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Joëlle Vergroesen, Bruno HC Stricker, Arfan M Ikram, Maryam Kavousi, Albert Hofman, Caroline Klaver, Wishal Ramdas; Systemic metformin use reduces open-angle glaucoma risk. Invest. Ophthalmol. Vis. Sci. 2020;61(7):656.
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The use of metformin, commonly prescribed in patients with Diabetes Mellitus type 2 (T2DM), leads to downstream inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). NF-κB activation in glial cells promotes neuronal cell death. Thus, metformin may possess neuroprotective properties in the development of open-angle glaucoma (OAG). The aim of the current study is to explore the associations of metformin with OAG.
Longitudinal data of three prospective population-based cohort studies (Rotterdam Study[RS]-I, RS-II, RS-III) were analyzed. Participants, aged ≥45 years with no OAG at baseline, were regularly monitored for incident OAG. Information on metformin use was obtained through continuous registration by pharmacies during the entire study period. The association of metformin with intraocular pressure (IOP) and incident OAG was analyzed using multivariate linear regression analyses and Cox proportional hazards models, respectively. Both analyses were adjusted for age, sex, BMI and use of statins and anti-hypertensive medication.
During a mean follow-up of 10.1±5.4 years, 210 (2.5%) of 8,529 participants developed OAG; metformin was used by 492 (5.8%) participants. Metformin use was significantly associated with elevated IOP in participants using >2g/day/year (Beta with corresponding 95% confidence interval [CI]: 0.544 [0.08-1.01]). T2DM by itself was not associated with IOP. Use of metformin was associated with reduced risk of developing OAG in the entire group (hazard ratio (HR) [95% CI]: 0.35 [0.14-0.85]) and in participants with T2DM (HR [95% CI]: 0.16 [0.05-0.49]), respectively. We observed a trend towards a reduced risk with prolonged use in both groups (HR [95% CI]: 0.83 [0.69-1.00] and HR [95% CI]: 0.74 [0.59-0.93], respectively).
Systemic use of metformin was associated with a reduced risk of OAG, in a duration-dependent manner; this could not be explained by IOP. Thus, mechanisms beyond IOP regulation may be involved in the metformin-induced OAG risk-reduction.
This is a 2020 ARVO Annual Meeting abstract.
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