Increased intraocular pressure can lead to damage to the optic nerve and consequently to a restriction of vision, taking the form of a slowly increasing restriction to the field of vision and possibly leading to blindness if treatment is neglected. The cause of this disease resides in an imbalance between the production of aqueous humour and the corresponding drainage system.
The production of aqueous humour is effected through the vascular system of the uvea, particularly through the vascular system of the ciliary bodies and the epithelial cells of the ciliary body. The aqueous humour is drained away through the trabecular system. The following pathological mechanisms are involved in producing increased intraocular pressure:
A partial drainage obstruction in the trabecular system caused by fibrosing or by increased resistance of the drainage vessels. PA1 Increased perfusion pressure (filtration pressure) of the ciliary vessels and obstructed flow caused by increased resistance of the venoles lead to an increased production of aqueous humour. PA1 Breaching of the blood-water barrier of the uveal vascular system with an escape of plasma and an increase in the colloid osmotic pressure, as a result of which more water is formed in compensation. Disorders of the intraocular blood-water barrier also frequently occur after intraocular operations, e.g. after trabeculectomy or cataract operations.
If the increased intraocular pressure is treated with .beta.-blockers which bring about a reduced production of aqueous humour by vasoconstriction of the vascular system of the uvea, this has the side effect of negatively influencing the ocular blood flow (A. Yoshida, G. T. Feke et al., Ophthalmic. Res. 23, 162-170 (1991) and M. Langham, Arvo Meeting 1992, Sarasota). This disadvantageous effect is not encountered when compounds with an osmoregulatory effect are used.
The oral or intravenous administration described in the literature of hypertonic substances, such as urea or polyalcohols, which have an osmotic effect on the intraocular fluid, involves, to some extent, considerable systemic side effects. P. Segal and J. Smolarz-Dudarewicz describe, in Klin. Monatsbl. Augenheilkd. 150, 509-522 (1967) the effect of glycerol, mannitol and sorbitol in lowering pressure in the eye, when administered orally. In the case of glycerol, the predominant side effects are the effects on the central nervous system, which can be put down to the osmotic activity of the drug, such as headaches, drowsiness and feeling of dizziness, whereas the use of mannitol and sorbitol additionally often lead to diarrhoea.
When mannitol was administered intravenously, in addition to dizziness, headache and shivering, respiratory problems were also caused, with cyanosis and coldness of the limbs and, particularly in patients with renal and cardiac insufficiency, there was also precordial pain with changes in the ECG curve and, in individual cases, fulminating heart failure. Side effects described for the intravenous use of urea solutions are loss of appetite, nausea, a rise in temperature, electrocardiographic changes and pulmonary oedema, which means that such therapy is contraindicated for patients with liver, renal and cardiac circulatory insufficiency (cf. G. B. Bietti, Klin. Monatsbl. Augenheilkd. 150, 317-324 (1967)).
The treatment of increased intraocular pressure by the intravenous infusion of sorbitol solutions, described as long ago as 1938, has also not been generally adopted [J. Bellows et al., J. Arch. Ophth. (A.M.A.) 20, 1036-1043 (1938)].
For this reason it would be desirable to develop a method of treating increased intraocular pressure in which, by topical application to the eye, it is possible to achieve a targeted drainage of humour locally restricted to the desired site and thereby lowering the intraocular pressure, thus avoiding the above-mentioned systemic side effects of compounds with an osmoregulatory activity, and having no negative effect on ocular blood flow.
U.S. Pat. No. 4,201,706 describes a method of reducing corneal oedema which consists in the topical application of an aqueous ophthalmic solution which contains as active substance a penta- or hexahydroxyalcohol such as sorbitol, inositol or xylitol. Corneal oedema can be produced by physical trauma or by irritations and is also observed in conjunction with diseases such as glaucoma.