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A Minimally Invasive Device for the Monitoring of 24-hour Intraocular Pressure Patterns

US Ophthalmic Review, 2013;6(1):10-14 DOI:


Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, and lowering of IOP remains the mainstay of glaucoma treatment. IOP is a dynamic biologic parameter, nevertheless, current glaucoma management usually relies on single IOP measurements during clinic hours. However, a majority of glaucoma patients have their high, including their highest, IOP levels outside clinic hours. These undetected IOPs may explain why certain patients have progressive disease despite treatment. The interest in continuous 24-hour IOP monitoring started over half a century ago, but only recent technologic advances have provided clinicians with a practical device for continuous IOP monitoring. In this article, we discuss innovative approaches with permanent and temporary devices for 24-hour IOP monitoring, such as a contact lens sensor. Despite being in their infancy, these devices may soon enable clinicians to use 24-hour IOP data to improve glaucoma management and reduce the glaucoma-related burden of disease.
Keywords: Glaucoma, intraocular pressure, 24-hour, contact lens sensor, circadian
Disclosure: Kaweh Mansouri MD, MPH and Robert N Weinreb MD are consultants of Sensimed and René Goedkoop MD is an employee of Sensimed.
Received: January 16, 2013 Accepted: February 23, 2013
Correspondence: Kaweh Mansouri, MD, MPH, Glaucoma sector, Department of Ophthalmology, Geneva University Hospitals, Switzerland. E:

Glaucoma is a progressive optic neuropathy, characterized by the loss of retinal ganglion cells and its axons ultimately leading to loss of vision and subsequent irreversible blindness.1 Elevated intraocular pressure (IOP) is the only proven modifiable risk factor for the development and progression of glaucoma.2–5 Despite dedicated efforts to develop alternative therapies, reduction of IOP remains the current mainstay of glaucoma treatment. One important limitation in current glaucoma management is that IOP is normally only measured during office hours, usually by Goldmann applanation tonometry (GAT).6 Yet IOP varies throughout the circadian period.7–11 In addition to the absolute IOP level,12–16 IOP fluctuations,2,13,17–20 and in particular peak IOP levels have been identified as risk factors for progression of glaucoma.21–23 The role of IOP fluctuations in glaucoma pathogenesis remains controversial. Several studies have hypothesized that IOP fluctuation is an independent risk factor for glaucoma progression.24–28 In an experimental setting in non-human primates, mean and maximum IOP but not IOP variability were able to predict the rate of structural change.29 The same investigators also reported that IOP fluctuates by up to 10 mmHg within hours and between consecutive days in non-human primates.30 However, other studies have not supported the predictive role of IOP fluctuation. Retrospective post-hoc analyses of two prospective studies did not find such an association or had it disappear after accounting for other ocular or demographic parameters.31,32 Most importantly, these studies (with the exception of the Early Manifest Glaucoma Trial) only obtained single IOP measurements on the same day and calculated IOP fluctuation as the standard deviation of IOP at different visits. They are, therefore, not able to address the question of whether (24-hour) IOP fluctuations incur independent risk on glaucoma progression. Given the dynamic behavior of IOP, it may be clinically insufficient to rely on isolated IOP measurements only, in particular in patients with progression of glaucoma. Even the modest goal of obtaining representative diurnal (versus circadian) IOP profiles, our current methods seem to be insufficient. In one study, the likelihood of a single IOP measurement taken between 07:00–09:00 hours to reflect the daytime peak IOP was a mere 25 %.33 Other studies reported that 20–25 % of glaucoma patients who reached target IOP during isolated office measurements exhibited IOPs above the target level when submitted to a daytime IOP curve assessment.9,24 Patients with progressive visual field loss are more likely to have IOP peaks. Among patients presenting with IOP peaks during self-tonometry, 75 % had progressive glaucomatous disease compared with the patients without IOP peaks out of which only 25 % progressed.25 Compared with 24-hour IOP measurement curves, office hour IOP measurements did not correctly identify peak IOP in 80 % of patients with primary open angle glaucoma (POAG).10 These studies attest to the weak predictive value of office hour IOP measurements for detecting peak circadian IOP. In healthy and glaucomatous patients, IOP is higher than mean diurnal (daytime) IOP during the nocturnal period.26,27,34–36 The nocturnal IOP increase is in part due to increased episcleral venous pressure (EVP) and possibly to fluid redistribution, when assuming a recumbent position during sleep. Another study reported the variability in IOP pattern in patients with normal tension glaucoma, showing both daily and nocturnal acrophases.28 The dynamics and repeatability of the 24-hour IOP may indicate the existence of a circadian pattern, following the day/night light cycle. Preserved IOP patterns have been demonstrated in different species, including cats, rhesus macaques, and rabbits.29,30 A variety of hormones, through regulation of aqueous humor production and outflow, have a circadian rhythm and have been linked to circadian IOP patterns in rabbits.37 There also is a strong dependence of IOP on variable factors such as activity, posture, and emotions. Realini et al. in a series of studies found a fair to good reproducibility of repeated diurnal IOP measurements at two visits one week apart, both in healthy subjects (intraclass correlation coefficient [ICC] range 0.35–0.71) and in patients with POAG (ICC range 0.45–0.71).38,39 By contrast, another study reported a high daytime reproducibility of the IOP measurements (every three hours) on two consecutive days in patients with OAG and ocular hypertension (ICC range 0.80–0.86).40 In these studies, a lower than normal IOP reproducibility may in part be explained by the limited number of daytime IOP measurements. Current treatment strategies for glaucoma are frequently based on setting a target IOP range at which the development of further glaucomatous damage is assumed be prevented or reduced to a minimum.41,42 This target IOP is based on the patient’s past IOP levels, glaucomatous changes of the optic disc, visual field status, and, if available, the rates of structural and functional change. Despite an IOP that remains within the target range, a significant proportion of patients progress.20,43–47 Treatment strategies that rely solely on static IOP information do not account for the dynamic behavior of IOP and, therefore, have a limited predictive value for evaluating the risk for glaucoma progression.
  1. Weinreb RN, Khaw PT, Primary open-angle glaucoma, Lancet, 2004;363(9422):1711–20.
  2. Nouri-Mahdavi K, Hoffman D, Coleman AL, et al., Predictive factors for glaucomatous visual field progression in the advanced glaucoma intervention study, Ophthalmol, 2004;111(9):1627–35.
  3. Lichter PR, Musch DC, Gillespie BW, et al., Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery,Ophthalmology,2001;108(11):1943–53.
  4. Kass MA, Heuer DK, Higginbotham EJ, et al., The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma, Arch Ophthalmol, 2002;120(6):701–13.
  5. Heijl A, Leske MC, Bengtsson B, et al., Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial, Arch Ophthalmol, 2002;120(10):1268–79.
  6. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern® Guidelines. Primary open-angle glaucoma. San Francisco, CA: American Academy of Ophthalmology; 2010. Available at:
  7. Shuba LM, Doan AP, Maley MK, et al., Diurnal fluctuation and concordance of intraocular pressure in glaucoma suspects and normal tension glaucoma patients, J Glauc, 2007;16(3):307–12.
  8. Quaranta L, Konstas AGP, Rossetti L, et al., Untreated 24-h intraocular pressures measured with Goldmann applanation tonometry vs nighttime supine pressures with Perkins applanation tonometry, Eye, 2010;24(7):1252–8.
  9. Hara T, Hara T, Tsuru T, Increase of peak intraocular pressure during sleep in reproduced diurnal changes by posture, Arch Ophthalmol, 2006 Feb.;124(2):165–168.
  10. Fogagnolo P, Orzalesi N, Ferreras A, Rossetti L, The circadian curve of intraocular pressure: can we estimate its characteristics during office hours?, Invest Ophthalmol Vis Sci, 2009;50(5):2209–15.
  11. Liu JHK, Bouligny RP, Kripke DF, et al., Nocturnal elevation of intraocular pressure is detectable in the sitting position, Invest Ophthalmol Vis Sci,2003;44(10):4439–42.
  12. Leske MC, Heijl A, Hussein M, et al., Factors for glaucoma progression and the effect of treatment: The Early Manifest Glaucoma Trial, Arch Ophthalmol, 2003;121(1):48–56.
  13. Stewart WC, Kolker AE, Sharpe ED, et al., Factors associated with long-term progression or stability in primary open-angle glaucoma, Am J Ophthalmol,2000;130(3):274–9.
  14. Suzuki Y, Shirato S, Adachi M, et al., Risk factors for the progression of treated primary open-angle glaucoma: a multivariate life-table analysis, Graefe’s Arch Clin Exp Ophthalmol, 1999;237(6):463–7.
  15. Wesselink C, Marcus MW, Jansonius NM, Risk factors for visual field progression in the Groningen longitudinal glaucoma study: a comparison of different statistical approaches, J Glaucoma,2012;21(9):579–85.
  16. Chauhan BC, Mikelberg FS, Balaszi AG, et al., Canadian Glaucoma Study: 2. Risk factors for the progression of open-angle glaucoma, Arch Ophthalmol, 2008;126(8):1030–6.
  17. Hasegawa K, Ishida K, Sawada A, et al., Diurnal variation of intraocular pressure in suspected normal-tension glaucoma, Jpn J Ophthalmol,2006;50(5):449–54.
  18. Bagga H, Liu JH, Weinreb RN, Intraocular pressure measurements throughout the 24 h, Curr Opin Ophthalmol, 2009;20(2):79–83.
  19. Dinn RB, Zimmerman MB, Shuba LM, et al., Concordance of diurnal intraocular pressure between fellow eyes in primary open-angle glaucoma, Ophthalmology,2007;114(5):915–20.
  20. Barkana Y, Anis S, Liebmann J, et al., Clinical utility of intraocular pressure monitoring outside of normal office hours in patients with glaucoma, Arch Ophthalmol,2006;124(6):793–7.
  21. Spry PGD, Sparrow JM, Diamond JP, et al., Risk factors for progressive visual field loss in primary open angle glaucoma, Eye,2005;19(7):643–51.
  22. Gardiner SK, Johnson CA, Demirel S, Factors predicting the rate of functional progression in early and suspected glaucoma, Invest Ophthalmol Vis Sci, 2012;53(7):3598–604.
  23. De Moraes CGV, Juthani VJ, Liebmann JM, et al., Risk factors for visual field progression in treated glaucoma, Arch Ophthalmol,2011;129(5):562–8.
  24. Malerbi FK, Hatanaka M, Vessani RM, et al., Intraocular pressure variability in patients who reached target intraocular pressure, Br J Ophthalmol,2005;89(5):540–2.
  25. Zeimer RC, Wilensky JT, Gieser DK, et al., Association between intraocular pressure peaks and progression of visual field loss, Ophthalmol,1991;98(1):64–9.
  26. Liu JH, Kripke DF, Hoffman RE, et al., Nocturnal elevation of intraocular pressure in young adults, Invest Ophthalmol Vis Sci, 1998;39(13):2707–12.
  27. Kida T, Liu JHK, Weinreb RN, Effect of 24-hour corneal biomechanical changes on intraocular pressure measurement, Invest Ophthalmol Vis Sci, 2006;47(10):4422–6.
  28. Renard E, Palombi K, Gronfier C, et al., Twenty-four hour (Nyctohemeral) rhythm of intraocular pressure and ocular perfusion pressure in normal-tension glaucoma,Invest Ophthalmol Vis Sci,2010;51(2):882–9.
  29. Gardiner SK, Fortune B, Wang L, et al., Intraocular pressure magnitude and variability as predictors of rates of structural change in non-human primate experimental glaucoma, Exp Eye Res,2012;103:1–8.
  30. Downs JC, Burgoyne CF, Seigfreid WP, et al., 24-hour IOP telemetry in the nonhuman primate: implant system performance and initial characterization of IOP at multiple timescales, Invest Ophthalmol Vis Sci,2011;52(10):7365–75.
  31. Komaromy AM, Brooks DE, Kubilis PS, et al., Diurnal intraocular pressure curves in healthy rhesus macaques (Macaca mulatta) and rhesus macaques with normotensive and hypertensive primary open-angle glaucoma, J Glauc, 1998;7(2):128–31.
  32. Del Sole MJ, Sande PH, Bernades JM, et al., Circadian rhythm of intraocular pressure in cats, Vet Ophthalmol, 2007;10(3):155–61.
  33. Jonas JB, Budde W, Stroux A, et al., Single intraocular pressure measurements and diurnal intraocular pressure profiles, Am J Ophthalmol, 2005;139(6):1136–7.
  34. Mansouri K, Medeiros FA, Tafreshi A, Weinreb RN, Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor. Safety, tolerability, and reproducibility in patients with glaucoma, Arch Ophthalmol, 2012;130(12):1534–9.
  35. Mansouri K, Weinreb RN, Liu JHK, Effects of aging on 24-hour intraocular pressure measurements in sitting and supine body positions, Invest Ophthalmol Vis Sci, 2012;53(1):112–6.
  36. Mansouri K, Liu JHK, Weinreb RN, et al., Analysis of continuous 24-hour intraocular pressure patterns in glaucoma, Invest Ophthalmol Vis Sci,2012;53(13):8050–6.
  37. Liu JH. Circadian rhythm of intraocular pressure, J Glauc, 1998;7:141–7.
  38. Realini T, Weinreb RN, Wisniewski SR, Diurnal intraocular pressure patterns are not repeatable in the short term in healthy individuals,Ophthalmol, 2010;117(9):1700–4.
  39. Realini T, Weinreb N, Wisniewski S, Short-Term Repeatability of diurnal intraocular pressure patterns in glaucomatous individuals,Ophthalmol,2012;118(1):47–51.
  40. Hatanaka M, Babic M, Susanna Junior R, Twenty-four-hour repeatability of diurnal intraocular pressure patterns in glaucomatous and ocular hypertensive individuals, Clinics, (Sao Paulo), 2011;66(7):1235–6.
  41. Jampel HD, Target pressure in glaucoma therapy, J Glaucoma, 1997;6(2):133–8.
  42. Detry-Morel M, Currents on target intraocular pressure and intraocular pressure fluctuations in glaucoma management, Bull Soc Belge Ophthalmol,2008;308:35–43.
  43. Musch DC, Gillespie BW, Lichter PR, et al., Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors, Ophthalmol, 2009;116(2):200–7.
  44. Wilensky JT, Gieser DK, Mori MT, et al., Self-tonometry to manage patients with glaucoma and apparently controlled intraocular pressure, Arch Ophthalmol,1987;105(8):1072–5.
  45. Hughes E, Spry P, Diamond J, 24-hour monitoring of intraocular pressure in glaucoma management: a retrospective review, J Glauc,2003;12(3):232–6.
  46. Collaer N, Zeyen T, Caprioli J, Sequential office pressure measurements in the management of glaucoma, J Glauc, 2005;14(3):196–200.
  47. Todani A, Behlau I, Fava MA, et al., Intraocular pressure measurement by radio wave telemetry, Invest Ophthalmol Vis Sci,2011;52(13):9573–80.
  48. Mansouri K, Shaarawy T, Continuous intraocular pressure monitoring with a wireless ocular telemetry sensor: initial clinical experience in patients with open angle glaucoma, Br J Ophthalmol, 2011 May;95(5):627–9. doi:10.1136/ bjo.2010.192922.
  49. Leonardi M, Pitchon EM, Bertsch A, et al., Wireless contact lens sensor for intraocular pressure monitoring: assessment on enucleated pig eyes, Acta Ophthalmologica, 2009;87(4):433–7.
  50. Lam AK, Douthwaite WA, The effect of an artificially elevated intraocular pressure on the central corneal curvature, Ophthalmic Physiol Opt,1997;17(1):18–24.
  51. Hjortdal JO, Jensen PK, In vitro measurement of corneal strain, thickness, and curvature using digital image processing, Acta Ophthalmol Scand,1995;73(1):5–11.
  52. Silver DM, Geyer O, Pressure-volume relation for the living human eye, Curr Eye Res,2000;20(2):115–20.
  53. Sit AJ, Liu JHK, Weinreb RN, Asymmetry of right versus left intraocular pressures over 24 hours in glaucoma patients, Ophthalmol, 2006;113(3):425–30.
  54. De Smedt T, Mermoud A, Schnyder C, 24-hour intraocular pressure fluctuation monitoring using an ocular telemetry sensor: tolerability and functionality in healthy subjects, J Glauc,2011; 21(8):539–44.
  55. Lorenz K, Kramann, Rauch N, et al., Tolerability of 24-hour intraocular pressure monitoring of a pressure sensitive contact, lens J Glauc, In press 2013.
  56. Medeiros F, Norbert Pfeiffer, André Mermoud, et al., 24-hour wear of a contact lens sensor for continuous intraocular monitoring is well tolerated. Eur Glauc Soc (Copenhagen) Poster P5.92 (
  57. Freiberg FJ, Lindell J, Thederan LA-L, et al., Corneal thickness after overnight wear of an intraocular pressure fluctuation contact lens sensor, Acta Ophthalmol,2012;90(7):e534–9.
  58. Freiberg F, Goedkoop R, Medeiros FA, et al., Continuous intraocular pressure recording using a contact lens sensor did not change central corneal thickness, Am Glauc Soc, (San Francisco) 2013 Poster 13-A-277-AGS.
Keywords: Glaucoma, intraocular pressure, 24-hour, contact lens sensor, circadian