Tackling Inherited Retinal Diseases in Southeast Asia: Insights from the Malay and Indian populations of Singapore and Malaysia

Abstract

Purpose : Southeast Asia has a population approaching 700 million individuals but there is very limited understanding of the phenotypic and genotypic diversity of inherited retinal disease (IRD) in this region. As a prelude to addressing this critical knowledge gap, we explored the phenotypic and genotypic characteristics of ethnic Malay and Indian IRD patients in Singapore and Malaysia.

Methods : This was a multi-center retrospective cohort study involving 100 consecutively enrolled patients with IRD from retina clinics in Singapore and Malaysia. A total of 46 ethnic Malay and 54 ethnic Indian patients were enrolled, and clinical charts, retinal imaging, functional testing, and genetic data were reviewed. Clinical phenotypes, age at symptom onset and diagnosis, functional and structural outcomes, and genotypes were analyzed.

Results : Median age at enrolment was 50 years (range 6–89 years) and 49.0% were females. Median visual acuity at enrolment was logMAR 0.60 (range 0.00–2.70) in Malay patients and 0.60 in Indian patients (range 0.00–2.30). Median delay between symptom onset and clinical presentation for cases with nonsyndromic retinitis pigmentosa (RP) was longer for Malay patients (8 years) compared to Indians (1 year) but this did not reach statistical significance (p = 0.19). A total of 12 distinct IRD phenotypes were identified, with nonsyndromic RP (n = 50), ABCA4-associated retinal dystrophy, (n = 20), and cone- or cone-rod dystrophy (n = 15) being the most prevalent. There was no known family history of IRD in 60% and 66.7% of Malay and Indian cases, respectively. Variants in ABCA4 were the most common cause of IRD, while ABCA4 R24H and G1961R, and MFSD8 (CLN7) M454T were identified as recurrent variants in the Malay and Indian cohorts, respectively. Homozygous variants were significantly more common among ethnic Indians (48.5%; p = 0.0008) than Malays (9.7%).

Conclusions : This is to our knowledge the first survey of IRD in the ethnic Malay and Indian populations of Singapore and Malaysia. We found a diversity of phenotypic and genotypic outcomes, with distinct differences between Malay and Indian populations. These data may be useful for the identification of regionally relevant IRD genotypes and development of targeted therapies for the Malay and Indian populations of Southeast Asia.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.