Session Title: AMD II
Session Date/Time: Friday 12/09/2014 | 08:00-10:00
Paper Time: 08:08
Venue: Boulevard D
First Author: : T.Jackson UK
Co Author(s): : A. Muldrew T. Peto S. Harding J. Sahni U. Chakravarthy
To assess the safety of external beam X-ray therapy adjunctive to anti-vascular endothelial growth factor therapy for the treatment of neovascular age-related macular degeneration (AMD), over 3 years.
21 European sites.
230 patients with active, chronic, neovascular AMD were entered into a double masked, sham controlled, randomized clinical trial. Of this group, 226 received the allocated treatments of 16 Gray (N=74), 24 Gray (N=73) or sham stereotactic radiotherapy (N=79). Participants were administered 0.5 mg intravitreal ranibizumab at baseline, and thereafter for one year using a monthly as needed dosing regimen with pre-defined retreatment criteria. Efficacy follow-up continued for 12 months. After month 12, patients resumed usual standard of care, but returned for a safety visit at months 24 and 36. Safety outcomes included adverse events (AEs) and serious AEs (SAEs), coded using MedDRA preferred terms. Fundus photographs and fluorescein angiograms were obtained at baseline and months 12, 24, and 36, and additional colour photographs were obtained at months 6 and 18. All images were graded by a central reading centre for AMD activity and for the safety outcome of radiation induced retinopathy. Cases with suspicious features were referred to a panel of experts for further evaluation.
The study met its primary endpoint, with a statistically significant reduction in ranibizumab retreatment over 12 months. At the 2 year endpoint there was 1 case of investigator reported radiation retinopathy. Reading center analysis at 2 years identified a total of 35 instances of microvascular change (MVC), including 6 in the control group, but only 18 were evaluated as radiation related, and only 2 that possibly affected vision. The most commonly encountered features were haemorrhage in the inner retinal layers and/or cotton wool spots on colour grading. Microvascular narrowing and irregularity of the lumen and/or telangiectasia with capillary drop out were the commonest abnormalities noted on fluorescein angiography. At the time of abstract submision, the reading center had evaluated images from 101 patients at 3 years;7 additional cases of MVC due to radiation were identified, none affecting vision. In addition, 2 of the previously identified cases of MVC showed spontaneous vascular remodeling and resolution.
Radiation induced retinal MVCs can occur after focal low energy radiotherapy by month 12. The frequency of occurrence through month 36 is low and the area of retinal involvement limited, with evidence that these focal lesions can resolve spontaneously.