Primary Open-Angle Glaucoma (POAG)

Glaucoma refers to the family of conditions characterised by optic neuropathy. There are typical optic nerve changes on slit-lamp examination and it is associated with specific visual field defects. It is frequently - but not invariably - associated with raised intra-ocular pressure (IOP).

• 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
• Generally bilateral (although not always symmetrical)
• Absence of underlying cause, as is the case in secondary glaucoma (such as the presence of new, abnormal vessels).²

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. This in turn 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.^1,3

• This is the most common form of glaucoma.
• Approximately 1:100 people over 40 years old are affected
• Male:female = 1:1 (some studies suggest a slightly higher prevalence in males).³
• Responsible for approximately 12% of all cases of blind registration in the UK.

• Age - the incidence increases with age, most commonly presenting after 65 years old (and rarely before 40 years old). ⁴
• 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 more common in Afro-Caribbean people in whom it tends to present earlier and is more severe.
• 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 diabetes and systemic hypertension 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 Suspicion arises during the course of a routine optician check where abnormal discs, IOPs or visual fields may be noted.

There are a number of signs that will be looked for when examining the glaucoma suspect:²

• Raised IOP - IOP is a little like blood pressure in that there is not an absolute correct value but a normally distributed range of values (from 11-21mmHg) with some normal individuals having IOPs outside these ranges. Furthermore, there are physiological diurnal fluctuations of up to 5mmHg in about 30% of the population, this variation being exaggerated in patients with POAG.¹ In addition to this, the IOP has to be measured in the context of corneal thickness as the latter affects IOP readings, a slightly thick cornea may give rise to an erroneously high reading and there is a 10% inter-examiner variation.² So all these factors combined with others such as changes with season, respiration and aerobic exercise,³ makes this measure a useful guide rather than an absolute standard if the readings are sitting on the borderline of normality.⁴
• Optic disc changes - 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 ration 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. These measurements are made by observation and comparisons to charts. There are also imaging techniques available to carry out objective measurements.
• Visual fields - these can assessed using a couple of different perimetry machines which objectively document what the patient perceives in the periphery of their vision. These can also assess the degree of false positive errors (the patient clicks away when they can't see much) so adding weight to the assessment. These assessments require the co-operation of the patient and can also be affected by fatigue, spectacle frames, miosis and media opacities.³ Where this is not possible, the assessor will have to rely on IOPs and cup:disc ratios alone.
• Gonioscopy - this will be carried out in the ophthalmology clinic to ensure that the iridocorneal angles are open, so confirming the diagnosis of this particular form of glaucoma. This test is performed on the first visit only and from the patient's perspective, it is not painful but may feel strange and some patients find it hard to tolerate as the direct contact of the gonio lens against the (anaesthetised) cornea induces blepharospasm (squeezing the eye shut) in some.
• Other signs - visual acuities and any comorbid factors will be assessed in each patient.

• 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).

Treatment aims

• Once the assessment has 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.
• 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. 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 onto surgery, educating their own family with regards to careful screening and so on.

Medical therapy^1,5,6

This is the first line and only treatment for many patients. 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 prostaglandin analogues are now often favoured as they are as efficient with fewer side effects.The drugs fall into the following groups:

• 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, blepharoconjunctivits and allergy anaphylactic reaction possible.
  • Common systemic side effects: bronchospasm, bradycardia, exacerbation of heart failure, nightmares.
• 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 pruritis, photophobia and keratitis.
  • Systemic side effects: rarely - hypotension, bradycardia, brow ache.
• 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.
• Carbonic anhydrase inhibitors and systemic drugs
  • 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.
• 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 therapy^1,4

• Argon laser trabeculoplasty - laser burns to the trabecular meshwork in the iridocorneal angle enhances aqueous outflow.
• 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 ^1,4

• 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.
• 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.

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 summarized as it being legal if the patient has a binocular vision of >120 degrees on the horizontal meridian with a central radius of 20 degrees. The important thing to note is that the onus is on the patient to inform the DVLA (and it is important to document that you have advised them of this) and 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 defense union as there will be issues of breach of confidentiality.

• 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 were the the nature of this condition and its treatment rationale have not been fully explained.
• Steroid responsiveness¹ - 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 (>30mmHg). 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 (22mmHg-30mmHg), 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.²

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 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.