Ocular Findings Associated With Oral Phosphate Binders in the Treatment of Pseudoxanthoma Elasticum

Abstract

Purpose:: Following a pilot study which demonstrated that treatment with aluminum hydroxide led to a significant regression of skin lesions in patients with pseudoxanthoma elasticum (PXE), the objective of this study was to assess the efficacy of sevelamer hydrochloride, an aluminum-free oral phosphate binder, on the reversal of elastic fiber calcification in patients with PXE. Calcification of Bruch’s membrane, angioid streaks and subsequent choroidal neovascularization (CNV) with central vision loss are complications of PXE. It was of interest to determine if the incidence and severity of these complications were reduced in the patients taking sevelamer.

Methods:: This was a randomized, investigator-blinded, two-part prospective study. The first part was a year-long, double-blind, placebo controlled study. Forty subjects with PXE were randomized to receive either sevelamer hydrochloride 800mp PO TID or placebo in a 1:1 ration. After one year, the second portion of the study was an open-label, year-long study. A complete eye examination, fundus photography and Indocyanine green angiography were performed at entry, 12 months and 24 months

Results:: Thirty-nine subjects completed the double-blinded portion of the study (19 in the placebo group and 20 in the sevelamer hydrochloride group). At year 1, the placebo group’s mean calcium score decreased from 29.52 to 15.97 (41.93% mean improvement), and the sevelamer hydrochloride’s mean calcium score decreased from 27.48 to 18.75 (38.37% mean improvement). Thirty-six patients completed the open-label portion of the study. At year 2, the original placebo group’s mean calcium decreased to 13.37 (53.94% improvement from baseline), and the sevelamer hydrochloride’s mean calcium score decreased to 14.03 (51.35% change from baseline). During the double-blind portion of the study two patients treated with sevelamer hydrochloride experienced three or greater lines of vision loss, and one patient experienced three lines of improvement. These changes were not statistically significant.

Conclusions:: Sevelamer hydrochloride produced a reduction in calcification levels over time; however, this difference was not statistically significant in comparison to the placebo group. There was no statistically significant difference in the incidence of CNV or visual acuity in the treatment group.This study was supported by FDA grant FD-R-002161-01 & 02.

Keywords: retinal degenerations: cell biology • retinal degenerations: hereditary • retinal neovascularization