Description

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).

This article gives an overview of the different types of glaucoma, their characteristics and the management which is usually within the setting of an eye clinic or by a specialist optician.

Pathophysiology of glaucoma

The primary problem in glaucoma is a disease of the optic nerve. The pathophysiology contributing to this is not fully understood. For most types of glaucoma, the neuropathy is associated with a raised intraocular pressure so leading to the hypothesis of 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.^1,2 This is reflected clinically in a progressive loss of peripheral visual field.

However, normal tension glaucoma does not lend itself to this theory as, by definition, there is not a rise in IOP. One suggestion is that these patients may suffer from a vascular perfusion problem or that there may even be an autoimmune component but these are tentative theories only.³ Others have postulated that the same theory applies as with other types of glaucoma but that the optic nerve head is particularly sensitive in these patients, with damage occurring at much lower IOPs than in normal individuals. This explains why these patients are also managed with IOP-lowering medication.

Epidemiology⁴

• Globally, 12.5 million people are blind from glaucoma.
• In the UK, it accounts for 10% of registrations of blindness.
• Primary open angle glaucoma (POAG) occurs in about 2% of people over 40 and 10% of those over 75 with a total of 480,000 affected individuals in England.
• There are over a million glaucoma-related hospital outpatient visits in England every year.

Assessing glaucoma

The diagnosis of this silent disease is critical: if missed, the window of opportunity to stop progression is lost. If it is falsely diagnosed, there ensues a lifetime of inappropriate anxiety and medication (since treatment is lifelong) as well as misuse of resources. In some cases, diagnosis is evident, particularly with the secondary glaucomas. Where POAG or ocular hypertension are suspected, the ophthalmologist will seek to exclude other causes of the positive findings before making this diagnosis.

The examinations carried out when a suspect case is referred are listed below but, additionally, they will also have a thorough ocular examination to rule out co-pathology or other possible diagnoses. Assessments are the same for glaucoma patients and those with - or suspected to have - ocular hypertension (see 'Ocular hypertension' below).

Initial assessment

Working from front to back, the examinations particularly relevant in the assessment of glaucoma are listed here. They are all painless examinations which can be simply carried out in a clinic setting:

• Gonioscopy - this is a technique used to measure the angle between the cornea and the iris to assess whether the glaucoma is open or closed angle (there is a grading system).
• Corneal thickness - this is important as it influences the IOP reading. If it is thicker than usual, it will take greater force to indent the cornea and an erroneously high reading will be obtained. The opposite is true for a thin cornea.
• Tonometry - this is the objective measurement of IOP, usually based on the assessment of resistance of the cornea to indent. Normal readings are between about 10 mmHg and 21 mmHg. There are various tonometers available but the most frequently used in a hospital setting is Goldmann's applanation tonometer.
• 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.
• 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. These assessments require the co-operation of the patient and can also be affected by fatigue, spectacle frames, miosis and media opacities.⁵ Where this is not possible, the assessor will have to rely on IOPs and cup:disc ratios alone.

Monitoring

Once diagnosis is confirmed, IOPs, optic disc assessment and visual fields are the parameters that will be routinely monitored. If there has been something to affect the central corneal thickness, e.g. laser refractive surgery or onset of corneal pathology, this will need to be reassessed too.⁴

Ocular hypertension^1,6

• Nature - this term is used where the IOP is found to be >21 mmHg on 2 consecutive occasions in the absence of any detectable glaucomatous damage. It is a major risk factor for the development of glaucoma. Lowering IOP has been shown to decrease this risk.
• Epidemiology⁴ - it is estimated to affect 3-5% of individuals aged over 40; about one million people in England.
• Management⁴ - the IOP, the central corneal thickness and the age of the patient will determine whether treatment is instigated or not. For those who are not treated, ongoing monitoring is essential as there is a risk of converting to POAG. For those who do require treatment, this involves IOP-lowering drugs (discussed in the POAG record, link provided below). There is considerable variation in practice with regards to who is treated and who is not⁷ but the recent NICE guidelines should reduce this variation.⁴ Patients will be monitored 6-monthly to yearly.
• Outcome - the Ocular Hypertension Treatment Study found that the 'conversion rate' to glaucoma is 9% over 5 years in untreated patients, compared to 4.4% in treated individuals. There is no absolute way of predicting which of these patients will go on to 'convert' but risk factors include:
  • Older age
  • Higher IOP
  • Larger cup:disc ratio
  • Thinner central corneal thickness

Primary open angle glaucoma (chronic simple glaucoma)

See separate Primary Open Angle Glaucoma record for more details.

Primary angle-closure glaucoma

See Primary Angle-closure Glaucoma (PACG) record for more details.

Normal tension glaucoma (low tension glaucoma)^1,8

• Nature - glaucomatous optic neuropathy with an open iridocorneal angle, in the absence of a raised mean IOP on diurnal testing.
• Risk factors - old age, female gender. May be associated with the Raynaud's phenomenon, migraines, paraproteinaemia.
• Management - as for POAG with the aim to reduce IOP by 30%.⁷ It is also recommended that systemic blood pressure be monitored over 24 hours, as normal tension glaucoma may be associated with nocturnal systemic hypotension and a significant nocturnal drop warrants a review of antihypertensive medication (calcium channel blockers are preferable⁷).
• Outcome - there is often a delay in diagnosis, resulting in more advanced visual field defects. Patients with unilateral defects have a 40% chance of developing defects in the fellow eye over 5 years.

Secondary glaucomas^1,8

• Nature - this is the group of glaucomas arising as a result of a blockage of the aqueous outflow system due to ocular co-morbidity.
  • Pseudoexfoliative glaucoma (PXF) - this arises secondary to pseudoexfoliation syndrome, whereby a dusty grey deposit of extracellular amyloid-like material is deposited on the anterior lens capsule, the zonules, the ciliary body and in the trabecular network, so clogging the latter up. It is more likely to occur in older (≥40 year-old) females.
  • Pigmentary glaucoma - pigment deposits from the posterior surface of the iris block the drainage system as with PXF. It is more likely to occur in young (20-40 year-old), male, Caucasian myopes.⁷
  • Neovascular glaucoma - this is a serious condition which arises as a result of iris neovascularisation (rubeiosis iridis). It occurs following episodes of hypoxia as may occur in ischaemic retinal vein occlusion, advanced diabetic eye disease, central retinal artery occlusion, intraocular tumours, long-standing retinal detachment and where there has been chronic intraocular inflammation.
• Management - this depends on the underlying cause. Glaucoma related to PXF and pigment dispersion syndrome is managed with drugs and possibly laser treatment or surgery. Neovascular glaucoma involves panretinal photocoagulation and possibly retinal surgery.
• Outcome - this is usually good in the first two cases but patients with rubeiotic glaucomas tend to fare badly as they necessarily have advanced ocular co-morbidity to develop rubeiosis iridis.

Primary congenital glaucoma

See separate Congenital Primary Glaucoma record for more detail.

Other types of glaucoma^7,9

• Inflammatory glaucoma - this difficult condition presents with fluctuating IOPs and a ciliary body shutdown. It is the most common cause of blindness in children and young adults with chronic anterior uveitis. Steroid responders (a rise in IOP in response to steroid treatment for the inflammation itself) present with the most tricky management issues. Treatment is broadly drug-based but severe cases may require surgery too.
• Lens-related glaucoma - the lens may either cause a phacolytic glaucoma (a hypermature cataract sheds proteins which clog up the drainage system) or phacomorphic (where the lens swells and bulges forward, compressing the trabecular meshwork). Both involve prompt cataract surgery, although this is associated with a greater risk of complications than routine cataract surgery.
• Traumatic glaucoma - red blood cells can block the trabecular meshwork (this is particularly the case in patients with sickle-cell haemoglobinopathies); angle recession (where blunt trauma ruptures the face of the ciliary body and damage to the trabecular meshwork) can also result in glaucoma in 6-9% of patients over a 10-year period.
• Iridocorneal endothelial (ICE) syndrome - this frequently unilateral condition (typically affecting young- to middle-aged women) is characterised by iris abnormalities which are associated with glaucoma in 50% of cases. Treatment is medical and surgical.
• Glaucoma in phacomatoses - Sturge-Weber syndrome is associated with early presentation of patients with glaucoma (60% within the first 2 years of life) and neurofibromatosis-1 patients may also (uncommonly) present with unilateral, congenital glaucoma.
• Iridocorneal dysgenesis - this can arise in a number of conditions (Axenfeld-Rieger syndrome, Peters' anomaly, aniridia) and is variously associated with glaucoma, the management of which lies within the remit of specialist units.
• Ghost cell glaucoma - degenerate erythrocytes present after a vitreous haemorrhage (± cataract surgery) and hyphaema may block up the trabecular meshwork so giving rise to glaucoma. These patients benefit from medical treatment but may require irrigation of the anterior chamber.
• Glaucoma in cavernous-sinus fistula - secondary glaucoma may come about as a result of raised episcleral venous pressure (resulting from a generalised increase in orbital venous pressure) impairing the aqueous outflow. If there is anterior segment ischaemia, neovascularisation may also complicate the picture. Medical treatment is required until the shunt resolves or is treated.
• Glaucoma in intra-ocular tumours - development of glaucoma depends on the site of the tumour but it occurs in about 5% of affected eyes.
• Glaucoma in ciliochoroidal detachment - in the event of a detachment of the ciliary body or choroid, there is an anterior displacement of the lens-iris complex resulting in shallow iridocorneal angles which may close off. Treatment is medical and surgical.
• Glaucoma in epithelial ingrowth - occasionally, after anterior segment trauma (including surgery), conjunctival and corneal epithelial cells migrate from the external surface of the eye, through the wound and grow across the structures within. This may block off the aqueous outflow. Treatment involves surgery and cryotherapy.
• Glaucoma in iridoschisis - this rare condition describes iris atrophy which is associated with glaucoma in 90% of cases. Laser treatment followed by drug treatment is necessary.

Document references

1. Kanski J. Clinical Ophthalmology, A Systematic Approach, 5th ed. Butterworth Heinemann (2003)
2. Merck Medicus; Glaucoma. Last updated January 2005.
3. Normal Tension Glaucoma, Handbook of Ocular Disease Management
4. Glaucoma, NICE Clinical Guideline (April 2009); Glaucoma: diagnosis and management of chronic open angle glaucoma and ocular hypertension
5. O'Sheae JG, Harvey RB, Infield DA; Diagnosis and management of primary open angle glaucoma: a photo-essay for health professionals. Published 2002.; There are optic disc photos to see what cupping looks like.
6. Bell JA, Charlton JF; Ocular Hypertension. eMedicine, November 2008.
7. Denniston AKO, Murray PI. Oxford Handbook of Ophthalmology (OUP), 2008
8. Kunimoto DY, Kanitkar KD, Makar MS; The Wills Eye Manual (4th ed.) 2004. Lippincott, Williams and Wilkins
9. Jackson TL; Moorfields Manual of Ophthalmology, Mosby (2008)

Internet and further reading

• Glaucoma Focus, International Glaucoma Association

Acknowledgements