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A Rationale for Lowering Intraocular Pressure in Glaucoma
SURVEY OF OPHTHALMOLOGY VOLUME 45 • SUPPLEMENT 4 • MAY 2001
INTRODUCTION
A Rationale for Lowering Intraocular Pressure in Glaucoma Robert N. Weinreb, MD Glaucoma Center, University of California—San Diego, La Jolla, California, USA Intraocular pressure (IOP) is the most important risk factor for the development of glaucoma. Although there has been a paucity of confirmatory data from prospective clinical trials, it has been long recognized that reduction of IOP is the only treatment method that generally lowers the rate of visual field loss in glaucoma. It also has been appreciated that decreasing IOP lessens the risk of visual field progression both for patients with primary open-angle glaucoma and patients with normal tension glaucoma. Accumulating research in prospective multicentered clinical trials confirms these clinical impressions.1,3 As one example, a retrospective analysis of data from the Advanced Glaucoma Intervention Study demonstrated that eyes with lower IOP on three visits over the first 18 months after surgical intervention had less visual field progression during the subsequent 6-8 years of follow-up than eyes with higher IOP.1 Further, visual fields were little changed in eyes with IOP readings consistently less than 18 mmHg at 6-year follow-up. This important study indicates clearly that lowering IOP slows or prevents visual field loss in glaucoma. Lower intraocular pressures are more effective at preventing visual field loss than higher pressures, and this effect increases over time. Assuming that lowering IOP is beneficial for glaucoma patients, a fundamental question is how much should it be lowered? Establishing a target IOP provides an operational answer to this question. An appropriate target IOP can be defined as the IOP at which the rate of retinal ganglion cell loss is no greater than the age-related rate. Alternatively, it can
be considered to be the highest IOP in a given eye at which IOP does not contribute to further glaucomatous optic nerve damage. For any individual patient, selecting an appropriate target IOP should be influenced by factors including the rate and extent of visual field loss, the presumed IOP at which damage to the optic nerve occurred, patient age, race, etc. There are several considerations that can limit the strict use of target pressures in glaucoma management. Although the effect of IOP is continuous, IOP is measured infrequently in clinical practice. Measurements of IOP within any individual patient may show wide variability during the day and night as well as over the course of days. IOP has been thought typically lowest during the night and peaks in the early morning or during the day.4 Many individuals also have a nocturnal spike in IOP.5 Because IOP is variable, it is not possible to directly assess the IOP at which optic nerve damage occurred. Large fluctuations in diurnal IOP have in themselves been shown to increase the risk for the progression of glaucoma,2 and it is not clear whether a target IOP should consider a peak value,6 or a mean value, or the mean value over days. Despite the potential benefit of future therapeutic approaches, including neuroprotection of the glaucomatous optic nerve, treatment of glaucoma continues to be directed at lowering IOP to decrease the likelihood of disease progression.8 Optic nerve damage can presumably be minimized by maximally lowering IOP throughout both the day and night.7 Presumably, any medical or surgical treatment that does this effectively also will be an effective treatment for
S335 © 2001 by Elsevier Science Inc. All rights reserved.
0039-6257/01/$–see front matter PII S0039-6257(01)00236-3
S336
Surv Ophthalmol 45 (Suppl 4) May 2001
glaucoma. At the current time, it is logical to conclude that the treatments that do this the most effectively and have the fewest side effects should be the ones preferentially used in glaucoma management.
WEINREB
5. 6.
References 1. The Advanced Glaucoma Intervention Study (AGIS): The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 130:429–40, 2000 2. 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 9: 134–42, 2000 3. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study group. Am J Ophthalmol 126:487–97, 1998 4. Liu JH, Kripke DF, Twa MD, et al: Twenty-four-hour pattern
7.
8.
of intraocular pressure in the aging population. Invest Ophthalmol Vis Sci 40:2912–7, 1999 Liu JH, Kripke DF, Hoffman RE, et al: Nocturnal elevation of intraocular pressure in young adults. Invest Ophthalmol Vis Sci 39:2707–12, 1998 Martinez-Bello C, Chauhan BC, Nicolela MT, et al: Intraocular pressure and progression of glaucomatous visual field loss. Am J Ophthalmol 129:302–8, 2000 Orzalesi N, Rossetti L, Invernizzi T, et al: Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension. Invest Ophthalmol Vis Sci 41:2566– 73, 2000 Weinreb RN, Levin LA: Is neuroprotection a viable therapy for glaucoma? Arch Ophthalmol 117:1540–4, 1999
The author has no proprietary or commercial interest in any product or concept discussed in this article. Reprint address: Robert N. Weinreb, MD, Glaucoma Center 0946, 9415 Campus Point Drive, N. Suite 251, La Jolla CA 92093-0946.
INTRODUCTION
A Rationale for Lowering Intraocular Pressure in Glaucoma Robert N. Weinreb, MD Glaucoma Center, University of California—San Diego, La Jolla, California, USA Intraocular pressure (IOP) is the most important risk factor for the development of glaucoma. Although there has been a paucity of confirmatory data from prospective clinical trials, it has been long recognized that reduction of IOP is the only treatment method that generally lowers the rate of visual field loss in glaucoma. It also has been appreciated that decreasing IOP lessens the risk of visual field progression both for patients with primary open-angle glaucoma and patients with normal tension glaucoma. Accumulating research in prospective multicentered clinical trials confirms these clinical impressions.1,3 As one example, a retrospective analysis of data from the Advanced Glaucoma Intervention Study demonstrated that eyes with lower IOP on three visits over the first 18 months after surgical intervention had less visual field progression during the subsequent 6-8 years of follow-up than eyes with higher IOP.1 Further, visual fields were little changed in eyes with IOP readings consistently less than 18 mmHg at 6-year follow-up. This important study indicates clearly that lowering IOP slows or prevents visual field loss in glaucoma. Lower intraocular pressures are more effective at preventing visual field loss than higher pressures, and this effect increases over time. Assuming that lowering IOP is beneficial for glaucoma patients, a fundamental question is how much should it be lowered? Establishing a target IOP provides an operational answer to this question. An appropriate target IOP can be defined as the IOP at which the rate of retinal ganglion cell loss is no greater than the age-related rate. Alternatively, it can
be considered to be the highest IOP in a given eye at which IOP does not contribute to further glaucomatous optic nerve damage. For any individual patient, selecting an appropriate target IOP should be influenced by factors including the rate and extent of visual field loss, the presumed IOP at which damage to the optic nerve occurred, patient age, race, etc. There are several considerations that can limit the strict use of target pressures in glaucoma management. Although the effect of IOP is continuous, IOP is measured infrequently in clinical practice. Measurements of IOP within any individual patient may show wide variability during the day and night as well as over the course of days. IOP has been thought typically lowest during the night and peaks in the early morning or during the day.4 Many individuals also have a nocturnal spike in IOP.5 Because IOP is variable, it is not possible to directly assess the IOP at which optic nerve damage occurred. Large fluctuations in diurnal IOP have in themselves been shown to increase the risk for the progression of glaucoma,2 and it is not clear whether a target IOP should consider a peak value,6 or a mean value, or the mean value over days. Despite the potential benefit of future therapeutic approaches, including neuroprotection of the glaucomatous optic nerve, treatment of glaucoma continues to be directed at lowering IOP to decrease the likelihood of disease progression.8 Optic nerve damage can presumably be minimized by maximally lowering IOP throughout both the day and night.7 Presumably, any medical or surgical treatment that does this effectively also will be an effective treatment for
S335 © 2001 by Elsevier Science Inc. All rights reserved.
0039-6257/01/$–see front matter PII S0039-6257(01)00236-3
S336
Surv Ophthalmol 45 (Suppl 4) May 2001
glaucoma. At the current time, it is logical to conclude that the treatments that do this the most effectively and have the fewest side effects should be the ones preferentially used in glaucoma management.
WEINREB
5. 6.
References 1. The Advanced Glaucoma Intervention Study (AGIS): The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 130:429–40, 2000 2. 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 9: 134–42, 2000 3. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study group. Am J Ophthalmol 126:487–97, 1998 4. Liu JH, Kripke DF, Twa MD, et al: Twenty-four-hour pattern
7.
8.
of intraocular pressure in the aging population. Invest Ophthalmol Vis Sci 40:2912–7, 1999 Liu JH, Kripke DF, Hoffman RE, et al: Nocturnal elevation of intraocular pressure in young adults. Invest Ophthalmol Vis Sci 39:2707–12, 1998 Martinez-Bello C, Chauhan BC, Nicolela MT, et al: Intraocular pressure and progression of glaucomatous visual field loss. Am J Ophthalmol 129:302–8, 2000 Orzalesi N, Rossetti L, Invernizzi T, et al: Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension. Invest Ophthalmol Vis Sci 41:2566– 73, 2000 Weinreb RN, Levin LA: Is neuroprotection a viable therapy for glaucoma? Arch Ophthalmol 117:1540–4, 1999
The author has no proprietary or commercial interest in any product or concept discussed in this article. Reprint address: Robert N. Weinreb, MD, Glaucoma Center 0946, 9415 Campus Point Drive, N. Suite 251, La Jolla CA 92093-0946.