Blood Pressure's Impact on Glaucoma

Evidence describes a role for hemodynamics, not just ocular but systemic too.

By Rohit Varma, MD, MPH

In recent years, we've learned a lot about ocular perfusion pressure (OPP), i.e., the pressure difference between blood entering the eye and IOP. It's clear that three forces — OPP, IOP and blood pressure — are interconnected in the glaucoma disease process. The mechanics of that relationship, however, remain ambiguous.

Nevertheless, we can still draw some practical conclusions from the current literature. For me, this has meant a greater appreciation of the patient's systemic blood pressure. Studies have linked blood pressures outside normotensive boundaries — whether hypo- or hypertensive — with a greater prevalence of open angle glaucoma.

The ties between hypertension and glaucoma are less well established but the data, in addition to my involvement in a new study (discussed below), have convinced me they probably do exist. Therefore, I believe potential hypertension, along with potential low blood pressure, should be investigated in patients whose glaucoma continues to progress despite what appears to be well controlled IOP.

Vascular Overview

The force that drives blood through the capillaries and into the posterior pole commonly goes by the name ocular perfusion pressure. Numerous studies, including large epidemiological surveys, have found a high prevalence and incidence of open-angle glaucoma with low OPP. Individuals with diastolic perfusion pressures lower than 30 mm Hg had a six times greater chance of developing glaucoma than those with pressures above 50 mm Hg, according to the Baltimore Eye Survey.¹ In 2007, data from the Early Manifest Glaucoma Trial verified low systolic OPP as a significant predictor for disease progression, finding a 50% increased risk.²

The link between low OPP and glaucoma cannot be doubted. In addition, a clear correlation prevails between high IOP and reduced blood flow within the eye.^3,4 The mechanical force of elevated IOP on the vascular structures evidently lowers OPP, thus reducing the delivery of oxygen and nutrients to the optic nerve and retina, and in due course causing cell death.

We suspect there is a close relationship among IOP, OPP, blood pressure and glaucoma, but the exact nature of these associations remains elusive. Complicating matters is the physiological phenomenon known as autoregulation.

Autoregulation alters blood flow by changing the tone of the blood vessel wall; it is the body's natural response to outside challenges to maintaining sufficient vascular flow. The process is not completely understood, but researchers speculate that those who develop glaucoma in the presence of elevated IOP might suffer from a poor autoregulation response. Conversely, those who do not develop glaucoma despite prolonged elevated IOP may be enjoying the protection of a robust autoregulation response.

Over the past five years, perfusion pressure has emerged as an exciting and potentially rewarding area of study. I certainly believe the future will bring greater knowledge of OPP's relationship with glaucoma. But readers should take note these efforts remain very much in their infancy. Few large-scale glaucoma studies have tackled the topic of perfusion pressure in a meaningful way, and the ones that have were hampered by difficulties in collecting data. A major challenge is our lack of a reliable method to measure IOP and OPP over a 24-hour period. For example, many researchers believe a nighttime dip in diastolic perfusion pressure may help predict which glaucoma patients will progress. Once we can track these readings over the course of night and day — investigators are close to achieving a modality for accomplishing this — we may then gain a better understanding of OPP's relationship to glaucoma damage, from which we can draw meaningful clinical inferences that could significantly impact how we mange patients with glaucoma.

However, until that day comes, OPP will remain in my view more of a research topic than a practical patient management tool. For one thing, it is difficult to measure. Though devices to measure ocular blood flow exist, they tend to be expensive and difficult to use accurately. More over, we are unsure whether existing technologies can precisely determine OPP even under optimal circumstances. Two different vascular beds, the retinal and choroidal, nourish the posterior pole, and each technology measures only a small fraction of one or the other. Because blood flow problems can occur at a variety of locations (i.e., the optic disc, choroid, retina and retrobulbar circulation), we don't know if relevant areas are being measured.⁵ (I would add here investigators are close to developing an ocular coherence tomography method for assessing total ocular blood flow, another potentially ground-breaking research advancement.)

For a crude approximation of OPP, simply subtract IOP from the patient's arterial blood pressure, which is good enough for everyday practice. But even if OPP could be accurately pinpointed in every patient, what good would that knowledge do us? Other than avoiding excessive systemic hypotension, we have no direct means of affecting perfusion pressure. Systemic blood pressure, on the other hand, is simple to measure and relatively easy to control.

The Pressure Connection

In our study (part of the Los Angeles Latino Eye Study), a large population of self-identified adult Latinos underwent logistic regression analysis to evaluate the association of openangle glaucoma in relation to systolic, diastolic and mean blood pressure, and ocular perfusion pressures.⁶ We were not unduly surprised to find low perfusion pressure and low diastolic blood pressure associated with a greater prevalence of glaucoma in Latinos. Our more interesting finding was an association with high systolic and mean blood pressures.

The relationship between high systemic blood pressure and glaucoma is controversial. Several studies have found a correlation between arterial hypertension and glaucoma. In the Blue Mountain Eye Study, for example, systemic hypertension accounted for the single most attributable risk factor for developing glaucoma.⁷ One the other hand, many studies have found no connection between systemic hypertension and the incidence or progression of glaucoma, including cross-sectional and longitudinal results from the Barbados Eye Study and Early Manifest Glaucoma Trial.^2,8-10

We found a small, insignificant trend toward a correlation between glaucoma and conventionally defined hypertension, but the data were more revealing when the relationship was examined across a range of blood pressures rather than against arbitrary definitions, which incidentally differ from study to study. Examined this way, we found elevated systolic and mean blood pressures significantly associated with a higher prevalence of glaucoma, independent of the impact of IOP.

Several factors may explain the conflicting study results. Different criteria for defining hypertension; the inclusion or exclusion of IOP in the definition of glaucoma; the impact of IOP-lowering or antihypertensive therapy; and different racial or ethnic susceptibility — all these could skew results.

We consider our study strong because of its large patient cohort; its exclusion of IOP in the definition of glaucoma; its control for factors such as IOP, IOP treatment, and hypertension treatment; and its stratification of subjects by specific blood pressure levels.

Of course we stayed within a narrow racial/ethnic profile, but having studied this aspect of glaucoma for several years, I suspect there is a plausible connection between hypertension and optic nerve head blood supply in broader demographics as well. Chronic high blood pressure may cause arteriosclerosis, changes in precapillary arteriole size and capillary dropout, leading to increased blood flow resistance and reduced ocular perfusion.

These conclusions have encouraged me to evaluate the patient as a whole, not just the eye. We tend to forget systemic factors can affect the eye. In addition to controlling IOP, keeping blood pressures in a normotensive range can a be a secondary tool in managing progressive glaucoma. OM

References

1. Tielsch JM, et al. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol. 1995;113:216-221.
2. Leske MC, et al. EMGT Group. Predictors of long-term progression in the Early Manifest Glaucoma Trial. Ophthalmology. 2007;114:1965-1972.
3. Trible JR, et al. Trabeculectomy is associated with retrobulbar hemodynamic changes. A color Doppler analysis. Ophthalmology. 1994;101:2:340-351.
4. Lesk MR, et al. Relationship between central corneal thickness and changes of optic nerve head topography and blood flow after intraocular pressure reduction in open-angle glaucoma and ocular hypertension. Arch Ophthalmol. 2006;124:11:1568-1572.
5. Costa VP, et al. Blood pressure and glaucoma. Br J Ophthalmol. 2009 Oct;93(10):1276-1282.
6. Memarzadeh F, et al. Blood pressure, perfusion pressure and open angle glaucoma: The Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci. Epub 2010 Jan. 20.
7. Mitchell P, et al. Blood pressure, perfusion pressure and open angle glaucoma: The Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci. Epub 2010 Jan. 20.
8. Wu SY, Leske MC. Associations with intraocular pressure in the Barbados Eye Study. Arch Ophthalmol. 1997;115:1572-1576.
9. Leske MC, et al. Risk factors for open-angle glaucoma: the Barbados Eye Study. Arch Ophthalmol. 1995;113:918-924.
10. Leske MC, et al. Risk factor for incident of open-angle glaucoma. Ophthalmology. 2008;115:85-9.