Faculty Bibliography

Purpose/UNASSIGNED:To explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy. Methods/UNASSIGNED:There were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared reflectance, fluorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness. Results/UNASSIGNED:SDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 ± 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% confidence interval [CI] 1.1-8.5, P = 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular fields at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0-8.9, P = 0.0461 and 95% CI 1.3-32.4, P = 0.0218, respectively). MA development was not associated with a specific SDD phenotype. Conclusions/UNASSIGNED:MA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular field, conferred higher odds of subsequent MA development.

PURPOSE: To investigate the tractional alterations of the central bouquet (CB) in idiopathic epiretinal membranes (ERMs). DESIGN: Retrospective, consecutive, observational case series. METHODS: ERMs were classified according to a 4-stage grading system. The CB was defined as a circular area of approximately 100 mum composed of densely packed cones (and Muller cells) in the central fovea. Tractional abnormalities of the CB were identified with spectral-domain optical coherence tomography. Ex vivo histopathologic analysis was performed. RESULTS: In this study 263 eyes with ERMs were included. Mean follow-up was 21.2 +/- 16.7 months. At baseline, tractional abnormalities of the CB were diagnosed in 58 out of 263 eyes (22%) and divided into 3 categories: cotton ball sign (defined as a fuzzy hyperreflective area between the ellipsoid zone and the interdigitation zone in the central fovea), foveolar detachment, and acquired vitelliform lesion. The presence of ectopic inner foveal layers was negatively correlated with the presence of CB tractional abnormalities (P = .002). Visual acuity was highest in association with the cotton ball sign and lowest in the acquired vitelliform lesion group. Sequential morphologic progression was identified in 7 eyes. Ex vivo histopathologic analysis illustrated characteristic staining patterns supporting a potential mechanism of traction by Muller cells in the CB. CONCLUSIONS: The cotton ball sign, foveolar detachment, and acquired vitelliform lesion may comprise a continuum in the same clinical spectrum and may represent subsequent stages of CB abnormalities. Foveal Muller cells may play an integral role in the transmission of mechanical forces to the central foveal cones.

PURPOSE/OBJECTIVE:To expand our understanding of the uncommon entity, referred to as perifoveal exudative vascular anomalous complex (PEVAC) by describing multimodal imaging findings, including optical coherence tomography angiography (OCT-A). DESIGN/METHODS:Retrospective cohort study. METHODS:Patients diagnosed with PEVAC were identified at 4 retina referral centers worldwide and underwent complete ophthalmologic examination including structural OCT, OCT-A, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Demographics and clinical findings were analyzed at baseline and at available follow-ups. RESULTS:Fifteen eyes (15 patients, mean age 73 ± 13 years) were included. Six of 15 eyes were diagnosed with coincident age-related macular degeneration (AMD) and 2 with myopic macular degeneration. On fundus examination PEVAC presented as a large perifoveal isolated aneurysm, unifocal in 12 of 15 eyes, associated with small retinal hemorrhages and intraretinal exudation. On structural OCT, PEVAC appeared as a round hyperreflective lesion with hyporeflective lumen, typically surrounded by intraretinal cystic spaces. Dye angiography demonstrated a well-defined hyperfluorescent lesion with variable leakage on FA and without leakage on ICGA. OCT-A showed flow signal correlating with the aneurysmal lesion connecting to retinal capillary plexuses. Seven patients were followed for 13.0 ± 10.5 months with no evidence of functional/anatomic changes. Three patients underwent anti-vascular endothelial growth factor (VEGF) intravitreal injections without improvement. Two eyes were associated with a type 3 neovascularization eccentric to PEVAC. CONCLUSIONS:PEVAC is an isolated, perifoveal, aneurysmal abnormality, occurring in otherwise healthy patients who may manifest other macular disease including AMD and myopic macular degeneration. PEVAC did not typically respond to anti-VEGF therapy, and may be associated with type 3 neovascularization.

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 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.