COMMENTARY

Better Treatments for Diabetic Macular Edema

Charles C. Wykoff, MD, PhD

Disclosures

September 27, 2013

In This Article

Anti-VEGF Treatments in Diabetic Macular Edema

Focal laser treatment remained the standard of care for the treatment of diabetic macular edema for about 25 years. In the 2000s, however, pharmaceuticals that specifically inhibit VEGF, including ranibizumab (Lucentis®), bevacizumab (Avastin®), and aflibercept (Eylea®), have revolutionized the management of diabetic macular edema as well as other retinal exudative diseases, such as age-related macular degeneration and retinal venous occlusive disease.[5,6,7] These medications are administered in the clinic using a 30-gauge or smaller needle inserted through the pars plana directly into the vitreous cavity.

The RISE and RIDE phase 3 trials[7,8] led to US Food and Drug Administration (FDA) approval in 2012 of the first medical treatment for diabetic macular edema. In these methodologically identical 36-month trials, ranibizumab was given every month and compared with sham treatment. All patients were allowed to receive focal laser treatment at the discretion of the treating physician after month 3. The study enrolled 759 patients; after 2 years, 33.6%-44.8% of ranibizumab-treated (0.3 mg) patients vs 12.3%-18.1% of sham-treated patients achieved the primary endpoint of gaining at least 15 letters of vision (P < .001), and 54.4%-60% of ranibizumab recipients achieved 20/40 or better vision vs 34.6%-37.8% of sham-treated patients.[8] These vision benefits were sustained through a third year of treatment in the ranibizumab recipients.[7]

The patients who initially received sham treatment were crossed over to ranibizumab treatment after 2 years. Of importance, delayed treatment in these patients did not result in the same degree of visual improvement that was observed in the patients originally assigned to ranibizumab, suggesting that earlier treatment may optimize visual outcomes.[7]

The DA VINCI phase 2 study[9] assessed the efficacy of aflibercept in the management of diabetic macular edema. Aflibercept led to excellent visual outcomes, in agreement with what was observed with ranibizumab. Aflibercept, however, may have a higher affinity for VEGF, allowing longer clinical activity and less frequent dosing.[10] Indeed, 1 arm of the aflibercept DA VINCI study used every-other-month dosing after 3 initial monthly doses, the same regimen used in the phase 3 VIEW trials that led to FDA approval of aflibercept for the treatment of wet age-related macular degeneration in 2011.[11] At the 1-year DA VINCI primary endpoint, aflibercept treatment led to 9.7-13.1 letters gained vs a loss of 1.3 letters in the sham treatment group (P ≤ .001).[9]

Aflibercept is being studied further in 2 phase 3, sham-controlled trials designed for FDA approval for the treatment of diabetic macular edema: VIVID-DME and VISTA-DME. In these trials, aflibercept (2 mg) is administered monthly or every other month after 5 initial monthly doses. A recent press release about the 1-year primary endpoint reported that aflibercept-treated patients gained a mean of 10.7-12.5 letters vs 0.2-1.2 letters with focal laser treatment (P < .001).[12] The full results of these phase 3 trials will probably be released in late September 2013.

Although ranibizumab is FDA-approved for the treatment of diabetic macular edema, and aflibercept is likely to follow very soon, bevacizumab has been widely used off-label for such treatment since about 2005.[13]The ongoing Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T is comparing the safety and efficacy of bevacizumab, ranibizumab, and aflibercept for the management of diabetic macular edema, and 1-year results may be available as early as fall 2014.[14]

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