Natural History of Microperimetry and Optical Coherence Tomography in USH2A-Retinopathy: A Structure-Function Association Study

Ajoy Vincent; Wendi Liang; Maureen G Maguire; Jacque L Duncan; Allison R Ayala; Paul S Bernstein; Joseph Carroll; Janet K Cheetham; Todd A Durham; Sina Farsiu; Carel B Hoyng; Rachel M Huckfeldt; Glenn J Jaffe; Jessica Loo; Mark E Pennesi; José-Alain Sahel; Mandeep S Singh; Zane Z Zemborain; David G Birch; Eleonora M Lad; Foundation Fighting Blindness Clinical Consortium Investigator Group

doi:10.1016/j.ajo.2025.04.034

Natural History of Microperimetry and Optical Coherence Tomography in USH2A-Retinopathy: A Structure-Function Association Study

Am J Ophthalmol. 2025 Aug:276:336-349. doi: 10.1016/j.ajo.2025.04.034. Epub 2025 May 3.

Authors

Ajoy Vincent¹, Wendi Liang², Maureen G Maguire², Jacque L Duncan³, Allison R Ayala⁴, Paul S Bernstein⁵, Joseph Carroll⁶, Janet K Cheetham⁷, Todd A Durham⁷, Sina Farsiu⁸, Carel B Hoyng⁹, Rachel M Huckfeldt¹⁰, Glenn J Jaffe¹¹, Jessica Loo¹¹, Mark E Pennesi¹², José-Alain Sahel¹³, Mandeep S Singh¹⁴, Zane Z Zemborain¹⁵, David G Birch¹⁶, Eleonora M Lad¹¹; Foundation Fighting Blindness Clinical Consortium Investigator Group

Affiliations

¹ From the Departments of Ophthalmology and Vision Sciences (A.V.), The Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada.
² Jaeb Center for Health Research (W.L., M.G.M., A.R.A.), Tampa, Florida, USA.
³ University of California (J.L.D.), San Francisco, California, USA.
⁴ Jaeb Center for Health Research (W.L., M.G.M., A.R.A.), Tampa, Florida, USA. Electronic address: ffbcorrespauth@jaeb.org.
⁵ Moran Eye Center, University of Utah (P.S.B.), Salt Lake City, Utah, USA.
⁶ Department of Ophthalmology and Visual Sciences (J.C.), Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁷ Foundation Fighting Blindness (J.K.C., T.A.D.), Columbia, Maryland, USA.
⁸ Department of Ophthalmology (S.F., G.J.J., J.L., E.M.L.), Duke University, Durham, North Carolina, USA; Department of Biomedical Engineering (S.F., Z.Z.Z.), Duke University, Durham, North Carolina, USA.
⁹ Radboud University (C.B.H.), Nijmegen, Netherlands.
¹⁰ Massachusetts Eye and Ear (R.M.H.), Boston, Massachusetts, USA.
¹¹ Department of Ophthalmology (S.F., G.J.J., J.L., E.M.L.), Duke University, Durham, North Carolina, USA.
¹² Casey Eye Institute, Oregon Health and Science University (M.E.P., D.G.B.), Portland, Oregon, USA; Retina Foundation of the Southwest (M.E.P.), Dallas, Texas, USA.
¹³ Institut de la Vision (J.A.S.), Sorbonne Université, INSERM, CNRS, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (J.A.S.), Centre de Référence Maladies Rares REFERET, Paris, France; Department of Ophthalmology (J.A.S.), The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
¹⁴ Wilmer Eye Institute (M.S.S.), Johns Hopkins Hospital, Baltimore, Maryland, USA; Department of Genetic Medicine (M.S.S.), Johns Hopkins University, Baltimore, Maryland, USA.
¹⁵ Department of Biomedical Engineering (S.F., Z.Z.Z.), Duke University, Durham, North Carolina, USA.
¹⁶ Casey Eye Institute, Oregon Health and Science University (M.E.P., D.G.B.), Portland, Oregon, USA.

PMID: 40324556
DOI: 10.1016/j.ajo.2025.04.034

Abstract

Purpose: To describe the natural history of optical coherence tomography (OCT) and mesopic microperimetry (MP) parameters in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

Design: Multicenter, international, prospective, longitudinal natural history study.

Methods: Study Population: 105 participants with biallelic disease-causing variants in USH2A with a clinical diagnosis of Usher Syndrome or autosomal recessive retinitis pigmentosa who underwent annual testing over 4 years.

Main outcome measure(s): Ellipsoid zone (EZ) area and central sub-field thickness (CST) on OCT. Mean sensitivity (MS) and mean pointwise sensitivity at predefined functional transition points (MS_FTP) on MP.

Results: A total of 101 and 94 participants met criteria for OCT and MP analysis, respectively. The average EZ area was 3.9 ± 5.3 mm² at baseline which decreased to 3.3 ± 4.1 mm² at 4 years (rate of change [ROC] [-0.18 mm²/year]). The average CST decreased from 249.7 ± 35.6 to 244.1 ± 39.3 microns over 4 years (-2.14 microns/year). The average MP MS declined from 6.0 ± 5.1 dB (baseline) to 4.5 ± 4.2 (4 years) (-0.39 dB/year). The MS_FTP significantly decreased over time (17.9 dB [baseline] to 10.8 dB [4 years]). Notably, at 4 years, there was a meaningful decrease (≥ 7dB) in MS_FTP in 46% of study eyes.

Conclusions: This study establishes the natural history of key structural and functional parameters in USH2A-retinopathy. The MS_FTP is a novel, robust parameter that showed clinically meaningful change over time and is a promising tool to monitor treatment efficacy in clinical trials.

Publication types

Multicenter Study

MeSH terms

Adolescent
Adult
Child
Disease Progression
Extracellular Matrix Proteins* / genetics
Female
Follow-Up Studies
Humans
Male
Middle Aged
Prospective Studies
Retina* / physiopathology
Retinitis Pigmentosa* / diagnosis
Retinitis Pigmentosa* / genetics
Retinitis Pigmentosa* / physiopathology
Tomography, Optical Coherence* / methods
Usher Syndromes* / diagnosis
Usher Syndromes* / genetics
Usher Syndromes* / physiopathology
Visual Acuity / physiology
Visual Field Tests* / methods
Visual Fields* / physiology
Young Adult

Substances

USH2A protein, human
Extracellular Matrix Proteins

Grants and funding

P30 EY002162/EY/NEI NIH HHS/United States