Ocular Manifestations of Wilson Disease: Pathophysiology, Clinical and Paraclinical Features.

Abstract

Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in impaired biliary copper excretion and progressive copper accumulation in multiple tissues. Ocular manifestations represent some of the most characteristic and clinically valuable features of the disease, contributing to diagnosis, monitoring, and assessment of neurological involvement. This narrative review summarizes current knowledge regarding the pathophysiology, clinical presentation, and imaging characteristics of ocular involvement in WD. Copper deposition within the eye occurs primarily through the aqueous humor, leading to accumulation in the corneal Descemet membrane and lens capsule. Kayser-Fleischer rings remain the most prevalent ocular sign being strongly associated with neurological disease, while sunflower cataracts represent a less common but highly characteristic manifestation. Anterior segment optical coherence tomography and in vivo confocal microscopy have recently improved the detection and monitoring of these lesions. Beyond copper deposition, growing evidence indicates that WD is associated with retinal and optic nerve neurodegeneration. Optical coherence tomography studies consistently demonstrate thinning of the retinal nerve fiber layer, ganglion cell complex, and macular structures, particularly in patients with neurological involvement. Electrophysiological investigations, including visual evoked potentials and electroretinography, reveal delayed neural conduction and retinal dysfunction, supporting the concept of widespread neuro-ophthalmological impairment. Optical coherence tomography angiography further identifies microvascular alterations affecting retinal and peripapillary capillary networks. Importantly, several ocular abnormalities correlate with neurological severity and may serve as non-invasive biomarkers of disease progression. Current treatments, including copper chelators and zinc therapy, can induce regression of Kayser-Fleischer rings and sunflower cataracts. Ocular assessment therefore provides a valuable window into systemic and neurological disease activity, highlighting the importance of multidisciplinary management and the potential role of emerging imaging biomarkers in Wilson disease.