Analysis of the Outer Retinal Bands in ABCA4 and PRPH2-Associated Retinopathy using OCT

Rachael C Heath Jeffery; Johnny Lo; Jennifer A Thompson; Tina M Lamey; Terri L McLaren; John N De Roach; Lauren N Ayton; Andrea L Vincent; Abhishek Sharma; Fred K Chen

doi:10.1016/j.oret.2023.05.010

Analysis of the Outer Retinal Bands in ABCA4 and PRPH2-Associated Retinopathy using OCT

Ophthalmol Retina. 2024 Feb;8(2):174-183. doi: 10.1016/j.oret.2023.05.010. Epub 2023 May 18.

Authors

Affiliations

¹ Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, Australia; Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia; Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
² School of Science, Edith Cowan University, Perth, Western Australia, Australia.
³ Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁴ Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, Australia; Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁵ Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia.
⁶ Department of Ophthalmology, FMHS, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand; Eye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand.
⁷ Ophthalmology Department, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
⁸ Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia, Australia; Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia; Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: fred.chen@lei.org.au.

PMID: 37209970
DOI: 10.1016/j.oret.2023.05.010

Abstract

Purpose: To evaluate the outer retinal bands using OCT in ABCA4- and PRPH2-associated retinopathy and develop a novel imaging biomarker to differentiate between these 2 genotypes.

Design: Multicenter case-control study.

Participants: Patients with a clinical and genetic diagnosis of ABCA4- or PRPH2-associated retinopathy and an age-matched control group.

Methods: Macular OCT was used to measure the thickness of the outer retinal bands 2 and 4 by 2 independent examiners at 4 retinal loci.

Main outcome measures: Outcome measures included the thicknesses of band 2, band 4, and the band 2/band 4 ratio. Linear mixed modeling was used to make comparisons across the 3 groups. Receiver operating characteristic (ROC) analysis determined the optimal cutoff for the band 2/band 4 ratio to distinguish PRPH2- from ABCA4-associated retinopathy.

Results: We included 45 patients with ABCA4 variants, 45 patients with PRPH2 variants, and 45 healthy controls. Band 2 was significantly thicker in patients with PRPH2 compared with ABCA4 (21.4 vs. 15.9 μm, P < 0.001) variants, whereas band 4 was thicker in patients with ABCA4 variants than those with PRPH2 variants (27.5 vs. 21.7 μm, P < 0.001). Similarly, the band 2/band 4 ratio was significantly different (1.0 vs. 0.6 for PRPH2 vs. ABCA4, P < 0.001). The area under the ROC curve was 0.87 for either band 2 (> 18.58 μm) or band 4 (< 26.17 μm) alone and 0.99 (95% confidence interval: 0.97-0.99) for the band 2/band 4 ratio with a cutoff threshold of 0.79, providing 100% specificity.

Conclusions: We report an altered outer retinal band profile whereby the band 2/band 4 ratio was able to discriminate between PRPH2- and ABCA4-associated retinopathy. This may have future clinic utility in predicting the genotype and provide further insight into the anatomic correlate of band 2.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Ellipsoid zone; Imaging biomarkers; OCT; Peripherin; Stargardt disease.

Publication types

Multicenter Study

MeSH terms

ATP-Binding Cassette Transporters / genetics
Case-Control Studies
Humans
Macular Degeneration* / diagnosis
Retinal Diseases* / diagnosis
Retinal Diseases* / genetics
Tomography, Optical Coherence / methods

Substances

ATP-Binding Cassette Transporters
ABCA4 protein, human