Vascular abnormalities linked to glaucomatous optic neuropathy

Vascular insufficiencies are suggested to be more deeply involved in cases of normal tension glaucoma.

LONDON — Vascular abnormality is associated with glaucomatous optic neuropathy and may be primarily responsible for glaucomatous optic neuropathy in at least a subset of normal tension glaucoma patients.

Yoshiaki Kitizawa, MD, PhD, professor emeritus at the Gifu University School of Medicine in Japan, spoke about the role of vascular insufficiencies near the optic nerve head at the European Glaucoma Society meeting here.

It is generally accepted that intraocular pressure (IOP) is merely a risk factor for glaucomatous optic neuropathy, Dr. Kitazawa said. In an attempt to elucidate the pathogenesis of glaucomatous optic neuropathy, researchers have extensively studied its progression in the role of vascular insufficiencies near the optic nerve head. Vascular insufficiencies may be induced by increased blood viscosity, an increase in vascular tone, reduction in focal ocular perfusion pressure and other factors.

However, in normal tension glaucoma, there is no evidence of increased IOP, he said. Vascular insufficiencies have been suggested to be more deeply involved in the development and progression of glaucomatous optic neuropathy than in high-tension glaucoma.

Study design

To identify some of the vascular factors, researchers have applied to glaucoma studies several sophisticated technologies such as ambulatory blood pressure monitoring (ABPM) and color Doppler imaging, a noninvasive ultrasound method for measuring blood flow velocity in the retrobulbar vessels.

ABPM is a well-established method for studies of systemic blood pressure. Repeated measurements of blood pressure by ABPM and IOP over a 24-hour period should provide more information about ocular perfusion pressure, Dr. Kitizawa said.

Dr. Kitizawa’s study examined the role of orbital hemodynamics in glaucomatous optic neuropathy by means of 24-hour ABPM and color Doppler imaging in a group of normal tension glaucoma patients with asymmetric visual fields and asymmetric ocular perfusion pressure.

Dr. Kitizawa consecutively enrolled 96 patients into a prospective study between November 1997 and February 1999. He defined asymmetric visual field defects as a difference in the mean deviation greater than 1 dB on the Central 30-2 Program of the Humphrey (Dublin, U.S.A.) Visual Field Analysis.

IOP was measured with a Goldmann applanation tonometer at 2-hour intervals for 24 hours, and ABPM was done for 48 hours from the following day.

Consistent difference in IOP throughout 24 hours between a set of two eyes indicates asymmetric IOP and ocular perfusion pressure. Color Doppler imaging was examined by an experienced, masked examiner.

In all cases, the peak systolic velocity (PSV) and the end diastolic velocity (EDV) were measured in the central retinal artery and ophthalmic artery. The resistance index was calculated from this.

Study results

Of 96 normal tension glaucoma patients hospitalized for the study, 39 patients met the criteria. Their ages ranged from 36 to 81 years, with a mean of 60.7 years.

In 29 (74.4%) patients, the eye with the higher ocular perfusion pressure had the better mean deviation. Dr. Kitizawa defined this group as the ocular perfusion pressure-mean deviation concordant group. In 10 subjects (25.6%), the eye with the higher ocular perfusion pressure had the worse mean deviation, which he defined as the ocular perfusion pressure-mean deviation discordant group.

“There was a significantly greater frequency of ocular perfusion pressure-mean deviation concordant cases,” Dr. Kitizawa said. “This result leads us to speculate that in the majority of normal tension glaucoma cases, IOP can be a significant risk factor for glaucomatous optic neuropathy.”

There was no statistically significant difference between the groups except in the IOP of the mean deviation worse eyes. Dr. Kitizawa said that this is understandable because visual field defects were found to depend on IOP in the IOP-mean deviation concordant group. Blood pressure was very similar between the two groups.

In the mean deviation better eyes, the EDV of the ophthalmic artery was significantly slower in the ocular perfusion pressure-mean deviation discordant group. In the mean deviation worse eyes, the PSV and EDV of the ophthalmic artery were significantly slower. Also, the resistance index of the ophthalmic artery was significantly higher in the ocular perfusion pressure-mean deviation discordant group.

Doppler results

When the mean deviation better eyes and the worse eyes were put together, the PSV and EDV of the ophthalmic artery were significantly higher in the ocular perfusion pressure-mean deviation discordant group. In this group, the EDV of the central retinal artery was slower in the eye with worse mean deviation. Also in this group, the color Doppler imaging parameters showed no significant differences between eyes with a better mean deviation and those with a worse mean deviation.

The results agree with previous studies that showed a low EDV and a high resistance index in the ophthalmic artery, an elevated resistance index of the central retinal artery and posterior ciliary artery, or an elevated resistance index in the internal carotid artery.

“It is not clear whether the decrease in velocities and the increase in resistance index are primary or secondary events caused by optic nerve damage,” Dr. Kitizawa said. “In our study, there were no significant differences in visual field defects between the ocular perfusion pressure-mean deviation concordant and the discordant groups. Optic nerve changes were quite similar in the ocular perfusion pressure-mean deviation concordant and ocular perfusion pressure-mean deviation discordant groups.

However, the color Doppler imaging parameters were significantly different, he said.

“This strongly suggests that the origin of the damage in the two groups is different,” he said. “We speculate that an IOP-related factor may be predominant in the ocular perfusion pressure-mean deviation concordant group. A hemodynamic abnormality is predominant in the ocular perfusion pressure-mean deviation discordant group, although we failed to demonstrate significant differences in the color Doppler imaging parameters between mean deviation better and mean deviation worse eyes in the subgroup.”

To further investigate the relationship between the color Doppler imaging parameters and the visual field defects, Dr. Kitazawa created two more subgroups. Subjects in which the eye with better color Doppler imaging parameters also had a better mean deviation were defined as “color Doppler imaging-mean deviation concordant” and those in which the eye with better color Doppler imaging parameters also had a worse mean deviation were defined as “color Doppler imaging-mean deviation discordant.”

Subjects who had identical color Doppler imaging parameters in both eyes were excluded. The color Doppler imaging-mean deviation concordant cases were more common than the color Doppler imaging-mean deviation discordant cases in the analysis of the PSV, EDV and resistance index of the central retinal artery.

This shows that the eyes with worse color Doppler imaging parameters in the central retinal artery are likely to have worse visual fields, as well as the presence of the significant association between retrobulbar hemodynamics and the severity of visual field defects in normal tension glaucoma.

“There are significant differences in blood flow velocities and the resistance index in retrobulbar arteries between the ocular perfusion pressure-mean deviation concordant and the ocular perfusion pressure-mean deviation discordant groups,” Dr. Kitizawa said. “The observation suggests that vascular abnormality is associated with glaucomatous optic neuropathy. Furthermore, our results suggest that vascular abnormality may be primarily responsible for glaucomatous optic neuropathy in at least a subset of normal tension glaucoma patients.”

For Your Information:

Yoshiaki Kitizawa, MD, PhD, can be reached at the Akasa Kitazawa Eye Clinic, 5-5-13 akasaka, Minato-ku, Tokyo, 107-0052, Japan; +(81) 3-5549-2873; fax: +(81) 3-5549-2874.