EARLY results

Anti-VEGF monotherapy insufficient for all DME patients

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Anat Loewenstein MD, PhD
Only a minority of diabetic macular oedema (DME) patients that show limited initial visual improvement with anti-VEGF therapy can be expected to develop a clinically significant visual response with continued intensive anti-VEGF treatment and monitoring over the following one-to-three years, according to Anat Loewenstein MD, PhD. “For patients with a suboptimal visual response after the first three intravitreal anti-VEGF injections it may be appropriate to consider adjustments to the treatment regimen, as we know there is a very good chance that these patients will not derive any benefit from ranibizumab injections over the long term,” she told delegates attending the 17th EURETINA Congress in Barcelona. Dr Loewenstein, Professor of Ophthalmology and Deputy dean of the medical school at the Sackler Faculty of Medicine, Tel Aviv University, Israel, presented results on behalf of the EARLY (Early Anti-VEGF Response and Long-term efficacY) programme, a series of post-hoc analyses of data from the Diabetic Retinopathy Clinical Research Network’s (DRCR.net) Protocol I study of ranibizumab plus laser in DME. EARLY was initiated to explore the relationship between early and long-term anatomic and visual acuity responses to anti-VEGF therapy. Dr Loewenstein’s presentation focused on the strength of the association between visual acuity outcome after three monthly anti-VEGF intravitreal injections and visual acuity outcomes at one and three years, with particular emphasis on non-responders to treatment. The visit schedule for the first year of treatment was every four weeks, with years two and three depending on the treatment group. In the ranibizumab-treated groups, the visit schedule could be extended up to a maximum of 16 weeks, said Dr Loewenstein. At each visit, a decision was taken on retreatment based on an assessment of the timing of visit, visual acuity, central retinal thickness, laser treatment history, failure or futility criteria and investigator discretion. While the visual acuity results overall were excellent at five years, there was a subpopulation of patients who were not responsive to treatment, defined as patients who showed less than five letters’ improvement at 12 weeks (39.7%) compared to two other cohorts: five-to-nine letter improvement (23.2%), and more than 10 letters’ improvement (37.1%). The investigators also looked at anatomical parameters and identified 35% of patients that had less than 20% improvement in central retinal thickness (CRT) at week 12 after three Ranibizumab injections. Post-hoc analysis of the non-responder group found that eyes with less than a five-letter gain after three injections showed limited additional improvement for the study duration of three years. “After one year, one-in-four of these patients will move to the group showing more than two lines’ improvement, and after three years one-in-three of them will move to the same group. However, 50% of them will remain in the non-responder category. This means that if we just continue to inject anti-VEGF as per Protocol I, we inject without giving these patients a chance to improve,” she said. Similar results were also achieved when the investigators looked at the OCT parameters, said Dr Loewenstein. “Those eyes with less than 20% CRT improvement at 12 weeks were found to have less chance of obtaining good visual acuity. Their mean visual acuity at three years was lower than that of the patients who had more than 20% reduction in CRT at three months,” she said. A further sub-analysis of the eyes in Protocol I also looked at the duration of the oedema and the impact, if any, it may have on long-term visual acuity in patients with DME. “One-third of study eyes showed persistent oedema over the first year. Among eyes with the most persistent oedema at week 52, the oedema tended to persist over the second year in three-quarters of them, and this had a very important impact on the visual acuity,” she said. Patients with the greatest duration of oedema at week 52 had worse average vision improvement over the study duration. Eyes with the most persistent oedema gained significantly fewer letters at week 52, and their poorer visual acuity persisted at weeks 104 and 156. Anat Loewenstein: anatl@tlvmc.gov.il
Tags: dme