STUDY DESIGN

• multicenter, double-masked, randomized controlled, exploratory study

STUDY OBJECTIVES and ENDPOINTS

• The primary objective was to demonstrate superiority of verteporfin PDT + ranibizumab or verteporfin PDT alone compared to ranibizumab alone in achieving complete polyp regression at 6 months.
• The secondary endpoints included determination of proportion of patients with ICGA-proven complete polyp regression at months 3, 4, and 5, proportion of patients with at least one complete polyp regression during the 6-month study, mean change in central retinal thickness at month 6, mean best corrected visual acuity (BCVA) change at month 6 and over time, and number of re-treatments applied as per re-treatment criteria in the 3 treatment groups.
• Safety was assessed via frequency of ocular and non-ocular adverse effects and vital sign collection.

RANDOMIZATION SCHEME AND INTERVENTIONS

• Subjects were randomized 1:1:1 for receiving verteporfin PDT (6 mg/m2 ) + ranibizumab (0.5 mg), verteporfin PDT (6 mg/m2 ) + sham injection, or ranibizumab (0.5 mg) + sham PDT.

STUDY SUBJECTS

• Subjects included treatment-naïve patients ≥18 years of age with symptomatic macular PCV from 7 Asian study centers.

STUDY EYE INCLUSION CRITERIA

• BCVA 20/40 to 20/320 Snellen equivalent
• greatest linear dimension of the lesion <5400 μm by ICGA
• ICGA-diagnosed PCV (presence of early subretinal focal ICGA hyperfluorescence and at least one of the following: association with branched vascular network, presence of a pulsatile polyp, nodular appearance on stereoscopic view, presence of a hypofluorescent halo on ICGA, orange subretinal nodules in stereoscopic color fundus photos, or association with massive submacular hemorrhage)

TREATMENT

• Patients received either verteporfin PDT + ranibizumab, verteporfin PDT + sham injection, or sham PDT + ranibizumab.
• Ranibizumab or sham intravitreal injections were given starting at baseline for three consecutive months.
• Retreatments were given following protocol-specific re-treatment criteria guided by ICGA-assessed polyp status, fluorescein angiography (FA) assessment for leakage, BCVA, and minimum re-treatment interval on the label (90 days for verteporfin PDT/sham and 30 days for ranibizumab/sham).

ASSESSMENT METHODS

• ICGA was performed on day 1 and at months 3, 4, 5, and 6 to measure polyp area.
• FA was performed to assess for leakage.
• Fundus photos were taken.
• Central retinal thickness was determined by ocular coherence tomography (OCT) (at baseline and months 1 – 6).
• The BCVA was assessed at all study visits.
• Safety and side effects were assessed via ophthalmic examination, vital signs, and acute BCVA decreases.

RESULTS

Polyp regression

• The proportion of complete regression of polyps at month 6 was significantly higher in the verteporfin PDT + ranibizumab group (77.8%, P=0.0018) or verteporfin PDT alone (71.4%, P=0.0037) versus ranibizumab monotherapy (28.6%).
• The proportion of patients with at least one completely regressed polyp at any study time-point was significantly higher in verteporfin PDT + ranibizumab (83.3%, P=0.0069) or verteporfin alone (85.7%, P=0.0032) versus ranibizumab alone (42.9%).

Polyp area

• There decrease in mean polyp area in all three groups was as follows: verteporfin PDT + ranibizumab group (91.8% reduction), verteporfin PDT monotherapy (85.5% reduction), and ranibizumab monotherapy (68% reduction).

Best-Corrected Visual Acuity

• Patients in all three treatment groups gained letters in visual acuity testing during the study, although this was not powered to demonstrated statistically significant differences.

Central Retinal Thickness

• The mean central retinal thickness decreased in all three groups over the six-month study duration.
• The decrease was greatest in the verteporfin PDT + ranibizumab group (145.6 ± 119.0) and verteporfin monotherapy group (98.1 ± 104.3), compared to the ranibizumab monotherapy group (65.7 ± 114.3).

Fluorescein Angiography Assessment of Leakage

• There was leakage at baseline in all three groups: verteporfin PDT + ranibizumab group (100%), verteporfin monotherapy group (90.5%), and ranibizumab monotherapy group (95.2%).
• Presence of leakage at month 6 was as follows: verteporfin PDT + ranibizumab (22.2%), verteporfin PDT monotherapy (33.3%), and ranibizumab monotherapy (61.9%).



Safety

• Ocular adverse effects occurred in the following proportions: verteporfin PDT + ranibizumab (26.3%), verteporfin PDT monotherapy (33.3%), and ranibizumab monotherapy (19%) and included retinal hemorrhage, intraocular pressure increase, conjunctival hyperemia, and more.
• Non-ocular adverse effects occurred in the following proportions: verteporfin PDT + ranibizumab (31.6%), verteporfin PDT monotherapy (42.9%), and ranibizumab monotherapy (33.3%) and included angina pectoris, noncardiac chest pain, blood pressure increase, and gastric cancer

CONCLUSIONS

• This randomized controlled trial, using ICGA-guidance, demonstrated that verteporfin PDT + ranibizumab or verteporfin PDT alone was superior to ranibizumab alone in inducing regression of polyps in patients with symptomatic PCV.
• Higher proportions of patients in the verteporfin PDT groups experienced polyp regression at some point in the study compared to the ranibizumab monotherapy group.