Placebo effect delivers in open-angle glaucoma

Treatment with placebo is successful in patients with open-angle glaucoma or ocular hypertension, achieving lower intraocular pressure (IOP), compared with untreated control participants, reports a recent study.

A team of investigators identified randomized controlled trials (RCTs) of topical ocular hypotensive therapy for patients with open-angle glaucoma or ocular hypertension conducted through 2 June 2022.

The perceived placebo effect was measured as the overall IOP change from baseline. The investigators assessed placebo effect in terms of effect size (ES; mean difference between baseline and endpoint) and compared with that from untreated controls. ES based on 4 weeks of treatment was the primary outcome.

Additionally, the investigators conducted meta-analysis‒based statistical pooling where appropriate and used 95 percent confidence intervals (CIs) for comparison. A multiple meta-regression model was used to examine the potential placebo effect determinants.

Forty RCTs (n=7,829 eyes) with 33 placebo groups (n=2,055 eyes), along with seven untreated groups (n=1,184 eyes), were included.

Among placebo-controlled trials, placebo was effective in lowering IOP (ES, ‒1.30 mm Hg, 95 percent CI, ‒1.75 to ‒0.84). In network meta-analysis, placebo-treated patients achieved ‒2.27 mm Hg (95 percent CI, ‒3.52 to ‒1.01) greater ES than that by untreated control participants.

The multiple meta-regression model showed that active treatment ES significantly predicted the amount of placebo effect. Placebo also reduced IOP by ‒0.45 mm Hg per ‒1 mm Hg of active treatment effect. Likewise, add-on study design and larger sample size correlated with greater amount of placebo effect.

Publication bias was not observed in either a funnel plot or the Begg and Mazumdar adjusted rank correlation test results (p=0.24).

“[C]aution is required in interpreting the results because of the small number of untreated controlled trials and potential bias from the lack of direct comparison between the placebo and untreated arms,” the investigators said.