Faculty Bibliography

PURPOSE: Subretinal drusenoid deposits (SDD) are the main structural lesion of reticular macular disease (RMD), a phenotype of age-related macular degeneration (AMD). We aim to demonstrate spatiotemporal relationships between SDD and choroidal thickness (CTh) alterations in RMD+ and RMD- eyes. METHODS: Thirty-three eyes (26 subjects) with early AMD/no SDD (RMD-) and 18 eyes (16 subjects) with early AMD/SDD (RMD+) underwent enhanced depth imaging spectral domain optical coherence tomography (SD-OCT) for CTh measurements at 11 points per scan, in 5 horizontal B scans, creating a grid of 55 points/eye. The 55 points were treated as a cluster, controlling within-subject correlation. Marginal generalized estimating equation modeling was used to estimate the association between CTh and RMD status. All eyes were divided by their median age (82 years) for stratified analyses. RESULTS: CTh was not significantly reduced in RMD+ eyes compared with RMD- eyes (mean difference [MD] -16.84 mum, P = 0.24). Among younger subjects, mean CTh was significantly reduced in RMD+ versus RMD- eyes (MD -53.72 mum, P = 0.01). Conversely, among older subjects, there was no significant difference in CTh between RMD+ and RMD-. CONCLUSIONS: In RMD, the association of SDD and CTh alterations varies with age but not by macular region. Among younger subjects (<82 years old), CTh was significantly thinner in RMD+ versus RMD- eyes.

PURPOSE: To determine if the area of the foveal avascular zone (FAZ) is correlated with visual acuity (VA) in diabetic retinopathy (DR) and retinal vein occlusion (RVO). DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-five eyes of 66 subjects with DR (65 eyes), branch retinal vein occlusion (19 eyes), and central retinal vein occlusion (11 eyes). METHODS: Structural optical coherence tomography (OCT; Spectralis, Heidelberg Engineering) and OCT angiography (OCTA; Avanti, Optovue RTVue XR) data from a single visit were analyzed. FAZ area, point thickness of central fovea, central 1-mm subfield thickness, the occurrence of intraretinal cysts, ellipsoid zone disruption, and disorganization of retinal inner layers (DRIL) length were measured. VA was also recorded. Correlations between FAZ area and VA were explored using regression models. Main outcome measure was VA. RESULTS: Mean age was 62.9+/-13.2 years. There was no difference in demographic and OCT-derived anatomic measurements between branch retinal vein occlusion and central retinal vein occlusion groups (all P >/= 0.058); therefore, data from the 2 groups were pooled together to a single RVO group for further statistical comparisons. Univariate and multiple regression analysis showed that the area of the FAZ was significantly correlated with VA in DR and RVO (all P /= 0.210). Remaining variables evaluated in this study were not predictive of VA (all P >/= 0.225). CONCLUSIONS: The area of the FAZ is significantly correlated with VA in DR and RVO and this relationship is modulated by patient age. Further study about FAZ area and VA correlations during the natural course of retinal vascular diseases and following treatment is warranted.

Purpose: Drusenoid pigment epithelial detachments (PEDs) are a defined path to atrophy in age-related macular degeneration (AMD). We analyzed the relationships between retinal pigment epithelium (RPE) and drusen volume changes during the PED lifecycle, using spectral-domain optical coherence tomography (SD-OCT). Methods: Twenty-one cases of drusenoid PED tracked using SD-OCT through periods of growth and collapse were evaluated. Volumetric calculations and piece-wise linear regression analysis were used to determine the breakpoint between growth and collapse. Spectral-domain OCT scans were independently evaluated for the appearance of intraretinal hyperreflective foci, acquired vitelliform lesions (AVLs), and disruptions to the RPE+basal lamina band. Timing of these events with respect to the breakpoint was statistically evaluated. Morphometric characteristics of drusenoid PEDs were correlated with rate of PED collapse and final visual acuity. Results: Mean age of subjects was 75.3 years and mean period of follow up was 4.1 years (median 4.5 years; range, 0.6-6.6 years). The lifecycle of drusenoid PEDs was asymmetric, in that the rate of collapse (0.199 mm3/month) is significantly faster (P < 0.001) than the rate of growth (0.022 mm3/month). Appearance of intraretinal hyperreflective foci and AVLs preceded the breakpoint (both P < 0.001). The timing of disruptions to the RPE+basal lamina band did not differ from the breakpoint (P = 0.510). Maximal height, volume, and diameter of drusenoid PEDs were inversely correlated with final visual acuity (all P < 0.001) and positively correlated with the rate of PED collapse (all P < 0.001). Conclusions: Spectral-domain OCT signatures, plausibly attributable to anteriorly migrated RPE and disintegration of the RPE layer, precede or occur simultaneously with changes in volume of drusenoid PED during the lifecycle of this lesion.

Purpose: We used fractal dimensional analysis to analyze retinal vascular disease burden in eyes with diabetic retinopathy using spectral-domain optical coherence tomography angiography (OCTA). Methods: A retrospective study was performed of 13 eyes with diabetic retinopathy without diabetic macular edema and 56 control eyes. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti. Automated segmentation was obtained through the superficial and deep capillary plexuses for each eye. Grayscale OCTA images were standardized and binarized using ImageJ. Fractal box-counting analyses were performed using Fractalyse. Fractal dimensions (FD) as well as software-generated vascular density analyses of the superficial and deep capillary plexuses were compared between diabetic and control eyes using 2-tailed t-tests and 1-way multivariate ANOVA (MANOVA) analyses. Results: The superficial and deep plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than control eyes for the superficial (P = 4.513 x 10-3) and deep (P = 2.653 x 10-3) capillary plexuses. In diabetic eyes, the vascular density also was significantly reduced in the superficial (P = 8.068 x 10-5) and deep (P = 3.120 x 10-6) capillary plexuses. One-way MANOVA showed a significant difference between diabetic and control eyes. Conclusions: The OCTA FD is significantly reduced in the superficial and deep capillary plexuses in eyes with diabetic retinopathy. Applying fractal analysis to OCTA imaging holds the potential to establish quantitative parameters for microvascular pathology.

PURPOSE: The range of subretinal hyperreflective material (SHRM) seen in macular disease includes type 2 macular neovascularization, fibrosis, exudation, vitelliform material and hemorrhage. The prognostic significance of SHRM has been evaluated retrospectively in clinical trials but discriminating SHRM subtypes traditionally requires multiple imaging modalities. The purpose of this study is to describe optical coherence tomography angiography (OCTA) flow characteristics and artifacts which might help to distinguish SHRM subtypes. DESIGN: Validity analysis. METHODS: Patients with age-related macular degeneration (AMD), myopia, pachychoroid disease and macular dystrophy, manifesting SHRM on optical coherence tomography (OCT), were recruited. Clinical chart review and multimodal imaging established the SHRM subtype. All patients underwent OCTA (RTVue XR, Optovue). OCT and OCTA images were examined together for i) intrinsic flow, ii) retinal projection onto the anterior SHRM surface (strong, weak, absent), iii) retinal projection through SHRM onto retinal pigment epithelium (RPE), iv) masking of choriocapillaris flow. RESULTS: Thirty-three eyes of 25 patients were included (type 2 neovascularizationx3; fibrosisx4; exudationx10; hemorrhagex5; vitelliformx17). Mean age per eye was 76 years (SD: 12). Intrinsic flow was strongest in type 2 neovascularization. Subretinal fibrosis showed limited flow in residual large caliber vessels and branches. Flow was not detected within foci of exudation, hemorrhage or vitelliform lesions. Retina-SHRM surface projection was strongest onto smooth surfaced SHRM and weaker onto exudation. Retinal projection was weakest on the surface of vitelliform lesions. Retina-RPE projection was masked by dense hemorrhage and vitelliform material. In compound SHRM, OCTA distinguished between vascular and avascular components. CONCLUSION: Optical coherence tomography angiography can distinguish vascular from avascular SHRM components. OCTA artifacts may distinguish certain avascular SHRM components.

Acute macular neuroretinopathy (AMN) is a relatively rare condition originally defined by the presence of intraretinal, reddish-brown, wedge-shaped lesions, the apices of which tend to point towards the fovea. Acute onset of paracentral scotomas corresponding to the clinically evident lesions is both common and characteristic. While the pathogenesis of AMN is complex, recent research suggests a microvascular etiology. Advances in multimodal imaging have enabled better characterization of this retinal disorder and have led to newly proposed diagnostic criteria. We review 101 reported cases in the English and non-English language literature identified from 1975, when AMN was first described, to December, 2014. We discuss common risk factors, demographic and clinical characteristics, and multimodal imaging findings, which together provide insights into pathogenesis and guide areas of future investigation.