Frequent Anti-VEGF Dosing Sustains Acuity in Diabetic Macular Edema

Optical coherence tomography (OCT) of a patient show has a retinal edema. (Photo by: BSIP/Universal Images Group via Getty Images)
Fixed-treatment regimen using injections or drug-eluting implant offers superior results to as-needed approach.

For patients with diabetic macular edema (DME), age and frequency of anti-vascular endothelial growth factor (VEGF) dosing proved to be two of the most important variables impacting visual acuity, according to the findings of a systematic review and meta-analysis published in Clinical Ophthalmology. Researchers analyzed 72 randomized, controlled trials and real-world, observational studies — a total of 45,032 eyes of patients who underwent anti-VEGF injection therapy and dosing using a dexamethasone implant, and were followed for 12 months. The dexamethasone controlled-release implant is bioerodible and was licensed for the treatment of DME in 2014.

With anti-VEGF drugs ranibizumab, bevacizumab and aflibercept, fixed treatment programs provided better outcomes than PRN regimens (coefficient +2.4 ETDRS letters, P =.009). Fixed programs also outperformed treat-and-extend therapy (coefficient +3.6 ETDRS letters, P =.043). Participants undergoing treatment with bevacizumab, though, attained comparable outcomes with fixed and PRN regimens (coefficient +3.5 ETDRS letters, P =.1).

The research also demonstrates better acuity outcomes with the dexamethasone controlled-release implant in observational studies than in randomized controlled trials.

The meta-analysis confirmed previous studies which demonstrate that the frequency of injections has an impact on visual acuity. “Each additional injection produces +0.88 letter gain at month 12,” according to investigators. Aflibercept was less dependent on injection frequency (with a coefficient +0.40 ETDRS letters per injection) than ranibizumab and bevacizumab at +1.08 and +0.99 per year, respectively. Researchers theorize that this is due to most aflibercept studies using fixed or treat-and-extend regimens, bringing about more regular visits and less variable number of injections.

Interestingly, when considering both randomized control trials and real-world observational studies, aflibercept exhibited better outcomes than bevacizumab (coefficient +3.01 ETDRS letters, P =.04). It was also superior to dexamethasone implant (coefficient +3.95 ETDRS letters, P =.01). Aflibercept compared with ranibizumab similarly (coefficient +2.01 ETDRS letters, P =.06). However, in observational studies alone, no statistically significant differences appeared between drugs.

While baseline central retinal thickness did not greatly impact visual outcomes in real life (P =.34), increased age did affect results (coefficient −0.54 ETDRS letters, P <.001). Diabetes duration was also a factor (coefficient +0.98 ETDRS letters, P <.0001), as well as baseline best-corrected visual acuity (coefficient −0.32 ETDRS letters, P <.0001).

A limitation of this meta-analysis is the quality of some studies, including the chance for risk of bias. Also, heterogeneity of the included studies is considerable due to different sample sizes, study designs, and types of treatment provided. However, the strength of the systematic review is its reflection of DME therapies currently practiced. 

In the total study population, participants’ best-corrected visual acuity grew by +8.13 ETDRS letters (95% CI, 7.26–9.00) at 12-month follow-up. Thus, the researchers affirm meaningful gains in visual acuity are attainable with intravitreal therapy. 

Disclosure: Several study authors declared affiliations with the biotech or pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.


Veritti D, Sarao V, Soppelsa V, Lanzetta P. Managing diabetic macular edema in clinical practice: systematic review and meta-analysis of current strategies and treatment optionsClin Ophthalmol. 2021;15:375-385. doi:10.2147/OPTH.S236423.