Combination Therapy Has Long-Lasting Therapeutic Effects for Exudative AMD

November 19, 2007 (New Orleans) — A single treatment of photodynamic therapy (PDT) combined with bevacizumab, triamcinolone, or bevacizumab plus dexamethasone can achieve long-lasting improvement in visual acuity among a significant percentage of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), according to a new study presented here at the American Academy of Ophthalmology 2007 Annual Meeting.

Inhibiting vascular endothelial growth factor (VEGF) through injections into the vitreous humor has proved to effectively cause regression of the abnormal blood vessels and improve vision in some cases. However, the injections frequently have to be repeated on a monthly or bi-monthly basis. Frequent intravitreal anti-VEGF therapy is associated with increased safety risk, financial burden, and inconvenience.

The objective of the study was to determine the efficacy and duration of effect of a single-session combination treatment for CNV in exudative AMD. Combination therapy with agents targeting different components of CNV pathophysiology may have additive effects, according to HarHiu Dawn Lam, MD, ophthalmology fellow at the University of California in San Francisco. For example, PDT uses a dye that binds to leaky vessels and destroys them; anti-VEGF agents (such as bevacizumab) prevent antiangiogenesis; corticosteroids (dexamethasone, triamcinolone) have anti-inflammatory and angiostatic effects.

The researchers retrospectively evaluated 112 patients (120 eyes) who received a single treatment of bevacizumab + PDT, who had been followed for 12 months or longer; intravitreal triamcinolone (IVTA) + PDT and followed for 12 months or longer; or bevacizumab + dexamethasone + PDT and followed for 6 months or longer. The researchers excluded patients who had been followed for fewer than 12 or 6 months, or who had received other treatment within 1 year before the combination therapy. Ophthalmic evaluations during follow-up included Snellen visual acuity, complete ophthalmic examination, optical coherence tomography, and/or fluorescein angiogram and were performed at 1, 2, 3, 6, 9, and 12 months, or as needed, after the initial treatment.

After a single bevacizumab + PDT treatment, AMD in 47% of the patients remained stable, and visual acuity improved by 0.3 logMAR or more (equivalent of 15 Early Treatment Diabetic Retinopathy study letters) in 26.5% of the patients at 12 months. After a single bevacizumab + dexamethasone + PDT treatment, 76.5% of the patients remained stable, and visual acuity improved by 0.3 logMAR or more in 35.3% of the patients at 6 months. After a single IVTA + PDT treatment, 36.7% of the patients remained stable at 12 months, but no significant improvement in vision was observed.

The researchers concluded that all 3 combination therapies resulted in long-lasting vision stabilization and/or improvement in a significant percentage of patients with CNV secondary to advanced AMD. At 12 months, approximately one quarter of the bevacizumab + PDT-treated patients achieved a significant improvement in visual acuity, and about one third of the bevacizumab + dexamethasone + PDT group had significant improvement in visual acuity at 6 months. "The results are encouraging," said Dr. Lam. "We were limited by a retrospective study design, the small number of patients, and no control group."

Thomas Steinemann, MD, associate professor of ophthalmology at Case Western Reserve University in Cleveland, Ohio, wondered how many patients there were in each test group, and whether the group sizes were balanced. "The results for group 3 were quite encouraging, but why were they followed for only 6 months when the other 2 groups were followed for 12 months? Also, this is a retrospective study with a small number of patients and no controls."

He continued, "Nevertheless, [it is] an intriguing study, and one that should be published in a clinical journal. This study addresses an important concern: Can we minimize risk, cost, and morbidity by using combination therapy as a one-time intervention?"

Dr. Lam and Dr. Steinemann have disclosed no relevant financial relationships.

American Academy of Ophthalmology 2007 Annual Meeting: Scientific Paper PA 060. Presented November 12, 2007.