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Randomized Controlled Trial
. 2025 Sep 12;6(9):100747.
doi: 10.1016/j.medj.2025.100747. Epub 2025 May 27.

Oral lamivudine in diabetic macular edema: A randomized, double-blind, placebo-controlled clinical trial

Felipe Pereira  1 , Joseph Magagnoli  2 , Meenakshi Ambati  3 , Talita Fernandes de Oliveira  1 , Juliana Angélica Estevão de Oliveira  1 , Vinicius Oliveira Pesquero  1 , Lucas Zago Ribeiro  1 , Dante Akira Kondo Kuroiwa  1 , Fernando Korn Malerbi  1 , Sergio Atala Dib  4 , Nilva Bueno Moraes  1 , Michel Eid Farah  1 , Eduardo Buchele Rodrigues  1 , Jayakrishna Ambati  5
Affiliations
Randomized Controlled Trial

Oral lamivudine in diabetic macular edema: A randomized, double-blind, placebo-controlled clinical trial

Felipe Pereira et al. Med. .

Abstract

Background: Diabetic macular edema (DME) affects millions worldwide. Intraocular injections of expensive anti-vascular endothelial growth factor (VEGF) inhibitors associated with complications are standard therapy. Lamivudine, an inexpensive oral drug, inhibits inflammasome activation, which is implicated in DME. This randomized, double-blind, placebo-controlled trial compared oral lamivudine to placebo for improving visual acuity in center-involved DME (CI-DME).

Methods: Twenty-four adults enrolled between February 2022 and September 2023 with 1 or 2 eyes with CI-DME and a best-corrected visual acuity (BCVA) of less than 69 letters (Brazilian Registry of Clinical Trials RBR-87b6r5s) were randomized to lamivudine (150 mg twice daily; 10 participants; 16 eyes) or placebo (14 participants; 21 eyes) for 8 weeks. Participants were assigned intravitreous bevacizumab (1.25 mg) at week 4. Co-primary outcomes were mean changes in BCVA from baseline to weeks 4 and 8. Comparisons to anti-VEGF drugs used synthetic controls from DRCR.net Protocol T. Secondary outcomes included retinal thickness and adverse events.

Findings: At 4 weeks, BCVA improved 9.8 letters with lamivudine and decreased 1.8 letters with placebo (p < 0.001). At 8 weeks, BCVA improved 16.9 letters with lamivudine and bevacizumab and 5.3 letters with placebo and bevacizumab (p < 0.001). Lamivudine was associated with greater BCVA improvement than bevacizumab or ranibizumab (p < 0.05) and was not different from aflibercept (p = 0.5). There was no significant difference in retinal thickness or adverse events between groups.

Conclusions: Lamivudine, an oral inflammasome inhibitor, significantly improved vision in patients with CI-DME.

Funding: This work was supported by Universidade Federal de São Paulo, Latinofarma, UVA SIF, and NIH.

Keywords: NRTI; Translation to patients; clinical trial; diabetic macular edema; inflammasome; lamivudine.

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Conflict of interest statement

Declaration of interests J.A. reports being a co-founder of iVeena Holdings, iVeena Delivery Systems, and Inflammasome Therapeutics and, unrelated to this work, receiving consulting fees from Retinal Solutions and Saksin LifeSciences and being on the board of Theragen. M.E.F. reports being a scientific consultant of Latinofarma. F.P., M.E.F., E.B.R., and J.A. reported being named as inventors on matter-related patent applications.

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