<i>ABCA4</i> Versus <i>PRPH2</i> -Associated Retinopathy: Clinical and Electrophysiological Findings

Purpose: The purpose of this study was to characterize the clinical features, electrophysiology, and variant spectrum in ABCA4- and PRPH2-retinopathies and to identify novel electrodiagnostic biomarkers to differentiate between these two genotypes. Methods: We conducted an international multicenter case-control study of patients with a clinical and genetic diagnosis of ABCA4- or PRPH2-retinopathy. Age at symptom onset, best-corrected visual acuity (BCVA), electroretinography (ERG) components, and fundus autofluorescence (FAF) imaging were compared. Subgroup exploratory analysis was performed on those patients with a phenotype similar to central areolar choroidal dystrophy ("CACD-like"), those with flecks distributed throughout the posterior pole ("fleck-like") and a healthy control group. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff for ERG parameters to distinguish PRPH2- from ABCA4-retinopathy. Results: This study included 155 patients with ABCA4-retinopathy, 133 patients with PRPH2-retinopathy, and 52 healthy controls. Significant electrophysiological biomarkers included the light-adapted (LA)30 hertz (Hz) flicker and LA3.0 single flash b-wave peak time (P < 0.001) for the "CACD-like" group with an area under the ROC curve (AUROC) of 0.78 and 0.76 and cutoff thresholds of 27.8 ms or 31.7 ms providing 77% and 85% sensitivity, respectively. Conversely, in the "fleck-like" group, the dark-adapted (DA)0.01 b-wave amplitude and DA3 a-wave amplitude (P < 0.001) had the highest AUROC, namely 0.88 and 0.88, respectively, with cutoff thresholds of 85 µV and 109 µV providing 93% and 88% sensitivity, respectively. Conclusions: Unique ERG profiles can distinguish PRPH2- from ABCA4-retinopathy. The LA30 Hz peak time and DA0.01 b-wave amplitude may have clinical utility in predicting and interpreting the genotype in patients with overlapping retinal phenotypes.

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Journal
Investigative Ophthalmology & Visual Science
Published
2026-04-14
DOI
https://doi.org/10.1167/iovs.67.4.29
Primary Topic
Retinal Development and Disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

ABCA4 Versus PRPH2 -Associated Retinopathy: Clinical and Electrophysiological Findings

Danial Roshandel, Kaoru Fujinami, Robyn V. Jamieson, Rachael C. Heath Jeffery et al.
Investigative Ophthalmology & Visual Science
Retinal Development and Disorders
article

ABCA4 Versus PRPH2 -Associated Retinopathy: Clinical and Electrophysiological Findings

Danial Roshandel, Kaoru Fujinami, Robyn V. Jamieson, Rachael C. Heath Jeffery, Andrea L. Vincent, Carmen Dell’Aquila, Lucia Ziccardi, Enid Chelva, Jonathan Hensman, Elisa Eleanor Cornish, Lorenzo Bianco, Lucilla Barbano, Samuel McLenachan, Ajoy Vincent, Benjamin M. Nash, Anupreet Tumber, Johnny Lo, Jennifer A Thompson, Chien-Yu Lin, Choi Mun Chan, Minal Patil, Elise Heon, Fred K. Chen, Jeremy Chou, Tina M. Lamey, Maurizio Battaglia Parodi, Camiel J. F. Boon, Terri L. McLaren, John R. Grigg, Wei Chao Tang, Ta-Ching Chen
article en

Abstract

Purpose: The purpose of this study was to characterize the clinical features, electrophysiology, and variant spectrum in ABCA4- and PRPH2-retinopathies and to identify novel electrodiagnostic biomarkers to differentiate between these two genotypes. Methods: We conducted an international multicenter case-control study of patients with a clinical and genetic diagnosis of ABCA4- or PRPH2-retinopathy. Age at symptom onset, best-corrected visual acuity (BCVA), electroretinography (ERG) components, and fundus autofluorescence (FAF) imaging were compared. Subgroup exploratory analysis was performed on those patients with a phenotype similar to central areolar choroidal dystrophy ("CACD-like"), those with flecks distributed throughout the posterior pole ("fleck-like") and a healthy control group. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff for ERG parameters to distinguish PRPH2- from ABCA4-retinopathy. Results: This study included 155 patients with ABCA4-retinopathy, 133 patients with PRPH2-retinopathy, and 52 healthy controls. Significant electrophysiological biomarkers included the light-adapted (LA)30 hertz (Hz) flicker and LA3.0 single flash b-wave peak time (P < 0.001) for the "CACD-like" group with an area under the ROC curve (AUROC) of 0.78 and 0.76 and cutoff thresholds of 27.8 ms or 31.7 ms providing 77% and 85% sensitivity, respectively. Conversely, in the "fleck-like" group, the dark-adapted (DA)0.01 b-wave amplitude and DA3 a-wave amplitude (P < 0.001) had the highest AUROC, namely 0.88 and 0.88, respectively, with cutoff thresholds of 85 µV and 109 µV providing 93% and 88% sensitivity, respectively. Conclusions: Unique ERG profiles can distinguish PRPH2- from ABCA4-retinopathy. The LA30 Hz peak time and DA0.01 b-wave amplitude may have clinical utility in predicting and interpreting the genotype in patients with overlapping retinal phenotypes.

Investigative Ophthalmology & Visual ScienceVol. 67(4)
Lions Eye Institute (AU), Edith Cowan University (AU), The University of Sydney (AU), University of Molise (IT), Children's Medical Research Institute (AU), University of Auckland (NZ), Vita-Salute San Raffaele University (IT), The University of Melbourne (AU), National Taiwan University (TW), The University of Western Australia (AU), University of Toronto (CA), Keio University (JP), Singapore National Eye Center (SG), Leiden University Medical Center (NL), Hospital for Sick Children (CA), Sir Charles Gairdner Hospital (AU), Children's Hospital at Westmead (AU), The Royal Victorian Eye & Ear Hospital (AU), Greenlane Clinical Centre (NZ), Tokyo Medical Center (JP), Fondazione G.B. Bietti (IT), Auckland District Health Board (NZ), Singapore Eye Research Institute (SG), National Taiwan University Hospital (TW), SickKids Foundation (CA), Sydney Children’s Hospitals Network (AU), Amsterdam University Medical Centers (NL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University College London (GB), University of Amsterdam (NL)
Macular Disease Foundation Australia, Japan Agency for Medical Research and Development, Retina Australia, McCusker Charitable Foundation, Australian Government, Great Britain Sasakawa Foundation, Ministry of Education, Culture, Sports, Science and Technology, Ministero della Salute, Fondazione Roma, Medical Research Council
Openalex Percentile: Top 28%
Retinal Development and Disorders
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