Abstract
Purpose :
To develop a deeper understanding of the progression of Retinitis Pigmentosa (RP), for the successful design of clinical trials assessing novel therapeutics.
Methods :
PHENOROD2 is an ongoing prospective, multicentric, natural history study documenting functional and structural changes in patients with RP due to mutations in RHO, PDE6A, or PDE6B. An interim analysis was performed at baseline and 12 months in the first 44 patients enrolled at the national reference center for rare diseases (REFERET) of the Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts (Paris, France). One patient was lost to follow-up and was excluded from the analysis. Population demographics, visual acuity (VA), and kinetic visual field (V4e) were analyzed in the entire cohort and per genotype.
Results :
Out of 43 patients, 32 (75%) carried a mutation in RHO, 7 (16%) in PDE6A, and 4 (9%) in PDE6B. Mean age at inclusion was 46 (12.2) years, and gender distribution was 53.5% males, 46.5% females.
At baseline, VA ranged between 20/13 and 20/800, with a mean of 0.14 (0.19) LogMAR (20/28) and 0.17 (0.22) LogMAR (20/30) in OD and OS, respectively. At 12 months, no significant changes were reported, although subjects with PDE6 variants showed a slight trend towards mild VA loss (+0.08 and +0.04 LogMAR in OD and OS, respectively).
At baseline, a mean visual field area of 5,532.4 (5,151.9) mm2 was reported in both eyes of all patients (6,320.6 mm2 in RHO patients, 2,675.2 mm2 in PDE6A patients, and 4,226.9 mm2 in PDE6B patients). At 12 months, a mean loss of -345.8 (1,572.8) mm2 (-6.3%) was observed in all patients: -323.2 mm2 (-5.1%) in RHO patients, -591.6 mm2 (-22.1%) in PDE6A patients, and -96.85mm2 (-2.3%) in PDE6B patients.
The small numbers of PDE6A and PDE6B patients did not allow for statistical analysis across groups.
Conclusions :
Virtually no decrease in VA was observed after 12 months of follow-up in this population of patients with relatively spared VA at baseline, in alignment with the documented natural history of RP. However, a loss of visual field was reported over the same period. This suggests that visual field assessment may be more appropriate to monitor disease progression in the early stages. Future interim analyses including the entire PHENOROD2 cohort will help validate these preliminary observations.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.