Anti-VEGF vs PRP: Which is best?

Panretinal photocoagulation (PRP) remains the gold standard of initial therapy for proliferative diabetic retinopathy (PDR) and its neovascular complications despite a recent trend towards front-line use of anti-VEGF agents, according to Nigel Davies PhD, FRCOphth. “There is no medical need to replace PRP with anti-VEGF treatment alone. We need to remember that PDR is a severe and progressive disease. It is important to treat aggressively and to do the PRP properly,” he told delegates attending the 9th Euretina Winter Meeting in Prague. Left untreated, PDR is a leading cause of blindness, with more than 50% of eyes with high-risk PDR experiencing severe vision loss within five years. Dr Davies, Consultant Ophthalmologist at Guy’s and St Thomas’ NHS Trust, London, United Kingdom, said that anti-VEGF agents should not be seen as a panacea for patients with diabetic retinopathy and PDR. “Anti-VEGF agents definitely have a role to play, but the future should involve personalised care for each patient. Ideally, we need further studies to help us understand which treatments or combinations work best at different stages of PDR in order to preserve the vision of our patients,” he said. A review of the scientific literature over the past decade underscores the utility of using combination PRP and anti-VEGF agents to limit the visual and anatomical damage from PRP, said Dr Davies. “What emerges is that the patients that had combination treatments with bevacizumab or ranibizumab did better than those that had PRP alone in terms of visual outcomes and control of their neovascularisation,” he said. The PROTEUS Study, which compared the efficacy of ranibizumab plus PRP versus PRP alone in patients with high-risk proliferative diabetic retinopathy over a 12-month period, found that combination treatment delivered better visual acuity and anatomical outcomes, said Dr Davies. Another important trial to note was the DRCR.net Protocol S study, which evaluated the efficacy and safety of ranibizumab versus PRP over five years for PDR, said Dr Davies. “The findings were very interesting. Visual acuity outcomes were clearly better at two years and throughout the whole study period for the patients who had ranibizumab alone, and this was better for the patients who had diabetic macular oedema than for those who did not. The PRP group also seemed to do much worse in terms of their visual field outcomes. The anatomical results were about the same, with approximately 30% of patients without active or regressive new vessels at the end of the study period,” he said. Similar findings also emerged from the UK-based CLARITY trial in which patients with PDR who were treated with intravitreal aflibercept had an improved outcome at one year compared with those treated with PRP standard care. While the evidence from such trials may seem to undermine the rationale for PRP treatment in favour of anti-VEGF agents, Dr Davies said it was important not to rush to hasty conclusions. He cited a recent paper by Susan Bressler MD that looked at factors that led to worsening of diabetic retinopathy in Protocol S patients. “Some factors were ones we might have expected, with patients at high-risk of PDR doing worse than moderate-risk patients. In the PRP group, eyes that received pattern scan PRP were more likely to have PDR-worsening events compared with eyes treated with conventional single-spot PRP,” he said. Possible explanations for the difference in efficacy include the type and number of burns or total area of retinal ablation created by the laser, added Dr Davies. “With conventional laser, it's a longer pulse duration, the burn expands over a larger area and it is a denser burn, which makes the treatment more effective. With the pattern laser, the burn tends to contract, with a smaller treated area and a lighter burn and less effective treatment. On the whole you need between 50% and 75% more burns with pattern laser than conventional laser to get the disease under control,” he said. Dr Davies noted that the five-year drop-out rate of 34% overall for the Protocol S study was also relatively high. “Of those lost to follow-up, half had anti-VEGF injections and half had PRP. While we don’t actually know what happened to those lost to follow up, there is a recent paper from Obeid et al. at Wills Eye Hospital (Ophthalmology 2018 Sep;125(9):1386-1392) that might give some indication of what to expect if our patients return after more than six months without any treatment,” he said. The study found that eyes with PDR that received only intravitreal anti-VEGF demonstrated worse anatomic and functional outcomes after being lost to follow-up compared with eyes that received PRP. “If a treated patient is lost for about a year despite previous treatment they will probably come back and their vision and anatomy will be worse. The Wills Eye Hospital evidence also indicates that patients treated with anti-VEGF alone may do worse than those treated with PRP,” he concluded.

Tags: anti-VEGF drugs, Panretinal photocoagulation, proliferative diabetic retinopathy