Spotlight on diabetic macular edema

Two recent studies analyzed treatment of diabetic macular edema (DME) with drugs that block vascular endothelial growth factor (VEGF).

The first study, published by the New England Journal of Medicine on Feb. 18, randomized 660 adults with DME to receive intravenous aflibercept (2 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg) as often as every 6 weeks. At 1 year, the patients' mean visual acuity had improved with all drugs. There was no clinically meaningful difference among drugs in effectiveness or adverse events in the overall study population. However, in patients who had 20/50 or worse vision at baseline, aflibercept was associated with significantly greater vision improvement (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). In patients with 20/40 or better vision at baseline, improvements in visual acuity were similar. The study authors concluded that all 3 treatments were effective and relatively safe and that aflibercept was most effective in the patients with worse visual acuity. The drugs differ significantly in their cost, an accompanying editorial noted, pricing bevacizumab at $50, ranibizumab at $1,200, and aflibercept at $1,950. Given that, the editorialists recommended bevacizumab as the first-line therapy for patients with 20/40 or better vision and aflibercept as the first-line therapy for those with 20/50 or worse vision (with bevacizumab the second choice for this group).

The other study, published by JAMA Ophthalmology on Feb. 26, looked specifically at ranibizumab and its association with sustained elevation of intraocular pressure (IOP). Researchers randomized 486 DME patients (with 582 treated eyes) to a sham injection and focal/grid laser treatment or ranibizumab injections and deferred or prompt focal/grid laser treatment. After 3 years, they found that the risk of sustained IOP elevation or initiation or augmentation of ocular hypotensive therapy was 9.5% in the ranibizumab group versus 3.4% in the sham injection group (difference, 6.1%; 99% CI, −0.2% to 12.3%; hazard ratio, 2.9; P=0.01). Elevated IOP is a risk factor for glaucoma, the study authors noted, recommending that patients who receive repeated injections of anti-VEGF have periodic monitoring of IOP. The study was limited by the treatment assignment being unmasked to treating physicians and wide confidence intervals, leading to uncertainty about the clinical significance of the results, the authors wrote.