Stargardt Disease: A Comprehensive Review of Pathophysiology, Clinical Features, and Emerging Therapeutic Strategies

Abstract

Stargardt disease (STGD), the most prevalent form of inherited juvenile macular dystrophy, is an autosomal recessive disorder primarily caused by pathogenic variants in the ABCA4 gene. This condition leads to progressive central vision loss due to the accumulation of lipofuscin-like deposits in the retinal pigment epithelium (RPE), ultimately resulting in photoreceptor degeneration. The pathophysiological mechanisms underlying STGD involve dysregulated vitamin A metabolism, aberrant bisretinoid accumulation, and chronic oxidative stress within the RPE. Clinically, patients present with reduced visual acuity, central scotomas, and characteristic fundoscopic findings, including flecks at the level of the RPE and a "beaten bronze" macular appearance. The diagnosis relies on multimodal imaging techniques such as fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), and electroretinography (ERG), alongside genetic testing for ABCA4 mutations. Current management is mainly supportive, focusing on low-vision rehabilitation and avoidance of excessive light exposure, given the potential exacerbation of phototoxic damage. However, recent advances in gene therapy, stem cell transplantation, and pharmacologic interventions targeting the visual cycle offer promising therapeutic prospects. This review aims to provide a comprehensive analysis of the molecular pathogenesis, clinical manifestations, diagnostic approach, and evolving treatment modalities for Stargardt disease, highlighting the translational potential of novel interventions in altering disease progression.