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We read with great interest the article of Gokhale et al  on their retrospective study of metformin use and risk of age-related macular degeneration (AMD) in individuals with type 2 diabetes mellitus (T2DM). In this study Gokhale and colleagues used data derived from IQVIA Medical Research Data (IMRD-UK), formerly known as The Health Improvement Network (THIN), and found no change in AMD risk in those taking metformin.
An issue with this study is the quality of the GP coding and data on AMD. The authors cite a validation study of THIN data  but this study only validated cases identified as having AMD. There was no validation of the quality of data on the absence of AMD. So, the confirmation of positives was high (confirmed AMD cases quoted as 97%) but the false negative rate, is unknown. Also, the validation was by an ophthalmologist reviewing all the GP data, not using recognised diagnostic criteria or a grading scheme for AMD. Furthermore, the authors included a code for “drusen” into their AMD group which was not a code included in the validation study by Vassilev et al . It is likely that this code includes patients with common physiological drusen and not an AMD diagnosis.
We have previously performed a systematic review and meta-analysis  of five studies [4–8] on the relationship between metformin use and AMD, which we have now updated to include Gokhale et al  and Jiang et al . Including their data, we found a beneficial odds ratio of...
We have previously performed a systematic review and meta-analysis  of five studies [4–8] on the relationship between metformin use and AMD, which we have now updated to include Gokhale et al  and Jiang et al . Including their data, we found a beneficial odds ratio of metformin use for “any AMD” remained (OR 0.75, 95% CI 0.54-0.97, I2=98.5%). This information should be interpreted with caution due to the high heterogeneity between studies including racial differences. We agree that further studies into the potential benefit of metformin for AMD are certainly warranted, including population-based datasets with accurate AMD diagnoses and prospective clinical trials.
1. Gokhale KM, Adderley NJ, Subramanian A, et al. Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study. British Journal of Ophthalmology Published Online First: 3 February 2022. doi:10.1136/bjophthalmol-2021-319641
2. Vassilev ZP, Ruigómez A, Soriano-Gabarró M, et al. Diabetes, Cardiovascular Morbidity, and Risk of Age-Related Macular Degeneration in a Primary Care Population. Invest Ophthalmol Vis Sci 2015;56:1585–92. doi:10.1167/iovs.14-16271
3. Romdhoniyyah DF, Harding SP, Cheyne CP, et al. Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis. Ophthalmol Ther 2021;10:245–60. doi:10.1007/s40123-021-00344-3
4. Brown EE, Ball JD, Chen Z, et al. The Common Antidiabetic Drug Metformin Reduces Odds of Developing Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 2019;60:1470–7. doi:10.1167/iovs.18-26422
5. Stewart JM, Lamy R, Wu F, et al. Relationship between Oral Metformin Use and Age-Related Macular Degeneration. Oph Retina 2020;0. doi:10.1016/j.oret.2020.06.003
6. Blitzer AL, Ham SA, Colby KA, et al. Association of Metformin Use With Age-Related Macular Degeneration: A Case-Control Study. JAMA Ophthalmology Published Online First: 21 January 2021. doi:10.1001/jamaophthalmol.2020.6331
7. Chen Y-Y, Shen Y-C, Lai Y-J, et al. Association between Metformin and a Lower Risk of Age-Related Macular Degeneration in Patients with Type 2 Diabetes. Journal of Ophthalmology. 2019. doi:10.1155/2019/1649156
8. Lee H, Jeon H-L, Park SJ, et al. Effect of Statins, Metformin, Angiotensin-Converting Enzyme Inhibitors, and Angiotensin II Receptor Blockers on Age-Related Macular Degeneration. Yonsei Med J 2019;60:679–86. doi:10.3349/ymj.2019.60.7.679
9. Jiang J, Chen Y, Zhang H, et al. Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: a retrospective study. BMJ Open 2022;12:e054420. doi:10.1136/bmjopen-2021-054420
Author: Dewi Fathin Romdhoniyyah (1), Nicholas AV Beare (1,2)
(1) Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
(2) St. Pauls Eye Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK