Ranibizumab (Anti-VEGF) for Visional Loss Due to Diabetic Macular Oedema – Results of Two Phase 3 RCT's

Ranibizumab (Anti-VEGF) for Visional Loss Due to Diabetic Macular Oedema – Results of Two Phase 3 RCT’s
David Boyer
ADA 2011.

Ranibizumab is an injectable antibody.
Diabetic Retinopathy (DR) is present in 28.5% of people with diabetes and is the leading cause of new blindness in people of working age. Whilst laser therapy can halt progression of neovascularization, the benefit treatment for macular edema (DME) is limited.
VEGF is a key mediator in the pathway, which leads to DME. Improved glycaemic and BP control in the UKPDS and lipid control in the ACCORD study have been shown to reduce the risk of progression/development of DR. It is important to recognize however that DR does still occur and the time to refer to ophthalmology is BEFORE any visual loss has occurred. To date, laser photocoagulation has been the only therapy for DME and whilst this reduces further visual loss it does not improve vision.
The RIDE and RISE trials were conducted in USA and S America. They included adults >18 years with a central subfield thickness > 275 micrometers. Primary endpoints were those gaining 3 or more lines from baseline. Secondary endpoints were laser therapy, QALY. Those in both the sham injection and ranibuzimab groups were similar.
Visual outcomes showed significant benefit for both the 0.3 and 0.5mg treatment groups for 3 or more lines of visual improvement. There was a mean 11-12 letter improvement shown in both the RISE and RIDE trials (15 letters = 3 lines). In terms of driving licenses requirement there was an almost doubling in the number of patients who would be allowed to drive. There was benefit irrespective of the HbA1c. There was also a significant benefit of contrast sensitivity.
The National Eye Institute VQF-25 score increased significantly in both trials, which means that patients derived meaningful clinical benefit in vision. It was found that the need for laser therapy was almost non-existent in the treatment groups and that the only group in whom there was worsening of retinopathy was the sham group.
Safety was consistent with all previous trials. There was a tiny increase in TIA but S/E were limited.