Anderson-Fabry Disease: Focus on Ophthalmological Implications

Abstract

Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a broad spectrum of clinical manifestations, including severe complications, such as end-stage renal disease, hypertrophic cardiomyopathy, and cerebrovascular disease. Enzyme replacement therapy (ERT), when initiated early, has been shown to reduce the incidence of severe events and slow disease progression. In the classic form, characterized by the absence of α-galactosidase A (α-Gal A) enzyme activity, diagnosis is straightforward. However, when residual activity is present, the delayed and less obvious presentation can make diagnosis more challenging. Ophthalmological alterations, which can be detected through non-invasive examinations may play a crucial role in correctly assessing the patient in terms of diagnosis and prognosis, particularly in these atypical cases. Recognizing these ocular signs allows for timely intervention with ERT, leading to improved patient outcomes. This review highlights the importance of ophthalmological findings in FD, emphasizing their role in diagnosis and treatment planning. By raising awareness among ophthalmologists and healthcare specialists, this review aims to improve disease management, offering tools for early detection and better long-term prognosis in patients with FD.

Keywords: Fabry disease; angio-OCT; confocal microscopy; cornea verticillata; enzyme replacement therapy; lysosomal storage disorder; retinal vessel density; vessel tortuosity.

Figure 1

Top left: illustration of X-linked inheritance in Fabry disease, showing various mutations that can affect the q22.1 region of the X chromosome (missense, frameshift, deletion, etc.). Top right: cell filled with Gl-3 and lyso-Gl-3 accumulation. Bottom left and right: schematic overview of Fabry disease pathophysiology, highlighting how the accumulation of Gl-3 and lyso-Gl3 leads to major organ dysfunction.

Figure 2

Schematic representation of the three main categories of ocular manifestations in Fabry disease: corneal alterations, vascular abnormalities, and lens opacification.

Figure 3

In vivo confocal microscopy examination of a healthy cornea (A) compared with a Fabry disease patient’s cornea (B), characterized by hyperreflective spots in the basal epithelium cells. The different appearance of corneal epithelial cells can help differentiate the etiology of cornea verticillata.

Figure 4

In vivo confocal microscopy examination of the sub-basal nervous plexus of a healthy cornea (A) compared with a Fabry disease patient’s cornea (B), characterized by a significant reduction in the length, number, and density of the nerve fibers, and by an increased tortuosity.