Purpose: Autosomal recessive retinitis pigmentosa (arRP) can be caused by mutations
in the phosphodiesterase 6A (PDE6A) gene. Here, we describe the natural course of
disease progression with respect to central retinal function (i.e., visual acuity,
contrast sensitivity, and color vision) and establish a detailed genotype-–phenotype
correlation.
Methods: Forty-four patients (26 females; mean age ± SD, 43 ± 13 years) with a confirmed
genetic diagnosis of PDE6A-associated arRP underwent comprehensive ophthalmological
examinations including best-corrected visual acuity (BCVA) with Early Treatment Diabetic
Retinopathy Study charts, contrast sensitivity (CS) with Pelli–Robson charts at distances
of 3 m and 1 m, and color vision testing using Roth 28-Hue and Panel D-15 saturated
color cups.
Results: The most frequently observed variants were c.998+1G>A/p.?, c.304C>A/p.R102S,
and c.2053G>A/p.V685M. Central retinal function in patients homozygous for variant
c.304C>A/p.R102S was better when compared to patients homozygous for variant c.998+1G>A/p.?,
although the former were older at baseline. Central retinal function was similar in
patients homozygous for variant c.304C>A/p.R102S and patients heterozygous for variants
c.304C>A/p.R102S and c.2053G>A/p.V685M, although the latter were younger at baseline.
Annual decline rates in central retinal function were small.
Conclusions: We conclude that the severity of the different disease-causing PDE6A
mutations in humans with respect to central visual function may be ranked as follows:
c.2053G>A/p.V685M in homozygous state (most severe) > c.998+1G>A/p.? in homozygous
state > c.304C>A/p.R102S and c.2053G>A/p.V685M in compound-heterozygous state > c.304C>A/p.R102S
in homozygous state (mildest). The assessment of treatment efficacy in interventional
trials will remain challenging due to small annual decline rates in central retinal
function.
