Abstract
Purpose :
To better understand the natural history of cone and rod degeneration in patients with Retinitis Pigmentosa (RP) carrying mutations in the RHO, PDE6A, and PDE6B genes.
Methods :
PHENOROD1 was a longitudinal retrospective study carried out at the national reference center for rare diseases (REFERET) at the Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts (Paris, France). A total of 110 patients with RP due to mutations in RHO, PDE6A, or PDE6B were enrolled, and the following parameters were collected from their medical records: best-corrected visual acuity (BCVA), binocular kinetic visual field (VF) (III4e), retinal sensitivity, color vision, full-field electroretinogram, optical coherence tomography, and fundus autofluorescence imaging. Differences between genotypic groups were analyzed using ANOVA, and the progression rates were estimated using a mixed error-component model.
Results :
A total of 75 (68%) patients carried a mutation in RHO, 14 (13%) in PDE6A, and 21 (19%) in PDE6B. Mean age at onset was 23.4, 13.9, and 16.2 years in RHO, PDE6A and PDE6B patients, respectively (p>0.1).
There were no significant differences between genotypes with regard to the presentation of initial symptoms (night blindness and VF restriction), BCVA progression rates (on average +0.01 LogMAR per year in both eyes), and preservation of the ellipsoid zone.
In contrast, the evolution of VF and area of preserved autofluorescence between the ages of 20 and 60 was statistically different between genotypes, with a slower decline observed in the PDE6B group.
Interestingly, BVCA remained stable until ~40 years of age before starting to decline, while the inflection point for VF occurred earlier, in the patient’s third decade.
Conclusions :
The analysis of functional and structural visual parameters allowed to better define the natural history of rod-cone dystrophy according to underlying genotypes. This is of particular interest for the selection of patients in the development of photoreceptor rescue treatments such as SPVN06, a novel dual gene therapy based on the expression of neurotrophic factor RdCVF and thioredoxin RdCVFL, both encoded by the nucleoredoxin-like 1 gene.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.