Abstract
Purpose:
Late-onset retinal degeneration (L-ORD) is a monogenic disease involving C1QTNF5 which is expressed primarily in the RPE and ciliary epithelium. Here we report longitudinal changes of patients with early stage L-ORD disease to document structural changes that may shed light on the pathogenesis of this disease.
Methods:
Two siblings with the S163R missense change in C1QTNF5 were followed with full ophthalmoscopic examinations and fundus imaging over the course of 8+ years (through ages 45-53 and 50-59) during early stages of L-ORD disease. Color fundus photos, fundus autofluorescence (FAF), infrared reflectance (IR) fundus images and spectral domain optical coherence tomography (SD-OCT) scans were acquired over the years of followup.
Results:
Both participants had visual acuities better than 20/20 OU throughout their follow up time and a history of prolonged dark adaptation. In both participants, color fundus photography revealed yellow-white, round, punctate lesions of regular size and shape located broadly in the temporal macula. These same areas on FAF imaging corresponded to hypoautofluorescent spots on a mildly hyperautofluorescent background, some of which appear halo-like and on IR imaging, the lesions have hyperreflectant cores with hyporeflectant surrounds. OCT scans through these lesions reveal subretinal deposits that resemble reticular pseudodrusen described in the setting of age-related macular degeneration (AMD). Longitudinal OCT analysis of L-ORD disease reveals that these lesions with subretinal deposits initially occur in the setting of preserved ellipsoid zones and these progress to areas of RPE thickening and detachment with ellipsoid zone disruption, and then eventually to overt RPE and outer retinal atrophy. Longitudinal fundus imaging demonstrated the lesions to spread from temporal macula to macular areas superior, inferior, and nasal to the fovea.
Conclusions:
This current study showed novel characteristic clinical findings in in two siblings with early stages of L-ORD based on multi-modal imaging followed over several years. Subretinal lesions, resembling reticular pseudodrusen seen in AMD, eventually lead to ellipsoid zone disruption, RPE thickening and later overt RPE and outer retinal atrophy. The longitudinal, in vivo imaging of L-ORD starting with early stages of disease suggests a pathway of retinal degeneration that may be common to several retinal diseases of different etiologies.