Applying an evidence-based approach to macular disorders

May 1, 2012

Currently there is a significant evidence-based shift toward anti-VEGF therapy as first-line treatment for diabetic macular edema, macular edema associated with vein occlusion, and active exudative age-related macular degeneration (AMD).

More conventional treatments such as laser therapy, steroid therapy, photodynamic therapy (PDT), and surgery are being strategically adapted to augment and complement the effectiveness of anti-VEGF therapy.

Peter Gehlbach, MD, PhD, reviewed available data in each of these areas, as well as current trends of use for these potential options, here at the 5th annual Evidence Based Care in Optometry conference in March. Dr. Gehlbach is associate professor of ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

Proliferative diabetic retinopathy (DR) remains the leading cause of blindness in individuals ages 20-64, he noted. Clinical manifestations of proliferative stages of DR include the appearance of neovascularization on the surface of the retina and optic disc. With progression, the neovascularization proliferates along the inner retinal surface and may extend into the vitreous cavity.

"The fate of these blood vessels may be regression with treatment; or proliferation, fibrosis and contraction leading to traction retinal detachment or vitreous hemorrhage," Dr. Gehlbach said.

Recently, investigators have studied the utility of optical coherence tomography (OCT) as a diagnostic tool. One review of nine studies that attempted to determine the diagnostic accuracy of OCT in detecting DME concluded that OCT to measure central retinal thickness could not be used as a stand-alone test to diagnose the central type of clinically significant macular edema. (Cochrane Database Syst Rev. 2011 Jul 6;(7))

The study reported a substantial disagreement of OCT with the Early Treatment Diabetic Retinopathy Study (ETDRS) definition of clinically significant macular edema, based on clinical examination.

Dr. Gehlbach explained that OCT is more sensitive than most clinicians using biomicroscopy to evaluate macular disease. Thus, the biomicroscopically established criteria for treatment are based on less sensitive techniques. This suggests that clinicians who begin treating based on OCT testing only would potentially treat more patients than a typical clinician utilizing biomicroscopic data.

Emerging role of PRP

One study compared panretinal photocoagulation (PRP) alone and PRP plus ranibizumab (Lucentis, Genentech) in patients at high-risk of proliferative DR with no prior PRP. (Acta Ophthalmologica. 2011; 89:e567-572) After a 48-week follow-up, the researchers reported a larger reduction in fluorescein leakage in the group randomized to treatment with PRP plus ranibizumab, as well as less loss of visual acuity and formation of DME.

"PRP remains a gold standard for treatment of proliferative disease. The addition of ranibizumab in high-risk eyes is effective in shutting down early neovascular disease, and in some cases, has eliminated or delayed the need for PRP," Dr. Gehlbach said. "If you are going to use PRP in combination with anti-VEGF therapy in severe proliferative disease, you must also have a discussion about the potential to develop traction retinal detachment, which would then need to be addressed surgically." He also noted a potential benefit on post-laser macular edema if the two therapies are combined strategically.