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J.R. Polansky, R.C. Juster, G.L. Spaeth; Accelerated Optic Disc and Visual Field Damage in POAG Patients Associated with the Myocilin Mt.1(+) Promoter Variant . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3230.
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Purpose: To evaluate the effects of the myocilin mt.1(+)genotype (TIGR/MYOC mt.1,-1000 C/G) on the rate of glaucoma progression, using independent analyses of optic disc and visual field measures of disease severity. Methods: The study involved 147 POAG patients over 35 years of age who had a minimum follow-up time of 8 years (average of approximately 15 years). Optic disc and visual field damage were graded separately in a masked fashion using 8-point graded scales defined in protocols at the Wills Eye Hospital glaucoma clinic. The mt.1(+) genotype was found in approximately 15% of the patients examined. Time to event analyses using the Cox proportional hazards model were performed by evaluating changes in disc and field scores from that observed at baseline. Results: Patients with the mt.1(+) genotype showed a substantial acceleration of disease worsening in separate statistical analyses of optic disc and visual field measures of severity.Strong statistical evidence for this effect was found, taking into account the effects of other baseline risk factors (age, family history, initial drug treatment, initial surgical treatment, diabetes, gender, myopia, and initial disease severity), for both disc and field analyses. There was a noticeable age effect on disease progression observed for the mt.1(-) individuals, but the age effect had less impact for those with the mt.1(+) genotype. The result was that comparisons of the rates of disease progression for mt.1(+) and (-) individuals showed larger differences with younger baseline ages. Mt.1(+) and (-) patients showed no major differences in IOP at baseline, and no apparent resistance to IOP lowering treatments. Conclusions: The finding that the mt.1(+) genotype is associated with accelerated glaucomatous optic neuropathy, above and beyond other baseline factors, supports the value of determining the presence of this promoter variant in POAG patients.
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