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Anti-glaucoma medication
The principal aim of glaucoma therapy is to reduce intraocular pressure (IOP) to a level that prevents further visual loss. Modern glaucoma management advocates the use of 'target pressures'. Target pressures will vary depending on risk factors and disease severity, but typically involve an IOP reduction of between 20-40 per cent from the pressure at which damage first occurred. This is usually achieved by topical agents that decrease aqueous secretion or increase outflow (achieved either by improving flow through the conventional trabecular pathway or increasing uveoscleral drainage). Drugs used in the treatment of glaucoma are covered in section 11.6 of the BNF and include:
- Prostaglandin analogues/prostamide
- Beta-blockers
- Carbonic anhydrase inhibitors
- Sympathomimetics/alpha2-agonists
- Cholinergic agonists/miotics.
Systemic therapy is sometimes used for short-term treatment of acutely elevated IOP, consisting of oral or intravenous (IV) acetazolamide (Diamox) or the osmotic diuretics IV mannitol or oral glycerol. This section will deal with the most commonly prescribed first-line and second-line anti-glaucoma drugs (Tables 6-9). Initial glaucoma therapy is almost always with a single agent (monotherapy) which may be substituted if unresponsive or a second drug added as adjunctive therapy.
Prostaglandin analogues
Prostaglandin analogues (PGAs) are thought to reduce IOP by increasing the rate of uveoscleral aqueous outflow. There is evidence that PGAs reduce IOP more effectively than the beta blockers and they are commonly the first drug of choice (Table 6). Latanoprost (Xalatan) is preferred since it has a better safety profile than other members of the class although there is some evidence that travoprost (Travatan) is more effective in patients of African origin. The most common side-effect of PGAs is conjunctival hyperaemia, particularly during the early weeks of treatment. Hyperaemia is most pronounced in patients taking travoprost (35 per cent of patients in clinical trials), although it rarely leads to a discontinuation of therapy. PGAs may also cause darkening of the iris and lengthening of the eyelashes.
Bimatoprost (Lumigan) is a prostamide, a synthetic structural analogue of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower IOP in humans by increasing outflow of aqueous humour through both the trabecular meshwork and uveoscleral routes. Side-effects of bimatoprost are similar to PGAs.
Beta blockers
Beta blockers reduce IOP principally by reducing the rate of aqueous secretion. The non-selective beta blocker timolol remains the gold standard against which all new therapies are compared and topical beta blockers remain an effective therapy for selected patients. For example, beta blockers are the drug of choice in pregnant women and children and several members of this class of drugs are available in preservative-free formulations (Table 7).
Particular caution must be exercised when prescribing topical beta blockers as there have been several reports of serious systemic adverse reactions, particularly with non-selective receptor blockers (beta-1 and beta-2). At least 80 per cent of the administered drop drains through the nasolacrimal canal from where it can be absorbed across the nasal mucosa. Since the systemically absorbed drug bypasses hepatic first-pass metabolism, the drug behaves like an intravenous dose, increasing the propensity to cause prolonged and severe side-effects. Several cardiovascular adverse events that have been reported, including arrhythmias, hypotension, angina pectoris, myocardial infarction, heart failure, and syncope (fainting). Topical beta blockers can also exacerbate bronchospasm in asthmatics and patients with chronic obstructive pulmonary disease.
Carbonic anhydrase inhibitors
Carbonic anhydrase is a key enzyme involved in aqueous production. Carbonic anhydrase inhibitors (CAIs) include both oral and topical agents (Table 8). Acetazolamide (Diamox) can be given by mouth or intravenous (IV) injection and is typically used in the treatment of angle closure (500mg IV stat dose followed by 250mg orally four times daily). Topical CAIs, dorzolamide and brinzolamide, are less potent than PGAs and beta blockers but can be used as adjunctive therapy or first line in those unresponsive to other agents. The most common side-effects of topical CAI include a foreign-body sensation, conjunctival hyperaemia and a bitter taste in the mouth.
Selective alpha-2 agonists
Selective alpha-2 agonists lower IOP by reducing aqueous formation as well as a possible increase in uveoscleral outflow. Apraclonidine (Iodipine) is indicated for short-term use in patients on maximum drug therapy or perioperatively who require further IOP lowering. Brimonidine (Alphagan) can be used long-term as monotherapy where beta blockers are contraindicated or as adjunctive therapy in primary open angle glaucoma (POAG) and ocular hypertension (Table 9)
Combination products
The effect of different drugs used together is not necessarily additive. Some drugs work synergistically and the overall effect is greater than the sum of their individual responses. This is particularly true where the drugs reduce IOP by different mechanisms. Several combination products are available commercially eg timolol with prostaglandin/prostamide analogues, and timolol combined with the carbonic anhydrase inhibitor dorzolamide. Combined preparations can potentially improve compliance and reduce exposure to preservatives (compared to two separate preparations).
Other medications
Miotics, such as pilocarpine, have been used for many years to treat chronic glaucoma. They reduce IOP by improving outflow through the conventional drainage pathway. Miotics are no longer prescribed as first line therapy in POAG, although they still have a role in the treatment of angle closure.
Artificial tears and ocular lubricants
A distinction is often made between products that are marketed as 'artificial tears' or 'tear substitutes' and lubricant ointments and gels. Artificial tears are characterised by hypotonic or isotonic buffered solutions that are formulated at a neutral or slightly alkaline pH. They are the mainstay of treatment for dry eye or an unstable tear film. However, since most products also contain viscosity-enhancing agents that help to facilitate the movement of the eyelid across the ocular surface, they also provide symptomatic relief in conditions associated with ocular surface irregularity eg trauma, degenerations or scarring. In situations where ocular lubrication is paramount, eg recurrent corneal erosion syndrome, lubricating eye ointments containing paraffin may be used. These are generally reserved for night time use, since they cause significant blurring of vision. Several lubricants/artificial tear preparations are available for supply against an NHS prescription and these are listed in section 11.8.1 of the BNF. However, most ocular lubricants can be purchased over the counter at a cost less than the current prescription charge.
There is little available clinical evidence to recommend one product over another (Table 10). The choice of preparation is often based on the severity of the condition and patient preference, usually reached by a process of trial and error. In patients with mild symptoms supplements with a low viscosity should be considered as first line therapy, eg 0.3 per cent hypromellose. Higher viscosity solutions and gels such as carbomers or polyvinyl alcohol may be more suitable in patients with moderate or severe disease. Most products are formulated in multidose containers, preserved with benzalkonium chloride (BAK). The choice between a preserved or unpreserved preparation depends on the patient's preservative sensitivity and the frequency of application. As a rule of thumb, preservative-free formulations should be considered in patients requiring more than six applications per day. Preserved formulations are also contraindicated in patients wearing hydrogel contact lenses and specially formulated products, classified as medical devices, are available for contact lens associated dry eye, eg Blink Revitalising Eyedrops
Since artificial tears and lubricants are classified as P medicines or medical devices they can be sold or supplied by all optometrists without restriction. The only exception is Ilube which contains 5 per cent acetylcysteine (with hypromellose) and is classified as a POM that is only available to additional supply optometrists. Acetylcysteine is a mucolytic drug that is used to break down thickened mucin or adherent mucin filaments in filamentary keratitis.
Selection of available products
Hypromellose (hydroxypropylmethylcellulose)
Hypromellose is semi-synthetic mixed cellulose ether. Its low cost, due to its availability in non-proprietary form, may explain its continued popularity in hospital eye departments. The standard 0.3 per cent preparation often requires frequent reapplication. Contact time with the ocular surface can be prolonged by increasing concentration (up to 1 per cent) however, too high a concentration may lead to blurring and lid crusting. Preservative-free forms are available as single-dose units, eg Artelac SDU or 0.3 per cent hypromellose (obtained from Moorfields Pharmaceuticals).
Polyvinyl alcohol (PVA)
PVA is used at a concentration of 1.4 per cent as a viscosity-enhancing agent and also promotes the spreading of the tear film, improving tear stability and increasing tear break-up time. It may be effective where hypromellose-based preparations have failed.
Carbomers
Carbomers are polymers of acrylic acid. They have excellent mucoadhesive properties and require less frequent application than hypromellose or PVA-based products.
Hydroxypropyl (HP) Guar
HP guar is the gelling agent in Systane. It is a derivative of a natural water soluble polysaccharide which cross links with borate in a pH dependent manner to form a gel-like matrix over the ocular surface. Systane contains polyquad as a preservative which claims to be less toxic to the corneal epithelium than BAK.
Conclusion
In the past, the management of eye disease by community optometrists has been restricted by their inability to supply all but a narrow range of therapeutic agents. Changes in medicines legislation are beginning to overcome this barrier and increasing numbers of optometrists are using drugs available through medicines act exemptions to treat a range of minor eye problems in community settings. Furthermore, opportunities are being created for specialist registration to further develop therapeutic practice. This article has provided an overview of the main classes of drug used in ophthalmology, and should be read in conjunction with the earlier parts of the series that covered ocular disease management (Part 6a, 6b and 7).
The competence and confidence to prescribe develops with experience, and builds on the skills and knowledge gained during undergraduate and postgraduate training. Whenever a decision is made to prescribe or supply a drug, the practitioner must possess adequate, up-to-date knowledge of its indications, contraindications, interactions, dose and side-effects. Several regularly updated, paper-based and online medicines information sources are available. Guidance on prescribing for common ophthalmic presentations is also provided in evidence-based clinical management guidelines that can be accessed online (eg Clinical Knowledge Summaries).
Bibliography
- British National Formulary (September 2007) (available at http://www.bnf.org.uk/bnf/).
- Competency Framework for Prescribing Optometrists (can be downloaded from: http://www.assoc-optometrists.org/uploaded_files/pdf/optometrist_document_final.pdf).
- Clinical Knowledge Summaries (available at: http://www.cks.library.nhs.uk/clinical_knowledge/clinical_topics/by_clinical_specialty/eyes).
- Doughty MJ, Dutton GN. Fusidic acid viscous eyedrops - an evaluation of pharmacodynamics, pharmacokinetics and clinical use for UK optometrists Ophthalmic Physiol Opt 200626:4 343-61.
- The electronic medicines compendium (available at http://emc.medicines.org.uk).
- European Glaucoma Society 2003 Terminology and Guidelines for Glaucoma, 2nd edition.(Available at: www.eugs.org).
Lucy Titcomb is lead ophthalmic pharmacist at the Birmingham and Midland Eye Centre. John Lawrenson is professor of clinical visual science in the Department of Optometry and Visual Science, City University, London.