ORIGINAL RESEARCH article
Front. Ophthalmol.
Sec. Retina
Volume 5 - 2025 | doi: 10.3389/fopht.2025.1672451
This article is part of the Research TopicGlobal Perspectives on Genetic Diagnosis and Treatments for Inherited Retinal DiseasesView all 5 articles
Deep phenotyping of eyes shut homolog-associated retinopathy based on visual impairment patterns
Provisionally accepted
Daiki Sakai1*
Yasuhiko Hirami1
Satoshi Yokota1Akishi Onishi1Masayo Takahashi1Makoto Nakamura2Yasuo Kurimoto1Akiko Maeda1- 1Kobe City Eye Hospital, Kobe, Japan
- 2Kobe Daigaku, Kobe, Japan
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This study aimed to classify the phenotypes of eyes shut homolog (EYS)-associated retinopathy based on visual impairment patterns and investigate their characteristics. This retrospective, single-center, cross-sectional study was conducted in 154 patients diagnosed with EYS-related retinopathy who underwent genetic testing between December 2017 and July 2023. Phenotyping was performed only in patients who underwent Goldmann perimetry (GP) and Humphrey visual field (HVF) 10-2 testing. Phenotypes were categorized as early, pericentral, typical, and advanced based on peripheral visual field preservation (GP: V-4e isopter extending beyond a 30-degree radius in ≥2 quadrants), central visual field impairment (HVF10-2: ≤20 points with 26 dB sensitivity), and macular impairment (logMAR ≥ 0.2). Genetic and ophthalmological characteristics were compared between the pericentral and typical types. A total of 39 eyes from 39 patients with EYS-associated retinopathy (average age: 48.2 ± 11.9 years, 21 women) were analyzed. Ten pathogenic variants were identified, with the three major variants (p.G843E, p.S1653fs, and p.Y2935X) accounting for a combined allele frequency of 83.3%. The phenotypes were classified as early (n=3), pericentral (n=18), typical (n=9), and advanced (n=9). No significant differences were observed between the pericentral and typical types in terms of the presence of major variants or biallelic null variants. Age and age at onset also did not differ significantly. However, macular impairment was significantly more frequent in the pericentral type (61.8%) than in the typical type (11.1%) (P = 0.014). In EYS-associated retinopathy, the pericentral type is considered a common phenotype, although its correlation with the genotype remains unclear. Despite preserved peripheral vision, careful monitoring is warranted due to the risk of macular impairment.
Keywords: eyes shut homolog (EYS)1, retinitis pigmentosa2, inherited retinal dystrophy3, pericentra4, genotype-phenotype correlation5, phenotyping6
Received: 24 Jul 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Sakai, Hirami, Yokota, Onishi, Takahashi, Nakamura, Kurimoto and Maeda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Daiki Sakai, Kobe City Eye Hospital, Kobe, Japan
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