Identification of potential genetic risk markers in familial primary open-angle glaucoma in Tasmania

Approximately 50% of all primary open-angle glaucoma (POAG) is familial. Investigation of clinical risk factors associated with familial POAG may help to identify phenotypic subtypes of the disease, each with different pathophysiologic mechanisms that may be modified by intervention and disease-prevention strategies. In a cross-sectional retrospective study of 2940 'glaucoma' patients over 10 years of age in Tasmania, the prevalence of nine potential clinical risk factors (hypertension, diabetes mellitus, migraine headache, corticosteroids use, smoking, atherosclerosis, cold extremities, blood transfusion, thyroid disorders) were compared using multi-stepped regression analysis between 1014 patients with familial glaucoma and 688 patients with sporadic or non-familial glaucoma classified by Glaucoma Inheritance Study in Tasmania (GIST) scores (intraocular pressure, optic disc and visual field changes) and genealogic data. 59.6% of all subjects with POAG have a positive family history of POAG. There is no significant difference in the distribution of gender between the familial and sporadic POAG groups (OR 1.053; 95%CI 0.819-1.353). No risk factor examined is significantly different in the familial glaucoma group in comparison to the sporadic glaucoma group, after adjusting for confounding effects of age and gender, GIST scores, degree of relatives or other potential clinical risk factors. The distribution of GIST scores in the familial glaucoma group is skewed towards the higher spectrum and is significantly different from that of the sporadic glaucoma group (p<0.001), suggesting the likelihood of an earlier onset and/or a greater severity of glaucoma in the familial group.