ABCA4 Versus PRPH2-Associated Retinopathy: Clinical and Electrophysiological Findings

Area of Science:

• Ophthalmology
• Genetics
• Clinical Electrophysiology

Background:

• ABCA4-retinopathy and PRPH2-retinopathy are genetic retinal disorders with overlapping clinical features.
• Distinguishing between these genotypes is crucial for accurate diagnosis and management.
• Novel electrodiagnostic biomarkers are needed to aid in differentiating these conditions.

Purpose of the Study:

• To characterize clinical features, electrophysiology, and variant spectrum in ABCA4- and PRPH2-retinopathies.
• To identify novel electrodiagnostic biomarkers for differentiating between ABCA4- and PRPH2-retinopathy genotypes.

Main Methods:

• An international multicenter case-control study involving 155 patients with ABCA4-retinopathy, 133 with PRPH2-retinopathy, and 52 controls.
• Comparison of age at symptom onset, best-corrected visual acuity (BCVA), electroretinography (ERG) components, and fundus autofluorescence (FAF) imaging.
• Receiver operating characteristic (ROC) analysis to determine optimal ERG cutoffs for distinguishing genotypes.

Main Results:

• Significant electrophysiological biomarkers were identified for differentiating phenotypes.
• For the "CACD-like" group, light-adapted (LA)30 Hz flicker and LA3.0 single flash b-wave peak time showed high diagnostic accuracy (AUROC 0.78-0.76).
• For the "fleck-like" group, dark-adapted (DA)0.01 b-wave amplitude and DA3 a-wave amplitude demonstrated high diagnostic accuracy (AUROC 0.88).

Conclusions:

• Unique ERG profiles effectively distinguish PRPH2-retinopathy from ABCA4-retinopathy.
• LA30 Hz peak time and DA0.01 b-wave amplitude may serve as valuable clinical tools for genotype prediction in patients with overlapping retinal phenotypes.