State of the art on inherited retinal dystrophies: management and molecular genetics

Abstract: Inherited retinal dystrophies (IRDs) represent a group of heterogeneous disor- ders caused by gene mutations primarily affecting retinal photoreceptors. In addition to vision loss, other symptoms may lead to visual impairment, such as altered visual fields, hemeralopia, glare sensitivity, and impaired color vision. These conditions almost always complicate with the onset of cataracts, macular edema or atrophy, glaucoma, etc. A brief overview of key genes involved in the most common and well-known IRDs is provided, followed by clinical and diagnostic implications. The study of IRDs has seen a significant acceleration in recent decades, owing to advances in molecular genetics with the introduc- tion of exome sequencing (WES) and genome-wide association studies (GWASs), which have facilitated the identification of a broad spectrum of genes associated with IRDs. This has led to the classification of five genetic variants, based on the criteria of the American College of Medical Genetics and Genomics (ACMG), serving as a guide for interpreting genetic reports. Next, approaches to genomic editing therapies and research directions regarding artificial intelligence (AI) and machine learning (ML) are discussed. The paper concludes with an examination of the inevitable ethical and regulatory issues, typically driven by regulatory bodies such as the Food and Drug Administration (FDA).