Stereotactic radiotherapy for neovascular age related macular degeneration: year 3 and 4 extended follow up results of a randomised, double masked, sham controlled, device trial (STAR).

OBJECTIVE

To assess the effects of stereotactic radiotherapy (SRT) for neovascular age related macular degeneration (AMD) beyond the two year primary outcome of the StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR) trial.

DESIGN

Randomised, double masked, sham controlled, device trial involving preplanned recall from standard care.

SETTING

30 NHS hospitals in the UK.

PARTICIPANTS

411 participants aged at least 50 years with chronic, pretreated, active AMD.

INTERVENTION: Participants received one-off 16 Gray SRT or sham SRT delivered using a robotically controlled device. After two years of monthly study visits, participants reverted to routine care, with anti-VEGF drug selection and dosing intervals based on local practice, but with masking maintained, and repeat data collection at years 3 and 4 study visits.

MAIN OUTCOME MEASURES: The main efficacy outcome at year 4 was the number of anti-VEGF injections, tested for superiority (fewer injections). The other main outcome was visual acuity, tested for non-inferiority (five letter margin). Safety outcomes included adverse events, serious adverse events, and microvascular abnormalities. The same analyses were undertaken at years 2, 3, and 4. A within trial costing analysis was undertaken for participants with four years' follow-up.

RESULTS

Of 411 participants (204 (58%) women), 274 were allocated to SRT and 137 to sham SRT. The year 4 intention-to-treat efficacy analysis included 222 (81%) participants in the SRT group and 106 (77%) in the sham SRT group. The SRT group received a mean of 19.1 (standard deviation 10.9) injections over four years versus 21.6 (11.3) with sham SRT, an adjusted decrease of 3.2 injections (95% confidence interval (CI) of difference -5.7 to -0.7). During years 3 and 4, the SRT group received a mean cumulative 8.4 injections versus 8.3 injections in the sham SRT group. The final change in visual acuity in the SRT group was 8.3 letters worse than in the sham group (95% CI of difference -12.7 to -4.0). Adverse event rates were similar between groups, but reading centre-detected microvascular abnormalities occurred in 126/218 SRT treated eyes (58%) and 16/102 (16%) sham SRT treated eyes.

CONCLUSION

Although the overall reduction in intravitreal therapy was maintained to year 4, the inferior vision in SRT treated eyes effectively reversed the conclusions of the year 2 primary outcome analysis and no longer supports the use of SRT to treat neovascular AMD. Including standard care, masked, extended follow-up within a clinical trial may provide useful clinical insight.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02243878.