Outcomes of the Advanced Visualization In Corneal Surgery Evaluation (ADVISE) trial; a non-inferiority randomized control trial to evaluate the use of intraoperative OCT during Descemet membrane endothelial keratoplasty

Purpose To evaluate if an intraoperative OCT (iOCT) optimized surgical protocol without prolonged overpressure is non-inferior to a standard protocol during Descemet membrane endothelial keratoplasty (DMEK). Design A multicenter international prospective non-inferiority randomized control trial Subjects Sixty-five pseudophakic eyes of 65 patients with corneal endothelial dysfunction resulting from Fuchs endothelial corneal dystrophy were enrolled in 3 corneal centers in The Netherlands and Belgium. Methods The study was powered to include 63 patients scheduled for routine DMEK. Subjects were randomized to the control arm (n=33) without iOCT-use and raising the intraocular pressure above normal physiological limits for 8 minutes (i.e., overpressure) or the intervention arm (n=32) with OCT-guidance to assess graft orientation and adherence while refraining from prolonged raising the intraocular pressure. The RD and 95% confidence intervals (95% CI) were calculated from a logistic regression model using 1,000 bootstrap samples. Secondary outcomes included the incidence of graft detachment, surgeon-reported iOCT-aided surgical decision making, surgical time, endothelial cell density (ECD), and corrected distance visual acuity (CDVA). Main Outcome Measures The primary outcome was the incidence of postoperative surgery-related adverse events, defined as rebubbling, graft failure, and iatrogenic acute glaucoma. The non-inferiority margin was set at a risk difference (RD) of 10%. Results In the control group, 13 adverse events were recorded in 10 subjects compared to 13 adverse events in 12 subjects in the intervention group. The mean unadjusted RD measured 0.38% (95%CI: - 9.64–10.64) and the RD adjusted for study site measured -0.32% (95%CI: -10.29–9.84). No significant differences in ECD and CDVA were found between the two groups 3 and 6 months postoperatively. Surgeons reported that iOCT aided surgical decision-making in 40% of cases. Surgical- and graft unfolding time were, respectively, 13% and 27% shorter in the iOCT-group. Conclusions iOCT-guided DMEK surgery with refraining from prolonged over-pressuring was non-inferior compared to conventional treatment. Surgery times were reduced considerably, and surgeons reported the iOCT aided surgical decision-making in 40% of cases. Refraining from prolonged overpressure did not affect postoperative ECD or CDVA.