Author Identifier (ORCID)
Johnny Lo: https://orcid.org/0000-0003-1913-5354
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.
Keywords
ABCA4, electrophysiology, fundus flavimaculatus, imaging biomarkers, pattern dystrophy, peripherin, peripherinopathy, PRPH2, pseudo-Stargardt disease, RDS, Stargardt disease
Document Type
Journal Article
Date of Publication
4-1-2026
Volume
67
Issue
4
PubMed ID
41979252
Publication Title
Investigative Ophthalmology & Visual Science
Publisher
Association for Research in Vision and Ophthalmology
School
School of Science
Funders
Australian Government Research Training Program / Retina Australia / Macular Disease Foundation Australia / Future Health Research and Innovation Fund / McCusker Charitable Foundation / Channel 7 Telethon Trust / National Health & Medical Research Council of Australia / Henry Brent Chair in Innovative Pediatric Ophthalmology Research / Foundation Fighting Blindness USA (CD-CMM-0224-0873-HSC) / Grant-in-Aid for Young Scientists of the Ministry of Education, Culture, Sports, Science and Technology, Japan (16H06269, 16KK01930002) / National Hospital Organization Network Research Fund, Japan (H30-NHO-Sensory Organs-03) / Foundation Fighting Blindness Alan Laties Career Development Program (CF-CL-0416-0696-UCL), USA / Health Labour Sciences Research Grant, AMED (23EK0109634H0001, 23EK0109632H0001) / Ministry of Health Labour and Welfare, Japan (201711107A, 23809955) / Great Britain Sasakawa Foundation Butterfield Awards, UK / Italian Ministry of Health and Fondazione Roma through the work at IRCCS- Fondazione Bietti
Grant Number
NHMRC Numbers : GNT1116360, GNT1188694, GNT1054712, MRF1142962
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
Jeffery, R. C. H., Thompson, J. A., Lo, J., Vincent, A. L., Patil, M., Bianco, L., Parodi, M. B., Ziccardi, L., Dell’Aquila, C., Barbano, L., Tang, W. C., Chan, C. M., Boon, C. J. F., Hensman, J., Chen, T., Lin, C., Chen, P., Vincent, A., Tumber, A., . . . Chen, F. K. (2026). ABCA4 versus PRPH2-associated retinopathy: Clinical and electrophysiological findings. Investigative Ophthalmology & Visual Science, 67(4), 29. https://doi.org/10.1167/iovs.67.4.29