The Water-drinking Test and Glaucoma Progression: Considerations Regarding the Test Usefulness as an Independent Risk Assessment Tool

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To the Editor:
We would like to congratulate De Moraes et al1 for the interesting and well-written article investigating the association between the water-drinking test (WDT) results and the risk of future visual field progression in treated primary open-angle glaucoma (POAG) patients. We believe this is an interesting topic, as the disease may advance in many patients despite clinical treatment and apparent well-controlled intraocular pressure (IOP), and therefore, much still has to be elucidated regarding significant predictors of POAG progression.
Searching for risk factors associated with visual field progression (through Cox proportional hazards models) in almost 100 patients from a single glaucoma referral practice, the authors found that peak IOP, as assessed by the WDT, was the only significant factor in their cohort.1 Interestingly, no other variable was able to explain why patients progressed or remained stable during follow-up. This finding contradicts most of the robust longitudinal data provided by other prospective studies.2–4 Several risk factors for POAG progression, such as older age, worse baseline damage, mean IOP, and thin central cornea, have been previously documented in various randomized clinical trials.2–4 Although results may vary between these reports, we were not able to find any prospective longitudinal study in which only 1 isolated risk factor for POAG progression was identified. In fact, only 1 retrospective study, published by the same group >10 years ago, based on a similar population, found such results.5 The fact that the authors were not able to identify none of these previously reported predictors of disease progression seems peculiar, and we wondered what would be the reasons for that. Although this issue was partially addressed in the manuscript, we believe it deserves a deeper discussion.
Another specific aspect of this study is the significant proportion of the patients (32.6%) that reached a progression endpoint during follow-up (mean follow-up was 28 mo).1 It should be noted that some patients were likely followed for <12 months, as follow-up period ranged from 6 months to almost 7 years. Having the natural history of POAG in perspective, the incidence of disease progression in untreated patients usually ranges between 5% and 10% per year.2–4 In treated patients, reported rates are even lower. Although population characteristics, progression definitions, type and aggressiveness of interventions, and follow-up time may vary between studies, it seems unusual to expect that over 30% of these patients, initially judged as well-controlled cases, would progress in <30 months despite clinical treatment (a rate of ∼14%/y). Interestingly, such high rate of progression was found by the same group in their above-mentioned retrospective study (during almost the same follow-up period).5 Once again, we wondered whether aspects related to the clinical management of these patients or specific characteristics of this study population would be responsible for such findings (an uncommon high progression rate in a relative short period of time), and how representative of the general POAG population this sample is.
Finally, we believe that a specific point related to the relationship between WDT results and study outcomes needs clarification. On study entry, all patients, deemed well controlled by their physician, underwent a WDT. A significant correlation between IOP peak during the WDT and baseline IOP was reported. In the Methods section, the authors stated that patients’ data were censored not only if visual field progression was confirmed, but also if any IOP-lowering intervention was necessary (changes on medical regimen, laser, or incisional glaucoma surgery).
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