Randomized non-inferiority trial of direct selective laser trabeculoplasty in open-angle glaucoma and ocular hypertension: GLAUrious

OBJECTIVE: Effective glaucoma treatment is limited by non-adherence to topical medications and suboptimal access to selective laser trabeculoplasty (SLT). GLAUrious compared direct selective laser trabeculoplasty (DSLT), an automated, gonioscopy-free, non-contact, image-guided procedure to reduce intraocular pressure (IOP), with conventional SLT in open-angle glaucoma (OAG) and ocular hypertension (OHT).

DESIGN: Prospective, multicenter, randomized, controlled, evaluator-masked non-inferiority trial.

PARTICIPANTS: Participants aged ≥40 years with OAG or OHT, on 0-3 hypotensive medications at screening, and washout IOP 22-35 mmHg were treated at 14 centers.

METHODS: Following washout, 192 participants randomized 1:1 were treated with DSLT (n=99) or SLT (n=93). IOP was assessed at pre-treatment and follow-up visits through 12-months post-procedure, with washout IOP measured at baseline and 6 months. Ocular adverse events (AEs) were assessed in both groups.

MAIN OUTCOME MEASURES: Difference between DSLT and SLT in mean IOP change from baseline to 6 months (non-inferiority margin -1.95 mmHg). Exploratory efficacy and safety outcomes were assessed over 12 months.

RESULTS: Of 156 (81.3%) participants without major protocol deviations analyzed at 6 months, mean (± SE) washout IOP reduction from baseline was 5.5 (± 0.5) mmHg (-20.6%) following DSLT and 6.2 (± 0.5) mmHg (-23.6%) following SLT. The between-group difference (SLT-DSLT) in mean IOP reduction was -0.7 mmHg (95% CI: -2.2, 0.8; P=0.09 [NS] for non-inferiority). Of 161 (83.9%) participants without major protocol deviations analyzed at 12 months, mean (±SE) non-washout IOP reduction from screening was 3.2 (± 0.4) mmHg (-12.2%) following DSLT and 3.2 (± 0.4) mmHg (-9.4%) following SLT. The between-group difference in mean IOP reduction was 0.01 mmHg (95% CI: -1.1, 1.1; P<0.001 for non-inferiority). Safety profiles were similar between groups, although clinically non-significant punctate subconjunctival hemorrhage was more frequent in the DSLT group. Ocular AEs were generally mild and resolved without intervention.

CONCLUSIONS: The 6-month primary endpoint did not achieve statistical noninferiority compared to conventional SLT. Nonetheless, DSLT was well tolerated and provided an effective reduction in IOP that was sustained for 12 months. Failure to demonstrate noninferiority does not prove inferiority: DSLT remains an effective option in the early treatment paradigm and can considered as a first-line treatment when SLT is not readily accessible.