One of the most exciting facets of being medical retina specialists is the continued evolution of age-related macular degeneration (AMD) therapies. We have come a long way from the days of photodynamic therapy and the fledgling anti-vascular endothelial growth factor (anti-VEGF) which was Macugen (pegaptanib sodium). We now have agents able to restore and maintain vision with neovascular AMD (nAMD) and agents potentially capable of stabilising atrophic AMD. This article provides an overview of established and emerging treatments.
Existing and newer agents for nAMD management
Anti-VEGF treatment continues to be the mainstay of treatment of nAMD in New Zealand. The initial agent used for most patients is bevacizumab 1.25 mg (Avastin), with access pathways to aflibercept 2mg (Eylea) in cases of non-response to treatment and ranibizumab 0.5mg (Lucentis) if certain criteria are met. Avastin and Lucentis are monoclonal antibodies to VEGF, whereas Eylea is a VEGF trap. The benefits of these agents are well established, but long-term challenges remain in maintaining the visual gains and in the burden of frequent injections for both the patient and eye clinics.
Advances in nAMD management came with the development of more durable anti-VEGF treatments requiring less frequent dosing and exploring different dosing regimens of existing agents. Of these, faricimab (Vabysmo) shows a lot of promise and targets both VEGF and angiopoetin-2, preventing them from binding with their respective receptors. The Tenaya and Lucerne phase 3 (industry sponsored) clinical trials compared Vabysmo with aflibercept in patients with naive nAMD (who had not been treated with other agents)1. Patients were randomised to either Vabysmo monthly for four injections, then at individualised treatment intervals up to 16 weeks, or aflibercept 2mg with three initial monthly injections followed by an injection every eight weeks. In both studies, Vabysmo was non-inferior to aflibercept in terms of visual acuity criteria. At two years, 80% of patients treated with Vabysmo were on 12-weekly intervals and 63% were stable on 16-weekly intervals. Intraocular inflammation developed in 2% of Vabysmo cases compared to 1.2% of aflibercept, but there were no cases of retinal vasculitis. As faricimab blocks both the VEGF and ang-2 pathway, it has been shown to provide greater vascular stability (as evidenced by a greater and faster resolution of macular leakage). This reduction in leakage, not seen with straight VEGF blockade, is important as leakage can lead to increased fibrosis and reduced vision.
Real-world studies Truckee and Faretina retrospectively analysed data from sight registries for Vabysmo’s efficacy and safety. They indicated the majority of eyes previously treated with other anti-VEGF agents and switched to Vabysmo were able to extend their treatment interval with maintenance of visual acuity2,3. In treatment-naive eyes there was acuity improvement and extension. Longer-term follow up will be needed to fully establish the role of Vabysmo in nAMD management worldwide but safety data from real world studies so far are reassuring










