Real-world practice validates published outcomes of PDT

In a National Health Service setting, photodynamic therapy was at least as effective as reported in the literature, English researchers found.

ByRod McNeil

Photodynamic therapy with verteporfin delivered in a National Health Service (NHS) setting can be at least as effective against age-related macular degeneration as reported in the literature, according to retinal specialists in England. In fact, in that setting, fewer treatments were required than in published reports, the specialists said.

Simon Harding, FRCOphth, a consultant ophthalmic surgeon at St. Paul’s Eye Unit of the Royal Liverpool University Hospital, and colleagues reported their real-world experience with PDT in the journal Eye.

“Results of randomized, placebo-controlled clinical trials show that verteporfin photodynamic therapy reduces the risk of moderate and severe vision loss in selected patients with wet age-related macular degeneration. Although enrolled numbers were not high, similar vision outcomes were seen in this audit of routine clinical practice in the NHS,” Mr. Harding said in an interview.

Writing in the advance online publication section of Eye, Mr. Harding and colleagues reported on the clinical efficacy of verteporfin PDT in the treatment of choroidal neovascularization (CNV) secondary to AMD in the National Health Service. The investigators compared treatment rates and outcomes with Visudyne (verteporfin for injection, Novartis Ophthalmics) to those in the published literature.

Outcomes match trial results

Patients with a visual acuity of 6/60 or better Snellen equivalent and predominantly classic or classic with no occult CNV within 200 µm of the center of the fovea were enrolled and followed for a minimum of 12 months. Assessment at baseline and all follow-up visits included refraction protocol logMAR visual acuity, contrast sensitivity and stereoscopic fluorescein angiography.

A total of 170 eyes of 159 patients were enrolled with CNV due to AMD (147 total: 90 classic with no occult, 21 recurrent after confluent laser, 36 predominantly classic with occult), pathological myopia (10) or other conditions (13).

Response to treatment (loss of less than 15 letters) at 12 months was 73% overall. In patients with CNV due to AMD, the response rate in terms of avoidance of moderate vision loss was 76% overall, 70% in those having classic CNV with no occult, and 89% in patients with predominantly classic CNV. The mean number of treatments in the first year was 2.7. Contrast sensitivity, which has been shown to be important in visual functioning in patients with AMD, remained stable in all subgroups at the 12-month follow-up. This mirrors findings in the TAP and VIP studies, Mr. Harding noted, in which the treated groups retained stable contrast sensitivity, whereas placebo groups experienced a decrease in contrast sensitivity.

Continuing service development

“Despite poorly established patient referral pathways, we are nonetheless achieving similar vision outcome results in routine clinical practice as those noted in clinical trials,” explained Mr. Harding. “So that means that the treatment does do what we think it does in terms of stabilizing remaining vision.”

The response rate at 12 months in eyes with AMD in the NHS compares well to the published response rate at 12 months of 67% in the TAP predominantly classic subgroup, Mr. Harding said. This is encouraging, according to the authors, as it not only adds weight to the findings of TAP, but also shows that equally good results are possible outside the rigorous setting of a multicenter clinical trial.

“And if we are going to do better, we need to have patients referred and assessed sooner, so that they come in with better levels of baseline vision,” Mr. Harding said. “Second, we have got to try to identify those patients with wet AMD who are less likely to benefit from treatment. For example, patients with large lesions (greater than 6,000 µm in greatest linear dimension) or those with chorioretinal anastomosis tend not to respond as well as others.”

Comparable results using verteporfin PDT are also evident in other regional medical retina service centers, other clinicians report.

James Talks, FRCOphth, a consultant ophthalmologist at the Royal Victoria Infirmary in Newcastle upon Tyne, commented, “Our audit of roughly 50 patients at 1 year follow-up showed that photodynamic therapy helped stabilize vision in around 67% (losing less than 15 letters). At Newcastle, we have only been funded in the past to treat second eyes. For the vast majority of our patients, while they may have lost vision, the eye that we have treated is a lot better than the eye left untreated. We are convinced it works.”

Beyond visual acuity

Andrew Lotery, MD, FRCOphth, a professor of ophthalmology at the University of Southampton School of Medicine and a consultant ophthalmologist at Southampton General Hospital, observed: “Our clinical experience demonstrates similar results to the TAP study, and we are currently auditing our results to confirm that.”

As well as significantly reducing the risk of vision loss, PDT treatment minimizes the degree of the central macular scotoma, which is considerably smaller in treated eyes, Prof. Lotery noted. “This allows patients to preserve greater peripheral vision, improving reading capacity and reading speed for example, and is an additional benefit of verteporfin treatment,” he said.

Mr. Harding added, “The prevention of moderate visual loss is a measure of clinical effectiveness. But avoidance of moderate vision loss is very significant to patients, because it means that they can maintain much of their independence.”

“In terms of the impact for the patient,” he continued, “they want to know what their vision will be at the end of treatment. And it generally seems to work out that patients get around 6/36 vision, which isn’t great, but is far better than 3/60 which is common if left untreated. So instead of patients having poor vision, they keep a quality of vision that allows them to maintain quite a lot of activities of daily living.”

NHS funds in place by summer

In line with guidance from the United Kingdom’s Department of Health, sustainable, nationwide NHS-funded PDT service is expected to be in place across the country for eligible patients with wet AMD by the end of June. It is anticipated that up to 50 centers will be needed for full implementation of the guidance from the National Institute for Clinical Excellence (NICE).

“Essentially NICE have recommended funding of PDT for those patients shown to benefit from treatment, both predominantly classic CNV and classic with no occult CNV secondary to macular degeneration,” said Mr. Talks. “We agree with the NICE decision to fund it and support the use of PDT for eligible patients.”

For Your Information:

Simon Harding, FRCOphth, can be reached at St. Paul’s Eye Unit, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, England; +44-151-706-2000; fax: +44-151-706-5806. Mr. Harding participated as a principal investigator at the clinical center for England and Wales in the TAP and VIP studies of photodynamic therapy.

James Talks, FRCOphth, can be reached at Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, England; +44-191-233-6161; fax: +44-191-227-5246.

Andrew Lotery MD, FRCOphth, can be reached at Southampton General Hospital, Tremona Road, Southampton SO16 6YD, England; +44-23-8079-5049; fax: +44-23-8079-4264.

References:

Barnes RM, Gee L, Taylor S, Briggs MC, Harding SP. Outcomes in verteporfin photodynamic therapy for choroidal neovascularisation: Beyond the TAP study. Eye. 2004 Feb 13 [E-publication in advance of print].

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin. One-year results of 2 randomized clinical trials – TAP Report 1. Arch Ophthalmol. 1999;117:1329-1345.

Verteporfin In Photodynamic Therapy (VIP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularisation in age-related macular degeneration: 2-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization – VIP Report 2. Am J Ophthalmol. 2001;131:541-560.