Best Vitelliform Macular Dystrophy: Molecular Pathogenesis, Clinical Features, and Therapeutic Advances

Best Vitelliform Macular Dystrophy (BVMD) is a rare, autosomal dominant inherited retinal disorder caused by mutations in the BEST1 gene. The disease, which typically manifests in childhood or early adulthood, is characterized by the presence of well-circumscribed, “egg-yolk”–like vitelliform lesions resulting from lipofuscin accumulation within the retinal pigment epithelium (RPE). The clinical presentation and disease progression of BVMD are highly variable; while some individuals remain asymptomatic, others develop decreased visual acuity and metamorphopsia. In addition to fundus examination, diagnostic modalities such as electrooculography (EOG), fundus autofluorescence (FAF), and optical coherence tomography (OCT) are essential, whereas BEST1 genetic testing remains critical for definitive diagnosis. The underlying pathophysiology involves dysfunction of the bestrophin-1 protein, a putative calcium-activated chloride channel expressed in the basolateral membrane of RPE cells. This defect disrupts ionic and fluid homeostasis between the RPE and photoreceptors, leading to photoreceptor outer segment accumulation and progressive RPE and photoreceptor atrophy. Although its prevalence varies across populations, BVMD represents one of the most common forms of monogenic macular degeneration worldwide. Current therapeutic approaches are limited to symptomatic and supportive measures; however, emerging strategies—including in vivo gene therapy, induced pluripotent stem cell (iPSC)–derived RPE transplantation, and pharmacologic modulation (e.g., sodium phenylbutyrate)—hold significant promise for halting disease progression and partially restoring visual function. In particular, gene augmentation and targeted suppression of mutant BEST1 mRNA, combined with iPSC-based RPE replacement, may play a pivotal role in future treatment paradigms.