The LUV Trial: Ultra-low Fluence Verteporfin (VISUDYNE®) Photodynamic Therapy (vPDT) Combined with Intravitreal Ranibizumab (LUCENTIS®) Versus Ranibizumab Monotherapy

Abstract

Purpose: : To determine the dose-response effects of ultra-low fluence vPDT on choroidal perfusion when used in combination with intravitreal ranibizumab injections, and to evaluate the efficacy and safety of this combination therapy in the treatment of age-related choroidal neovascularization (CNV).

Methods: : In this controlled single site trial, patients (pts) with naïve CNV secondary to ARMD were randomized to sham PDT (2 pts), 20% fluence vPDT (2 pts), or 40% fluence vPDT (3 pts). All pts received concomitant induction with 3 monthly injections of 0.5 mg ranibizumab. Pts underwent ETDRS refractions, clinical exam & OCT at baseline and every follow-up visit. ICG and fluorescein (FFA) angiography was performed at day 0, day 1, week 1, month 1-3, month 6 and month 9. Retreatment with ranibizumab was given if any evidence of active CNV was seen on clinical exam, OCT, or FFA. ICG choroidal hypoperfusion was graded in a masked fashion.

Results: : Median EDTRS refracted visual acuity at baseline was 20/32 in the sham group, 20/40 with 20% fluence, and 20/40 with 40% fluence. No pt in any arm lost or gained ≥10 letters at one year by ETDRS refracted VA. Pts in the sham vPDT arm required an average of 7.5 injections in 12 months versus 7.0 injections in both the 20% and 40% fluence vPDT groups. No pt receiving sham vPDT had any evidence of choroidal hypoperfusion on ICG angiography at baseline or follow-up, but all pts with 20% and 40% fluence vPDT had definite vPDT related hypoperfusion defects most noted at week 1 and week 4. Pts with 40% fluence vPDT had persistence of hypoperfusion at 6 months.

Conclusions: : Choroidal hypoperfusion related to vPDT was routinely observed with ultra-low fluence vPDT. This hypoperfusion was transient and was not demonstrated after 1 month with 20% fluence but persisted 3 months or longer in pts with the 40% fluence. Despite this evidence of the effect of vPDT on the choroidal vasculature, there did not seem to be any significant decrease in either visual acuity outcomes or in the number of required ranibizumab injections.

Clinical Trial: : www.clinicaltrials.gov NCT00423189

Keywords: age-related macular degeneration • photodynamic therapy • vascular endothelial growth factor