Using Healthcare Databases to Refine Understanding of Exploratory Associations Between Drugs and Progression of Open‐Angle Glaucoma

Abstract

We sought to refine understanding about associations identified in prior studies between angiotensin‐II receptor blockers, metformin, selective serotonin reuptake inhibitors, fibric‐acid derivatives, or calcium channel blockers and progression to glaucoma filtration surgery for open‐angle glaucoma (OAG). We used new‐initiator, active‐comparator cohort designs to investigate these drugs in two data sources. We adjusted for confounders using stabilized inverse‐probability‐of‐treatment weights and evaluated results using “intention‐to‐treat” and “as‐treated” follow‐up approaches. In both data sources, Kaplan–Meier curves showed trends for more rapid progression to glaucoma filtration surgery in patients taking calcium channel blockers compared with thiazides with as‐treated (MarketScan P = 0.15; Medicare P = 0.03) and intention‐to‐treat follow‐up (MarketScan P < 0.01; Medicare P = 0.10). There was suggestion of delayed progression for selective serotonin reuptake inhibitor compared with tricyclic antidepressants in Medicare, which was not observed in MarketScan. Our study provided support for a relationship between calcium channel blockers and OAG progression but not for other investigated drugs.

Commentary - Association of metformin use among diabetics and the incidence of primary open-angle glaucoma – The Chennai Eye Disease Incidence Study

“…[ 8 ] Previously, Wang et al . [ 4 ] have also reported similar findings. In their study, the administration of metformin did not halt the progression of POAG.…”

“…[ 2 ] Studies have hypothesized that metformin upregulates adenosine monophosphate-activated protein kinase (AMPK). [ 3 4 5 ] AMPK upregulation alters the tone of cells in the trabecular meshwork, thus lowering the IOP and preventing the progression of glaucoma. [ 6 7 ] Preliminary results from animal studies have also shown that metformin exerts neuroprotective effect by upregulation of AMPK.…”

“…Moreover, metformin affects neurogenesis and longevity pathways and protects cells from ischemia and reperfusion injury. [ 3 4 5 ]…”

Systemic therapy a risk factor for glaucoma development and progression

“…-группа американских ученых не выявила аналогичных протекторных эффектов метформина. Возможно, это связано с различиями в дизайне исследований, в частности вызывает определенные вопросы использование в качестве основного критерия прогрессирования ПОУГ во втором исследовании необходимость выполнения антиглаукомной операции [39].…”

Association of metformin use among diabetics and the incidence of primary open-angle glaucoma – The Chennai Eye Disease Incidence Study

“…They studied ten years of data from the Clinformatics Data-Mart Database for diabetic individuals and reported that metformin is associated with a reduced risk of developing POAG in people with diabetes when taken above a threshold prescription amount of 1110 g.[ 5 ] Studies have also shown metformin not being associated with the reduced risk of progression of glaucoma. [ 6 ] We explored the possible association between metformin use and the incidence of glaucoma among individuals of Indian ethnicity using population-based cohort data from the Chennai Glaucoma Study and the Chennai Eye Disease Incidence Study.…”