the water-drinking test: the elegance of simplicity

Editorial

The water-drinking test: the elegance of simplicity

Eighty years following the initial observation by Schmidt thatintraocular pressure (IOP) increases following ingestion of water1

there is a resurgence of interest in the role of the water-drinking test(WDT) in the investigation of glaucoma. Why?

The impetus behind these studies has been two-fold. First, thereis a school of thought that suggests that IOP spikes and diurnal IOPvariation are important in the progression of glaucoma. Second,there is an increased understanding that a single IOP measurementin the clinic does not necessarily reflect what is happening to anindividual’s IOP through the course of the day. The importance ofIOP peaks and diurnal variation to the development of visual fielddamage in glaucoma has been reported by several investigators.2,3

Higher peaks of IOP have been noted to affect both the extent andrate of glaucomatous damage.2,4–8 Indeed, a recent Consensusstatement has suggested that further research is necessary to explorethe role of such fluctuations of IOP in the progression rate ofglaucoma.9

If IOP fluctuation and spikes are considered important to glau-coma progression then identifying such IOP variations may lead tomodifications in our management. For example, it is well-recognized that some patients continue to show evidence ofprogression despite seemingly well-controlled IOP.10–12 This isoften attributed to IOP-independent mechanisms that lead to con-tinued retinal ganglion cell death. However, an alternative hypoth-esis might be that apparently controlled IOP (as measured in singlepoint clinic determinations) may not reflect the varied range of IOPto which the eye is exposed.13,14 Investigators have employedseveral strategies to identify such variations in IOP. Twenty-fourhour IOP measurements have demonstrated that IOP does indeedshow significant fluctuation – even in ‘well-controlled’ glaucomapatients. However, there are some obvious inherent limitations in24-hour IOP monitoring: it is not routinely practical, it is timeconsuming and it is conducted in an artificial setting modifying thetotal patient environment as well as adherence with therapy com-pared to their average day. Obviously, at home IOP monitoring hasalso been trialled but these devices have not shown adequatereliability.15 Modified diurnal IOP measurements during outpatient/office visits are useful, but have been shown to fail to identifysignificant spikes in IOP.13

This is where the WDT comes in. It has been suggested that theIOP elevation associated with drinking one litre (some investigatorsprefer 10 mL/kg of body weight) of water within a period of five tofifteen minutes may be a useful technique for identifying patientswho may be experiencing diurnal spikes of IOP and hence, maybe at a risk for glaucomatous progression. Initially, the WDT wasinvestigated as a possible screening test for glaucoma. However,studies demonstrated that while glaucoma patients have an increasein IOP, the WDT had inadequate sensitivity and specificity.16,17

Investigators have also demonstrated that the response of patientsto the WDT may be correlated with the severity of glaucoma andthat a patients’ response to the WDT may be predictive of visual

field progression.18,19 A more recent line of investigation has been inrelation to whether the WDT may be used as a surrogate fordetecting patients who have IOP spikes not identified during clinichours.20,21 The pilot study by Kumar et al. elegantly adds to the bodyof literature which supports that the WDT may have a place as apractical investigation of IOP amongst glaucoma patients anddeserves further investigation.22

Other studies have also demonstrated that the response of IOPduring WDT reflects the diurnal pattern of IOP. Konstas et al. iden-tified that those with advanced glaucoma who had undergonetrabeculectomy had a 24-hour range of IOP of 2.3 +/- 0.8, whilecorresponding patients managed with maximal medical treatmenthad a range of 4.8 +/- 2.3.23 A recent study by our research groupthat compared the response to the WDT amongst a similar cohortof patients reported comparable results: those who had undergonesuccessful trabeculectomy with mitomycin-C had an IOP range of2.2 mmHg +/- 1.3 mmHgto while their medically controlledcounterparts had a statistically greater range of 5.6mmHg +/-1.9 mmHg.24 Interestingly, 37% of patients in the medically treatedgroup had spikes greater than 18 mmHg during 24-hour diurnalIOP testing, while none of the corresponding surgical patientsexhibited such a spike. Importantly, 43% of the medically managedpatients showed a spike greater than 18mmHg following WDTcompared with no such IOP elevations in the trabeculectomygroup.

What is the mechanism of the WDT? Several mechanisms havebeen postulated to explain the IOP fluctuation that occurs inresponse to the WDT. Changes in IOP are produced by eitherfactors that influence aqueous influx or alter its outflow or both.Theories have focused on changes in blood osmolarity or alter-ations in episcleral venous pressure. It has been suggested thatdrinking water, or any hypotonic fluid, results in an influx of waterinto body tissues including the eye as a consequence of changes inblood–ocular osmotic pressure gradient.25 However, several studieshave found no variation in haematocrit, total plasma osmolality, orplasma colloid osmotic pressure 26,27 suggesting that neither vitreoushydration nor increased aqueous production can entirely explainthe changes in IOP.

Brubaker theorized that the WDT is an indirect tool to measureoutflow facility28 as explained by the Goldman equation

Fa Fu C Pev= + −( )IOP

where Fa is aqueous flow, Fu is uveoscleral outflow, and trabecularoutflow = trabecular outflow facility (C) and outflow pressure(IOP - Pev), with Pev being the episcleral venous pressure.

The ingestion of one litre of water results in changes in theepiscleral venous pressure29 as a consequence of the increase incentral venous pressure and peripheral venous pressure. Anincreased episcleral venous pressure may result in increased IOP notonly because of the decreased pressure head for aqueous outflowbut also may be initially related to engorgement of the choroidal

Clinical and Experimental Ophthalmology 2008; 36: 301–303doi: 10.1111/j.1442-9071.2008.01782.x

© 2008 The AuthorJournal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists

vasculature. It is possible that this increased episcleral venous pres-sure after WDT increases outflow resistance and the trabecularoutflow. Therefore, the variation in IOP associated with the WDTis thought to be a result of individual outflow facility. The lowfacility of outflow in the glaucomatous eye may explain, at least inpart, the larger IOP fluctuation. A similar theory is proposed toexplain the well-documented increase in IOP that occurs in therecumbent or inverted head posture positions.30,31 It is also thoughtto partly explain the observation that supine IOP measurementsestimate peak nocturnal IOP better than sitting measurements.32

However, other possible mechanisms may contribute to theresponse to the water-drinking test. Several studies have establishedthat water drinking induces a profound autonomic pressor responsein patients with autonomic failure and a modest response in theelderly, but not in healthy controls. However, healthy controls didshow an increase in peripheral vascular resistance following waterdrinking. Consequently, it has been used therapeutically to treat thesyncope associated with autonomic failure or orthostatic stressoften associated with blood donation.33 Water drinking has alsobeen shown to increase blood pressure in older normal controlsubjects but has no effect on younger patients. Interestingly, plasmavolume, plasma renin activity, and plasma vasopressin concentra-tion do not change with water drinking.34 None the less, it has beenshown that sympathetic activity occurs as a result of water drinkingand plasma noradrenalin levels increase after water drinking by amagnitude at least as great as that elicited by smoking two unfilteredcigarettes (97 pg/mL increase)35 or ingesting 250 mg of caffeine(102 pg/mL increase).36 This may contribute to the increase in IOPseen in glaucoma patients if such patients have a component ofautonomic dysfunction, as has been proposed by some. Abnormalautoregulatory mechanisms in choroidal vasculature may result inalterations in choroidal volume in eyes with glaucoma similar tomechanisms proposed by Quigley37 as a mechanism for aqueousmisdirection. Interestingly, Spaeth and Vacharat noted that atro-pine 1% attenuates the IOP spike seen in glaucoma patients inresponse to water drinking.38 Additional research involving theresponse to water drinking in patients with angle closure may shedfurther light on this possible mechanism.

At a time when investigations for glaucoma seem to be increas-ingly ‘hi-tech’ dependent, the re-emergence of the humble WDTmay provide the clinician with an opportunity to extrapolate useful,simply acquired, and hitherto often overlooked, informationregarding the status of individual’s IOP diurnal fluctuation.

Helen V Danesh-Meyer MD FRANZCODepartment of Ophthalmology,

University of Auckland, New Zealand

REFERENCES

1. Schmidt K. Untersuchungen über Kapillarendothelstörungenbei Glaukoma simplex. Arch Augenheilkd 1928; 98: 569–81.

2. Zeimer RC, Wilensky JT, Gieser DK, Viana MA. Associationbetween intraocular pressure peaks and progression of visualfield loss. Ophthalmology 1991; 98: 64–9.

3. Martinez-Bello C, Chauhan BC, Nicolela MT, McCormick TA,LeBlanc RP. Intraocular pressure and progression of glaucoma-tous visual field loss. Am J Ophthalmol 2000; 129: 302–8.

4. Drance SM. Diurnal Variation of Intraocular Pressure inTreated Glaucoma. Significance in Patients with ChronicSimple Glaucoma. Arch Ophthalmol 1963; 70: 302–11.

5. O’Brien C, Schwartz B, Takamoto T, Wu DC. Intraocular pres-sure and the rate of visual field loss in chronic open-angleglaucoma. Am J Ophthalmol 1991; 111: 491–500.

6. Mao LK, Stewart WC, Shields MB. Correlation betweenintraocular pressure control and progressive glaucomatousdamage in primary open-angle glaucoma. Am J Ophthalmol 1991;111: 51–5.

7. Bergea B, Bodin L, Svedbergh B. Impact of intraocular pressureregulation on visual fields in open-angle glaucoma. Ophthalmol-ogy 1999; 106: 997–1004; discussion 1004–5.

8. Asrani S, Zeimer R, Wilensky J, Gieser D, Vitale S, LindenmuthK. Large diurnal fluctuations in intraocular pressure are anindependent risk factor in patients with glaucoma. J Glaucoma2000; 9: 134–42.

9. Medeiros FA, Brandt J, Liu J, Schi M, Weinreb RN, Susanna R.IOP as a risk factor for glaucoma development and progression.In: Weinreb RN, Brandt JD, Garway-Heath D, Medeiros FA,eds. World Glaucoma Association. Intraocular pressure. Consensus Series4. Hague: Kuglar Publications, 2007: 59–74.

10. Kass MA, Kolker AE, Becker B. Prognostic factors in glauco-matous visual field loss. Arch Ophthalmol 1976; 94(8): 1274–6.

11. Chauhan BC, Drance SM. The relationship between intraocu-lar pressure and visual field progression in glaucoma. GraefesArch Clin Exp Ophthalmol 1992; 230 (6): 521–6.

12. Schulzer M, Mikelberg FS, Drance SM. Some observations onthe relation between intraocular pressure reduction and theprogression of glaucomatous visual loss. Br J Ophthalmol 1987;71 (7): 486–8.

13. Liu JH, Kripke DF, Twa MD et al. Twenty-four-hour pattern ofintraocular pressure in the aging population. Invest OphthalmolVis Sci 1999; 40 (12): 2912–7.

14. Liu JH, Kripke DF, Hoffman RE, et al. Nocturnal elevation ofintraocular pressure in young adults. Invest Ophthalmol Vis Sci1998; 39 (13): 2707–12.

15. Hughes E, Spry P, Diamond J. 24-hour monitoring of intraocu-lar pressure In glaucoma management: a retrospective review.J Glaucoma 2003; 12 (3): 232–6.

16. Roth JA. Inadequate diagnostic value of the water-drinking test.Br J Ophthalmol 1974; 58 (1): 55–61.

17. Rasmussen KE, Jorgensen HA. Diagnostic value of the water-drinking test in early detection of simple glaucoma. Acta Oph-thalmol (Copenh) 1976; 54 (2 p): 160–6.

18. Armaly MF, Krueger DE, Maunder L et al. Biostatistical analysisof the collaborative glaucoma study. I. Summary report of therisk factors for glaucomatous visual-field defects. Arch Ophthal-mol 1980; 98 (12): 2163–71.

19. Susanna R, Jr, Hatanaka M, Vessani RM, Pinheiro A, Morita C.Correlation of asymmetric glaucomatous visual field damageand water-drinking test response. Invest Ophthalmol Vis Sci 2006;47 (2): 641–4.

20. Miller D. The Relationship between Diurnal Tension Variationand the Water-Drinking Test. Am J Ophthalmol 1964; 58: 243–6.

21. Medeiros FA, Pinheiro A, Moura FC, Leal BC, Susanna R, Jr.Intraocular pressure fluctuations in medical versus surgicallytreated glaucomatous patients. J Ocul Pharmacol Ther 2002; 18(6): 489–98.

302 Editorial


22. Kumar RS, Pia de Guzman MH, Ong PY, Goldberg I. Doespeak intraocular pressure measured by water drinking testreflect peak circadian levels? A pilot study. Clin Experiment Oph-thalmol 2008; 36: 312–5.

23. Konstas AG, Topouzis F, Leliopoulou O, et al. 24-hourintraocular pressure control with maximum medical therapycompared with surgery in patients with advanced open-angleglaucoma. Ophthalmology 2006; 113 (5): 761–5e1.

24. Danesh-Meyer HV, Papchenko T,Tan Y-H, Gamble GD.Medically Controlled Glaucoma Patients Show GreaterIncrease in intraocular pressure than Surgically ControlledPatients Following Water Drinking Test. Ophthalmology E-PubMarch.

25. Susanna R, Jr, Vessani RM, Sakata L, Zacarias LC, Hatanaka M.The relation between intraocular pressure peak in the waterdrinking test and visual field progression in glaucoma. Br JOphthalmol 2005; 89 (10): 1298–301.

26. Spaeth GL. The water drinking test. Indications that factorsother than osmotic considerations are involved. Arch Ophthalmol1967; 77 (1): 50–8.

27. Brucculeri M, Hammel T, Harris A, Malinovsky V, Martin B.Regulation of intraocular pressure after water drinking.J Glaucoma 1999; 8 (2): 111–6.

28. Brubaker RF. Importance of outflow facility. Int Glaucoma Rev2001; 3: 5.

29. Diestelhorst M, Krieglstein GK. The effect of the water-drinking test on aqueous humor dynamics in healthyvolunteers. Graefes Arch Clin Exp Ophthalmol 1994; 232 (3):145–7.

30. Carlson KH, McLaren JW, Topper JE, Brubaker RF. Effect ofbody position on intraocular pressure and aqueous flow. InvestOphthalmol Vis Sci 1987; 28 (8): 1346–52.

31. Friberg TR, Sanborn G, Weinreb RN. Intraocular and episcleralvenous pressure increase during inverted posture. Am J Ophthal-mol 1987; 103 (4): 523–6.

32. Mosaed S, Liu JH, Weinreb RN. Correlation between officeand peak nocturnal intraocular pressures in healthy subjectsand glaucoma patients. Am J Ophthalmol 2005; 139 (2): 320–4.

33. Lu CC, Diedrich A, Tung CS et al. Water ingestion as prophy-laxis against syncope. Circulation 2003; 108 (21): 2660–5.

34. Jordan J, Shannon JR, Black BK et al. The pressor response towater drinking in humans: a sympathetic reflex? Circulation2000; 101 (5): 504–9.

35. Cryer PE, Haymond MW, Santiago JV, Shah SD. Norepineph-rine and epinephrine release and adrenergic mediation ofsmoking-associated hemodynamic and metabolic events. N EnglJ Med 1976; 295 (11): 573–7.

36. Robertson D, Frolich JC, Carr RK et al. Effects of caffeine onplasma renin activity, catecholamines and blood pressure. NEngl J Med 1978; 298 (4): 181–6.

37. Quigley HA, Friedman DS, Congdon NG. Possible mecha-nisms of primary angle-closure and malignant glaucoma.J Glaucoma 2003; 12 (2): 167–80.

38. Spaeth GL, Vacharat N. Provocative tests and chronic simpleglaucoma. I. Effect of atropine on the water-drinking test: inti-mations of central regulatory control. II. Fluorescein angiogra-phy provocative test: a new approach to separation of thenormal from the pathological. Br J Ophthalmol 1972; 56: 205–16.

Editorial 303


the water-drinking test: the elegance of simplicity

Documents