While intraocular pressure (IOP) has traditionally been considered the most important risk factor for the development and progression of glaucoma, it is not likely to be the sole pressure parameter involved. Recent studies suggest that diastolic perfusion pressure—the difference between diastolic blood pressure and IOP—may be as, if not more, important a factor.
Under normal physiological conditions, organs and tissues are not damaged by increased pressure per se but by pressure gradients that distort and strain their structures or that impede the inflow of vital fluids such as blood into the tissue. Increased IOP may compromise blood flow into the eye because of the increased pressure gradient through the ocular arterial system. Perfusion of blood into the eye may be decreased either by increased IOP or by decreased blood pressure.
Several important epidemiological studies have shown that lower diastolic perfusion pressure is associated with a progressively higher prevalence of glaucoma, even across several different ethnic and geographic populations.1-3
The diurnal variation in perfusion pressure may also play an important role in the development or progression of open-angle glaucoma. Sehi et al measured diurnal IOP and blood pressure in 14 subjects with untreated glaucoma and in 14 normal control subjects.4 Not surprisingly, the glaucoma group had higher IOP and lower mean ocular perfusion pressure. The pattern of diurnal variation in IOP, systolic blood pressure, and diastolic blood pressure were similar between the glaucoma and the normal groups. However, diurnal variation of the mean ocular perfusion pressure was significantly wider in the glaucoma group, which had the most pronounced drop in perfusion pressure at 7 a.m.
In the Thessaloniki Eye Study, Topouzis et al found that low perfusion pressure is associated with increased optic disc cupping, increased cup-to-disc ratio, and decreased optic disc rim area in individuals without frank glaucoma.5 This was true for subjects who had normal diastolic blood pressure while being treated for systemic hypertension. In fact, individuals with untreated elevated diastolic blood pressure had less cupping than those adequately treated for systemic hypertension.
Treatment of systemic hypertension was also found to be important in the European Glaucoma Prevention Study.6 Moreover, in this study, the class of medication used in treating systemic hypertension appeared to be important. The use of diuretics was a significant predictor of the development of open-angle glaucoma. Those on systemic beta blockers or ACE inhibitors were not at higher risk, perhaps because of the effects of these medications on intraocular pressure.
These recent studies, as well as earlier investigations, support the theory of a vascular-associated pathogenesis of glaucomatous optic neuropathy, by which optic nerve head ischemia results from decreased blood perfusion. The drop in perfusion may be caused by elevated IOP or decreased systemic blood pressure.
Jonas suggests another theory by which low blood pressure may increase the risk of glaucoma.7 Glaucomatous optic neuropathy results from increased pressure gradient across the lamina cribrosa. This translaminar pressure gradient is the difference between IOP and cerebrospinal fluid (CSF) pressure surrounding the optic nerve. Because the vascular-CSF pressure gradients within the brain must presumably be tightly maintained, low systemic blood pressure is associated with low CSF pressure. Thus, a low CSF pressure combined with an elevated IOP will result in a high translaminar pressure gradient and possibly optic nerve cupping.
Recently, Leske et al also reported on progression factors at the end of the Early Manifest Glaucoma Trial for all study patients and in separate evaluations of patients with higher and lower baseline IOP.8 In addition to the continued influence of treatment and follow-up IOP as well as other previously determined factors, lower systolic perfusion pressure, lower systolic blood pressure, and history of cardiovascular disease emanated as predictors of glaucoma progression.
While the precise mechanism of glaucomatous optic nerve damage has not yet been fully explained, it is clear that IOP plays only a part, albeit an important one, of the overall pathogenesis. Both blood pressure and CSF pressure, particularly at the level of the optic nerve, are important parameters and would be expected to influence the effects of IOP. Particular attention should be paid to glaucoma patients who are also undergoing treatment for systemic hypertension (especially those using diuretics) and to those who have lower systolic perfusion pressure, lower systolic blood pressure, or a history of cardiovascular disease. Since controlling systemic hypertension is important for overall health, the ophthalmologist should not discourage aggressive blood pressure control. However, the ophthalmologist may need to be more aggressive with intraocular pressure reduction for those patients receiving antihypertensive treatment.
References
1. Bonomi L, Marchini G, Marraffa M, et al. Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology. 2000;107(7):1287-1293.
2. Quigley HA, West SK, Rodriguez J, et al. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch Ophthlmol. 2001;119(12):1819-1826.
3. Leske MC, Wu SY, Nemesure B, Hennis A, for the Barbados Eye Studies Group. Incident open-angle glaucoma and blood pressure. Arch Ophthalmol. 2002;120(7):954-959.
4. Sehi M, Flanagan JG, Zeng L, et al. Relative change in diurnal mean ocular perfusion pressure: a risk factor for the diagnosis of primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2005;46(2):561-567.
5. Topouzis F, Coleman AL, Harris A, et al. Association of blood pressure status with the optic disk structure in non-glaucoma subjects: the Thessaloniki Eye Study. Am J Ophthalmol. 2006;142(1):60-67.
6. Miglior S, Torri V, Zeyen T, et al, and the European Glaucoma Prevention Study Group. Intercurrent factors associated with the development of open-angle glaucoma in the European Glaucoma Prevention Study. Am J Ophthalmol. 2007;144:266-275.
7. Jonas JB. Association of blood pressure status with the optic disk structure. Am J Ophthalmol 2006;142(1):144-145.
8. Leske MC, Heijl A, Hyman L, et al, and the Early Manifest Glaucoma Trial Group. Predictors of long-term progression in the Early Manifest Glaucoma Trial. Ophthalmology 2007;114 (11):1965-1972.
Author Disclosure
The authors state that they have no financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service.