An update on the ocular phenotype in patients with pseudoxanthoma elasticum

Abstract

Pseudoxanthoma elasticum (PXE) is an inherited multi-system disorder characterized by ectopic mineralization and fragmentation of elastic fibers in the skin, the elastic laminae of blood vessels and Bruch’s membrane in the eye. Biallelic mutations in the ATP-binding cassette (ABC) transporter gene ABCC6 on chromosome 16 are responsible for the disease. The pathophysiology is incompletely understood. However, there is consent that a metabolic alteration leads to dysfunction in extracellular calcium homeostasis and subsequent calcification of connective tissues rich in elastic fibers. This review summarizes and aims at explaining the variety of phenotypic ocular findings in patients with PXE. Specialized imaging techniques including white light fundus photography, blue light autofluorescence, near-infrared confocal reflectance imaging, high resolution optical coherence tomography, fluorescein and indocyanine green (ICG) angiography have revealed characteristic lesions at the ocular fundus of PXE patients. These include the classic signs of angioid streaks, peau d’orange, comet lesions, and choroidal neovascularizations (CNVs), but also the more recently recognized features such as chorioretinal atrophy, subretinal fluid independent from CNV, pattern dystrophy-like changes, debris accumulation under the retinal pigment epithelium, reticular drusen and a decreased fluorescence on late phase ICG angiography.

Reticular Pseudodrusen Associated With a Diseased Bruch Membrane in Pseudoxanthoma Elasticum

“…21 Thus, PXE appears suitable to specifically investigate the consequences of alterations in the BM.…”

“…Subsequently, chorioretinal atrophy and choroidal neovascularization may develop, mimicking phenotypic characteristics of AMD. 21 To date, there is some evidence of lesions resembling RPD in PXE, 21,22 suggesting a possible role of the BM in the pathophysiology of RPD. Therefore, we investigated the phenotype, prevalence, and topographic localization of RPD and their relation to BM calcification in patients with PXE using various imaging modalities to further clarify the association of diseased BM and the presence of RPD.…”

Reticular Pseudodrusen in Sorsby Fundus Dystrophy

“…In contrast, PXE is a monogenic disease with a defined ocular pathophysiologic process characterized by initial calcification and thickening confined to BM. 37 Sorsby fundus dystrophy, AMD, and aging also are associated with progressive thickening of BM as well as with deposits at the interface between BM and the RPE. 19e22,38e43 It therefore seems plausible that abnormal changes of BM and the BMeRPE interface contribute to the pathogenesis of RPD.…”

Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment

“…The disease can be isolated or associated with systemic disorders such as pseudoxanthoma elasticum [4,5] , pseudoxanthoma elasticum-like syndromes [6] , β-thalassemia [7] , sickle cell disease [8] , and Paget disease [9] . The occurrence of choroidal neovascularization (CNV) in the subretinal space complicates the disease and frequently results in legal blindness, especially in middleaged patients.…”