Study Finds No Protective Benefit against Retinopathy with Omega-3 Fatty Acids

Jane Armitage, FRCP, FFPH
Credit: Oxford Population Health

There was no protective benefit against diabetic retinopathy with use of omega-3 fatty acids, according to a new study.

A substudy of the ASCEND trial, results indicate there was no clinically meaningful benefit associated with use of omega-3 fatty acids relative to placebo on development of diabetic retinopathy.¹

“Preclinical studies support a protective role for omega-3 fatty acids on diabetic retinopathy, but these observations have not been confirmed in randomized trials,” wrote investigators.¹

The safety and efficacy of omega-3 fatty acids on health has been under the microscope of trialists in cardiometabolic health for the last decade. Although such of the attention to these trials has been dedicated to the REDUCE-IT and STRENGTH trials, which examined icosapent ethyl (Vascepa) and an EPA/DHA agent, respectively, multiple other trials were launched to further examine associations between different forms of omega-3 fatty acids, such as the ASCEND trial.^2,3

A double-blind, randomized, placebo-controlled trial of adult patients aged 40 years and older with diabetes but no evident cardiovascular disease, the A Study of Cardiovascular Events in Diabetes (ASCEND) trial randomized 15,480 patients to 1-gram capsules containing 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid or a matching placebo containing olive oil daily. The trial had a primary outcome of interest defined as first serious vascular event and a mean follow-up duration of 7.4 years.⁴

Results of the study suggested a serious vascular event occurred among 8.9% of the omega-3 fatty acid group and among 9.2% of the placebo group (rate ratio [RR], 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=.55). Further analysis indicated death from any cause occurred among 9.7% in the omega-3 fatty acid group and among 10.2% in the placebo group (RR, 0.95; 95% CI, 0.86 to 1.05).⁴

A substudy of the ASCEND trial, named ASCEND-EYE, a team of investigators led by Jane Armitage, FRCP, FFPH, of the Nuffield Department of Public Health used linked data from the NHS Diabetic Eye Screening Program records in England and Wales to identify participants from the trial who developed diabetic retinopathy. Investigators pointed out eye-reported events were assessed via a medical record review.¹

The primary efficacy outcome of interest for the subsidy was time to the first post-randomization recording of referable disease, which investigators defined as a composite of referable retinopathyor referable maculopathy based on the grading criteria defined by the UK National Screening Committee. The substudy also included multiple secondary and tertiary outcomes, such as referable disease outcome stratified by the severity of DR at baseline, any progression in retinopathy grade, and incident diabetic maculopathy.¹

A total of 7360 participants with linkage data were included in the current study, which represents 48% of those randomized in ASCEND. At baseline this cohort had a mean age of 63.5 (Standard Deviation, 8.9) years, 62% of the group was male, 96% were White, and 95% had type 2 diabetes. The mean follow-up duration among this cohort was 6.5 years.^1,4

Upon analysis, 14.8% in the omega-3 fatty acids group and 13.9% in the placebo group experienced a referable disease event (RR, 1.07; 95% CI, 0.95-1.20; P=.29). Further analysis revealed there were no statistically significant between-group differences in the proportion of events for either row the secondary or tertiary outcomes.¹

“Representing the first large-scale, prospective test of its kind, these data exclude any clinically meaningful benefits of 1 g daily omega-3 [fatty acids] on [diabetic retinopathy],” wrote investigators.¹

References:

1. Sammons EL, Buck G, Bowman LJ, et al. ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy. Ophthalmology. Published online December 3, 2023. doi:10.1016/j.ophtha.2023.11.030
2. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. doi:10.1056/NEJMoa1812792
3. Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020;324(22):2268–2280. doi:10.1001/jama.2020.22258
4. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018;379(16):1540-1550. doi:10.1056/NEJMoa1804989
5. Sammons E, Bowman L, Stevens W, et al. ASCEND-Eye: Rationale, design and baseline characteristics for a sub-study of the ASCEND randomised trial, exploring the effects of aspirin and omega-3 fatty acids on diabetic retinopathy and age-related macular degeneration. Contemp Clin Trials Commun. 2023;35:101184. Published 2023 Jul 5. doi:10.1016/j.conctc.2023.101184