Management of Glaucoma

Overview of glaucoma
Glaucoma is a mixed group of disorders characterised by one or more of the triad of optic neuropathy, visual field loss and raised intraocular pressure (IOP). It causes significant visual disability, accounting for 15% of registrable blindness in the UK.1 These disorders are classified as: P Primary versus secondary Open versus closed angle (this refers to the angle between the cornea and the iris, the iridocorneal angle, where aqueous drainage t takes place) Congenital versus acquired Primary open angle glaucoma (POAG) is the most common form of the disorder, affecting 1% of the population over 402 and 10% of over 80s.3 Acute angle closure glaucoma is a medical emergency requiring prompt referral and treatment. In ocular hypertension, there is a raised IOP in the absence of optic neuropathy and visual loss; it may represent the tail end of a skewed Gaussian distribution of normal IOP but these patients have been shown to benefit from treatment with ocular hypotensives.4 Normal tension glaucoma (also called low tension glaucoma) refers to patients showing signs of glaucoma in the absence of ocular hypertension. T Treatment aims Glaucoma is a progressive condition: treatment aims to limit optic nerve damage through optimal IOP control, so preventing significant visual impairment. s A 30% reduction in IOP is considered to give the best chance of achieving this aim.5 This target is also used in patients with normal tension glaucoma, despite the IOP lying within the normal range1 although there is limited evidence to support active intervention in this set of patients whose disease seems to progress regardless of treatment.6 6 IOP control is achieved via monitoring in specialist clinics coupled with medical and/or surgical intervention where needed. Initiation and monitoring of treatment is not appropriate in a primary care setting. There is also a role for optometrists and to monitor stable patients in the community.7 7 Treatment revolves around decreasing aqueous production at the ciliary body or increasing aqueous outflow through one of two routes: trabecular route (90% of outflow, through to the Schlemm Canal) and the uveoscleral route (10% of outflow, where the aqueous passes back across the face of the ciliary body). a Treatment tends to be life-long once started, although patients who

go on to have surgery occasionally no longer need medical treatment and are eventually discharged to the close observation of the community optician.1

Management options
Assessment and monitoring8 8
Initial assessment should include a history (with specific questions relating to risk factors e.g. family history, high myopia, diabetes1) and an ocular examination, concentrating on an assessment of visual fields, IOP and optic disc. It should also include gonioscopy (looking at the iridocorneal angle with an angled mirror lens to assess if it is open or not) and a measurement of corneal thickness as this can affect the IOP reading. Additional features will be sought or ruled out (e.g. p presence of factors giving rise to secondary glaucoma). Ideally, fundus photographs are taken at the point of diagnosis and t then used for comparison of the disc later on. Subsequent assessments focus on visual fields, IOPs and optic discs. This may be tricky with some patients who are unable to follow instructions for visual field assessment or who cannot tolerate IOP readings. In these difficult situations, management options a are based on the appearance of the optic disc alone. Occasionally, there may be several visits where the patient is simply monitored before the diagnosis is finally made and treatment is started - this is due to IOP variations between and within individuals.
D Drug therapy

Generally, drugs are initiated one at a time but subsequent addition of further drugs may be necessary if IOP remains unsatisfactorily high.9 9 T Treatment may be to one or both eyes. Traditionally, beta-blockers were the preferred first option but prostaglandin analogues are now generally favoured as they are as a efficient with fewer side effects. Carbonic anhydrase inhibitors and alpha agonists tend to be second choice agents.1 1 There are a number of agents now available that combine two different drugs so as to improve adherence to therapy. d Side-effects from medication may be local or systemic and may be severe enough to warrant a change in medication.4 Laser therapy2 2 Argon laser trabeculoplasty: laser burns to the trabecular meshwork i in the iridocorneal angle enhances aqueous outflow. Diode laser trabeculoplasty: similar principle as above, using a higher l laser power. Nd:YAG laser iridotomy: a small hole is made in the iris in patients

with angle closure glaucoma, to enhance aqueous outflow. Both eyes are treated to prevent subsequent acute episodes in the f fellow eye. Diode laser cycloablation: part of the secretory component of the ciliary body is destroyed, so reducing aqueous secretion. This is used in intractable end-stage glaucoma. Surgical therapy10 1 Surgical intervention tends to occur when all other treatment has failed; there is not much evidence that it is superior to medical interventions in the early stages of the disease and is associated w with an increased risk of complications. Trabeculectomy: this, the most common procedure, creates a fistula between the anterior chamber of the eye and the sub-Tenon space (immediately around the globe), so allowing aqueous outflow. There is a resultant blister on the surface of the eye (a 'bleb') which can cause discomfort or occasionally get infected (blebitis). Adjunctive anti-metabolites such as 5-fluorouracil and m mitomycin C may be used to prevent scarring over of the fistula. Artificial shunts in the form of plastic devices connecting the anterior chamber to the sub-Tenon space can be inserted but are associated with many post-operative complications.

Developing therapies11

There is work underway looking at oral and topical neuroprotective agents (such as antioxidants, N-methyl-D-aspartate receptor antagonists, inhibitors of glutamate release etc) that could be used in the treatment or even prevention of glaucoma. However to date, there has yet to be a comprehensive review of the use of these therapies in this context.

Alternative therapy12
It has been suggested that there might be a role for acupuncture in the treatment of glaucoma. However to date, there is no evidence that this works.

Drugs used in management of glaucoma3 5 8

, ,

B Beta-blockers

Use - POAG: until recently, first drug of choice Action - reduce aqueous secretion by inhibiting beta-adrenoceptors on o ciliary body Contraindications - bradycardia, heart block, uncontrolled heart failure, asthma and patients with a history of chronic obstructive pulmonary disease o Caution - depression, myasthenia gravis, possibility of interactions with other medication such as v verapamil Common ocular side-effects - irritation, erythema, dry eyes,

blepharoconjunctivits and allergy (anaphylactic reaction possible but b rare) Common systemic side-effects - bronchospasm, bradycardia, exacerbation of heart failure, nightmares e Examples - betaxolol hydrochloride, carteolol hydrochloride, levobunolol hydrochloride, timolol maleate
P Prostaglandin Analogues

Use - POAG, ocular hypertension: increasingly first line treatment Action - increase aqueous outflow via uveoscleral route Contraindications - active uveitis, pregnancy and breast feeding , Caution - brittle or severe asthma, aphakia, pseudophakia, do not take within 5 minutes of using thiomersal-containing preparations t Common ocular side-effects - change in eye colour: brown pigmentation, thickening and lengthening of eye lashes, more rarely: uveitis, ocular pruritis, photophobia and k keratitis Common systemic side-effects - rarely: hypotension, bradycardia, brow ache b Examples - bimatoprost, latanoprost, travoprost
S Sympathomimetics (alpha-2 receptor stimulants)

Use - POAG, ocular hypertension, beta-blocker sensitivity, adjunctive therapy where IOP control is poor t Action - reduce aqueous secretion and increase outflow through trabecular meshwork t Contraindications - angle-closure glaucoma (due to mydriatic effects), patients currently taking monoamine oxidase inhibitors (possibility of hypertensive crisis) ( Caution - hypertension, heart disease Common ocular side-effects - mydriasis, dry eye, severe smarting and redness of the eye a Common systemic side-effects - lethargy, hypotension Examples - brimonidine tartrate, dipivefrine hydrochloride
C Carbonic Anhydrase Inhibitors

Use - topical: beta-blocker resistant glaucoma, systemic: acute and severe raised IOP s Action - reduce aqueous secretion by ciliary body; weak diuresis in systemic use s Contraindications - renal impairment, metabolite imbalance, severe hepatic impairment, sulphonamide sensitivity (acetazolamide), breast-feeding b Caution - elderly, hepatic impairment, history of renal calculi, history of intra-ocular surgery, pregnancy and breast-feeding; extravasation at infusion site of intravenous acetazolamide can cause necrosis c Common ocular side effects - localised discomfort, lacrimation, topical allergy, more rarely: superficial punctate keratitis,

uveitis, transient myopia u Common systemic side effects (particularly with systemic administration) - taste disturbance, nausea / vomiting, headache, dizziness, fatigue, paraesthesia and sulphonamide-related side effects with acetazolamide e Examples - acetazolamide (systemic use), brinzolamide (topical use), dorzolamide (topical use)
M Miotics

Use - generally in acute angle closure glaucoma Action - open up the drainage channels in the trabecular meshwork by b ciliary muscle contraction Contraindications - in situations where pupillary constriction is undesirable (such as uveitis), presence of retinal holes u Caution - darkly pigmented irides require higher concentrations but overdosage must be avoided, patients with retinal disease (especially previous detachment), cardiac disease, hypertension, asthma, peptic ulceration, urinary tract obstruction and Parkinson's disease P Common ocular side effects - miosis: this can cause blurred vision (patients should be warned of this as it can affect driving and other skilled tasks, especially in the presence of a cataract), accommodative spasm with brow ache (often causing intolerance in i patients over 40), localised discomfort, pupillary block Common systemic side effects - sweating, bradycardia, gastrointestinal disturbance g Example - pilocarpine
O Other

management issues

There are particular challenges in the treatment of a condition that is asymptomatic (until the very late stages) and where the drugs used may cause side-effects. Studies show that up to a third of patients have a poor adherence to treatment13 (depending on the drug used) with up to 70% of newly diagnosed patients not collecting repeat prescriptions.9 There is the added problem of difficulties in handling the dispenser for a significant number of patients. Patient education, counselling and follow-up are t therefore as essential as the treatment itself. Patients who have been diagnosed with glaucoma will have been told to contact the DVLA (the onus is on them) and it is worth reiterating this to them. They will have to visit DVLA-accredited opticians who will carry out appropriate visual field testing to assess their suitability for driving. Document your conversation.

Management of acute angle closure glaucoma

S Symptoms P Pain, blurred vision and coloured halos around lights Frontal headache, nausea or vomiting, generally unwell

S Signs R Red eye C Cloudy cornea O Oval, fixed pupil L Loss of red reflex Decreased visual acuity M Management Emergency referral to ophthalmologist: patient needs to be seen w within hours of presentation to prevent permanent blindness S Systemic analgesia Systemic anti-emetic if required Subsequent treatment will usually include a combination of topical beta-blockers, topical steroids, topical apraclonidine and systemic acetazolamide. Should the IOP remain very elevated despite repeated treatment, systemic mannitol may be considered. Peripheral iridotomy will be performed bilaterally at the earliest opportunity (depending on the degree of reduced visibility of the iris secondary to corneal haziness) and any underlying contributory factor will be addressed. Please click here to refer to our article dedicated to acute angle closure glaucoma for more detail on the treatment of this emergency.

The head pain may be so severe that the patient does not localise it to the eye. Think about acute angle closure glaucoma with all presentations of recent onset severe frontal headache or in the elderly patient who is generally unwell with a red eye.

Document references
1. Royal College of Ophthalmologists; Guidelines for the Management

of Open Angle Glaucoma and Ocular Hypertension, 2004.

2. Kanski J. Clinical Ophthalmology, A Systematic Approach (5th ed.) 3. 4.

5. 6.

7.

8.

2003 Butterworth Heinemann Batterbury M, Bowling B. Ophthalmology: An Illustrated Colour Text, 2002 Churchill Livingstone Vass C, Hirn C, Sycha T et al.; Medical interventions for primary open angle glaucoma and ocular hypertension. Cochrane Database of Systematic Reviews 2007, Issue 4. Kunimoto DY, Kanitkar KD, Makar MS; The Wills Eye Manual (4th ed.) 2004 Lippincott, Williams and Wilkins Sycha T, Vass C, Findl O et al.; Interventions for normal tension glaucoma. Cochrane Database of Systematic Reviews 2003, Issue 4. British and Irish Orthoptic Society; Competency Standards and Professional Practice Guidelines for the Extended Role of the Orthoptist, June 2006. F Bell JA, Noecker RJ; Glaucoma, primary open angle; eMedicine;

August 2005. Useful pictures and flow charts at the end of the article. 9. Gray TA, Orton L, Henson D et al.; Interventions for improving adherence to ocular hypotensive therapy. (protocol) Cochrane Database of Sytematic Reviews 2006, Issue 3. 10. Burr J, Azuara-Blanco A, Avenell A; Medical versus surgical interventions for open angle glaucoma. Cochrane Database of Systematic Reviews 2005, Issue 2. 11. Sena DF, Ramchand K.; Neuroprotection for prevention and treatment of glaucoma in adults. (Protocol) Cochrane Database of Systematic Reviews 2007, Issue 2. 12. Law SK, Li T; Acupuncture for glaucoma. Cochrane Database of Systematic Reviews 2007, Issue 4. American Academy of Ophthalmology; Preferred practice patterns: primary open angle glaucoma. Published 2005.; Useful flow diagram summarising management on p.23 of document.