Purpose: To quantitatively analyze clinically relevant features on longitudinal multimodal imaging of late-onset retinal degeneration to characterize disease progression.Methods: Fundus autofluorescence (FAF), infrared reflectance, and optical coherence tomography imaging of 4 patients with late-onset retinal degeneration were acquired over 3 to 15 years (20 visits total). Corresponding regions of interest were analyzed on FAF (reticular pseudodrusen [RPD], "speckled FAF," and chorioretinal atrophy) and infrared reflectance (hyporeflective RPD and target RPD) using quantitative measurements, including contour area, distance to fovea, contour overlap, retinal thickness, and texture features.Results: Cross-sectional analysis revealed a moderate correlation (RPD FAF \ RPD infrared reflectance = 63%) between contour area across modalities. Quantification of retinal thickness and texture analysis of areas contoured on FAF objectively differentiated the contour types. A longitudinal analysis of aligned images demonstrates that the contoured region of atrophy both encroaches toward the fovea and grows monotonically with a rate of 0.531 mm/year to 1.969 mm/year (square root of area, n = 5 eyes). A retrospective analysis of precursor lesions of atrophy reveals quantifiable progression from RPD to speckled FAF to atrophy.Conclusion: Image analysis of time points before the development of atrophy reveals consistent patterns over time and space in late-onset retinal degeneration that may provide useful outcomes for this and other degenerative retinal diseases.

Purpose: To describe longitudinal multimodal imaging findings of nonexudative choroidal neovascularization in CTRP5 late-onset retinal degeneration. Methods: Four patients with CTRP5-positive late-onset retinal degeneration underwent repeated ophthalmoscopic examination and multimodal imaging. All four patients (two siblings and their cousins, from a pedigree described previously) had the heterozygous S163R mutation. Results: All four patients demonstrated large subretinal lesions in the mid-peripheral retina of both eyes. The lesions were characterized by confluent hypercyanescence with hypocyanescent borders on indocyanine green angiography, faintly visible branching vascular networks with absent/minimal leakage on fluorescein angiography, Type 1 neovascularization on optical coherence tomography angiography, and absent retinal fluid, consistent with nonexudative choroidal neovascularization. The neovascular membranes enlarged substantially over time and the birth of new membranes was observed, but all lesions remained nonexudative/minimally exudative. Without treatment, all involved retinal areas remained free of atrophy and subretinal fibrosis. Conclusion: We report the existence of massive advancing nonexudative Type 1 choroidal neovascularization in CTRP5 late-onset retinal degeneration. These findings have implications for age-related macular degeneration. They provide a monogenic model system for studying the mechanisms underlying the distinct events of choroidal neovascularization development, enlargement, progression to exudation, and atrophy in age-related macular degeneration. They suggest that choroidal hypoperfusion precedes neovascularization and that nonexudative neovascularization may protect against atrophy.