Primary Open Angle Glaucoma

Glaucoma refers to the family of conditions characterised by optic neuropathy manifested by characteristic loss of optic nerve fibres. There are typical optic nerve changes on slit-lamp examination and it is associated with specific visual field defects over time. It is frequently - but not invariably - associated with raised intra-ocular pressure (IOP). An elevated IOP is associated with an increased risk of the disease but is not the disease itself.¹ The focus on IOP with regards to glaucoma relates to the fact that, to date, it is the only known risk factor that can be clinically manipulated.

Glaucoma and Ocular Hypertension
Angle-closure Glaucoma
Congenital Primary Glaucoma

Simple (or primary) open angle glaucoma (POAG) refers to the progressive, chronic condition that is characterised by:²

• Adult onset
• An IOP greater than 21 mmHg (normal range: about 10-21 mmHg) at some point in time
• An open iridocorneal angle (between the iris and the cornea, where the aqueous flows out)
• Glaucomatous optic neuropathy
• Visual field loss compatible with nerve fibre damage
• Generally being bilateral (although not always symmetrical)
• Absence of underlying cause, as is the case in secondary glaucoma (such as the presence of new, abnormal vessels)¹

The mechanism of damage involves an increased resistance to aqueous outflow within the trabecular meshwork (a circumferential sieve-like structure sitting in the iridocorneal angle through which 90% of the aqueous drains) so causing a rise in IOP. There are several theories as to how the raised IOP causes optic nerve damage.¹ It is thought that it influences retinal ganglion apoptosis, the rate of which is influenced by the IOP itself mechanically increasing pressure on the optic nerve head and by compromise of the local microvasculature.^2,3

• This is the most common form of glaucoma.
• Approximately 1-2% of the population over 40 years old are affected⁴ but about half of them are unaware of this.⁵
• The prevalence increases with age, affecting about 10% of people aged over 70.⁴
• Male:female = 1:1 (some studies suggest a slightly higher prevalence in males).³
• Responsible for 10-12% of all cases of blind registration in the UK.⁴

• Age - the incidence increases with age, most commonly presenting after 65 years old (and rarely before 40 years old).⁶
• Family history - there is a clear inherited component in many individuals (IOP, aqueous outflow facilities and disc size are inherited characteristics). However, it is thought that there is incomplete penetrance and variable expressivity of the genes involved. There are also several factors thought to contribute to the inheritance and therefore the risk to relatives is currently only an estimate: 4% to children and 10% to siblings of an affected individual.
• Race - it is 3 to 4 times more common in Afro-Caribbean people in whom it tends to present earlier and is more severe.
• Ocular hypertension - this is a major risk factor for the development of glaucoma with about 9% of patients developing glaucoma over 5 years if left untreated.⁴
• Other factors - myopia (short-sightedness) and retinal disease (e.g. central retinal vein occlusion, retinal detachment and retinitis pigmentosa) can predispose individuals to POAG. It is postulated that diabetes⁵ and systemic hypertension⁵ (and possibly also systolic hypotension) may also contribute to risk.

The difficulty with this condition is that, in the vast majority of cases, patients do not notice anything at all. Indeed, it is estimated that up to 50% of cases in the western world go undetected.³ By the time the patient is symptomatic, up to 90% of the optic nerve fibres may have been irreversibly damaged.⁴ Suspicion arises during the course of a routine optician check where abnormal discs, IOPs or visual fields may be noted.

An ophthalmologist will examine the eye thoroughly for evidence of glaucoma, co-morbidity or an alternative diagnosis to the apparent findings. The details of a glaucoma assessment are covered in our record on Glaucoma and Ocular Hypertension. They can be summarised as:

• Gonioscopy - measurement of the angle between the cornea and the iris to assess whether the glaucoma is open or closed angle. Initial assessment only (unless there is a change such as trauma).
• Corneal thickness - this influences the IOP reading. Initial assessment only unless there is subsequent trauma, surgery (including laser treatment) or degenerative condition of the cornea.
• Tonometry - this is the objective measurement of IOP. Normal readings are between about 10 mmHg and 21 mmHg. Every visit.
• Optic disc examination - this is a key assessment in these patients as it is a direct marker of disease progression. Optic disc damage is assessed by looking at the vertical ratio of the pale centre (cup) to the overall size of the disc. A small cup and a thick neuroretinal rim (the darker bit surrounding the cup) may give a ratio of 0.3 or less (normal). A small number of people have a cup:disc ratio up to 0.7 but anything beyond that is definitely pathological. Every visit.
• Visual fields - these can be assessed using a couple of different perimetry machines which objectively document what the patient perceives in the periphery of their vision. Every visit, as long as the patient is able to go through with test. Where this is not possible, the assessor will have to rely on IOPs and cup:disc ratios alone.

• Mild - early visual field defects.
• Moderate - presence of an arcuate scotoma ("n" shaped visual field loss arching over the central visual field) and thinning of neuroretinal rim (cupping).
• Severe - extensive visual field loss and marked thinning of the neuroretinal rim.
• End-stage - only a small residual visual field remains and there may be very little neuroretinal rim left (so the cup:disc ratio would be in the region of 0.9-1.0).

There are wide variations across the NHS in management of this condition, reflecting conflicting literature and scattered reports.⁴ The recent NICE guidelines (2009) are an important step towards standardising management approaches.

Treatment aims

• Treatment is not necessarily started immediately on simple detection of an elevated IOP. Bearing in mind the potential for variation of findings from one assessment to the next, the patient should be assessed on several occasions unless the findings are unequivocal; the diagnosis is significant and treatment lifelong.⁴ Apparent disc cupping will be considered in conjunction with visual fields and IOP. In some patients, the disease is obvious and advanced, in which case treatment should start promptly.
• Once a diagnosis and decision to treat have been made, a target IOP is set according to the degree of damage: this is the pressure below which further damage is considered unlikely.³ This is usually in the region of a 30% drop of IOP. It is different between patients and may be different in each eye.
• Regular monitoring via ophthalmology clinics to assess IOP, the optic disc and the visual fields. Some areas have schemes whereby trained opticians carry out all the monitoring.
• Patient education is key, as this is a largely asymptomatic condition until it is very advanced.⁴ It is important that they understand the irreversible nature of the disease and that they feel involved in issues around taking drops (including how to take them correctly and potential side-effects), when and why one might move on to surgery, educating their own family with regards to careful screening and so on.

Medical therapy^2,7

This is the first-line and only treatment for many patients. There is no single drug that stands out above others as the optimal treatment of glaucoma.⁸ It may take a few trials with different agents before one is found that effectively lowers the IOP without causing unwanted side-effects. Generally, drugs are initiated one at a time but subsequent addition of further drugs may be necessary if IOP remains unsatisfactorily high. Treatment may be to one or both eyes. Traditionally, beta blockers were the preferred first option but, since about the year 2000, prostaglandin analogues have been favoured as they are as efficient with fewer side-effects.⁹ NICE recommends these as the first-line treatment.⁴ The drugs fall into the following groups:

• Prostaglandin analogues:
  • Action: increase aqueous outflow via uveoscleral route.
  • Contra-indications: active uveitis, pregnancy and breast-feeding.
  • Caution: brittle or severe asthma, aphakia (patient with no lens), pseudophakia (patient with artificial lens such as the one put in following a cataract extraction), do not take within 5 minutes of using thiomersal-containing preparations.
  • Common ocular side-effects: change in eye colour: brown pigmentation, thickening and lengthening of eye lashes, more rarely: uveitis, ocular pruritus, photophobia and keratitis.
  • Systemic side-effects: rarely - hypotension, bradycardia, brow ache.
• Beta blockers:
  • Action: reduce aqueous secretion by inhibiting beta-adrenoceptors on ciliary body.
  • Contra-indications: bradycardia, heart block, uncontrolled heart failure, asthma and patients with a history of chronic obstructive pulmonary disease.
  • Caution: depression, myasthenia gravis, possibility of interactions with other medication such as verapamil.
  • Common ocular side-effects: irritation, erythema, dry eyes, blepharoconjunctivitis and allergy anaphylactic reaction possible.
  • Common systemic side-effects: bronchospasm, bradycardia, exacerbation of heart failure, nightmares.
• Carbonic anhydrase inhibitors:
  • Action: reduce aqueous secretion by ciliary body. Weak diuresis in systemic use.
  • Contra-indications: renal impairment, metabolite imbalance, severe hepatic impairment, sulphonamide sensitivity (acetazolamide), breast feeding.
  • 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.
  • Ocular side-effects: localised discomfort, lacrimation, topical allergy, more rarely: superficial punctate keratitis, uveitis, transient myopia.
  • Systemic side-effects: (particularly with systemic administration), taste disturbance, nausea/vomiting, headache, dizziness, fatigue, paraesthesia and sulphonamide-related side-effects with acetazolamide.
• Sympathomimetics:
  • Action: reduce aqueous secretion and increase outflow through trabecular meshwork.
  • Contra-indications: 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.
  • Common systemic side-effects: lethargy, hypotension.
• Miotics:
  • Action: open up the drainage channels in the trabecular meshwork by ciliary muscle contraction.
  • Contra-indications: situations where pupillary constriction is undesirable (such as uveitis), presence of retinal holes.
  • 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.
  • Ocular side-effects: miosis: this can cause blurred vision and 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 patients over 40), localised discomfort, pupillary block.
  • Systemic side-effects: sweating, bradycardia, gastrointestinal disturbance.

Laser and surgical treatments should be considered after unsuccessful trials with two different pharmacological treatments.⁴ However before this, it is important to ascertain that the patient is actually managing to get the drops in. This issue can be addressed in specialist nurse clinics within the Eye Unit.

Laser therapy^2,6

• Argon laser trabeculoplasty - this outpatient procedure places laser burns to the trabecular meshwork in the iridocorneal angle so enhancing aqueous outflow. It has the benefit of reducing (or stopping) the need for drops whilst not having the complications of surgery. However, trials relating to its effectiveness are old and compare it to drops that have been replaced by newer, more efficacious drugs. Research has yet to be done in this area as well as into the different responses of different patients (particularly of different ethnicities) and a definitive treatment protocol has yet to be established.¹⁰
• Diode laser trabeculoplasty - similar principle as above, using a higher 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 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 therapy^2,6

• Trabeculectomy - this procedure creates a fistula between the anterior chamber of the eye and the sub-Tenon space (immediately around the globe), so allowing aqueous outflow. Adjunctive anti-metabolites such as 5-fluorouracil and mitomycin C may be used to prevent scarring over of the fistula. A deep sclerectomy is a variation of this procedure.⁴
• 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.
• New techniques and devices are being developed to minimise the complications of laser and surgical treatment. An example is canaloplasty whereby Schlemm's canal is artificially widened with a temporary tube and viscoelastic.¹¹

If there is ongoing disease progression after surgery, the options will be to go back on to medical treatment, to consider further surgical intervention or to try laser treatment.⁴

A visual field defect counts as a "relevant disability" (as opposed to the "absolute disability" of a reduced visual acuity) in the eyes of the law. There are certain criteria set out and assessed by the Driver and Vehicle Licensing Agency (DVLA). This can be summarised as it being legal if the patient has a binocular vision of >120° on the horizontal meridian with a central radius of 20°.

It is estimated that about 20% of POAG patients may fail to meet the visual field criteria for fitness to drive.⁵ The onus is on the patient to inform the DVLA (and it is important to document that you have advised them of this). It is the DVLA (and approved opticians) who will assess the visual fields and decide whether the patient can continue to drive. If you are concerned that the patient has not told the DVLA and you have re-stated the need to do this, it may be appropriate to inform the DVLA medical advisors but liaise with your defence union as there will be issues of breach of confidentiality.

It is worth noting that the ability to drive is one of the most important factors identified by patients when assessing the impact of glaucoma, and loss of this ability is a significant event. Elderly people who have stopped driving have been observed to be at greater risk of worsening depressive symptoms.⁵

• Treatment side-effects - identified in the discussion on medical treatment (see above).
• Non-compliance³ - as this is primarily a silent condition until it is very advanced, there is a risk of non-compliance, particularly in patients where the nature of this condition and its treatment rationale have not been fully explained.
• Steroid responsiveness² - topical steroids are known to have the potential to affect IOP in the long-term (generally, systemic steroids are less likely to have this effect). Broadly speaking, the population can be divided into three groups according to their IOP response to a 6-week course of steroids;
  • High responders - they show a marked elevation (>30 mmHg). This occurs in 5% of the general population but in 90% of the POAG population (and in 30% of their siblings and 25% of their offspring).
  • Moderate responders - 35% of the general population will show a modest elevation in IOP (22 mmHg-30 mmHg), the figure dropping to 10% in POAG patients (and in 50% of their siblings and 70% of their offspring).
  • Non-responders - 60% of the population fall into this group. There are no POAG patients in this group (but 20% of their siblings and 5% of their offspring).

Unless treated, this condition progresses relentlessly. Any treatment aims at stalling it and cannot reverse it. However if treatment is maintained, useful vision should be maintained throughout the patient's lifetime.¹ Factors involved in more rapid progression are still being examined but it would seem that myopia, the presence of optic disc haemorrhages, vascular and genetic factors all have a role to play.⁵ This may be related to the finding in a recent study (part of a larger, long-term study group), that although there is not an associated mortality per se, cardiovascular mortality tended to increase in black persons with previously diagnosed/treated POAG and ocular hypertension.¹³

POAG cannot be prevented as such but its progression can be slowed. By and large, the patient will not notice symptoms relating to POAG until the visual field changes are very advanced, at which point very little can be done. For this reason, screening remains the only tool for detection³ with shared care between optometrists and ophthalmologists underpinning the detection and management of these patients. It should involve tonometry (measuring the IOP), visual fields and an examination of the optic disc. Where there is no family history, opportunistic screening can be performed (ideally every two years) when the patient goes for a routine visit to their optician. From the age of 65 it should be carried out yearly. In patients with a first-degree relative suffering with POAG, a full specialist optician or ophthalmologist review should be carried out aged 40, with further screening every two years until the age of 50 and yearly thereafter.