Latest Development on Genetics of Common Retinal Diseases

Many complex forms of retinal diseases are common and pan-ethnic in occurrence. Among them, neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and central serous choroid retinopathy involve both choroidopathy and neovascularization with multifactorial etiology. They are sight-threatening and potentially blinding. Early treatment is crucial to prevent disease progression. To understand their genetic basis, candidate gene mutational and association analyses, linkage analysis, genome-wide association studies, transcriptome analysis, next-generation sequencing, which includes targeted deep sequencing, whole-exome sequencing, and whole genome sequencing have been conducted. Advanced genomic technologies have led to the identification of many associated genes. But their etiologies are attributed to complicated interactions of multiple genetic and environmental risk factors. Onset and progression of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy are affected by aging, smoking, lifestyle, and variants in over 30 genes. Although some genetic associations have been confirmed and validated, individual genes or polygenic risk markers of clinical value have not been established. The genetic architectures of all these complex retinal diseases that involve sequence variant quantitative trait loci have not been fully delineated. Recently artificial intelligence is making an impact in the collection and advanced analysis of genetic, investigative, and lifestyle data for the establishment of predictive factors for the risk of disease onset, progression, and prognosis. This will contribute to individualized precision medicine for the management of complex retinal diseases.