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

ABSTRACT

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 (nAMD) was initiated with bevacizumab or ranibizumab. DESIGN: Multicenter 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 2 sites and who died or withdrew during the trial, 537 were included in this follow-up cohort. METHODS: Data were collected between May 26, 2016, and August 24, 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-vascular endothelial growth factor (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 (interquartile range [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% confidence interval [CI], 3.7-4.9) letters per year. Injection rate did not influence the rate of change in DVA after adjusting for key covariates. After IVAN exit, 174 participants (32%) received no treatment; 332 of 358 (93%) were treated first with ranibizumab, 78 (23%) of whom switched to aflibercept. The DVA was similar among participants who switched or did not switch at the 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 greater than that previously reported for incomplete trial cohorts. Anti-VEGF injection rates and treatment switches were not important factors in determining visual acuity outcomes.