10.1586/EOP.12.51 413ISSN 1746-9899© 2012 Expert Reviews Ltdwww.expert-reviews.com

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Elevated intraocular pressure (IOP) is consid-ered the main risk factor for the development and progression of glaucomatous disease [1–3]. To date, treatment options are based mainly on IOP reduction to a level at which no addi-tional damage is expected to occur. This pres-sure level, frequently referred to as target IOP, is established on individual basis and is frequently assessed by single office measurements during working hours.

Despite maintaining IOP levels apparently well controlled, some patients continue to develop glaucomatous progression. Although some authors state that this may be a result of IOP fluctuation [4–6], recent studies dem-onstrate that peak IOP is a better predictor of glaucomatous progression [7–9].

Twenty-four hour pressure monitoring could be considered the best way to assess the IOP pro-file and detect peaks. However, this is a time and resource-consuming test not always feasible in the routine practice. As an alternative, a modi-fied diurnal tension curve (mDTC) is more fre-quently performed and consists of four to five IOP measurements during office hours (from 8 am to 6 pm). However, as demonstrated by Drance [10], a third of patients with IOP measurements at office hours may present pressure peaks which would only be detected during a 24-h DTC. According to the results from Barkana et al. [11], a complete IOP evaluation during 24 h may reveal

higher peaks than office hours measurements in 62% of patients, resulting in treatment change in 36% of their sample.

In this context, the water-drinking test (WDT) has been proposed as a practical alternative method to evaluate IOP profile of glaucomatous patients.

The water-drinking test: review of existing dataThe WDT was first described a few decades ago for the diagnosis of open-angle glaucoma, being later abandoned due to its high level of false-positive and false-negative results [12,13] and little diagnostic value [14]. Recently, this test was revived with new purposes. It has been used as a surrogate marker of the outflow facility reserve and may be an indicator of the likelihood of progression [15,16].

This new concept led to a growing interest in this test. The WDT has been the subject of three editorials in peer-reviewed journals [17–19]. In an editorial about publication and citation in Ophthalmology, the authors state that the WDT experienced a major and recent revival based on the facts from 32 articles considering this test; these have been cited a mean of 10.26-times (range: 10–49), a mean citation count above the normal and expected mean [17].

In this low cost and clinically applicable examination, eligible patients (i.e., not under

Remo Susanna Jr* and Marcelo HatanakaUniversity of São Paulo School of Medicine, São Paulo, Brazil*Author for correspondence: Tel.: +55 11 3022 5177 rsusanna@terra.com.br

The water-drinking test (WDT) was first described as a diagnostic tool for glaucoma, which was later abandoned due to its poor diagnostic accuracy. This test has gained significant interest in recent years as different studies have shown its use as a surrogate for detecting patients who have intraocular pressure (IOP) spikes not detected during regular office hours. According to peer-reviewed literature, IOP peak detected by the WDT positively correlates with the severity of visual field defects in glaucoma and may be predictive of visual field progression. It was demonstrated that IOP peaks during the WDT are correlated and are in agreement with IOP peaks that normally occur during the day. The WDT has also been used to evaluate the quality of different clinical and surgical treatment options in glaucoma. The main objective of this article is to present and discuss these evidences and the applicability of the WDT as an assessment tool for glaucomatous disease.

The water-drinking test: a reviewExpert Rev. Ophthalmol. 7(5), 413–416 (2012)

Keywords: aqueous humor dynamics • glaucoma • intraocular pressure • stress testing

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The water-drinking test

Susanna & Hatanaka

Expert Rev. Ophthalmol.

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f luid ingestion restriction due to systemic conditions) are instructed not to eat or drink during the 4-h period anteceding the test which is then carried out as follows: baseline IOP is measured and patient is instructed to drink 1000 ml (33.8 ounces) of tap water in 5 min. The IOP is measured thrice at 15-min intervals [20]. Baseline IOP is considered as the IOP measured immediately before water ingestion. The maximum value of the three measurements is considered as the peak IOP during the WDT. Peaks depicted by this test strongly correlate and are in agreement with IOP peaks that normally occur during the day [21–23]. This increase in IOP is reversible and usually lasts for a few minutes and, as such, the WDT may be considered not harmful to patients. It may also be observed that eyes with higher IOP peaks after water ingestion take longer time to return to baseline levels [16], possibly reflecting the status of the drainage system of the eye. The clinical importance of this time lag has not been assessed yet.

It is important to standardize the method as described in order to perform it correctly. One direct comparison between ingestion of 1000 ml (33.8 ounces) or 500 ml (16.9 ounces) demonstrated that the lower volume of water failed to estimate peak diurnal pressure [24]. It has been suggested that the WDT may be per-formed with 800 ml (27.0 ounces) of tap water [SuSanna R JR, peRS.

comm.] with similar results. Stamper [25] also showed that the peak of the WDT elicited with 800 ml of water was significantly asso-ciated with progression of open-angle glaucoma. It seems that 800 ml may be used instead of 1000 ml although further studies are necessary with this volume of water.

The mechanism by which the IOP increases after water over-load remains unclear. A recent study suggests that it is caused, at least in part, by the expansion of choroidal tissue. The increased choroidal volume would be transmitted to the intraocular com-partments and to the anterior segment of the eye [26]. Considering that eyes might show a higher or lower IOP elevation depending on its outflow facility [27], the WDT might be used as a stress test to evaluate the aqueous humor outflow facility.

This concept supports the clinical application of the WDT and is clearly demonstrated when the test is used to compare the effect of clinical and surgical treatment modalities in glau-coma. Medically controlled glaucoma patients have a greater IOP increase with the WDT than patients who have undergone filtration surgery, such as trabeculectomy [20,28] and deep sclerec-tomy [29], despite similar mean IOP at baseline. This behavior is most likely due to the fact that filtering procedures facilitate aqueous humor outflow more effectively than medical therapy. In a study where a 24-h DTC was performed in patients with maxi-mum medical treatment in comparison with patients submitted to trabeculectomy, 37% of patients in the medically treated group had an increase in IOP to higher than 18 mmHg whereas none of the surgically treated patients presented such an increase [30]. These results were in parallel to the findings of Danesh-Meyer et al. who demonstrated that 30% of patients presented IOP increase to >18 mmHg after the WDT in patients under clinical treatment compared with no such IOP rise in the trabeculectomy group [28].

The same rationale may be used to understand the application of the WDT to assess to efficacy of different hypotensive medi-cations for glaucoma. In a comparison between latanoprost and the fixed combination of dorzolamide and timolol, patients who received latanoprost had significantly smaller elevations in IOP levels following the WDT. The authors considered the dampen-ing effect on IOP elevation in the latanoprost group as a result of this agent’s mechanism of action, that is, increase in uveoscleral outflow [31]. Similarly, Vetrugno et al. demonstrated that pros-taglandin analogs and α-agonists, which improve outflow, are associated to better IOP stabilization during WDT in comparison with drugs that act by decreasing aqueous humor production such as β-blockers and carbonic anhydrase inhibitors [32].

In addition, based on these studies, the WDT may be used to assess the efficacy of ocular hypotensive therapy or treatment. Malerbi et al. analyzed the results of the mDTC and WDT in a series of 65 eyes of 65 patients with achieved predetermined target IOP based on glaucomatous damage level (IOP ≤15 mmHg) at single office readings [33]. mDTC revealed IOP measurements >18 mmHg in 13.8% of eyes, being 20 mmHg the highest detected IOP. The WDT demonstrated that 33.8% of eyes pre-sented peaks >18 mmHg. Moreover, this test even depicted IOP levels >20 mmHg in 21.5% of tested eyes.

In 101 patients with open-angle glaucoma and asymmetric vis-ual field defect, eyes with worse mean deviation values presented higher IOP peaks after water ingestion in comparison to their contralateral eyes with better visual fields despite similar mean IOP at baseline [16]. This study demonstrated a lower capacity of eyes with worse glaucomatous lesion to control its pressure and concluded that the “dysregulation in outflow facility could help explain why one eye has more severe damage than the fellow eye.” Another study performed by the same group of investigators ana-lyzed IOP profile after WDT and concluded that mean IOP peak and percentage of IOP variation during the test were significantly higher in patients with visual field progression compared with patients who did not present progression [15].

Earlier studies also found a correlation between WDT response and progressive damage. In a prospective study of 5000 patients with open-angle glaucoma, Armaly et al. identified five out of 26 potential risk factors significantly related to the development of visual field defect which are outflow facility, age, IOP, cup-to-disc ratio and change in IOP after water ingestion [34]. In a sample of normotensive glaucomatous patients evaluated by Yoshikawa et al., the WDT was considered the main predictive test for glaucomatous progression [35].

To be considered clinically applicable, a test must present reproducible results. There are two studies that addressed WDT reproducibility. In the study by Medina et al. the WDT was performed at different times of the day (7 am, 2 pm and 5 pm) and on different days. At total of 80% of glaucomatous patients, regardless of the time of the day, presented differences in IOP peaks among test not >3 mmHg [36]. When performed at the same time of the day on two consecutive days, Hatanaka et al. demonstrated that IOP peaks during the WDT presented excellent reproducibility (ICC: 0.79; p < 0.001) [37].

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Expert commentaryThe WDT is a harmless assessment of glaucomatous disease. It takes a maximum of 1 h and involves only the ingestion of one liter (33.8 ounces) or 800 ml (27.0 ounces) of water to be performed. IOP data obtained with this simple test may provide valuable information regarding the efficacy of therapy for a given patient as well as the likelihood of glaucoma progression.

Five-year viewConsidering the increased value attributed to the occurrence of IOP peaks as risk factors for glaucomatous disease progression [8], future studies regarding methods to better evaluate the IOP pro-file during 24 h are warranted. Special devices for continuous ocular pressure monitoring are under analysis. However, their

practical use on daily basis and in high-volume outpatient settings in short-term is uncertain. Meanwhile, the WDT with reproduc-ible and clinically significant results validated several times by peer-reviewed studies is an important tool for the assessment of the IOP profile and management of glaucoma.

Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The water-drinking test (WDT) may be used not for the diagnosis of glaucoma, but for the assessment of the intraocular pressure (IOP) profile of a given patient. Thus, there are no positive or negative values for this test.

• Peaks depicted by this test strongly correlate and are in agreement with IOP peaks that normally occur during the day.

• The WDT may be used as a stress test to evaluate the aqueous humor outflow facility.

• Quality of hypotensive therapy may be evaluated with the WDT.

• High IOP peaks elicited during the WDT may be considered a risk factor for glaucomatous damage and progression.

ReferencesPapers of special note have been highlighted as:• of interest•• of considerable interest

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•• Arelationshipbetweenwater-drinkingtest(WDT)resultsandvisualfieldprogressionisestablishedinthispaper.

16 Susanna R Jr, Hatanaka M, Vessani RM, Pinheiro A, Morita C. Correlation of asymmetric glaucomatous visual field damage and water-drinking test response. Invest. Ophthalmol. Vis. Sci. 47(2), 641–644 (2006).

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