Studies: Reduced ocular perfusion can affect glaucoma

Issue: September 2008

ByMurray Fingeret, OD

Murray Fingeret

The question of a possible association between an individual’s cardiovascular status and an increased risk for the development or progression of glaucoma has been discussed within the glaucoma literature for many years. While evidence exists identifying older age, elevated intraocular pressure, family history, central corneal thickness and African descent as risk factors, inconsistent evidence exists regarding vascular conditions.

Still, reduced diastolic perfusion pressure has been described as being associated with the development of glaucoma in several studies including the Baltimore Eye Survey and Barbados Eye Study. Recent publications have shed further light on an association between ocular perfusion pressure and the development or progression of glaucoma.

EMGT: Hypotension may be more important

The Early Manifest Glaucoma Trial (EMGT), a randomized clinical trial performed in Sweden, has documented the effectiveness of glaucoma therapy in reducing the risk of progression in individuals with open-angle glaucoma. This study consisted of 255 individuals with early open angle glaucoma between the ages of 50 and 80 years. Individuals were randomized to either therapy (betaxolol and argon laser trabeculoplasty) or control (no immediate treatment) group. Outcomes included changes in either visual fields or optic nerves.

In prior reports, a series of baseline characteristics were described related to progression including higher IOP at entry and worse disease severity. When data collected during the follow-up period was analyzed, higher IOP and disc hemorrhages were predictors for those who will get worse.

A recent publication further evaluated the cohort, which continues to be followed, and now between 7 and 11 years of follow-up are available as part of the EMGT.

The EMGT has shown that progression is due to many different risks, showing differing levels of importance for a given patient. At the close of this period of the study, 67% of all patients had progressed, with the median time to progression as 60 months. Univariate analysis showed an association with progression and older age (>68 years), worse mean deviation on the visual field (worse than -4dB), thinner central corneal thickness (<548 um), exfoliation, having two eyes eligible, lower systolic blood pressure (<160 mm Hg), cardiovascular disease history and lower ocular systolic perfusion pressure (<125 mm Hg).

In regard to progression times, the largest difference was in individuals with exfoliation, who demonstrated progression within 25 months. Therapy reduced the risk for progression by 53%. Multivariable factors related to progression included most of those found in the univariate analysis with some surprises.

Lower systolic perfusion pressure was identified as a risk along with lower systolic blood pressure. Analysis was performed after separating the cohort based upon their median IOP over the length of the study. Individuals with elevated IOP (> 21 mm Hg, median 24 mm Hg) showed additional risk factors including thin central corneal thickness (hazard ratio 1.42 per 40 um) and history of cardiovascular disease (hazard ratio 2.75).

Lower systolic perfusion pressure, which is the difference between the systolic blood pressure and IOP, was a new and significant risk factor for progression. An increase in risk of approximately 50% was discovered with this finding.

Systolic perfusion pressure is affected by both blood pressure and IOP readings and is influenced by individuals with elevated IOP as well as lower blood pressures. It may also be influenced by therapy for these parameters. In the EMGT, both higher IOP and lower systolic blood pressure were associated with progression. Exactly how reduced ocular perfusion affects the ocular nerve circulation has been debated and is one theory for why glaucoma develops.

As previously mentioned, the evidence from many studies looking at hypertension and associations between blood pressure and glaucoma has been inconsistent. Still, this recent work suggests that hypotension, not hypertension, is the more important condition.

Years ago, conventional wisdom indicated that aggressive reduction of blood pressure was associated with the development or progression of glaucoma. While this information was put on the back burner, it appears there is credence to this concept. We may want to educate our internal medicine colleagues about the harm they may cause in aggressively lowering blood pressure in individuals with glaucoma.

BES: Hypertension protects against glaucoma

Further demonstrating the importance of vascular risk factors in the development of open angle glaucoma was a recent publication from the Barbados Eye Study (BES). The BES is a National Eye Institute-supported study in which 4,709 individuals between the ages of 40 and 84 were enrolled using a random sample of individuals living in Barbados who did not have glaucoma at baseline.

Ninety-three percent of those enrolled were black and initially examined between 1987 and 1992. The surviving members were examined 4 and 9 years later.

This prospective, cohort incidence study with a longitudinal design allows the recognition of risks associated with developing a new disease. Over the 9 years of the study, 125 people developed glaucoma with age, thinner corneal thickness, lower systolic blood pressure, lower ocular systolic blood pressure and lower systolic, diastolic and mean perfusion pressures identified as risk factors for the development of glaucoma.

In regard to vascular factors and the development of glaucoma, hypertension was not found to be a risk at any age and, if anything, was found to protect against developing glaucoma. The BES also found no relationship between diabetes and the development of glaucoma.

The BES did find a relationship between ocular perfusion pressures and the development of glaucoma, with the lower the pressure the greater the risk for the development of glaucoma. The risk doubled in those with the greatest compromised perfusion pressure. As stated previously, perfusion pressure represents the dynamic between blood pressure and IOP and may be reduced due to high IOP, lower blood pressure or a combination of both events. Therapy may contribute to lower blood pressures.

In summary, two recently published papers from important clinical trials demonstrate the role of reduced ocular perfusion on either the development of or progression of glaucoma. This involves the relationship between elevated IOP and reduced blood pressure and may lead to several changes in our clinical routine such as the communication with patients’ family physicians about the role of treated blood pressure and glaucoma progression as well as the need for blood pressure measurement to be included in the evaluation of individuals with glaucoma.

For more information:

Murray Fingeret, OD, is chief of the optometry section at the Department of Veterans’ Affairs Medical Center in Brooklyn and Saint Albans, N.Y., and a professor at SUNY College of Optometry. He is also a member of the Primary Care Optometry News Editorial Board. He may be contacted at St. Albans VA Hospital, Linden Blvd. and 179th St., St. Albans, NY 11425; (718) 298-8498; fax: (516) 569-3566; e-mail: murrayf@optonline.net.

Suggested reading:

Bonomi L, Marchini G, Marraffa M, et al. Vascular risk factors for primary open-angle glaucoma: the Egna-Neumarkt Study. Ophthalmology. 2000;107:1287-1293.

Leske C, Connel AM, Wu SY, et al. Risk factors for open-angle glaucoma: the Barbados Eye Study. Arch Ophthalmol. 1995;113:918-924.

Leske MC, Wu SY, Nemesure B, et al. Incident open-angle glaucoma and blood pressure. Arch Ophthalmol. 2002;120:954-959.

Leske MC, Heijl A, Hyman L, et al. Predictors of Long-term progression in the Early Manifest Glaucoma Trial. Ophthalmology. 2007;114:1965-1972.

Leske MC, Wu SY, Hennis A, et al. Risk factors for incident open-angle glaucoma: the Barbados Eye Study. Ophthalmology. 2008, 115(1):85-93.

Miglior S, Torri V, Zeyen T, et al. Intercurrent factors associated with the development of open-angle glaucoma in the European Glaucoma Prevention Study. Am J Ophthalmol. 2007;144:266-275.

Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans: the Baltimore Eye Survey. Arch Ophthalmol. 1991;109:1090-1095.