PDT trials aim to refine AMD treatment indications

Cheryl Guttman In Fort Lauderdale

Peter K. Kaiser MD

Longer-term follow-up studies and protocols evaluating alternative treatment regimens should help clarify the optimal role of photodynamic therapy in the treatment of age-related macular degeneration, reported researchers at the annual meeting of the Association for Research in Vision and Ophthalmology.

During a session dedicated to PDT for AMD, Peter K. Kaiser MD, reported the latest data from the third year of the open-label extension of the TAP (Treatment of AMD by PDT). The data indicate study that for eyes with predominantly classic choroidal neovascularisation (CNV), the need for retreatment decreases over time while visual acuity remains stable and safety favourable.

"This information supporting the long-term safety and efficacy of verteporfin PDT for maintaining vision is useful for ophthalmologists to share with patients affected by this chronic, progressive disease. We have to keep in mind that the extension phase had no untreated control group and not all patients in the TAP Investigation continued into the extension trial. Nevertheless, we are confident that identification of wet lesions early in their onset, before many have become very large in size, is an important factor in stabilising vision and maintaining patients’ quality of life," commented Dr. Kaiser.
Any patient who completed the 24-month exam of the TAP Investigation could enter the open-label extension trial if the investigator thought the study eye might benefit from further treatment or if the fellow eye had a lesion fulfilling the original TAP inclusion criteria.

One hundred and twenty four patients with predominantly classic CNV entered the follow-up study, of whom 77 reached the 60-month follow-up visit. As in the initial two-year double-blind phase of TAP, patients returned for fluorescein angiography every three months during the extension trial and received verteporfin PDT if leakage was detected.
During the three years of the extension study, the mean number of treatments administered per year for patients with predominantly classic CNV decreased progressively from 1.5 to 0.5 to 0.1.

Visual Acuity preserved
Visual acuities remained stable during the entire three-year open-label period both in patients who had been assigned to verteporfin PDT at baseline in the TAP Investigation and in those who were originally placebo-treated controls but who became eligible to receive verteporfin PDT in the open-label extension phase.

No new safety issues emerged with ongoing treatment. In particular, there was no evidence for an increased risk of acute severe vision decreases associated with chronic therapy.
Neil M. Bressler MD, presented data from the 12-month visit of the two-year study of verteporfin in minimally classic CNV due to AMD (VIM). Those results suggested that PDT might be reducing vision loss in eyes with minimally classic subfoveal CNV related to AMD.
"This is particularly good news for some patients with minimally classic lesions, but further clinical research and continued follow-up of this study cohort is needed to determine if verteporfin PDT becomes the standard of care for those lesions," said Dr Bressler, who is Chair of the Visudyne Study Advisory Group.

VIM is a Phase II trial being conducted in 19 clinical centres in Europe and North America. It was undertaken based on a post hoc analysis of TAP investigation data indicating that for eyes with smaller lesions of minimally classic composition and especially those having lower levels of visual acuity (less than 20/50), verteporfin PDT appeared to reduce the risk of vision loss compared with placebo. The results of a multilinear regression analysis were consistent with those findings, Dr. Bressler said.

In VIM, 117 patients were randomised 2:1 to verteporfin or placebo infusion. Within each study arm, half of the patients received light treatment with the standard fluence of 600 mW/cm2 or a reduced fluence of 300 mW/cm2.

Eligible patients had to have a lesion no greater than six MPS disc areas in size, with a baseline visual acuity (Snellen equivalent) 20/250 or better if the lesion was up to four MPS disc areas and between 20/50 and 20/250 for lesions four to six MPS disc areas. As in TAP, retreatment was administered every three months for eyes with CNV leakage on the fluorescein angiogram.

At 12 months, the mean change in visual acuity scores was significantly better (P0.02) among patients treated with PDT compared with placebo whether the analyses were performed for all patients combined or in comparing the reduced fluence and standard fluences separately. The trial also demonstrated that PDT patients developed predominantly classic CNV less often than the placebo patients and required fewer retreatments.

No definitive differences were apparent between the different fluence rates among the verteporfin PDT-treated patients. The safety profile was similar to that which has been described for standard verteporfin PDT, although the rate of infusion-related pain was reduced with use of the lower light fluence
Ursula M. Schmidt-Erfurth MD, described the findings from a six-month interim analysis of a multicentre Phase IIIb study comparing a two-month versus a three-month PDT retreatment interval in eyes with subfoveal CNV and a predominantly classic component.

After six months, there were numeric trends favouring the shorter treatment interval in various outcome measures, although there were no statistically significant between-group differences in analyses of mean visual acuity changes, proportions of patients experiencing significant vision loss (less than 15 ETDRS letters), or changes in lesion size.
However, a subgroup analysis performed with eyes stratified by baseline lesion size found the vision outcome was more favourable in eyes with an initial lesion size less than 2.0 mm receiving retreatment every three months versus at three-month intervals.

"We knew from Phase I/II trials that verteporfin PDT could be repeated as often as every two-to-four weeks without safety concerns, and so this trial was designed to evaluate the effects of earlier retreatment on vision and lesion outcomes. There is some suggestion from the interim analysis that early retreatment might be beneficial in eyes with smaller lesions, although the question remains whether the important prognostic factor is lesion size or size of the treatment area," said Dr. Schmidt-Erfurth.

Peter K. Kaiser
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
pkkaiser@aol.com

Neil M. Bressler MD
Wilmer Eye Institute
Johns Hopkins University School of Medicine,
Baltimore, Maryland, US
nbressler@jhmi.edu

Ursula M. Schmidt-Erfurth
University Eye Hospital, Lubeck, Germany
uschmidterfurth@ophtha.mu-luebeck.de

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