CLINICAL TRIAL SPOTLIGHT
Paying Attention to DETAIL
A small trial is looking at how much of an impact RPE detachments have in wet AMD.
ANDREW E. MATHIS, PhD, MEDICAL EDITOR
One of the more serious conditions to accompany exudative age-related macular degeneration (AMD) is retinal pigment epithelium detachment (RPED). Patients with AMD and RPE detachment can maintain relatively good vision for several months, but the eventual likelihood of serious vision loss is significant as a result of tearing of the RPE detachment or fibrosis.
While ranibizumab (Lucentis, Genentech) has been approved for use in managing wet AMD and has been shown to arrest choroidal neovascularization (CNV) and, in some cases, even reverse vision loss due to AMD, RPEDs were not included in the phase 3 trials. The PrONTO study was the first AMD trial to allow the inclusion of patients with RPEDs. In this early phase trial, an arbitrary decision was made to treat only until macular fluid was absent.
However, the study called Determining Optimal Treatment Algorithms for Macular Degeneration Pigment Epithelial Detachments Treated With Intraocular Lucentis (DETAIL), which completed enrollment in February, builds on the PrONTO experience and has been looking at this relationship. Anne Fung, MD, who is the principal investigator on the study, told Retinal Physician about the current status of the trial.
PRONTO PROMPTS NEW RESEARCH
According to Dr. Fung, of Pacific Eye Associates and the California Pacific Medical Center, both in San Francisco, the inspiration for the DETAIL study was a finding in the earlier PrONTO trial, which had used optical coherence tomography (OCT) to guide retreatment of AMD patients with ranibizumab. The existence of RPE detachment was not a retreatment criterion in the trial, and RPE detachments were allowed to be present.
"We saw a good effect in the PrONTO study," Dr. Fung said. "Therefore, we wanted to better understand whether treatment until retinal fluid disappeared was, on its own, sufficient vs whether resolution of retinal fluid as well as the flattening of RPE detachment is ideal." The study began in October 2006.
Thus the DETAIL study has two arms: One group of patients will receive injections of ranibizumab only until retinal fluid is resolved, while the other arm will receive ranibizumab injections until retinal fluid is resolved and RPE retachment is flattened as well. The endpoints measured will include the number of injections patients receive over the course of one year, changes on OCT, and visual acuity change as measured on the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale. The study will also look at durability of outcome, eg, the time from the last ranibizumab injection to retreatment, if needed.
Asked whether any such studies had been conducted before, Dr. Fung replied, "There was one other Lucentis trial conducted on RPE detachments, but it did not show any difference between the two doses tested." Other studies are ongoing.
WHY THIS FOCUS?
If not all RPEDs result in vision loss, there may be some question as to why RPE detachment is the particular focus of this trial.
"In my experience, vision is affected more by the overlying macular fluid (sub or intraretinal) than by the RPED itself." Dr. Fung explained, "Often, I find that eyes with RPED alone without any thickening of the overlying retina or subretinal fluid can have rather good vision. But we do not know if it is worse in the long run for the patient to have a PED that is allowed to persist."
The DETAIL study is a two-site study that has enrolled 18 patients: Dr. Sophie Bakri at the Mayo Clinic is the second site. "It's a pilot study, and consistent subfoveal neovascular RPE detachments are hard to find," Dr. Fung said by way of explaining the trial's small size and long recruitment phase. Because the study only recently completed enrollment, final data will likely not be released until early next year. RP