Ophthalmic Manifestations of Danon Disease: A Systematic Review.

Abstract

Danon disease is a rare X-linked disorder caused by pathogenic variants in the LAMP2 gene. It is characterized by severe cardiomyopathy, arrhythmias, and skeletal myopathy. Ophthalmic findings have been described but are often overlooked due to limited awareness of their prevalence and characteristics. This study aims to review the ophthalmic manifestations of Danon disease and their clinical relevance. Systematic review. A systematic review of PubMed and EMBASE was conducted from inception through October 15, 2025, to identify studies reporting ophthalmic findings in genetically or clinically confirmed Danon disease. Data were extracted on demographics, LAMP2 variants, ocular features, and imaging results. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists. Descriptive statistics were performed in SPSS Statistics v29. The protocol was prospectively registered in PROSPERO (CRD42024608745). We identified 34 studies (25 case reports, 8 case series, and 1 retrospective cohort) describing 70 patients, aged 6 to 81 years. Retinal abnormalities were the most common finding (81%), typically midperipheral and peripheral salt-and-pepper pigmentary changes. Macular involvement was frequent (62%), usually presenting as nonspecific retinal pigment epithelium changes; a minority (13%) developed more severe pathology, including macular atrophy, bull's-eye maculopathy, or cystoid macular edema. Optical coherence tomography, available in nearly half of patients, most often showed retinal pigment epithelium and ellipsoid zone disruption (85%) and outer nuclear layer hyperreflectivity (61%). Fundus autofluorescence and electroretinography, when abnormal, revealed mottled hypo- and hyperautofluorescence and mild cone and rod dysfunction, respectively. Other ocular findings included myopia (16%) and lens opacities (13%). Retinal manifestations are the most common ophthalmic finding in Danon disease and can lead to significant vision loss. Ophthalmic findings, particularly retinal abnormalities, may precede or represent the only manifestation of disease in some patients. Recognition of these features may prompt earlier systemic evaluation, genetic testing, and multidisciplinary management of this life-threatening lysosomal disorder.