Editors Selection IGR 23-1

Clinical Forms of Glaucoma: Glaucoma and Treated Diabetes

Rupert Bourne

Comment by Rupert Bourne on:

100638 Association of Diabetes Medication With Open-Angle Glaucoma, Age-Related Macular Degeneration, and Cataract in the Rotterdam Study, Vergroesen JE; Thee EF; Ahmadizar F et al., JAMA ophthalmology, 2022; 140: 674-681

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Long-term caloric restriction can reduce risk in some age-associated diseases such as cancer, diabetes, and cardiovascular disease. In this article by Vergroesen et al., metformin treatment was associated with a lower risk of primary open-angle glaucoma (POAG). This follows several cross-sectional and retrospective studies, for example, a medical claims database cohort of diabetic patients by Lin et al.,1 who reported that metformin, a caloric restriction mimetic drug, was associated with a reduction in POAG risk. Indeed, that study predicted that taking a standard dose of 2 mg metformin hydrochloride per day for two years would result in a 21% reduction in risk of POAG. Further evidence is provided by Vergroesen et al., involving the Rotterdam Study, a population-based cohort of 11,260 participants. Due to the nature of its prospective design and long follow-up (24 years), the authors were able to examine the association between untreated and treated Type-2 diabetes before the onset of POAG, and thereby determine cumulative lifetime risk of POAG. POAG was defined as glaucomatous visual field loss in at least one eye with reproducibility of the defect, independent of the intraocular pressure. Metformin treatment was associated with a lower POAG risk (OR, 0.18; 95% CI, 0.08-0.41, P < 0.001) compared with no treatment with diabetes medication.

Metformin treatment was associated with a lower POAG risk (OR, 0.18; 95% CI, 0.08-0.41, P<0.001) compared with no treatment with diabetes medication

Additionally, the cumulative lifetime risk of POAG was lower for individuals taking metformin (1.5%; 95% CI, 0.01-3.1%) than for individuals without Type-2 diabetes (7.2%; 95% CI, 5.7%-8.7%). Longer periods of treatment and higher cumulative dose of metformin was associated with lower POAG risk.

This study has confirmed the association of metformin with reduced POAG risk and by assessing the association between POAG and Type-2 diabetes in persons without medication, the study has also addressed confounding by indication, a problem in the interpretation of previous studies. The analysis also adjusted for other confounders and offers the reader an interesting explanation of how they tested for a causal relationship using Bradford Hill criteria.2 As the authors point out in their discussion, the next step is external replication and functional proof, and the prospect of interventional randomized clinical trials. To follow up on the latter, readers may like to read the editorial by Emily Eton and Paula Newman-Casey that directly follows Vergroesen et al.'s report, which discusses how such trials may be designed and the ethical implications therein.3


  1. Lin H, Stein JD, Nan B, et al. Association of geroprotective effects of metformin and risk of open-angle glaucoma in persons with diabetes mellitus. Jama Ophthalmol. 2015;133(8):915-923.
  2. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58(5):295-300. 3. Eton E, Newman-Casey P. A call for health equity in diabetic care to improve eye health. Jama Ophthalmol. 2022 Jul 1;140(7):681-682.

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