Evaluation of Retreatment Indications in a Randomized, Double-Masked Study Comparing Lucentis® Monotherapy and Combination Therapy With PDT in Neovascular AMD

Abstract

Purpose: : This double-blind, randomized study was designed to investigate the efficacy and safety of Lucentis (ranibizumab) monotherapy compared to standard verteporfin photodynamic therapy (PDT) in combination with Lucentis in all subtypes of CNV due to AMD during a one year monthly follow-up.

Methods: : Patients were randomized to receive initial PDT or sham PDT in both groups followed by 3 consecutive monthly intravitreal Lucentis 0.3mg injections. Thereafter, both groups received Lucentis injections on a PRN basis if disease activity was detectable based on loss of > 5 ETDRS letters in BCVA or increase of central retinal thickness (CRT) by at least 100µm (OCT) compared to any prior visit.

Results: : 40 patients (21 in the monotherapy and 19 in the combination group) were randomized. A significant difference (p<0.05) was found for the need of re-treatment with a total of 44 re-treatments in the monotherapy and 19 in the combination group. 74% of patients in the monotherapy and 50% in the combination arm needed retreatment during the maintenance phase. Retreatment inducing criteria were loss of BCVA (59%/58%) and increase in CRT at OCT (27%/26%) or both criteria together (14%/16%). But intraretinal cysts were already present at OCT one month before the retreatment criteria were fulfilled in 84%/74% of eyes! One month before retreatment subretinal fluid (SRF) was found in 70%/63% and at least one of the both, intraretinal cysts or SRF, occurred in 84%/89% of eyes. PED did not show any correlation to the need for retreatment. During the last month before retreatment was indicated the mean loss of BCVA was 2.7/3.6 letters, the last but one month before just 0.6/0.1 letters. That means that before significant vision loss occurred at least one of the both, intraretinal cysts or SRF, were present at OCT in almost all eyes.

Conclusions: : Patients receiving monotherapy required earlier and more frequent retreatments compared to patients on combination therapy. In our trial re-treatment indications were mostly based on a loss in BCVA, probably due to the weak OCT criterium of increase of CRT by at least 100µm. Intraretinal cysts or/and SRF were strong early predictors for the need of retreatment. These results suggest that qualitative OCT parameters do better than the quantitative parameter CRT as an early re-treatment indication and may help to prevent vision loss.

Clinical Trial: : www.clinicaltrials.gov NCT00429962

Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • imaging/image analysis: clinical