Defining the ‘ideal’ DME treatment

By Cheryl Guttman Krader

Reviewed by Julia A. Haller, MD

Philadelphia-Solid scientific rationale exists for anti-vascular endothelial growth factor (VEGF) treatment of diabetic macular edema (DME).

Results of clinical trials show it has efficacy and safety advantages compared with other modalities.

“We know that VEGF is a primary pathological driver of DME, and blocking VEGF activity effectively treats DME and limits the progression of diabetic retinopathy as well,” said Julia A. Haller, MD, ophthalmologist-in-chief, Wills Eye Hospital, and professor and chairwoman, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson Medical College, Philadelphia.

“In addition, anti-VEGF therapy has fewer side effects than the other available treatments for DME, which are laser photocoagulation and steroids,” she said.

Why anti-VEGF?

Discussing the scientific rationale for anti-VEGF treatment of DME, Dr. Haller explained that an alternative name for VEGF when first described was vascular permeability factor because it caused edema. Results of preclinical studies, including experiments performed in a guinea pig cheek model and in the monkey eye, showed injection of VEGF stimulated vascular leakage. Studies in which vitreous fluid was sampled from patients with DME showed increased VEGF immunoreactivity in retinal vessels.

Briefly reviewing some anti-VEGF clinical treatment trials, Dr. Haller observed that studies investigating different anti-VEGF agents consistently show that intravitreal anti-VEGF injection is an effective treatment for DME and provides superior anatomic and functional outcomes than the active comparators.

“Whether in the DRCR network protocol I trial comparing ranibizumab (Lucentis, Genentech) with deferred or prompt laser against triamcinolone or laser, or the READ 2 study comparing ranibizumab alone, laser, or ranibizumab plus laser, mean reductions in central subfield thickening and final visual acuities achieved in eyes treated with other modalities never measure up to the levels achieved in those treated with anti-VEGF injections,” Dr. Haller said.

“In the DRCR network trial, the anti-VEGF treated eyes also won out in analyses of worsening of diabetic retinopathy, and in the DA VINCI trials, eyes treated with aflibercept (Eylea, Regeneron) benefited with more thinning than those treated with focal laser,” she said.

Safety data from the controlled trials also show the fewest side effects occurred in eyes in the anti-VEGF treatment groups, and in the available DME treatment trials for ranibizumab and aflibercept, there were no significant differences in serious adverse event rates comparing the anti-VEGF and sham groups.

“Laser treatment leaves burns that result in permanent scotomata, which can spread,” Dr. Haller said. “This effect may partly explain why eyes treated with laser only have the worse visual acuity outcomes across the controlled DME studies. With steroids, there are risks of glaucoma and cataract.”

She cited results from the DRCR.net protocol I study showing that overall 50% of eyes treated with triamcinolone experienced IOP increase of at least 10 mm Hg form baseline, IOP ≥30 mm Hg, and/or required initiation of an IOP-lowering medication. In parallel treatment arms that did not receive corticosteroid treatment, only 7% to 11% of eyes experienced one or more of the IOP-related adverse events.

In an interview after the debate, Dr. Haller emphasized that her remarks have to be taken in the context of the format of the program.

“Although in fact anti-VEGFs have become the first line for DME treatment in many cases, laser and steroids do have a role as well, and are key weapons in the armamentarium used to combat DME,” she said.OT

FYI

Julia A. Haller, MD

E-mail: jhaller@willseye.org

Dr. Haller has been a consultant in the past for Allergan, Genentech, and Regeneron. This article was adapted from Dr. Haller’s presentation during Retina 2012 at the annual meeting of the American Academy of Ophthalmology, where she provided her perspective on whether anti-vascular endothelial growth factor therapy is the ideal treatment for diabetic macular edema in an Oxford-style debate.