Analysis of the time course of visual acuity outcomes during the first year of the ANCHOR study indicates that the mean visual acuity benefit of ranibizumab (Lucentis, Genentech) compared with photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis) for the treatment of exudative age-related macular degeneration (AMD) was observed after the first month of treatment, and this benefit continued with increased vision that was maintained over the 2 years of the study.
Even patients who did not show this early benefit might have a response later in the treatment course, said Jeffrey Heier, MD, who presented the time course of the VA changes following treatment with ranibizumab at the Association for Research in Vision and Ophthalmology annual meeting.
"Two years ago, with the presentation of the initial phase 3 ranibizumab results, that presentation marked the first time that promising phase 1 and phase 2 results of the treatment of wet AMD were replicated in pivotal phase 3 studies. In fact, not only were they replicated, but in many cases the results of the pivotal studies were actually better than expected," stated Dr. Heier, vitreoretinal specialist, Ophthalmic Consultants of Boston, and assistant professor of ophthalmology, Tufts University School of Medicine.
"The key visual acuity endpoints of the [ranibizumab] study were quite robust," Dr. Heier said. "The primary outcome was prevention of moderate vision loss at 1 year, which occurred in more than 90% of the patients treated with ranibizumab compared with about two-thirds of the patients who received PDT. At 2 years, the results were well-maintained."
Thirty-six percent to 40% of patients in the ranibizumab groups had a gain in VA of 3 lines or more compared with only 6% in the PDT group. At 2 years, this result was maintained. The mean change in vision at 1 year with ranibizumab, which was a 4-line difference in VA between the ranibizumab groups and the PDT group, was maintained at the 2-year time point, and the 4-line difference remained, Dr. Heier reported.
The development of ocular adverse events associated with ranibizumab was uncommon. "There was no overall imbalance in systemic safety events," Dr. Heier said.
Time course of acuity changes
The follow-up in the study was excellent, with about 90% of the patients completing follow-up through 1 year and more than 80% of patients completing follow-up at 2 years in the ranibizumab group. The percentages of patients completing follow-up in the PDT group were slightly lower.
"Moderate vision loss was unlikely to occur in the ranibizumab groups," Dr. Heier said. "The absence of moderate vision loss was evident early on. This was maintained throughout the course of the study. In the PDT group, a fair amount of moderate vision loss occurred, most of which occurred during year 1 and remained stable over year 2.
"Most of the 3-line gains in VA occurred during the first 3 to 4 months in the patients treated with ranibizumab. However, there still were patients who gained the same degree of vision during the subsequent several months. Vision tended to stabilize at the 1-year time point and remained stable during the course of the second year. Patients treated with PDT were unlikely to have this gain, and their vision remained stable," he reported.
When the study investigators evaluated the patients who maintained their baseline vision or gained vision, whose vision Dr. Heier referred to as being truly stable, the vision was found to be "remarkably stable" over the 2-year course of the study.
"This was very comforting to us when we saw these patients during the first year of the study, because we knew that they would likely maintain their vision through the second year," he said.
In the patients assigned to PDT, VA loss occurred during the first months after treatment, and that loss continued during the first year of the study before the vision stabilized.