reflectivity of these entities. The role of Muller cell activation and extension in the pathogenesis of AMD should be explored in future studies.