The eye is a 25-mm sphere made up of two fluid-filled compartments (the aqueous humour and the vitreous humour) separated by a translucent lens, all encased within four layers of supporting tissue. These layers are:
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The cornea and sclera
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The uveal tract, comprising the iris, ciliary body and choroid
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The pigment epithelium
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The retina (neural tissue containing photoreceptors)
Light entering the eye is focused by the lens onto the retina, and the signal reaches the brain via the optic nerve.
Glaucoma
Glaucoma describes a group of disorders characterized by a loss in the visual field associated with cupping of the optic disc and optic nerve damage. Glaucoma is the second most common cause of blindness in the world and the most common cause of irreversible blindness. Glaucoma is generally associated with raised intraocular pressure (IOP) but can also occur when the IOP is within normal limits. There are two types of glaucoma: open-angle and closed-angle, the most common type being open-angle. It is caused by pathology of the trabecular meshwork that reduces the drainage of the aqueous humour into the canal of Schlemm. Treatment involves either reducing the amount of aqueous humour produced ( Fig. 24.1 ) or increasing its drainage. Acute closed-angle glaucoma symptoms include painful, red eye and blurred vision. Acute closed-angle glaucoma is a medical emergency and requires admission to save sight. It is difficult for the patient to notice a gradual loss of visual fields associated with chronic open-angle glaucoma and so regular check-ups are vital for at risk groups, such as elderly people.
The most effective way of preventing damage to the eye is by lowering the IOP. Most drugs used to treat eye disease can be given topically in the form of drops and ointments. To enable these drugs to penetrate the cornea, they must be lipophilic or uncharged. Drugs used to treat open-angle glaucoma include beta-adrenoceptor antagonists timolol and betaxolol. Prostaglandin analogues are used as treatments for inhibiting aqueous production.
Beta-adrenoceptor antagonists
Beta-adrenoceptor antagonists block β 2 -receptors on the ciliary body and on ciliary blood vessels, resulting in vasoconstriction and reduced aqueous production ( Fig. 24.1 ).
Route of administration – These drugs are administered topically.
Contraindications – Beta-adrenoceptor antagonists should not be given to patients with asthma, bradycardia or heart block.
Adverse effects – Systemic side effects include bronchospasm in asthmatic patients, and potentially bradycardia owing to their nonselective action on beta-receptors. Other side effects include transitory dry eyes and allergic blepharoconjunctivitis.
Prostaglandin analogues
Examples include latanoprost and travoprost.
Mechanism of action – Promote outflow of aqueous from the anterior chamber via an alternative drainage route, called the uveoscleral pathway.
Indications – Open-angle glaucoma, ocular hypertension.
Contraindication – Pregnancy.
Adverse effects – Brown pigmentation of the iris may occur.
Sympathomimetics (adrenoceptor agonists)
Adrenaline, dipivefrine and brimonidine are commonly used sympathomimetics.
Mechanism of action – Agonism at α-adrenoceptors is thought to be the principal means by which these agents reduce aqueous production from the ciliary body. Adrenaline may also increase drainage of aqueous humour.
Route of administration – Topical.
Indications – Open-angle glaucoma. Sympathomimetics are also used in the management of cardiac (see Chapter 14 ) and anaphylactic emergencies, and in the treatment of asthma and COPD (see Chapter 19 ).
Contraindications – Closed-angle glaucoma, hypertension, heart disease.
Adverse effects – Pain and redness in the eye.
Therapeutic notes – Adrenaline is not very lipophilic, and therefore it does not penetrate the cornea effectively. This can be overcome by administering dipivefrine hydrochloride, a prodrug that crosses the cornea and that is metabolized to adrenaline once inside the eye.
Carbonic anhydrase inhibitors
Acetazolamide and dorzolamide are carbonic anhydrase inhibitors (CAIs).
Mechanism of action – CAIs inhibit the enzyme carbonic anhydrase, which catalyses the conversion of carbon dioxide and water to carbonic acid, which dissociates into bicarbonate and hydrogen ions (H + ). Bicarbonate is required by the cells of the ciliary body, and underproduction of bicarbonate limits aqueous secretion ( Fig 24.1 ). CAIs given systemically also have a weak diuretic effect (see Chapter 18 ).
Route of administration – Oral, topical, intravenous.
Indications – Open-angle glaucoma.
Contraindications – Hypokalaemia, hyponatraemia, renal impairment. These effects can be reduced if the drug is given in a slow-release form.
Adverse effects – Irritation of the eye, nausea, vomiting, diarrhoea, diuresis.
Drugs used to increase the drainage of aqueous humour
Miotics–muscarinic agonists
Pilocarpine is a muscarinic agonist.
Mechanism of action – Pilocarpine causes contraction of the constrictor pupillae muscles of the iris, thus constricting the pupil, allowing aqueous humour to drain from the anterior chamber into the trabecular meshwork ( Fig 24.1 ).
Route of administration – Topical.
Indications – Open-angle glaucoma.
Contraindications – Acute iritis, anterior uveitis.
Adverse effects – Eye irritation, headache and brow ache, blurred vision, hypersalivation. May exacerbate asthma.
Treatment of closed-angle glaucoma
Drugs to treat closed-angle glaucoma are used in emergencies as a temporary measure to lower IOP. Pilocarpine and a CAI are often first-line treatments, with mannitol and glycerol being administered systemically to reduce IOP for resistant or more serious cases. Yttrium-aluminium-garnet (YAG) laser surgery provides a permanent cure for closed-angle glaucoma. A hole is made in the iris (iridectomy) to allow increased flow of aqueous humour.
Examining the eye
Mydriatic drugs dilate the pupil, that is, cause mydriasis, whereas cycloplegic drugs cause paralysis of the ciliary muscle, that is, cycloplegia. Mydriatic and cycloplegic drugs are used in ophthalmoscopy to allow a better view of the interior of the eye. Mydriasis and cyclopegia reduce the drainage of the aqueous humour, and they should therefore be avoided in patients with closed-angle glaucoma.
Muscarinic antagonists
The most effective mydriatics are the muscarinic receptor antagonists. These block the parasympathetic control of the iris sphincter muscle. The type of muscarinic receptor antagonist chosen will depend on the length of the procedure and on whether or not cycloplegia is required. The most commonly used muscarinic receptor antagonists, their duration of action, and their mydriatic and cycloplegic effects are summarized in Table 24.1 .
