ORIGINAL STUDY Predictive Value of the Water Drinking Test and the Risk of Glaucomatous Visual Field Progression Carlos G. De Moraes, MD, MPH,*w Remo Susanna, Jr, MD,w Lisandro M. Sakata, MD, PhD,z and Marcelo Hatanaka, MD, PhDw Key Words: glaucoma, water drinking test, visual fields, progression, Purpose: The purpose of this is to test the hypothesis the intra- risk factors ocular pressure (IOP) peaks during a stress test [the water drinking test (WDT)] can estimate the risk of future visual field progression (J Glaucoma 2017;26:767–773) in treated primary open-angle glaucoma (POAG) patients. Patients and Methods: Design: Prospective, longitudinal study. Setting: Clinical practice. Study population: Treated POAG he goal of glaucoma therapy is to prevent or minimize patients whose IOP was r18 mm Hg and who had no IOP- Tthe decay of vision-related quality of life during lowering interventions between the date of the WDT and the last patients’ lifespan.1 The irreversibility of glaucomatous eligible visual field. Intervention: At baseline examination, patients damage argues for estimation of progression before it underwent the WDT and were then followed at regular intervals occurs, rather than after, to modify the treatment approach with office-based IOP measurements and visual field testing. Main before progression. In addition, the more damaged the outcome measure: Cox-proportional hazards survival analysis testing the predictive value of IOP peaks during the WDT versus optic nerve, the lower the intraocular pressure (IOP) IOP measurements during office hours on visual field progression. required to slow progression and the higher the risk of blindness.2 A number of studies have investigated the main Results: A total of 144 eyes of 96 patients with baseline visual field risk factors for future glaucomatous visual field pro- damage ranging from mild to severe followed for a mean of 28 gression, of which the major randomized clinical trials have months were analyzed. In the multivariable analysis adjusting for played a major role.3–6 Although their results were not potential confounders, higher IOP peaks during the WDT were 7–9 10,11 predictive of future visual field progression (hazard ratio = 1.11; always identical, reviews and consensus guidelines in 95% confidence interval, 1.02 to 1.21; P = 0.013). The average and open-angle glaucoma have underscored the importance of peak IOP during office hours over the same follow-up period were elevated IOP, decreased central corneal thickness, older not significantly associated with progression (P = 0.651 and 0.569, age, worse baseline damage, disc hemorrhages, and low respectively). systemic blood pressure, among others. Nonetheless, with the advent of new technologies and Conclusions: IOP peaks detected with the WDT were predictive of a better understanding of the pathogenesis of glaucoma, future visual field progression in a treated POAG population. This 12 stress test could be a useful tool for risk assessment in daily new emerging risk factors have been reported and may practice. aid clinicians when stratifying patients based upon their risk. Some of these emerging risk factors (eg, corneal hys- teresis; lamina cribrosa defects seen with high-resolution optical coherence tomography (OCT); 24-hour IOP-related measurements with a contact lens sensor)12 require tech- Received for publication December 20, 2016; accepted June 12, 2017. From the *Bernard and Shirlee Brown Glaucoma Research Labo- nologies not always available in clinical practice or have not ratory, Department of Ophthalmology, Columbia University yet been evaluated with sufficient scientific thoroughness to Medical Center, Edward S. Harkness Eye Institute, New York, NY; define a level of evidence comparable with those reported in w Department of Ophthalmology, University of Sao Paulo School of clinical trials. Medicine, Avenue Dr. Ene´as de Carvalho Aguiar, Sa˜ o Paulo, SP; and zDepartment of Ophthalmology, Federal University of Parana Although there is a high-level of evidence that elevated School of Medicine, Rua Gen. Carneiro, Curitiba, PR, Brazil. mean IOP is a risk factor for glaucoma onset and pro- Supported by unrestricted departmental grant from Research to Pre- gression, such evidence is based upon longitudinal collec- vent Blindness, New York, NY (Department of Ophthalmology, tion of IOP measurements over months or years,3–9 which Columbia University Medical Center) and the Research Fund of the Department of Ophthalmology, University of Sao Paulo School can be influenced by the interval between visits and the of Medicine, Sao Paulo, Brazil. number of IOP measurements. Longitudinal studies and C.G.D.M.: Grants—National Institutes of Health, National Eye clinical trials have failed to show that a single baseline IOP Institute, Bethesda, MD; Consultant—Sensimed, AG, Lausanne, measurement can differentiate treated glaucoma patients at Switzerland; Honoraria, Allergan Inc., Sao Paulo, Brazil; L.M.S.: 13–16 Consultant—Allergan Inc., Sao Paulo, Brazil; Mundipharma Inc., low-risk versus high-risk of future progression. This is Sao Paulo, Brazil; M.H.: Consultant—Allergan Inc., Sao Paulo, in part because of the high IOP variability within-days and Brazil; Mundipharma Inc., Sao Paulo, Brazil; Alcon Inc., Sao between-days, so that there is an equal chance of detecting Paulo, Brazil; R.S.: Consultant—Allergan Inc., Sao Paulo, Brazil; the IOP at its peak or trough with a single snap-shot Mundipharma Inc., Sao Paulo, Brazil; Alcon Inc., Sao Paulo, Brazil. measurement. This limitation ultimately affects the pre- Reprints: Carlos G. De Moraes, MD, MPH, Edward S. Harkness dictive value of single IOP measurements when assessing Eye Institute, Columbia University Medical Center, 635 West the risk visual field progression. 165th Street, Box 69, New York, NY 10032 In an attempt to overcome the limitations of single- (e-mail: [email protected]). Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved. visit IOP measurements, numerous studies have inves- DOI: 10.1097/IJG.0000000000000725 tigated the role of within-day IOP variability on the risk of J Glaucoma Volume 26, Number 9, September 2017 www.glaucomajournal.com | 767 Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved. De Moraes et al J Glaucoma Volume 26, Number 9, September 2017 future progression.17–20 In that context, studies investigat- hemifield test outside normal limits. These results had to be ing IOP stress tests have been conducted to evaluate confirmed on at least 2 consecutive examinations. All their repeatability and validity, a first step towards defining included eyes had a best-corrected visual acuity of 20/40 or their role as predictors of glaucoma progression.21,22 In better during the entire period of the study, spherical other words, by challenging the eye’s outflow facility, stress refraction within ± 5.00 diopters, and cylinder correction tests may reveal IOP peaks that could be predictive of within ± 3.00 diopters. future visual field progression. Similar approaches have Participants were excluded if they had a closed or nar- been employed in different fields of medicine. In cardiology, row angle upon gonioscopic examination, nonglaucomatous for instance, even though a single blood pressure meas- optic neuropathy, secondary glaucoma, retinal disease, or urement at rest may not be indicative of ischemia and the any other abnormality that could interfere with visual future risk of myocardial infarction, when undergoing a field testing. stress test (pharmacologically or through exercise) clini- All study patients were on antiglaucoma topical cians can detect signs that allow a more accurate estimation medications or had undergone laser trabeculoplasty or of future events.23 The same is true in diseases like diabetes trabeculectomy before enrollment. All IOP measurements (ie, glucose tolerance test)24 and asthma (ie, methacholine were r18 mm Hg based upon office-based measurements challenge test).25 during follow-up. IOP measurements were performed with One such IOP stress test, the water drinking test a calibrated Goldmann applanation tonometer (Haag- (WDT), has shown good correlation and agreement with Streit, GmbH, Switzerland). The results of the WDT physiological IOP peaks seen in treated and untreated performed at the beginning of follow-up—before the first open-angle glaucoma patients.26–28 In addition, in patients visual field test of the sequence evaluated for progression— with bilateral glaucoma, eyes with higher IOP peaks during were considered for analyses (herewith called the “Baseline the WDT (despite similar baseline measurements) have WDT”). Only office-hour IOP measurements and visual worse visual field damage than their fellow eyes.29 Given field information up to the date of confirmed visual field the lack of large longitudinal studies assessing the role of progression and/or IOP-lowering interventions (eg, adding the WDT as a predictor of visual field progression, the new drugs or changing medications, laser trabeculoplasty, recent consensus of the World Glaucoma Association or incisional glaucoma surgery) were included in the anal- stated that “there is insufficient evidence supporting the role yses. All data after this point in time were censored. of provocative tests, such as the WDT, as providing inde- The WDT consisted in obtaining a baseline IOP meas- pendent contribution to assess risk of glaucoma develop- urement, followed by the ingestion of 800 mL (27 ounces) of ment and progression” and that “prospective studies are potable water