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Editors Selection IGR 22-3

Glaucoma and Systemic Diseases: Is glaucoma associated to metformin use?

Sasan Moghimi

Comment by Sasan Moghimi on:

95544 Association of metformin use among diabetics and the incidence of primary open-angle glaucoma - The Chennai Eye Disease Incidence Study, George R; Asokan R; Vijaya L, Indian Journal of Ophthalmology, 2021; 69: 3336-3338


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Pathophysiological similarities between diabetes mellitus and primary open angle glaucoma (POAG) include higher intraocular pressure, increased oxidative stress, promotion of retinal cell apoptosis, and impaired perfusion of the optic nerve head. Although experimental models based on animal-induced chronic hyperglycemia have shown a consistent association of POAG and diabetes,1 epidemiologic data2 have been inconsistent. Many of these studies suffer from limitations including the vague definition of diabetes and not considering the level of glycemic control and systemic medications. Specifically, metformin, an antihyperglycemic agent commonly prescribed for treating type 2 diabetes, has been shown to be geroprotective and reduce risks for a variety of ageassociated systemic diseases.3 Recently, this agent was found to be associated with reduced risk of POAG4 or glaucoma progression,5 suggesting that metformin may mediate some of the observed protective effects of diabetes on POAG.

George et al. carried out a prospective cohort study on 4302 participants of the rural and urban South Indian population (Chennai Eye Disease Incidence Study) to determine the association of metformin usage among subjects with diabetes mellitus and the six year incidence of POAG

Incidence of POAG was defined as subjects who did not have glaucoma at baseline but developed glaucoma and was reported to be 3%. 905 participants (21.0%) had diabetes mellitus. While in their study the incidence of POAG tended to be greater in DM patients (28.1%) compared to no-diabetes participants, (20.8%) (p=0.05), no difference in the incidence of POAG in subjects with diabetes mellitus, with (5.6%) and without metformin use (3.6%) was found (P = 0.25).

The strengths of the study include using large populationbased data from a cohort of Indian populations and assessment of the incidence of POAG over 6 years. Interestingly, only 15 % of the diabetic patients were using metformin (compared to up to 40% in prior reports) and thus the study is specifically underpowered for evaluation of the association of metformin and POAG. The reasons for the low number of metformin use might be attributed to the differences in guidelines for the treatment of diabetes in the Indian population or lower severity of diabetes due to the population-based nature of the study. Moreover, participants were evaluated only at two-time points and therefore survival analysis could not be completed. A recent meta-analysis has demonstrated that disease duration and fasting glucose levels were associated with an increase in glaucoma risk.6 However, they did not show data on HbA1c and amount of metformin usage and thus could not control the final model for status of glycemic control.

The question remains about the threshold of the amount of metformin that is protective for POAG in diabetes and whether the reduced risk of glaucoma with metformin is independent of improved glycemic control. Future clinical studies will also be needed to evaluate the effects of metformin on prediabeteic or nondiabetic populations and on glaucoma severity and progression.

References

  1. Wong VH, Bui BV, Vingrys AJ. Clinical and experimental links between diabetes and glaucoma. Clin Exp Optom. 2011;94(1):4-23.
  2. Tham YC, Cheng CY. Associations between chronic systemic diseases and primary open angle glaucoma: an epidemiological perspective. Clin Exp Ophthalmol. 2017;45(1):24-32.
  3. Cox LS, Mattison JA. Increasing longevity through caloric restriction or rapamycin feeding in mammals: common mechanisms for common outcomes? Aging Cell. 2009;8(5):607-613.
  4. Lin HC, 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.
  5. Hou H, Moghimi S, Baxter SL, Weinreb RN. Is diabetes mellitus a blessing in disguise for primary open-angle glaucoma? J Glaucoma. 2021;30(1):1-4.
  6. Zhao D, Cho J, Kim MH, Friedman DS, Guallar E. Diabetes, fasting glucose, and the risk of glaucoma: a meta-analysis. Ophthalmol. 2015;122(1):72-78.


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