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], 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.
To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms.Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up.Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy.Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.
