Natural history of retinitis pigmentosa due to RHO, PDE6A OR PDE6B mutations

Abstract

Purpose : Very few studies focused on the progression of retinitis pigmentosa (RP) in patients with mutations in genes specifically expressed in rods and presenting a rod-cone dystrophy. We analyzed functional and structural changes in patients from a French cohort with mutations in RHO, PDE6A and PD6B that are specifically expressed in rods

Methods : We analyzed clinical data from medical records (between January 2007 and January 2019) of patients followed in the clinical investigation center 1423 CHNO XV-XX (Paris, France). Data were collected for 110 patients with evidence of mutations in RHO, PDE6A or PDE6B, with at least 2 visits, and no other condition impacting vision than RP. We analyzed the age and symptoms at the time of diagnosis, the personal and family history, visual acuity (BCVA), color vision alteration, visual field, full-field electroretinography, spectral-domain optical coherence tomography (SD-OCT), and short-wavelength fundus autofluorescence (SWAF) imaging for measuring the autofluorescent ring. Differences between genotypic groups were analyzed using ANOVA and the progression rate were estimated using a mixed error-component model.

Results : Progression rates of BVCA were not significantly different between the RHO, PDE6A and PDE6B genotypic groups (P = .402). Annual decline between 20 and 60 years of age was 2.95%, but BVCA remained constant until 40 years before it started to decline. Rates of VF (III4e) constriction were statistically different between RHO patients (-2.43°[0.27]) and PDE6A patients (-0.75°[0.86]; P=0.528) and PDE6B patients (-0.31°[0.27]; P=0.0043). Decline rates of structural parameters were not statistically different between the RHO, PDE6A and PDE6B genotypic groups: 1.78 % for the Ellipsoid Zone (EZ) (P =0 .5885) and 1.89 % for the horizontal diameter of the hyperfluorescent ring (P = 0.4881). Furthermore, correlation was found between EZ and the horizontal diameter (P = .95615).

Conclusions : The analysis of functional and structural parameters allowed to determine rates of progression and to identify the age range when photoreceptor degeneration is accelerated. This is of interest for a better definition of rod-cone dystrophy and selection of patients for photoreceptor rescue treatment, as the gene therapy under development based on the expression of the neurotrophic factor rod-derived cone viability factor (RdCVF).

This is a 2020 ARVO Annual Meeting abstract.