The Protective Effect of Metformin Use on Early Nd:YAG Laser Capsulotomy

Invest Ophthalmol Vis Sci. 2021 Aug 2;62(10):24. doi: 10.1167/iovs.62.10.24.


Purpose: To determine the effect of metformin on early Nd:YAG laser treatment for posterior capsule opacification (PCO) and to explore a molecular mechanism to explain a possible protective effect of metformin against PCO.

Methods: We conducted: 1) a retrospective cohort study of patient eyes undergoing phacoemulsification at our institution; and 2) laboratory investigation of the effect of metformin on the behavior of lens epithelial cells in the context of an animal model for PCO. Population-averaged Cox proportional hazards modeling was used to estimate risk for time to Nd:YAG. For laboratory studies, expression of markers for epithelial-to-mesenchymal transition (EMT) implicated in PCO pathogenesis was measured in tissue culture and following extracapsular lens extraction in a mouse model.

Results: The rate of Nd:YAG laser capsulotomy was 13.1% among the 9798 eyes. Both metformin use and diabetes were protective factors for Nd:YAG laser capsulotomy in univariate analysis. However, in multivariable analysis with nondiabetics as the reference group, only metformin use among diabetics was significantly protective of Nd:YAG (hazard ratio: 0.68, 95% CI: 0.54-0.85, P = 0.0008), while eyes of patients with diabetes without metformin use did not significantly differ (P = 0.5026). Treatment of lens epithelial cells with metformin reduced the level of the EMT markers ⍺-SMA and pERK induced by TGF-β2. Similarly, metformin treatment reduced ⍺-SMA expression in lens epithelial cells following extracapsular lens extraction in a mouse model.

Conclusions: The protective effect of metformin against early Nd:YAG may relate to its ability to downregulate EMT in residual lens epithelial cells that otherwise trend toward myofibroblast development and PCO.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Capsule Opacification / therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Laser Therapy / methods*
  • Lasers, Solid-State / therapeutic use*
  • Lenses, Intraocular
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Posterior Capsule of the Lens / drug effects*
  • Posterior Capsule of the Lens / surgery
  • Posterior Capsulotomy / methods*
  • Postoperative Complications / prevention & control*
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome


  • Hypoglycemic Agents
  • Metformin