Are Glaucomatous Disc Changes Evident Prior to Diagnosis of Glaucoma in Myocilin Pedigrees?

Abstract

Abstract: : Purpose:The aim of this study was to investigate whether structural differences of the optic nerve head are evident in young people who do not have manifest glaucoma, yet are known to carry common myocilin mutations. Methods: Pedigrees with either the Gln368X or Thr377Met myocilin mutations identified through the Glaucoma Inheritance Study in Tasmania were reviewed. Subjects aged less than 30 years were examined for signs of glaucoma. Stereoscopic disc photographs were digitalized. Analysis of optic disc area, optic cup area and neuroretinal rim area was performed stereoscopically using custom software with a Z–screen. Mutation analysis was conducted using DHPLC and restriction enzyme digestion. A case–control analysis was conducted using the Mann–Whitney test. Results: Twelve non–myocilin mutation (control) and 17 myocilin mutation (case) subjects were reviewed. The mean age was 15 (SD: 1.8) and 18 (SD: 1.4) years for the non–mutation and mutation groups respectively (P=0.19). The mean disc, neuroretinal rim and cup areas did not statistically significantly differ between the groups. The mean neuroretinal rim area was 1.51mm² (SD: 0.02) in the non–mutation group, whilst it was 1.42 mm² (SD: 0.17) in the mutation group (P=0.20). Conclusions: No quantified structural difference in the optic nerve head was observed in individuals who had a myocilin mutation prior to the diagnosis of glaucoma. Although confounded by penetrance, these preliminary results support the hypothesis that myocilin glaucomatous optic nerve changes occur after elevation of intraocular pressure. In contrast optineurin mutations are thought to act directly on the optic nerve.

Keywords: optic disc • genetics