Long-term Visual Outcomes after Release from Protocol in Patients who Participated in the Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) Trial

Purpose : To describe visual outcomes, frequency of treatment and monitoring visits, and anti-vascular endothelial growth factor drugs used in usual care in participants who exited a trial in which treatment for neovascular age-related macular degeneration (AMD) was initiated with bevacizumab or ranibizumab. Design : Multi-centre cohort study up to 7 years after trial exit. Participants : Patients enrolled in the Inhibition of VEGF in age-related choroidal neovascularisation (IVAN) trial; after excluding participants from one site and who died or withdrew during the trial, 537 were included in this follow-up cohort. Methods: Data were collected between 26 May 2016 and 24 August 2017. Distance visual acuity (DVA, letters read) in both eyes and treatments for nAMD administered to either eye at all usual care visits were extracted from medical records of all participants until the point of data collection (duration of study eye monitoring). Main Outcome Measures : Rate of change of DVA during active surveillance of the study eye (study eye monitoring), estimated using a multivariable linear random effects model. Other outcome measures were visit and treatment frequency and switches in anti-VEGF drug. Results: Data were obtained for 99% (532/537) of eligible participants. The median duration of study eye monitoring after IVAN exit was 3.3 years (IQR 1.3, 4.7), and median DVA was 58.0 letters (IQR 34.0, 73.0). Study eye DVA deteriorated by 4.3 (95% CI 3.7 to 4.9) letters per year. Injection rate did not influence the rate of change in DVA after adjusting for key covariates. After IVAN exit, 174 (32%) participants received no treatment; 332/358 (93%) were treated first with ranibizumab, 78 (23%) of whom switched to aflibercept. DVA was similar among participants who switched or did not switch at end of study monitoring. Conclusions: Approximately 5 years after the IVAN study finished, with unprecedented completeness of follow-up for such a trial, the trajectory of functional decline in the study eye was shown to be ...