Epidemiology of Mutations in the 65-kDa Retinal Pigment Epithelium (RPE65) Gene-Mediated Inherited Retinal Dystrophies: A Systematic Literature Review

INTRODUCTION: Inherited retinal dystrophies (IRDs) represent a genetically diverse group of progressive, visually debilitating diseases. Adult and paediatric patients with vision loss due to IRD caused by biallelic mutations in the 65-kDa retinal pigment epithelium (RPE65) gene are often clinically diagnosed as retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA). This study aimed to understand the epidemiological landscape of RPE65 gene-mediated IRD through a systematic review of the literature, as the current evidence base for its epidemiology is very limited. METHODS: Medline, Embase, and other databases were searched for articles on the epidemiology of RPE65 gene-mediated IRDs from inception until June 2021. Studies were included if they were original research articles reporting the epidemiology of RP and LCA and/or proportion of RPE65 gene mutations in these clinically diagnosed or molecularly confirmed IRDs patients. RESULTS: A total of 100 studies with relevant data were included in this systematic review. The range for prevalence of LCA and RP in the literature was 1.20–2.37 and 11.09–26.43 per 100,000, respectively. The proportion of RPE65 mutations in clinically diagnosed patients with LCA was found to be between ~ 2–16% within the US and major European countries (France, Germany, Italy, Spain, and the UK). This range was also comparable to our findings in the Asian region for RPE65-LCA (1.26–16.67%). Similarly, for these European countries, RPE65-RP was estimated between 0.23 and 1.94%, and RPE65-IRD range was 1.2–14%. Further, in the Americas region, mutations in RPE65 were reported to cause 1–3% of RP and 0.8–3.7% of IRD cases. Lastly, the RPE65-IRD range was 4.81–8% in the Middle East region. CONCLUSIONS: There are significant variations in reporting of RPE65 proportions within countries as well as regions. Generating robust epidemiological evidence on RPE65 gene-mediated IRDs would be fundamental to support rare disease awareness, timely therapeutic intervention, and public health decision-making. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12325-021-02036-7.