title: Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens.
  
  
  METHODS
  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.
authors.affiliation: Retina Department, University Eye Hospital, Lübeck, Germany. uschmidterfurth@ophtha.mu-luebeck.de
authors.forename: U
authors.initials: U
authors.lastname: Schmidt-Erfurth
authors.forename: J W
authors.initials: JW
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Sickenberg
authors.forename: H
authors.initials: H
authors.lastname: Laqua
authors.forename: I
authors.initials: I
authors.lastname: Barbazetto
authors.forename: E S
authors.initials: ES
authors.lastname: Gragoudas
authors.forename: L
authors.initials: L
authors.lastname: Zografos
authors.forename: B
authors.initials: B
authors.lastname: Piguet
authors.forename: C J
authors.initials: CJ
authors.lastname: Pournaras
authors.forename: G
authors.initials: G
authors.lastname: Donati
authors.forename: A M
authors.initials: AM
authors.lastname: Lane
authors.forename: R
authors.initials: R
authors.lastname: Birngruber
authors.forename: H
authors.initials: H
authors.lastname: van den Berg
authors.forename: H A
authors.initials: HA
authors.lastname: Strong
authors.forename: U
authors.initials: U
authors.lastname: Manjuris
authors.forename: T
authors.initials: T
authors.lastname: Gray
authors.forename: M
authors.initials: M
authors.lastname: Fsadni
authors.forename: N M
authors.initials: NM
authors.lastname: Bressler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002199:Capillary Permeability / Q000187:drug effects; D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D008268:Macular Degeneration / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011166:Porphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D019233:Retreatment; D012449:Safety; D016896:Treatment Outcome; D000077362:Verteporfin; D014792:Visual Acuity
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D019793:Fluorescein