Hyperguides

Ophthalmology / Glaucoma

Role of Intraocular Pressure in Glaucomatous Optic Neuropathy

Karanjit S. Kooner, MD, MBA
Article


Supported in part by an unrestricted research grant from Research to Prevent Blindness, Inc., New York, New York

Glaucoma is a multifactorial disease associated with intraocular pressure (IOP)-dependent and pressure-independent factors.1 For more than 150 years, IOP has been implicated in the initiation and pathogenesis of glaucomatous optic atrophy. The cause and effect relationship between pressure and optic nerve (or retinal ganglion cell) damage is not only believable, but ample evidence also exists in the literature that reducing ocular tension is neuroprotective. This evidence was the basis of the mechanical theory2 that now forms the backbone of the modern concept of pressure-dependent damage in glaucoma.

Supporting Evidence

Several investigators have studied factors relating to development and progression of glaucoma with variable conclusions. These differences may be due to variables including study design (retrospective or prospective), methods of data collection, specific factors evaluated (level of IOP, ocular or systemic risk factors, definition of glaucoma), and statistical methods used.

Experimental elevation of IOP in animals produces similar signs of glaucoma damage.3 Anderson has observed the close association between the degree of pressure elevation and glaucomatous nerve damage.4 Approximately 6% of patients with moderately elevated IOP presented with damage, whereas 28% to 36% had damage at pressures higher than 30 mm Hg and 57% had damage at pressures of 40 mm Hg or higher. In patients with asymmetric normal-tension glaucoma, glaucomatous damage was greater in the eye with higher IOP.5

A large prospective collaborative study found that among other factors, IOP and pressure change after water drinking were significant risk factors for the progression of glaucomatous visual field defects.6 If the initial IOP was less than 20 mm Hg, only 1.46% of patients progressed, whereas 6.66% of patients with IOP higher than 20 mm Hg showed worsening.

In patients with advanced glaucomatous visual field defects, loss of central vision was 4% if medical treatment maintained IOP lower than 18 mm Hg.7 But loss of central vision increased to 30% if the pressure stayed above 22 mm Hg. Quigley and Maumenee reported that in long-term follow-up of patients in whom the average IOP was 16 mm Hg, only 12% had field progression.8

The Ocular Hypertension Treatment Study (OHTS) has shown that reducing IOP by at least 20% reduced the 5-year risk of progression to primary open-angle glaucoma (POAG) by 54%.9 In the Early Manifest Glaucoma Trial (EMGT),10 only one-half of the patients with POAG were treated. The treatment reduced the risk of disease progression by half compared to the controls. IOP at baseline also was important. For every 1 mm Hg above the median IOP at baseline, the risk of progression increased by 5%. Similarly, the magnitude of initial change in IOP reduction from baseline to the initial follow-up visit with treatment affected the progression. For every 1 mm Hg of IOP reduction, the risk of progression was diminished by 10%. Other significant factors were the level of IOP achieved at first visit and the mean IOP at follow-up. For both of these factors, there was a 10% higher progression risk for each 1 mm Hg of higher IOP.

The Collaborative Normal-Tension Glaucoma Study (CNTGS)11 evaluated the effect of a 30% reduction of IOP in one eye in patients with normal-tension glaucoma. The endpoint was documented progression in terms of visual field defects threatening fixation or disc hemorrhage. The progression was observed in only 12% of the treated group compared to 35% of the control group (P<.0001).

The Advanced Glaucoma Intervention Study (AGIS)12 found a close association between lower IOP and decreased visual field progression. Patients who achieved an IOP reduction of 14 mm Hg or lower than 18 mm Hg throughout the follow-up had few changes in the visual fields. IOP less than 17 mm Hg was found to be protective against visual field progression in a long-term study.13 In patients with pressures between 17 mm Hg and 21 mm Hg, almost one-half progressed. Patients with an initial IOP higher than 26 mm Hg were 10 times more prone to visual field progression.14 Newly diagnosed patients with POAG in Olmstead County, Minnesota, had a mean initial IOP of 30 ± 8 mm Hg and 90% had an IOP >21 mm Hg.15 Visual field defects were observed in one eye in 66% of patients, while 34% had changes in both eyes. Trabeculectomy in Japanese patients was successful in slowing further visual field progression in patients with normal-tension glaucoma.16

Diurnal and Nocturnal IOP

In clinical practice, IOP is measured at one particular time on a certain day. But IOP is a dynamic physiologic parameter that changes over a 24-hour period.17 Diurnal IOP relates to the measurement of IOP during the waking time whereas nocturnal IOP describes pressure during sleep. In most people, highest IOP is recorded in the morning, whereas the lowest values are in the afternoon.18 Daily fluctuations may be related to IOP level. A large fluctuation in diurnal IOP is recognized as a significant risk factor in patients with glaucoma.19 Therefore, both diurnal and nocturnal IOP measurements would be useful to better understand the role of IOP in glaucoma. Knowing the peak and various fluctuations of IOP may provide a better estimate of an individual's IOP. A continuous pressure monitoring device would be most helpful to gauge the role of IOP in glaucoma.

Accuracy of IOP Measurement

Current methods of measuring IOP are not flawless.20 Goldmann applanation tonometry assumes a central corneal thickness (CCT) of 520 µm. But CCT depends on several factors, such as race, refractive error, corneal curvature, astigmatism, and possibly age. Furthermore, the role of elastic properties of the cornea, sclera, and limbus on IOP measurements is poorly understood. Without well-proven correction factors, our current IOP measurements may not be estimating "true" IOP.

IOP Autoregulation

Brubaker1 has proposed a mechanism of autoregulation of IOP. When IOP is elevated (upon awakening or intaking fluid) a built-in autoregulation system is triggered. The eye reacts with increasing the outflow facility (or decreasing resistance) through the trabecular meshwork. The uveoscleral outflow has a minimal role in this process.

Summary

IOP remains one of the most important risk factors for the development or progression of glaucomatous damage. The current IOP measuring devices have inherent shortcomings, and the level of IOP over a 24-hour period in a particular patient is unknown. The pressure measurements in the office may be insufficient for monitoring glaucoma. Nevertheless, enough evidence exists that pressure reduction is beneficial in patients with glaucoma. The understanding of the intricate relationship between pressure-dependent factors and independent factors is essential in treating glaucoma.

References

  1. Brubaker RF. Delayed functional loss in glaucoma. LII Edward Jackson Memorial Lecture. Am J Ophthalmol. 1996;121:473-483.

  2. Mueller H. Anatomische bietrage zur ophthalmologie: Ueber niveauveranderungen an der eintrittsselle des schnerven. Graefe's Arch Ophthalmol. 1858;4:1-23.

  3. Quigley HA, Addicks EM. Chronic experimental glaucoma in primates. II. Effects of extended intraocular pressure elevation on optic nerve head and axonal transport. Invest Ophthalmol Vis Sci. 1980;19:137-152.

  4. Anderson DR. The management of elevated intraocular pressure with normal optic discs and visual fields. I. Therapeutic approach based on high risk factors. Surv Ophthalmol. 1977;21:479-489.

  5. Cartwright MJ, Anderson DR. Correlation of asymmetric damage with asymmetric intraocular pressure in normal-tension glaucoma (low-tension glaucoma). Arch Ophthalmol. 1988;106:898-900.

  6. Armaly MF, Krueger DE, Maunder L, et al. Biostatistical analysis of the collaborative glaucoma study. Arch Ophthalmol. 1980;98:2163-2171.

  7. Kolker AE. Visual prognosis in advanced glaucoma. A comparison of medical and surgical therapy. Trans Am Ophthalmol Soc. 1977;75:539-555.

  8. Quigley HA, Maumenee AE. Long-term follow-up of treated open-angle glaucoma. Am J Ophthalmol. 1979;87:519-525.

  9. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study. Arch Ophthalmol. 2002;120:701-713.

  10. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment. Arch Ophthalmol. 2003;121:48-56.

  11. Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol. 1998;126:487-497.

  12. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS). 7: The relationship between control of intraocular pressures and visual field deterioration. Am J Ophthalmol. 2000;130:429-440.

  13. Mao LK, Stewart WC, Shields MB. Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. Am J Ophthalmol. 1991;111:51-55.

  14. Kass MA, Kolker AE, Becker B. Prognostic factors in glaucomatous visual field loss. Arch Ophthalmol. 1976;94:1274-1276.

  15. Schoft EO, Hattenhauer MG, Ing HH, et al. Estimated incidence of open-angle glaucoma in Olmstead County, Minnesota. Ophthalmology. 2001;108:882-886.

  16. Shigeeda T, Tomidokoro A, Araie M, et al. Long-term follow-up of visual field progression after trabeculectomy in progressive normal-tension glaucoma. Ophthalmology. 2002;109:766-770.

  17. Liu JH, Kripke DF, Twa MD, et al. Twenty-four hour pattern of intraocular pressure in the aging population. Invest Ophthalmol Vis Sci. 1999;40:2912-2917.

  18. Sacca SC, Rolando M, Marletta, et al. Fluctuations of intraocular pressure during the day in open-angle glaucoma, normal-tension glaucoma and normal subjects. Ophthalmologica. 1998;212:115-119.

  19. Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:487-488.

  20. Damji KF, Muni RH, Munger RM. Influence of corneal variables on accuracy of intraocular pressure measurement. J Glaucoma. 2003;12:69-80.