June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Central Visual Function and Genotype-Phenotype Correlations in PDE6A-Associated Retinitis Pigmentosa in Preparation for a Gene Supplemental Trial
Author Affiliations & Notes
  • Ditta Zobor
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
    Semmelweis Egyetem Szemeszeti Klinika, Budapest, Budapest, Hungary
  • Torsten Strasser
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • Gunnar Blumenstock
    Department of Clinical Epidemiology, Eberhard Karls University Tuebingen, Tübingen, Germany
  • Katarina Stingl
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • M. Dominik Fischer
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • Barbara Wilhelm
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • Eberhart Zrenner
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
    Werner Reichardt Centre for Integrative Neuroscience (CIN), Eberhard Karls University Tuebingen, Germany
  • Bernd Wissinger
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • Susanne Kohl
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • Nicole Weisschuh
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • Laura Kuehlewein
    Universitatsklinikum Tubingen Forschungsinstitut fur Augenheilkunde, Tubingen, Baden-Württemberg, Germany
  • Footnotes
    Commercial Relationships   Ditta Zobor None; Torsten Strasser None; Gunnar Blumenstock None; Katarina Stingl None; M. Dominik Fischer None; Barbara Wilhelm None; Eberhart Zrenner None; Bernd Wissinger None; Susanne Kohl None; Nicole Weisschuh None; Laura Kuehlewein None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4499 – F0286. doi:
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      Ditta Zobor, Torsten Strasser, Gunnar Blumenstock, Katarina Stingl, M. Dominik Fischer, Barbara Wilhelm, Eberhart Zrenner, Bernd Wissinger, Susanne Kohl, Nicole Weisschuh, Laura Kuehlewein; Central Visual Function and Genotype-Phenotype Correlations in PDE6A-Associated Retinitis Pigmentosa in Preparation for a Gene Supplemental Trial. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4499 – F0286.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Autosomal recessive RP (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 : 44 patients (26 females; mean ± SD age 43 ± 13 years) with a confirmed genetic diagnosis of PDE6A-associated arRP underwent comprehensive ophthalmological examination and follow-ups including best corrected visual acuity (BCVA) with ETDRS charts, contrast sensitivity (CS) with Pelli-Robson charts at 3 m and 1 m distance, and color vision testing using Roth 28 Hue and Panel D15 saturated color cups. Mean ± SD duration between baseline and last follow-up was 28 ± 12 months.

Results : The most frequently observed variants were c.998+1G>A/p.?, c.304C>A/p., and c.2053G>A/p. In general, symmetry between right and left eyes was high (r = 0.89). Central retinal function in patients homozygous for variant 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 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 (0.015 logMAR/year).

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.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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