Patients with type 2 diabetes who took common anti-inflammatory drugs like prednisone, ibuprofen, or cetirizine had a 37% to 64% lower risk of vision-threatening diabetic retinopathy, according to a study in Ophthalmology, which suggests inflammation control may be a key therapeutic target.
The study published in Ophthalmology found that adults with type 2 diabetes who used anti-inflammatory medications such as prednisone, ibuprofen, or cetirizine had significantly lower risks of developing severe diabetic eye complications compared to nonusers. This discovery, led by Henry S. Bison, MD, at the University of Maryland School of Medicine, challenges existing treatment paradigms by highlighting inflammation as a potential therapeutic target for diabetic retinopathy.
Anti-Inflammatory Drugs Linked to Reduced Risk
The research analyzed health records of a large number of patients with type 2 diabetes, identifying a 37% to 64% risk reduction for vision-threatening complications like diabetic macular edema and proliferative diabetic retinopathy among users of anti-inflammatory drugs. Cetirizine, a common antihistamine, was associated with a 38% lower risk of diabetic macular edema (hazard ratio [HR], 0.62; 95% CI, 0.51–0.74) and a 41% reduced risk of proliferative diabetic retinopathy (HR, 0.59; 95% CI, 0.46–0.77). Ibuprofen users saw a 37% lower risk of macular edema (HR, 0.63; 95% CI, 0.56–0.69) and a 52% lower risk of proliferative retinopathy (HR, 0.48; 95% CI, 0.41–0.56). Prednisone users experienced over 50% risk reductions for both conditions.
The study also found that fenofibrate, a drug already known to protect diabetic eyes, showed similar risk reductions. This convergence across four distinct anti-inflammatory agents—cetirizine, ibuprofen, prednisone, and fenofibrate—supports the hypothesis that inflammation control could influence retinopathy progression. However, gabapentin, a non-anti-inflammatory pain medication, showed no protective effect, reinforcing the link between anti-inflammatory activity and reduced risk.
Early anti-VEGF treatment of diabetic retinopathy yields no benefit
Methodology and Limitations of the Retrospective Study
The retrospective analysis, conducted through the TriNetX US Collaborative Network, matched 18,762 to 86,846 pairs of drug users and nonusers based on 44 factors, including age, comorbidities, and baseline retinopathy severity. Researchers tracked new cases of diabetic macular edema and proliferative retinopathy over three years, starting from each patient’s second qualifying visit. While the study found strong associations, it could not prove causation due to its observational design.
Limitations included the lack of detailed dosage data and the fact that drug users and nonusers entered the study through slightly different types of visits. Despite these constraints, the researchers emphasized that the consistent risk reductions across multiple anti-inflammatory drugs suggest a meaningful biological relationship between inflammation and retinopathy progression.
Implications for Diabetic Eye Disease Treatment
The findings could reshape treatment strategies for diabetic retinopathy, particularly for patients who may not tolerate or respond to existing therapies like anti-VEGF injections. While the NIH study from 2023 found no visual acuity benefit from early anti-VEGF treatment, this Ophthalmology study highlights a different pathway: inflammation management. However, the authors caution that further research, including randomized controlled trials, is needed to confirm these results and establish safe, effective protocols.
Anti-Inflammatory Meds Tied to Low Diabetic Retinopathy Risk
Our findings indicate that fenofibrate may not be the only oral medication associated with reduced risk of vision-threatening diabetic retinopathy, the researchers wrote. The study’s lead author, Henry S. Bison, MD, noted that the convergence of results across pharmacologically distinct anti-inflammatory agents strengthens the case for targeting inflammation in retinopathy care. However, he acknowledged that the retrospective nature of the study means causality remains unproven.
For patients and clinicians, the study underscores the importance of monitoring inflammation as a potential risk factor. While no new treatments have been approved based on these findings, the data may prompt reevaluation of existing medications and encourage further investigation into anti-inflammatory therapies. The next step, according to the authors, is to conduct prospective trials to validate these associations and explore their clinical applications.
Additional Context from the DRCR Retina Network Study
A 2023 study from the DRCR Retina Network, funded by the National Eye Institute (NEI), found that early treatment of diabetic retinopathy with anti-VEGF drugs like Eylea (aflibercept) did not improve visual acuity compared to treating more severe cases once they developed. The study, led by Raj Maturi, M.D., of Indiana University School of Medicine, followed 328 participants with 399 study eyes over four years. Preventive anti-VEGF injections were given in 200 eyes at one month after enrollment, two months, and four months, then every four months for two years. Sham injections were used in 199 eyes. At four years, 34% of eyes in the preventive group showed disease progression, compared to 57% in the sham group. The average number of injections was 11 in the preventive group versus three in the sham group.
We expected early treatment to prevent progression of diabetic retinopathy, but even with preventative injections, about one-third of eyes developed vision-threatening complications,
said Adam Glassman, of the Jaeb Center for Health Research. Jennifer Sun, M.D., of the Joslin Diabetes Center, noted that while the individual risk of complications per injection is low, the risk increases with each additional injection. The study was published in the Journal of the American Medical Association (JAMA).
Patients are advised to consult qualified healthcare professionals to determine the best approach for managing diabetic retinopathy, as the evidence does not support a one-size-fits-all solution. The DRCR study emphasizes the importance of monitoring and treating only when necessary, while the 2026 Ophthalmology study suggests inflammation control as a promising avenue for future research.