Abstract
Abstract: :
Purpose: PDT when applied to neovascular AMD patients appears to elicit a significant inflammatory response, specifically the activation of the prostaglandin pathway, which may limit the clinical response of this treatment. In addition, further neovascularization may occur during PDT treatment intervals. Therefore, the use of celecoxib (Celebrex) a potent inhibitor of an enzyme in this pathway, which also appears to have anti–angiogenic properties, may provide additional benefit to PDT treatment. Methods: A phase I/II randomized prospective multi–center clinical trial in 60 participants was initiated to investigate the ability of Celebrex to alter the inflammatory and neovascular responses in participants with AMD undergoing PDT. Enrollment was stratified by predominant lesion type (predominantly classic, minimally classic, or predominantly occult). Participants were randomized to 400 mg Celecoxib or placebo 1 week prior to PDT and continued their randomized treatment through 8 months on study. The primary outcome is a drop in best–corrected visual acuity of ≥15 letters from baseline to 1–year post–PDT. Secondary outcome measures include changes in CNV lesion on fluorescein angiography and optical coherence tomography III, both as graded by the University of Wisconsin Fundus Photography Reading Center (FPRC). In addition, this will be the first trial to access the ability of high–speed indocyanine green angiography to quantify changes in neovascular structures. Results: Sixty participants were enrolled between December 2002 and June 2003 (57 white, 33 female, and median age 78 years). At writing, baseline angiographic outcomes are available for 58 participants classified by the FPRC as 17 predominantly classic, 6 minimally classic, and 35 predominantly occult. The mean and median total lesion area is 5.22 and 3.33 DA's, respectively. Percentage of CNV lesions with detectable "feeder" vessels will also be reported. Conclusions: This clinical trial will provide: 1) information on the use of concomitant anti–inflammatory and anti–angiogenic therapy in PDT and 2) the utility of ancillary imaging techniques in neovascular AMD trials. The results of the present study will also allow investigators to design further studies exploring anti–inflammatory therapies in AMD.
Keywords: age–related macular degeneration • inflammation • photodynamic therapy