Diurnal Variation in IOP

IOP fluctuation is an independent and important risk factor in glaucoma management.

By Sanjay Asrani, MD
Landmark studies such as the Collaborative Normal-Tension Glaucoma Study,1 Collaborative Initial Glaucoma Treatment Study,2 and Advanced Glaucoma Intervention Study3 have demonstrated the benefit of lowering patients’ mean IOP for the management of glaucoma. Ophthalmologists are also aware of the detrimental effects of peaks of IOP above a given patient’s normal range. Nevertheless, many patients continue to experience glaucomatous progression despite having mean IOPs below what their physicians consider appropriate targets for those individuals. Relatively few studies have attempted to distinguish between diurnal variation in IOP and mean pressure as regards how each affects the long-term management of glaucoma. My colleagues and I recently completed a study that made this distinction, and our findings indicate that large diurnal fluctuations in IOP are independent risk factors for patients with glaucoma.4

Study subjects (n = 105 eyes) with primary open-angle glaucoma used the Zeimer Self-Tonometer (CDS Technology, LLC, Chicago, IL) to measure their IOPs over a period of 5 days. To obtain the measurement, each patient instilled an anesthetic in his eye, aligned his eye with an internal target, and then activated the knob on the tonometer that causes the plunger to retract, applanate the cornea, and store a reading. A physician had also measured each patient’s IOP in the office. Patients obtained tonometry readings upon waking, at noon, in the midafternoon, at dinnertime, and at bedtime.
My colleagues and I performed statistical analyses on the readings and found that the relative risk of disease progression within 5 years was six times higher for patients who had a diurnal IOP range of 5.4 mm Hg than for those with a diurnal IOP range of 3.1 mm Hg.

Investigators at the Orebro Medical Center in Orebro, Sweden, evaluated the effects of IOP fluctuation in patients with pseudoexfoliation glaucoma.5 Over a period of 2 years, all patients’ conditions worsened at the same rate despite different mean IOP levels. When investigators stratified eyes by the range of IOP, however, patients who had the greatest range also experienced the fastest rate of visual deterioration.

Douglas Johnson, MD, of Olmstead County, Minnesota, and his colleagues compared the IOPs of patients who had progressed to blindness from glaucoma with those of patients who maintained their vision despite the disease.6 The researchers reported that the variation of IOP over a period of several decades was significantly higher in the blind patient group, even though the mean IOP was identical for both groups.

How does an increased fluctuation of IOP affect the progression of visual field loss? One study demonstrated that portions of the lamina cribrosa move maximally during pressure changes of 5 to 7 mm Hg, in contrast to minimal movement at pressure changes exceeding 15 mm Hg.7 These findings suggest that kinking of the axons may occur in small pockets of the lamina cribrosa, which move maximally at small pressure changes while other pockets remain relatively stationary. Another proposed theory is that fluctuations may result in an ischemia reperfusion injury similar to those that occur in the brain and heart. Researchers provided evidence of this nature when they demonstrated that patients with higher fluctuations of IOP have damaged DNA in their circulating lymphocytes.8

Another significant pressure fluctuation involves the phenomenon of IOP spikes that occurs when people awake. Individuals with normal eyes (eg, normal trabecular outflow) typically experience a spike of 6.4 mm Hg upon waking. This elevation dissipates in approximately 12 minutes, and the IOP returns to presleep levels. In a patient with glaucoma who has an impaired aqueous outflow mechanism, the spike of IOP may be higher and may take much longer to dissipate.

Medications with longer half-lives have a greater chance of reducing IOP fluctuations. For example, because drugs such as prostaglandin analogues reach their peak 12 hours after dosing, near-bedtime dosing of these agents may offer a dual benefit. Prostaglandin analogues do not lower IOP during the natural trough in blood pressure that occurs while a person sleeps, and their peak effect would occur around the time of the morning pressure spike. Researchers have shown that fixed-combination drugs such as the timolol/dorzolamide combination also offer round-the-clock IOP control equivalent to that provided by prostaglandins.9

The studies described herein show that diurnal fluctuations in IOP increase the risk of visual field loss for patients with glaucoma. By monitoring IOP more closely and prescribing medication that best controls IOP with the least amount of fluctuation, ophthalmologists can offer patients the best therapy for their glaucoma.

Sanjay Asrani, MD, is Assistant Professor of Ophthalmology at the Duke University Eye Center in Durham, North Carolina. He does not hold a financial interest in the products and company mentioned herein. Dr. Asrani may be reached at (919) 851-2065; asran002@mc.duke.edu.

1. Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126:498-505.
2. 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;108:1943-1953.
3. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130:429-440.
4. Asrani SG, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in IOP are an independent risk factor in glaucoma patients. J Glaucoma. 2000;9:134-142.
5. Bergea B, Bodin L, Svedbergh B. Impact of intraocular pressure regulation on visual fields in open-angle glaucoma. Ophthalmology. 1999;106:997-1004.
6. Oliver JE, Hattenhauer MG, Herman D, et al. Blindness and glaucoma: a comparison of patients progressing to blindness from glaucoma with patients maintaining vision. Am J Ophthalmol. 2002;133:764-772.
7. Morgan WH, Chauhan BC, Yu DY, et al. Optic disc movement with variations in intraocular and cerebrospinal fluid pressure. Invest Ophthalmol Vis Sci. 2002;43:3236-3242.
8. Flammer J et al. A blood test for glaucoma diagnosis. Paper presented at: The International Congress of Eye Research; October 10, 2002; Geneva, Switzerland.
9. Konstas AG, Papapanos P, Tersis I, et al. Twenty-four hour diurnal curve comparison of commercially available latanoprost 0.005% versus the timolol and dorzolamide fixed combination. Ophthalmology. 2003;110:1357-1360.


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