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Vasospasm and glaucoma
  1. Department of Ophthalmology, The Mater Hospital, Dublin, Ireland

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    A 54 year old emmetropic woman is referred to the hospital eye service because her optometrist detected a visual field defect in the presence of normal intraocular pressure using non-contact tonometry. She is otherwise fit and well, is a non-smoker, takes no medications, and has no family history of ocular disease. Examination shows cupping of the optic discs and significant visual field loss. The applanation ocular pressures are never greater than 18 mm Hg at the clinic and during 24 hour phasing, and the clinical diagnosis is low tension—that is, normal pressure, glaucoma (NPG). Why, in the absence of elevated ocular pressure, has this woman developed glaucomatous optic neuropathy?

    On further questioning, she admits to having cold hands and feet (“my husband says that my feet are always freezing when I cuddle up to him at night”), and also has a history of migraine headaches since her teenage years. What is the relevance of these two vasospastic conditions—Raynaud-like peripheral circulation and migraine—to the case presented above.

    Vasospasm is the term used to describe an abnormal vascular responsiveness to common everyday stimuli such as cold, stress, or nicotine.1 This process may reflect an underlying dysfunction of the vascular endothelium, and has been implicated in other systemic diseases such as coronary artery spasm with angiographically normal or slightly diseased coronary arteries (variant angina)2 and cerebral vasospasm following subarachnoid haemorrhage.3

    A number of endothelium derived vasoactive substances play a key role in the maintenance of basal vascular tone throughout the body and in the ocular circulation.4 Generally speaking, the balance between the relaxing (for example, nitric oxide, prostacyclin) and constricting (for example, endothelin-1 (ET-1), angiotensin II) agents tends towards a state of basal vasodilatation. These vasoactive substances exert their effects on vascular tone by causing relaxation or contraction of the vascular smooth muscle cells, and an imbalance in their levels may result in vascular spasm. Circulating levels of the potent vasoconstrictor ET-1 have been found to be elevated in several vasospastic conditions including Raynaud’s disease,5 migraine,6 variant angina,7 and subarachnoid haemorrhage.3

    Flammer et al first introduced the concept of vasospasm to glaucoma, particularly NPG.8 In a series of papers this group initially concentrated on ocular vasospasm (including choroidal vasospasm9) but later they expanded on this idea to include more widespread evidence of systemic vasospasm10 in glaucoma, such as silent myocardial ischaemia in NPG patients.11 Others have shown an impaired digital circulatory response to cold provocation1213 and a higher than expected prevalence of migraine in NPG.14

    Two recent papers show that patients with NPG have elevated systemic plasma levels of ET-115 and an abnormal postural ET-1 response.16 An impaired endothelium mediated vasodilatation to intra-arterial acetylcholine infusion in forearm blood flow has also been demonstrated in NPG.17 These findings would suggest that the “vascular” abnormality in NPG is not just confined to the ocular circulation, and may indicate that the eye is just one manifestation of a more generalised vascular disorder characterised by endothelial cell dysfunction.

    There is evidence that some glaucoma patients may show a reversible form of ocular vasospasm in that ocular blood flow (and possibly visual function) improves with the use of recognised vasodilators such as carbon dioxide and intravenous acetazolamide.1819 Some long term observations on the concurrent use of calcium antagonists in glaucoma suggest a protective effect on the visual field in some patients.2021

    The Vancouver group has previously reported that vasospasm may equally be a feature of both NPG and the high pressure form of this disease—primary open angle glaucoma.22 They noted that vasospastic glaucoma patients appeared to be sensitive to the level of intraocular pressure in that they observed a relation between the height of the ocular pressure and the amount of visual field loss in a group of vasospastic patients, but that this relation did not exist in non-vasospastic patients. In the current issue of theBJO (p 862) Broadway and Drance repeat their observation that vasospasm occurs with equal frequency in both the normal and high pressure forms of open angle glaucoma. However, the main finding of their paper is that glaucoma patients with the so called focal ischaemic type of optic disc appearance tend to be women with some form of vasospasm (history of cold extremities, migraine, or reduced digital circulation following cold provocation).

    How does this vasospasm relate to optic disc damage, especially to localised rim notching? Is this due to some form of focal ischaemia in the ciliary circulation (capillary network or larger branches of the short posterior ciliary vessels) of the anterior nerve head? Why does this form of damage typically occur at the superotemporal and inferotemporal poles of the optic disc? What are the anatomical and physiological factors that predispose to such damage? Does vasospasm in some way interfere with local autoregulatory mechanisms in the vasculature of the nerve head? Is the vasospasm reversible? These are questions which require further investigation. Of particular importance is the recent development of an animal model of optic nerve head ischaemia with repeated perineural injections of ET-1.23This results in vasoconstriction, a reduction in blood flow, and glaucoma-like topographic changes in the optic nerve head. Such a model might provide us with a better understanding of the connection between vasospasm and glaucoma.

    Vasospasm or vascular endothelial dysfunction appears to be a feature of glaucoma in some patients. It may only affect a small proportion of the total glaucoma population, but in trying to understand the connection between vasospasm and optic disc damage, we will gain insight into the pathogenesis and management of one form of glaucomatous optic neuropathy. Perhaps then the relevance of Raynaud’s disease and migraine to the NPG case history described above will become clear.


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    • Original Article
      David C Broadway Stephen M Drance