Reversal of Cystoid Macular Edema in Gyrate Atrophy Patients

Abstract

Purpose : Gyrate atrophy (GA) of the choroid and the retina is an autosomal recessive disorder related to mutations in the ornithine-aminotransferase gene (OAT). This study reports the presentation of two families with GA. The aim of this study was to show the effect of low protein diet and pyridoxine treatment on accompanying macular edema.

Methods : Two unrelated patients with GA were studied for the effect of low protein diet (≤ 0.8 g/kg/d), and oral administration of pyridoxine (500mg/day) on serum ornithine levels, best corrected visual acuity (BCVA), slit-lamp, OCT, and auto-fluorescence findings.
Blood samples for DNA, mRNA and exons of the OAT gene were screened for mutations, and splicing effect when relevant.

Results : At presentation both patients manifested typical ophthalmic features of GA including cystoids macular edema (CME). One patient also exhibited optic nerve head astrocytic hamartomas. Following treatment, in patient A, ornithine levels have lessened by 178 μmol/l, BCVA improved from 6/120 in both eyes to 6/30 OD and 6/21 OS. Central macular thickness (CMT) decreased by 270 µm OD and 161 µm OS.
Patient B showed improvement in BCVA from 6/15 to 6/12 OD and from 6/12 to 6/8.5 OS. CMT decreased by 80 µm OD and 47 µm OS. Ornithine levels decreased by 140 μmol/l. In both patients the effect remained for 14 months.
OAT sequencing identified two known mutations: OAT c.159delC; p.H53Qfs7*, c.386C>T_p.Thr129Ile (patient A, patient B respectively) and a novel splice site mutation, c.900+1 G>A (patient B).

Conclusions : We have identified a novel mutation and two formerly described mutations in patients with GA. Of them, one patient comprised an unusual phenotype including bilateral astrocytic hamartomas. We have recognized for the first time, improvement in CME following treatment with low protein intake and pyridoxine supplement. This finding may have significance in the understanding of treatment options for macular edema regardless of underlying etiology.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.