Dynamic cerebral autoregulation is impaired in glaucoma

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Abstract

Objectives: Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. Materials and Methods: In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. Results: 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68±1.2 cm2 s−2) and POAG (6.79±2.1 cm2 s−2) than in controls (2.40±0.4 cm2 s−2). Furthermore, the MAP–CBFV gain was higher in NPG (2.44±0.5 arbitrary units [a.u.]) and POAG (1.99±0.2 a.u.) than in controls (1.21±0.1 a.u.). Conclusion: Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases.

Introduction

Glaucoma is characterised by progressive optic neuropathy resulting in optic nerve head damage and visual field loss. It is a leading cause of blindness [1]. The most common form of the disease is primary open angle glaucoma (POAG), which is associated with an elevated intraocular pressure (IOP) to above 21 mmHg. In normal pressure glaucoma (NPG), similar glaucomatous damage occurs in the absence of an elevated IOP [2], [3]. Although NPG and POAG have been described as different clinical entities and vary with respect to some risk factors and clinical characteristics, there is evidence of some overlap between the two diseases. For example, NPG patients tend to have higher diurnal variations in IOP than healthy persons [2]. In contrast, some persons with IOP greater than 21 mmHg do not develop glaucoma [4], [5]. Indeed, some authors believe that there is no clear demarcation between normal pressure and primary open angle glaucoma [2], [3].

Systemic factors are considered to play a role in the pathophysiology of the glaucomas. Impaired vascular function might contribute to normal pressure glaucoma because this disease is associated with vascular disorders such as vasospasm [6], [7], [8], [9] and migraine [10], [11]. Moreover, hypertension [12], [13], [14], hypotension [14] and diabetes [12], [15] have been identified as risk factors for primary open angle glaucoma. There is also evidence that blood perfusion to the optic nerve is reduced in primary open angle glaucoma [16], [17]. Furthermore, in both primary open angle and normal pressure glaucoma, the peripheral vasomotor responses to baroreflex stimulation are impaired [18]. These findings not only demonstrate vascular involvement in the glaucomas but also suggest that primary open angle and normal pressure glaucoma both share a common pathophysiological mechanism.

Retinal and optic nerve head circulation is dependent on local autoregulatory mechanisms, which serve to maintain blood perfusion independently of eye perfusion pressure changes [19], [20], [21]. Several studies have demonstrated altered ocular autoregulation in glaucoma, which further indicates that vascular dysregulation plays an important role in the pathogenesis of glaucomatous optic neuropathy [21], [22], [23].

Cerebral autoregulation refers to the ability of the cerebral resistance vessels to maintain a near-constant cerebral perfusion despite changes in blood pressure [24]. Myogenic, neurogenic, neurohormonal, metabolic and local chemical factors probably contribute to cerebral autoregulation (CA) [25]. The vascular dysregulation observed in the glaucomas [6], [9], [18], [26] might be also manifested by an impairment of cerebral autoregulation. This would explain the findings that glaucoma is associated with disorders such as vasospasm and migraine [6], [7], [8], [9], [10], [11]. Moreover, magnetic resonance imaging (MRI) studies have demonstrated diffuse small-vessel ischemic changes in the brains of normal pressure glaucoma patients [27], [28]. However, cerebral autoregulation in patients with glaucoma has not yet been evaluated.

The aim of our study was to assess dynamic cerebral autoregulation in patients with POAG and NPG using a simple test that can be applied in a clinical setting. We evaluated responses of the cerebral blood flow velocity (CBFV) to cyclic changes in blood pressure elicited by deep breathing at 0.1 Hz (6 cycles/min) [29]. We hypothesised that cerebral autoregulation is compromised in patients with NPG and POAG and that this might be demonstrated by an enhanced transmission of breathing-induced 0.1 Hz oscillations in blood pressure onto the cerebral blood flow velocity.

Section snippets

Subjects

We studied 10 patients with NPG aged 57±18 (mean±S.D.) years, 11 patients with POAG aged 52±11 years and 11 healthy controls aged 51±19 years. A medical history was taken, and detailed neurological and ophthalmologic examinations were performed in all study participants. The diagnosis of glaucoma had been made using standard criteria [2]. To ensure that our results were not confounded by other conditions that might influence autonomic or cerebrovascular function, we intended to exclude patients

Results

None of the patients or controls screened for enrollment in this study had other diseases or were on any medication other than the glaucoma medication that might interfere with the autonomic cardiovascular control.

Mean cardiovascular parameters and their spectral characteristics recorded during 0.1 Hz deep breathing are summarised in Table 1. Mean values of MAP, CBFV, CVR and end-tidal CO2 values did not differ significantly between controls and glaucoma patients.

There was no difference in the

Discussion

Our study shows compromised cerebral autoregulation in patients with normal pressure and primary open angle glaucoma, as revealed by increased transmission of oscillations in mean arterial blood pressure onto the mean cerebral blood flow velocity. These results suggest that the cerebral resistance vessels are affected in glaucoma and seem to strengthen the hypothesis that this disease might be a manifestation of a more widespread systemic disorder.

Blood pressure oscillations at the respiratory

Conclusion

Our study showed that cerebrovascular autoregulation is compromised in normal pressure and primary open angle glaucoma. Cerebrovascular resistance regulation in glaucoma might be impaired, at least in part, by altered sympathetic and endothelial dependent vasomotor control of cerebral vessels in these patients. The assessment of cerebrovascular autoregulation before and in combination with therapy might refine the understanding of the pathophysiology of NPG as well as POAG and possibly

Acknowledgements

This study was supported by grants from the Kosciuszko Foundation (recipients: Marcin Tutaj and Miroslaw Brys).

We would like to thank Dr. Joanna Harazny for her valuable comments and suggestions during the preparation of this manuscript.

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