Treatment of neovascular age-related macular degeneration with a variable ranibizumab dosing regimen and one-time reduced-fluence photodynamic therapy: the TORPEDO trial at 2 years

Retinal Disorders



The combination of verteporfin photodynamic therapy (PDT) and anti-angiogenics has been shown to be safe and efficacious in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The purpose of this study is to demonstrate long-term prevention of vision loss and improvement in best-corrected visual acuity (BCVA) after treatment with one-time reduced-fluence-rate PDT followed by administration of ranibizumab on a variable dosing regimen over 24 months in patients with neovascular AMD. Secondary outcome measures included the change in central macular thickness (CMT), reinjection frequency, and safety.


This prospective, nonrandomized, open-label, single-center study enrolled 27 consecutive patients (27 eyes) presenting at the Leuven University Eye Hospital with previously untreated, active neovascular AMD between September 2006 and January 2007. All patients were treated with one-time, reduced-fluence-rate verteporfin PDT, followed by intravitreal ranibizumab 0.5 mg on the same day. A second and third ranibizumab injection were given at weeks 4 and 8, respectively, after which patients were followed up monthly for 24 months. Additional treatment with ranibizumab was administered to eyes with active neovascularization as indicated clinically and on imaging studies. Retreatment was based on the following criteria: (1) presence of subretinal fluid (SRF), intraretinal edema or sub-retinal pigment epithelial fluid, as seen on OCT; (2) increase of CMT by >100 mm on OCT; (3) signs of active CNV leakage on fluorescein angiography; (4) new sub- or intraretinal hemorrhage; and (5) BCVA decreased of ≥5 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. If any single criterion for reinjection was fulfilled, retreatment with ranibizumab was administered.


Twenty-five patients completed the 2-year study. Occult CNV was present in 64% and retinal angiomatous proliferative (RAP) lesions were present in 24% of the study eyes. The remaining three eyes had lesions classified as classic (one eye) or predominantly classic (two eyes) CNV. Month 24 data are available for 25 eyes (25 patients; age 55–86 years; mean 77; standard deviation (SD) = 7.2). Mean baseline VA was 58.6 letters (range: 35–70; SD = 8.4); 24-month VA was 66.2 letters (35–82; 12.7), not including one warfarin-treated patient who suffered vitreous hemorrhage. The mean visual acuity improved by 7.2 letters (p < 0.05) and the mean CMT decreased by 146 μm. VA improved >3 lines (15 letters) in 16%; improved 1–3 lines in 20%; remained within one line of baseline in 32%, decreased 1–3 lines in 16%, and decreased >3 lines in 16%. Losses of >3 lines were due to vitreous hemorrhage, geographic atrophy, fibrosis, and growth of an initially small CNV lesion. An average of 5.1 injections (range: 3–9) were administered during the first 12 months, and 7.1 injections (3–13) over 24 months. A total of 178 injections were performed; no systemic side-effects, uveitis, or choroidal collateral vascular damage were observed. Two patients were lost to follow-up.


Combined PDT and ranibizumab injection the same day was well tolerated in all patients. Eighty-four percent of patients had stable or improved vision at month 24.


Age-related macular degeneration Choroidal neovascular membrane Lucentis (ranibizumab injection) Photodynamic therapy Vascular endothelial growth factor (VEGF) 


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of OphthalmologyUniversity Hospital LeuvenLeuvenBelgium

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