IOP Stress Testing Identifies Glaucoma Eyes at Risk of Fast Progression Despite Controlled Office Pressure.

PURPOSE: To evaluate whether an intraocular pressure (IOP) stress test can identify glaucoma eyes at risk for faster functional and structural progression despite apparently controlled office IOP. DESIGN: Prospective cohort study. PARTICIPANTS: Sixty-seven eyes of 36 participants with glaucoma. METHODS: Participants underwent a standardized water-drinking test (WDT) as an IOP stress test. Visual field (VF) and spectral-domain optical coherence tomography (SD-OCT) testing were obtained in clusters (5 visits) at baseline and end of follow-up, with interim single visits every 6 months between clusters. Rates of mean deviation (MD) change and retinal nerve fiber layer (RNFL) thinning were estimated by ordinary least-squares regression. Associations between WDT-derived IOP parameters and rates of change were assessed, including analyses stratified by severity-specific target IOP. Multivariable generalized estimating equation models evaluated WDT peak IOP and its association with progression after adjustment for office IOP and clinical covariates. MAIN OUTCOME MEASURES: Rates of MD change and global RNFL thinning over time. RESULTS: Mean follow-up after the WDT was 2.2 ± 1.0 years, with a mean of 14 ± 5 testing visits per eye. Among 59 eyes whose office IOP was within severity-specific target, 22 (37%) had WDT peak IOP >21 mmHg and showed significantly faster rate of MD loss (-0.67 vs +0.16 dB/year, P = 0.009) and RNFL thinning (-0.74 vs -0.18 μm/year, P = 0.002) than the remaining office-controlled eyes. Thirteen eyes (19%) were classified as fast progressors. Most rapidly progressing eyes would have been considered adequately controlled by office tonometry, with only 3 of 13 (23%) above target, whereas the WDT peak exceeded 21 mmHg in 10 of 13 (77%). In multivariable models, WDT peak IOP >21 mmHg remained significantly associated with faster MD change (β = -0.659 dB/year, P = 0.006) and RNFL change (β = -0.467 μm/year, P = 0.035) after adjustment for office IOP, indicating complementary prognostic information; results were similar when WDT peak and office IOP were modeled continuously or symmetrically. CONCLUSIONS: IOP stress testing was associated with faster functional and structural glaucoma progression and identified higher-risk eyes among those with apparently controlled office IOP, providing risk information complementary to routine office tonometry.