Update on the Management of ABCA4 Retinopathy (Stargardt Disease)

ABCA4-associated retinopathies (Stargardt disease) are the most common inherited macular dystrophy and a leading cause of early onset central vision loss. Biallelic pathogenic variants in the ABCA4 gene cause impaired clearance of retinoid byproducts, leading to toxic bisretinoid accumulation, retinal pigment epithelium dysfunction, and progressive photoreceptor degeneration. Clinical presentation and disease progression are highly heterogeneous, largely influenced by genotype, age at onset, and environmental modifiers. Current management remains supportive and includes low-vision rehabilitation and counseling. Recent advances in molecular genetics, retinal imaging, and translational science have substantially expanded the therapeutic pipeline for ABCA4 retinopathy. Disease-modifying strategies under active investigation include visual-cycle modulation, deuterated vitamin A analogs, retinol-binding protein antagonists, gene augmentation and editing approaches, antisense oligonucleotides, and cell-based regenerative therapies. Several pharmacologic agents have demonstrated promising structural outcomes in clinical trials, while gene-based and regenerative approaches continue to evolve amid challenges related to gene size, delivery efficiency, and long-term safety. Optogenetic therapy has emerged as a gene-agnostic option for functional vision restoration in advanced disease stages. This review provides an integrated overview of ABCA4 retinopathy, summarizing disease mechanisms, current management strategies, emerging therapies, and the evolving clinical trial landscape. Emphasis is placed on stage-adapted treatment paradigms, appropriate monitoring endpoints, and the potential role of combination therapies. Ongoing innovation and precision-based approaches offer cautious optimism for durable disease modification and functional preservation in this currently untreatable condition.