PDT trials for AMD help in timing, patient selection

August 15, 2004

Cleveland-A series of ongoing clinical trials helps the clinician better understand the proper timing and selection of photodynamic therapy (PDT) with verteporfin (Visudyne, QLT Phototherapeutics/Novartis Ophthalmics) for age-related macular degeneration (AMD), said Peter K. Kaiser, MD, staff physician at the Cole Eye Institute, Cleveland Clinic Foundation.

In the Visudyne in Early Retreatment (VER) trial, which compared early (6-week) re-treatment with ocular PDT with standard 3-month therapy, investigators found no statistically significant difference in moderate vision loss between patient groups.

"There is no evidence from the VER trial to suggest that early re-treatment improves visual outcomes," said Dr. Kai- ser, who presented findings from several of trials. However, he also added that early re-treatment does not appear to cause any additional safety concerns.

Dr. Kaiser also presented results from the Visudyne in Minimally Classic CNV (VIM) trial, which compared PDT with verteporfin at standard and reduced light fluence rates (600 versus 300 mW/cm2 ). In this phase II, randomized, prospective, placebo-controlled trial, 116 patients with subfoveal, minimally classic lesions •6 MPS disc areas in size were randomly assigned in a 2:1 scheme to PDT with verteporfin or placebo treatment then further randomly assigned to standard or reduced fluence.

"The results of the VIM trial at 1 year suggest that in patients with smaller, subfoveal, minimally classic lesions, PDT reduces the risk of vision loss, reduces the risk of developing predominantly classic CNV, and has an overall positive safety profile," Dr. Kaiser said. "Although there was a trend toward reduced fluence being better, there was no definitive difference in terms of statistical significance when compared with standard fluence rates."

The trend favoring the reduced fluence rate continued in visual acuity scores (reduced fluence, p = 0.02; standard fluence, p = 0.01; all verteporfin combined, p = 0.08), but again this was not statistically significant.

The patients who were treated with PDT with verteporfin also appeared to do better than the placebo group in conversion of predominantly classic lesions, but Dr. Kaiser cautioned that the 95% confidence levels overlapped between the groups.

The rationale to perform the VIM study came from an earlier trial, the Treatment of AMD with Photodynamic Therapy (TAP) Investigation. In that study, no statistically significant difference in vision loss was found in the subgroup of patients with minimally classic lesions when patients treated with PDT with verteporfin were compared with those who had been given placebo. However, retrospective analysis showed that minimally classic lesions •4 MPS disc areas and with vision worse than 20/50 had statistically significant improvement in the amount of moderate visual loss, suggesting that standard PDT with verteporfin could be beneficial for smaller lesions, Dr. Kaiser said.

The VIM trial was launched to investigate the theory that if the benefits of PDT with verteporfin were lost in larger lesions due to collateral damage to the surrounding choroid, reducing the fluence could result in more selective treatment of the CNV membrane.

The results should be interpreted cautiously since the VIM study had a limited number of participants, and follow-up was limited as well, Dr. Kaiser said. He also alluded to another problem. "When we looked at the TAP investigation in the minimally classic lesions and applied the VIM inclusion criteria to this group, there was also no statistically significant difference between placebo and standard fluence rates," he added. So the results of the trial should be interpreted with caution, he said.