Objective: To describe the clinical characteristics of Inherited retinal dystrophy (IRD) caused by EYS (EYS-RD), the most common causative gene of this disease in the Japanese population. Design: A multicenter retrospective study Participants: 295 patients (143 men and 152 women) with EYS-RD registered in the Japan Retinitis Pigmentosa Registry Project at eight Japanese facilities. Methods: We evaluated age at the first visit, duration of observation, age of onset, first symptoms, family history, history of consanguineous marriage, disease type, macular complications, history of cataract surgery, logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA), and its progression. The mean ± standard deviation or the proportion of each parameter was calculated and compared across different variant levels. Main Outcome Measures: Clinical parameters including age of onset, BCVA, and progression of BCVA. Results: The mean age at the first visit was 45.5 ± 14.9 years, and the mean duration of observation was 7.7 ± 6.2 years. The mean age at disease onset was 25.5 ± 14.7 years. The first symptoms of EYS-RD included night blindness (78.5%), visual field impairment (9.6%), and loss of visual acuity (8.0%). Family history and consanguineous marriages accounted for 29.7% and 9.3% of the patients, respectively. Rod-cone dystrophy and cone-rod dystrophy accounted for 96.3% and 2.4% of patients, respectively. The mean logMAR BCVA was 0.33 ± 0.56, and the mean progression was 0.03 ± 0.07 per year. In variant-based analyses, three East Asian-specific pathogenic variants (S1653fs, Y2935X, and G843E) caused 69.7% of Japanese EYS-RD patients. In cases with homozygous pathogenic variants, the mean age at onset was 17.9, 27.5, and 26.2 years, and the mean progression of logMAR BCVA was 0.05 ± 0.09, 0.04 ± 0.06, and 0.04 ± 0.05 per year for S1653fs (n = 31), Y2935X (n = 13), and G843E (n = 24), respectively. Conclusions: We described the clinical characteristics of Japanese patients with EYS-RD. The clinical differences among major East Asian-specific pathogenic variants indicate the utility of genetic testing in personalized medicine for IRD patients tailored to population characteristics.

The authors have disclosed their Conflict of Interest information in the format of the ICMJE DISCLOSURE FORM.

This study was supported by grants from the Japan Society for the Promotion of Science KAKENHI (grant numbers 20K23005, 22K16969, 23K27750 and 24K12771), Japan Agency for Medical Research and Development [the Practical Research Project for Rare/Intractable Disease (grant number: JP23ek0109632) and 24ek0109707h0001], Japanese Retinitis Pigmentosa Society (JRPS) Research Grant (YK), Takayanagi Retina Research Award (YK) and Medical Research Grant from the Nasu Foundation (YK).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Ethics Committee/IRB of Jikei University, Teikyo University, Hamamatsu University School of Medicine, Nagoya University, Kobe City Eye Hospital, Kyushu University, Miyata Eye Hospital, and University of Miyazaki provided ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.