Combination therapy shows promise for AMD

Combination therapy to treat age-related macular degeneration seems to be a promising avenue of research. The gain in visual acuity can be sustained with fewer intravitreal injections. This approach might also reduce the overall cost of treatment.

Key Points

Dallas-Combination therapy of anti-vascular endothelial growth factor (VEGF) drugs and photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis) seems to reduce the number of treatments needed to sustain a beneficial effect in patients with age-related macular degeneration (AMD). Fewer treatments also might translate into a decrease in the cost of treatment. So said David Callanan, MD, associate clinical professor, University of Texas Southwestern Medical Center, Dallas, and a partner in Texas Retina Associates.

"Why are we considering combination therapy? It is hoped that combination therapy will allow patients to undergo fewer intravitreal injections with similar visual outcomes and possibly reduce the overall costs of treatment," he said.

Early studies

Dr. Callanan recounted that Richard Spaide, MD, was a pioneer in the use of combination therapy in 2005 when he and his colleagues evaluated the use of PDT and triamcinolone acetonide (Kenalog, Bristol-Myers Squibb). In that study of 26 eyes, 13 had undergone previous treatment with PDT and 13 were newly treated with the combination therapy. The results indicated that adding triamcinolone acetonide to the treatment regimen might improve the visual outcome and reduce the need for the number of PDT applications that were needed when PDT was the only therapy, Dr. Callanan explained.

Another study carried out by Mandeep Dhalla, MD, and colleagues evaluated the use of bevacizumab (Avastin, Genentech) and PDT. Of the 24 eyes, 63% required only one treatment after 7 months of follow-up, and in 83% the vision was stable.

In the Verteporfin in Minimally Classic Choroidal Neovascularization Study, after 2 years of follow-up, the patients treated with reduced fluence (25 J/300 mW per cm2 ) tended to have better vision compared with the patients treated with standard fluence (50 J/300 mW per cm2 ). The duration of the laser application and the dose of verteporfin were the same in both groups.

Combination trial

Based on those results, Dr. Callanan, Ed Ryan, MD, and Wayne Solley, MD, carried out a study of 155 eyes with AMD, all of which were treated with 1.25 mg/0.05 ml bevacizumab and reduced-fluence PDT (25 J). One group of patients was treated with both treatments on the same day; the second group of patients was treated with bevacizumab first and then reduced-fluence PDT within 5 to 14 days of the bevacizumab treatment. The patients were examined every 4 to 6 weeks. Treatment was repeated only as needed based on the following criteria: evidence of intraretinal or subretinal fluid on examination or optical coherence tomography imaging, or evidence of leakage on fluorescein angiography, Dr. Callanan said.

Patients began to undergo this treatment in November 2005. The mean follow-up was 358 days. Fifty percent of lesions were classic, and 50% were minimally classic or occult lesions. Eighty-one patients (52%) had not received any previous treatment for AMD; the rest had undergone previous treatment with PDT, pegaptanib (Macugen, Pfizer), or steroids. The patients who were treated early in the study had about 2 years of follow-up as of this presentation; 50% of patients had almost 1 year of follow-up.

Dr. Callanan reported that about 60% of all patients received one reduced-fluence PDT treatment. In those patients who required a second treatment, the average time to the second treatment because of accumulated fluid was about 6 months. Thirty percent of all patients received one bevacizumab injection, and the average time to the second bevacizumab injection was about 4 months. The mean number of combination treatments was 1.5; the mean number of bevacizumab injections was 2.75. No significant difference was noted between patients who were treated on the same day and those treated in a consecutive manner, according to Dr. Callanan.