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Photodynamic Therapy With Verteporfin for Choroidal Neovascularization Caused by Age-related Macular Degeneration
Results of Retreatments in a Phase 1 and 2 Study
Ursula Schmidt-Erfurth, MD;
Joan W. Miller, MD;
Michel Sickenberg, MD;
Horst Laqua, MD;
Irene Barbazetto, MD;
Evangelos S. Gragoudas, MD;
Leonidas Zografos, MD;
Bertrand Piguet, MD;
Constantin J. Pournaras, MD;
Guy Donati, MD;
Anne-Marie Lane, MPH;
Reginald Birngruber, PhD;
Hubert van den Berg, PhD;
H. Andrew Strong, PhD;
Ulrike Manjuris, PhD;
Todd Gray, MSPH;
Mario Fsadni, MRCOphth;
Neil M. Bressler, MD
Arch Ophthalmol. 1999;117:1177-1187.
Objectives To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT.
Design Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens.
Setting Four ophthalmic centers in Europe and North America providing retinal care.
Methods Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment.
Results The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, - 5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications.
Conclusions Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treatment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss.
From the Retina Department, University Eye Hospital, Lübeck, Germany (Drs Schmidt-Erfurth, Laqua, Barbazetto, and Birngruber); Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Mass (Drs Miller and Gragoudas and Ms Lane); Hopital Ophtalmique Jules Gonin, Lausanne, Switzerland (Drs Sickenberg, Zografos, and Piguet); Department of Oto-Neuro-Ophthalmology, Hopital Cantonal Universitaire de Genève, Geneva, Switzerland (Drs Pournaras and Donati); Laboratory of Air Pollution Studies, Department of Environmental Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (Dr van den Berg); QLT PhotoTherapeutics Inc, Vancouver, British Columbia (Drs Strong and Manjuris); CIBA Vision Inc, Duluth, Ga (Mr Gray); CIBA Vision AG, Bülach, Switzerland (Dr Fsadni); and The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Md (Dr Bressler). The Massachusetts Eye and Ear Infirmary is an owner of a patent covering the use of verteporfin. Should the Massachusetts Eye and Ear Infirmary receive royalties or other financial remuneration related to that patent, Drs Miller and Gragoudas would receive a share of same in accordance with the Massachusetts Eye and Ear Infirmary's institutional Patent Policy and Procedures, which includes royalty-sharing provisions.
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