Treatment

For many years, the mainstay of treatment for primary open-angle glaucoma has been the use of miotic drops. The miotic of choice was pilocarpine, starting with a 1% solution and increasing to 4% if needed. Subsequently, beta-blockers, for example, timolol, levubunolol (Betagan) and betaxolol (Betoptic) replaced pilocarpine, and now prostaglandin analogues, for example, latanoprost (Xalatan) have largely replaced beta-blockers as first-line medications (Table 12.1). In practice, these medications are often used in combination.

Pilocarpine itself is effective in reducing intraocular pressure. After about half an hour from the moment of instillation, the pupil becomes small and the patient experiences dimming of the vision, aching over the eyebrow and a spasm of accommodation, which blurs the distance vision. At the same time, the intraocular pressure in the majority of fresh cases of glaucoma falls to within the normal range. After about 4 h, the intraocular pressure begins to rise again and the side effects wear off. This, of course, means that a further drop of pilo-carpine must be instilled if good control is to be continued. It is here that we find the most difficult problem of treatment. Human nature is such that drops are rarely instilled four times daily on a regular basis, although patients are genuinely anxious to preserve their eyesight. Compliance with glaucoma medication is a major problem when medications are taken more than once daily, and is a relatively common reason for disease progression.

Timolol and other beta-blockers are effective over a 12-h period and need to be instilled only twice daily. As an ocular hypotensive agent, these are probably not quite as effective as pilo-carpine,but many cases of chronic glaucoma are now satisfactorily controlled by them and furthermore, the drug may be used in combination with pilocarpine. Beta-blockers have the further advantage that they do not cause any miosis. The main side effects of beta-blockers are bronchospasm, reduced cardiac contractility and bradycardia. They are, therefore, contraindicated in patients with chronic obstructive airway disease, heart block, hypotension and bradycardia.

The cholinergic drugs (such as pilocarpine) and the anticholinesterase drugs (such as echothiopate iodide) act by increasing the rate of outflow of aqueous, whereas timolol is thought to inhibit the production of aqueous. Adrenaline drops also have the effect of reducing aqueous production and they have been in use for some years as a supplement to pilocarpine. However, their effect is not powerful and they tend to cause chronic dilatation of the conjunctival vessels in some patients, as well

Table 12.1. Topical glaucoma medication.

Drug type

Examples

Mechanism of action

ß-Blockers

Timolol Betaxolol Levubunolol Carteolol

Reduce aqueous production

Cholinergics

Parasympathomimetics:

Pilocarpine Anticholinesterases: Phospholine iodide

Increase aqueous outflow through trabecular meshwork

Adrenergic agonists a2-Agonist

Adrenaline and prodrug

(Dipivefrine) Brimonidine

Decrease aqueous production and increase uveoscleral outflow

Carbonic anhydrase inhibitors

Dorzolamide

Reduce aqueous production

Prostaglandins

Latanoprost (prostaglandin 2a)

Increased uveoscleral outflow

as the deposition of pigment in the conjunctiva and subconjunctival fibrosis.

Oral acetazolamide is only occasionally used in chronic glaucoma because of its long-term side effects. Acetazolamide (Diamox) is a carbonic anhydrase inhibitor, which was introduced many years ago as a diuretic. Its diuretic action is not well sustained, but it is a potent drug for reducing intraocular pressure. If a normal subject takes a 250-500mg tablet of the drug, the eye becomes soft after about an hour. Most patients taking acetazolamide experience paresthesiae of the hands and feet and some complain of gastric symptoms. Occasionally, patients become lethargic or even confused. Young patients, particularly young males, could suffer renal colic. It should be pointed out that these more serious side effects are rare, and long-term acetazolamide is still sometimes used when no other means of controlling the intraocular pressure is available.

Newer glaucoma medications include latanoprost, dorzolamide and brimonidine. Latanoprost is a prostaglandin analogue, which produces its intraocular pressure-lowering effect through increased uveoscleral outflow. The main side effects are slight conjunctival congestion (hyperaemia) and increased iris pigmentation in some patients with mixed coloured irides. Prostaglandin analogues are licensed as first-line medication for glaucoma and have superseded beta-blockers in effectiveness and tolerability. Other prostaglandin-related medications include bimatoprost (Lumigan) and travoprost (Travatan), which have similar mechanisms of action to latanoprost.

Dorzolamide (Trusopt) and brinzolamide (Azopt) are topically administered carbonic anhydrase inhibitors. Their pressure-lowering effect is inferior to that of timolol, but they are useful adjunctive medications.

Brimonidine (Alphagan) is an a2-adrenergic agonist, which decreases aqueous production and also increases the uveoscleral outflow. It has a pressure-lowering effect comparable with that of timolol. It has the advantage of not having any effect on the respiratory system. It can, therefore, be used in patients with obstructive airway disease.

If the intraocular pressure remains uncontrolled by safe medical treatment and there is evidence of continued loss of visual field, surgical treatment is indicated. A large number of operations have been devised for the management of primary open-angle glaucoma and most of these entail allowing the aqueous to drain subconjunctivally through an artificial opening made in the sclera. The commonest operation performed currently is known as a "trabeculectomy". In this operation, a superficial "trapdoor" of sclera is raised and the deeper layer, including the trabecular mesh-work, is removed. The trapdoor is then sutured back into position. Aqueous drains out around the edge of this scleral flap into the subcon-junctiva (Figure 12.5). Although most of these operations can reduce the intraocular pressure effectively and often for many years, they all tend to increase the rate of formation of cataract. This and the risk of postoperative endophthalmitis are the main reasons why surgery is usually not considered the first line of treatment in chronic open-angle glaucoma by most ophthalmologists. Often, such surgery is augmented by the use of antifibrotic agents per-operatively, such as 5-fluorouracil and mito-mycin C. These agents inhibit fibroblast activity, and increase the success rate of surgery, but carry potential side effects and need to be used cautiously.

In some patients, laser treatment known as "cyclodiode" is applied externally to the eye to lower intraocular pressure by ablating part of the ciliary body (this area produces the aqueous humour). Such treatment, however, is irreversible, and although easier to perform than conventional glaucoma surgery, is generally reserved for patients with advanced uncontrolled glaucoma.

Figure 12.5. Trabeculectomy bleb. 133
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