purpose. To investigate the clinical features of subjects with glaucoma with the E50K mutation in the optineurin (OPTN) gene and to compare the onset, severity, and clinical course of these patients with a control group of subjects with glaucoma without this mutation.

methods. The phenotype of well-characterized subjects from Moorfields Eye Hospital, London, who had been identified as carrying the OPTN E50K mutation was examined. A wide range of structural, psychophysical, and demographic factors were then compared with those in a control group of subjects with glaucoma without this mutation.

results. Eleven subjects with glaucoma with the E50K mutation (nine in two families and two sporadic cases) were studied. All 11 subjects had normal tension glaucoma (NTG), with presenting and highest IOP of 15.3±3.0 and 16.5±2.5 mm Hg (±SD) on diurnal testing. Compared with 87 NTG control subjects who did not have this mutation, subjects with E50K presented at a younger age (40.8±15 years, P= 0.0001) and had more advanced optic disc cupping (mean cup-disc ratio±SD 0.86±0.1, P= 0.001) and smaller neuroretinal rim area (±SD; 0.5±0.28 mm 2, P= 0.001) at diagnosis. The rate of filtration surgery performed for progressive visual field loss in those with and without the E50K mutation was 72.7% and 25.3%, respectively (P= 0.003), and all subjects with E50K were found to have progressing visual fields. In addition, seven E50K mutation-carrying individuals in two families (age range, 23–58 years) presented with normal optic discs and visual fields and, as yet, no signs of glaucoma.

conclusions. In this study, subjects with glaucoma who had the OPTN E50K mutation were found to have NTG that appeared to be more severe than that in a control group of subjects with NTG without this mutation. The findings emphasize the importance of early detection and treatment of glaucoma in such individuals, to minimize visual loss.