Author: Juliana Maria Ferraz Sallum (Brazil)
Co-authors: Vinay Preet Kaur, Javed Shaikh, Judit Banhazi, Claudio Spera, Daniel Viriato, M Dominik Fischer
Purpose
Inherited retinal dystrophies (IRDs) comprise a wide range of phenotypically and genetically heterogeneous group of rare genetic diseases that are generally characterised by progressive loss of vision. Mutations in more than 270 different genes have been identified as the cause of IRDs. Among these, biallelic mutations in the RPE65 gene i.e. retinal pigment epithelium (RPE)-specific protein 65 kiloDalton (kDa) affects the visual cycle in the retinal epithelium, resulting in a progressive rod (primarily) and cone degeneration. Biallelic mutations in the RPE65 gene are often associated with Leber’s congenital amaurosis 2 (LCA2) and retinitis pigmentosa 20 (RP20). The current evidence base for the epidemiology of RPE65 gene-mediated IRDs is limited. Such epidemiological evidence will be important for evaluating impact of the disease in the population in terms of disease burden and unmet needs. Thus, this study aims to understand the epidemiology landscape of RPE65 gene-mediated IRD through a systematic review of the literature.
Setting/Venue
not a relevant section for this abstract
Methods
A review of the global medical literature was conducted by following the systematic principles of the Cochrane handbook for systematic reviews and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The electronic databases (Embase, Medline, and Cochrane Library) were searched from inception until the 12 January 2021 to retrieve studies reporting prevalence and incidence of LCA and RP and the proportion of biallelic RPE65 mutations in these IRDs. The Orphanet rare diseases platform and the bibliography of relevant literature reviews was also screened for including potential studies. The databases were searched for terms related to RPE65, RPE65-IRD, RPE65-RP, RPE65-LCA, incidence, prevalence and/or epidemiology. The search results were limited to English language. Publications were included in the full-text review if they reported on the epidemiology of IRDs caused by RPE65 gene mutations or prevalence/ incidence of RP or LCA (irrespective of any mutation) or proportion of RPE65 gene mutation in RP or LCA.
Results
The literature search yielded 3744 citations from which 69 studies were identified with relevant epidemiology data for inclusion. The prevalence of LCA was estimated to be 1.24 to 2.37 per 100,000 based on three studies conducted in Denmark, Norway and the US and the prevalence of RP ranged between 11.09 to 26.43 per 100,000. For Israel, the prevalence of RP was reported to be high (47.62 per 100,000) probably because of a high level of consanguinity and a high number of siblings within certain ethnic groups. The worldwide proportion of RPE65 mutations in LCA was estimated at 6.10% and varied between 1.0% to 22.2%. The proportion of RPE65 mutations in LCA and RP ranged between 1.79% to 16% and 0.23% to 7.41% for the European region, respectively. For the US, the proportion of RPE65 mutation ranged between 3.0% to 15.55% for LCA and 0.81% to 1.85% for RP patients. A recent Mexican study had reported that RPE65 in RP occurred in 3.28% of clinically diagnosed RP and LCA patients.
Conlusions
Patients with RPE65 gene-mediated IRD are reported from across the world including Europe, North America, South America, Middle-East, and Asian countries. Robust epidemiology data for RPE65-mediated IRDs is limited and therefore accurate assessments of prevalence and incidence are challenging. Insufficient data on prevalence have contributed to the insufficient funding and resources available to conduct genetic testing for IRDs, and to provide genetic counselling for IRD patients and families. There is also a high heterogeneity in reporting of the data and the lack of sufficient high-quality studies highlights the need to conduct higher quality studies on rare genetic diseases. Therefore, further research is needed to generate strong evidence with high quality studies to get a better understanding of the disease. This can help in early identification of the affected patients and their early treatment can prevent progression to severe visual impairment or complete blindness.
Financial Disclosure
• Juliana MF Sallum has nothing to disclose • Judit Banhazi, Claudio Spera, and Daniel Viriato are employees of Novartis Pharma AG. • Vinay Preet Kaur and Javed Shaikh are employees of Novartis Healthcare Pvt. Ltd. • Professor Fischer reports consulting fees from Advent France Biotechnology, Alphasights, Atheneum, Axiom Healthcare Strategies, Biogen, Decision Resources, Dialectica, Frontera Therapeutics, Janssen Research & Development, Navigant, Novartis, Roche, Sirion, STZ eyetrial.
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