Phenotypic features of glaucoma patients with the Optineurin E50K mutation

Abstract

Abstract: : Purpose:To investigate the clinical features of glaucoma subjects with the E50K mutation in the Optineurin (OPTN) gene, and to compare these patients with a control group of glaucoma subjects without the mutation. Methods:A retrospective analysis was performed on 11 well–characterized glaucoma subjects from Moorfields Eye Hospital, London who had been identified to carry the E50K OPTN mutation. A wide range of structural, psychophysical and demographic factors were then compared with a control group of 87 glaucoma subjects who were screened and found not to have the mutation, matched on the basis of normal tension glaucoma (NTG) or high tension glaucoma classification status. For patients with at least 5 years of follow–up, pointwise linear regression analysis was applied to the visual field series. Results: All subjects with the E50K mutation in this study were found to have NTG, with presenting and highest IOP (on diurnal testing) of 15.3 + 3.0 mm Hg (mean + SD) and 16.5 + 2.5 mm Hg respectively. Compared to other NTG controls, those with the E50K mutation tend to present at a younger age (40.8 + 11 years, p=0.0001), and have more advanced cupping (mean CD ratio 0.86 + 0.1, p=0.001), and smaller neuroretinal rim area, as measured by HRT (0.5 + 0.28 mm,² p=0.001), at the time of initial diagnosis. Using pointwise linear regression analysis, all subjects with E50K were found to have significant progressing points in their visual fields. The rate of filtering surgery performed for progressive visual field loss in those with and without E50K was 72.7% and 25.3% respectively (p=0.003). Conclusions:Subjects with the E50K mutation in the OPTN gene were found to have a severe and progressive NTG phenotype that manifests in young adulthood. Family members of such individuals should be screened in order to minimize visual loss.

Keywords: genetics • clinical (human) or epidemiologic studies: natural history • intraocular pressure