Genetics, Clinical Characteristics, and Natural History of PDE6B-Associated Retinal Dystrophy

Am J Ophthalmol. 2024 Jul:263:1-10. doi: 10.1016/j.ajo.2024.02.005. Epub 2024 Feb 15.

Abstract

Purpose: To analyze the clinical characteristics, natural history, and genetics of PDE6B-associated retinal dystrophy.

Design: Retrospective, observational cohort study.

Methods: Review of medical records and retinal imaging, including fundus autofluorescence (FAF) imaging and spectral-domain optical coherence tomography (SD-OCT) of patients with molecularly confirmed PDE6B-associated retinal dystrophy in a single tertiary referral center. Genetic results were reviewed, and the detected variants were assessed.

Results: Forty patients (80 eyes) were identified and evaluated longitudinally. The mean age (±SD, range) was 42.1 years (± 19.0, 10-86) at baseline, with a mean follow-up time of 5.2 years. Twenty-nine (72.5%) and 27 (67.5%) patients had no or mild visual acuity impairment at baseline and last visit, respectively. Best-corrected visual acuity (BCVA) was 0.56 ± 0.72 LogMAR (range -0.12 to 2.80) at baseline and 0.63 ± 0.73 LogMAR (range 0.0-2.80) at the last visit. BCVA was symmetrical in 87.5% of patients. A hyperautofluorescent ring was observed on FAF in 48 and 46 eyes at baseline and follow-up visit, respectively, with a mean area of 7.11 ± 4.13 mm2 at baseline and mean of 6.13 ± 3.62 mm2 at the follow-up visit. Mean horizontal ellipsoid zone width at baseline was 1946.1 ± 917.2 µm, which decreased to 1763.9 ± 827.9 µm at follow-up. Forty-four eyes had cystoid macular edema at baseline (55%), and 41 eyes (51.3%) at follow-up. There were statistically significant changes during the follow-up period in terms of BCVA and the ellipsoid zone width. Genetic analysis identified 43 variants in the PDE6B gene, including 16 novel variants.

Conclusions: This study details the natural history of PDE6B-retinopathy in the largest cohort to date. Most patients had mild to no BCVA loss, with slowly progressive disease, based on FAF and OCT metrics. There is a high degree of disease symmetry and a wide window for intervention.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Cyclic Nucleotide Phosphodiesterases, Type 6* / genetics
  • DNA Mutational Analysis
  • Electroretinography
  • Female
  • Fluorescein Angiography*
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Retinal Dystrophies* / diagnosis
  • Retinal Dystrophies* / genetics
  • Retinal Dystrophies* / physiopathology
  • Retrospective Studies
  • Tomography, Optical Coherence*
  • Visual Acuity* / physiology
  • Young Adult

Substances

  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • PDE6B protein, human