Optical coherence tomography biomarkers in MYO7A-inherited retinal dystrophy: longitudinal study in pediatric patients

Graefes Arch Clin Exp Ophthalmol. 2024 Oct;262(10):3375-3384. doi: 10.1007/s00417-024-06545-3. Epub 2024 Jun 13.

Abstract

Purpose: This study aims to answer a key question: is MYO7A-inherited retinal dystrophy (MYO7A-IRD) a photoreceptor-first or retinal pigment epithelium-first disease? A second aim was to determine the most useful biomarkers to monitor disease progression in pediatric patients with Usher syndrome type 1B (USH1) secondary to MYO7A mutation.

Methods: Fifty-two eyes from 26 patients with genetically-confirmed MYO7A-IRD underwent swept-source optical coherence tomography (SS-OCT). Structural abnormalities were evaluated and correlated with follow-up time and best corrected visual acuity (BCVA). All patients were evaluated at baseline and after ≥ 40 months of follow-up.

Results: The mean (SD) patient age was 9.92 (± 4.1) years. Mean follow-up time was 43 (± 3.2) months. At the final evaluation, the most common qualitative abnormalities in the subfoveal area were alterations in the photoreceptor outer segments (76.9% of eyes) and in the interdigitation zone (IZ) (80.8%). The presence of cystoid macular edema at baseline was independently associated with worse BCVA at the final assessment (increase in LogMAR estimate = 0.142; t(45.00) = 2.78, p = 0.009). The mean width of the ellipsoid and interdigitation zones decreased significantly (by 668 μm and 278 μm, respectively; both p < 0.001).

Conclusion: This study shows that disruption of the photoreceptor outer segments and the IZ are the first alterations detected by SS-OCT in the early phases of MYO7A-IRD. These data highlight the potential value of measuring the width of the ellipsoid and IZ to evaluate disease progression. These findings also demonstrate the utility of monitoring for the emergence of cystic lesions as biomarkers of worse visual prognosis in patients with MYO7A-IRD.

Keywords: MYO7A mutations; Retinitis pigmentosa; Rod-cone dystrophy; Usher syndrome.

MeSH terms

  • Adolescent
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • DNA / genetics
  • Disease Progression*
  • Female
  • Fluorescein Angiography / methods
  • Follow-Up Studies
  • Fundus Oculi
  • Humans
  • Male
  • Mutation*
  • Myosin VIIa*
  • Retinal Dystrophies / diagnosis
  • Retinal Dystrophies / genetics
  • Retinal Dystrophies / metabolism
  • Retinal Dystrophies / physiopathology
  • Retinal Pigment Epithelium / pathology
  • Retrospective Studies
  • Tomography, Optical Coherence* / methods
  • Visual Acuity* / physiology

Substances

  • Myosin VIIa
  • MYO7A protein, human
  • Biomarkers
  • DNA