Anti-VEGF drugs successful against DME


Growing evidence shows agents to be viable option in treating ocular diseases caused by diabetes


Anti-vascular endothelial growth factor agents may produce good results quickly and sustainably in patients with diabetes who are affected by diabetic macular edema and other eye disorders.


By Liz Meszaros; Reviewed by Adam S. Wenick, MD, PhD

Baltimore-Successful treatment of many ocular diseases, including diabetic macular edema (DME), is closer to becoming a reality.

This is especially encouraging in light of the epidemic proportions diabetes and the ocular damage it can cause in patients, noted Adam S. Wenick, MD, PhD.

Worldwide, about 346 million people are affected by diabetes, and by 2030, the number of patients with diabetes is expected nearly to double. Diabetes is currently the leading cause of vision loss in working-age adults, and DME is the leading cause of vision loss related to diabetes. The 9- to 14-year incidence for DME after the onset of type 1 diabetes Is 26% to 27%, and this incidence is higher in patients with type 2 diabetes.

“Anti-vascular endothelial growth factor (VEGF) [therapy] has become the preferred therapy for the treatment of DME involving the central macula associated with decreased vision,” said Dr. Wenick, assistant professor of ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

“For eyes with non-central DME and center-involving DME with preserved vision, observation, focal/grid laser, or anti-VEGF therapy can be considered,” he said.

Laser photocoagulation

Since researchers conducted the Early Treatment Diabetic Retinopathy Study (ETDRS), argon laser photocoagulation has been the mainstay of treatment for macular edema, noted Dr. Wenick.1

After ETDRS, both the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study showed that tight glycemic control and blood pressure control can reduce the risks of the microvascular complications of diabetes, and these became the standard of care.

Yet, results from the Diabetic Retinopathy Clinical Research Network ( showed that, even with tight control of these factors, 14% of patients who underwent focal/grid laser for foveal-centered DME lost ≥15 ETDRS letters after 2-year follow up.2

Evidence favoring anti-VEGF

In recent years, intravitreal corticosteroids and intravitreal anti- VEGF agents have come into use for the management of DME, Dr. Wenick added. Several recent randomized clinical trials have indeed shown the superior efficacy of ranibizumab (Lucentis, Genentech) compared with focal/grid laser.

Another study from has also shown that ranibizumab, used with either prompt or deferred laser, brought about better outcomes than those achieved using laser alone or laser plus triamcinolone.3

Results from the RESTORE study,4 in which patients were treated with laser and a sham injection (111 eyes), ranibizumab plus laser (118 eyes), or ranibizumab plus sham laser (116 eyes) over a 12-month period, showed that ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in best-corrected visual acuity (BCVA) letter score from baseline to months 1 through 12 (+6.1, +5.9 versus +0.8, respectively; p < 0.0001).

In the RISE/RIDE phase III clinical randomized trials,5 ranibizumab was shown to improve vision quickly and sustainably, reduce the risk for further vision loss, and improve macular edema in patients with DME. In both the RIDE (382 patients) and RISE trials (377 patients), significantly more patients treated with ranibizumab compared with laser alone gained ≥15 letters.

The BOLT study is a prospective randomized, masked, single-center clinical trial. The 2-year, two-arm study includes subjects who were randomly assigned to either intravitreal bevacizumab (Avastin, Genentech) dosed every 6 weeks for three treatments and subsequently as needed, or modified ETDRS macular laser therapy at baseline and then as needed as often as every 4 months as indicated by ETDRS treatment guidelines.6

Two-year data show that patients treated with bevacizumab gained a mean of 8.6 ETDRS letters, compared with the laser group, which lost a mean of 0.5 ETDRS letters (p = 0.005). Further, the odds of gaining 10 or more ETDRS letters over 2 years were nine times greater in patients treated with bevacizumab compared with laser (p = 0.001).

Finally, results from the DA VINCI study, a phase II trial, showed that patients treated with the newest anti-VEGF agent, aflibercept (Eylea, Regeneron) had more significant gain in BCVA compared with laser alone from baseline by week 24, and calls for further investigation of aflibercept for the treatment of DME.7

In addition, they had significant reductions in central retinal thickness compared with those treated with laser (p < 0.001).

Based on data from the RISE and RIDE trials,8 “anti-VEGF therapy for the treatment of DME has the added benefit of preventing progression to more severe retinopathy and can lead to reversion to less advanced retinopathy,” Dr. Wenick concluded.


Early Treatment Diabetic Retinopathy Study research group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985;103:1796-1806.

Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115:1447-1449. e1-10.

Elman MJ, Aiello LP, Beck RW, et al. Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone pus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1064-1077.

Mitchell P, Bandello F, Schmidt-Erfurth U, et al, and the RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118:615-625.

Nguyen QD, Brown DM, Marcuse DM, et al, and the RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789-801.

Rajendram R, et al. A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3.Arch Ophthalmol. 2012;130:972-979.

Do DV, Nguyen QD, Boyer D, et al, and the DA VINCI Study Group. One-year outcomes of the DA VINCI Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012;119:1658-1665.

Ip MS, et al. Long-term effects of ranibizumab on diabetic retinopathy severity and progression. Arch Ophthalmol. 2012;130:1145-1152.



Adam S. Wenick, MD, PhD

Phone: 410/955-3518

Dr. Wenick has no disclosures. This article is adapted from Dr. Wenick’s presentation during the 25th annual Current Concepts in Ophthalmology meeting, held in association with the Wilmer Eye Institute and Ophthalmology Times.


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