Abstract
Purpose :
Rod-cone dystrophy (RCD) is a rare inherited retinal disorder leading to significant vision loss, and for which no treatment is currently available to most patients. Photoreceptor degeneration progresses unevenly and slowly over decades, making it hard to assess investigational drugs aiming at delaying or stopping photoreceptor degeneration. PHENOROD2 is an ongoing prospective natural history study assessing RCD progression, to help select relevant clinical efficacy endpoints for the evaluation of novel therapies.
Methods :
Adult patients with RCD caused by a variant in the RHO, PDE6A, or PDE6B gene were enrolled in Paris, France and Pittsburgh, PA, USA. At inclusion, visual acuity had to be ≥ 20/200 (1.0 LogMAR) in at least one eye, and binocular visual field ≥ 5° (as measured on the III4e isopter). Retinal anatomy was imaged by spectral-domain optical coherence tomography (Spectralis, Heidelberg) and short-wavelength fundus autofluorescence (Heidelberg Retina Angiograph HRA2), at inclusion and Year 1. A ‘progressor’ eye was defined as having lost at Year 1 more than -110 µm or -9% in either the horizontal width of the ellipsoid zone (hEZ), or the horizontal or vertical diameters of the inner ring of autofluorescence (hFAF or vFAF).
Results :
A total of 83 patients were included, 82 completed their baseline assessment, and 80 were assessed at Year 1. At inclusion, mean (SD) age was 47.4 (12.8) years and patient-reported disease duration ranged from 5 to 61 years. On average, hEZ was 1939 (1267) µm, hFAF was 1886 (808) µm, and vFAF was 1530 (680) µm. At Year 1, mean change from baseline was -105.6 (121.6) µm for hEZ, -108.5 (147.6) µm for hFAF, and -85.2 (125.7) µm for vFAF, representing a mean loss of -7.4 (9.5) %, -6.7 (9.1) %, and -6.9 (10.1) %, respectively. Among the 131 eyes for which a change from baseline was available in at least one of the 3 parameters of interest, 89 (68%) were progressors at Year 1, representing 61/70 (87%) patients; and 40 (31%) eyes showed a loss of more than twice the threshold of progression, representing 33 (47%) patients.
Conclusions :
After one year of prospective follow-up, markers of retinal degeneration showed progression above the thresholds of test-retest, inter-reader variability, and significant change, in a majority of patients with RCD.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.