Glaucoma Diagnosis in Randomized Trials: Variability and the Need for Standardization.

PURPOSE: Glaucoma, a leading cause of irreversible blindness, lacks a universally accepted diagnostic definition, resulting in significant variability across clinical trials. This systematic review evaluates and categorizes the diagnostic criteria employed for glaucoma in randomized controlled trials (RCTs) over the past decade.

METHODS

A systematic review of PubMed and ClinicalTrials.gov databases was performed for RCTs published between January 1, 2014, and December 31, 2024, involving adults diagnosed with primary open-angle glaucoma or normal-tension glaucoma. Studies explicitly stating diagnostic criteria were included. Extracted diagnostic criteria were categorized into clinically relevant groups.

RESULTS

Of 482 identified articles, 83 met inclusion criteria. Significant variability in glaucoma definitions was observed, encompassing 57 unique definitions. Criteria differed notably in intraocular pressure (45 unique definitions), visual field impairment (40), structural optic nerve parameters (35), and retinal nerve fiber layer assessments (15). Definitions were grouped into Mixed Criteria (37.3%), Combined Comprehensive (31.3%), IOP-Emphasized (27.7%), Visual Field-Emphasized (2.4%), and Imaging-Focused (1.2%).

CONCLUSIONS

Substantial heterogeneity exists in glaucoma diagnostic criteria across recent RCTs, complicating clinical comparability and risking diagnostic inaccuracies. This highlights the urgent need for universally standardized definitions informed by collaborative international consensus, incorporating structural-functional correlations and advanced imaging technologies.