Primary open angle glaucoma

It is estimated that approximately 50% of patients with primary open angle glaucoma( POAG ) remain undiagnosed in most Western communities. This review encompasses recent scientific advances in the diagnosis and treatment of POAG these include elucidation of the genetic mechanism behind the disease and the study of haemodynamic co-factors in the development of glaucomatous optic neuropathy. New types of topical medication have recently developed for therapy of glaucoma. The impact of these therapies and their cost effectiveness remains yet to be fully evaluated. There are widely differing regimes which effectively treat glaucoma, some ophthalmologists prefer early surgical intervention whilst others reserve surgery for relatively advanced disease. All methods of current treatment rely on the reduction of intraocular pressure- as yet there is no medication which has been consistently proven as neuro-protective or will favourably influence optic nerve perfusion.

Glaucoma can be considered a generic name for a group of diseases causing optic neuropathy ( disc cupping ) and visual field loss usually , but not always, in the presence of raised IOP, it is increasingly being realised that other factors- such as optic nerve head perfusion, are concomitantly responsible for optic neuropathy in adult glaucoma. (1) The most common type of glaucoma in Western societies is Primary open angle glaucoma (POAG). (2) This review will emphasise the diagnosis, morbidity and treatment of POAG and normal tension glaucoma ( NTG).

Glaucoma is a major cause of blindness and also lesser degrees of visual impairment. Glaucoma and its management has an enormous impact in our society in terms of the number of loss of productivity, number of ophthalmic consultations and health costs. (2,3,4) World-wide, glaucoma is the third leading cause of blindness with 22.5 million affected and an estimated more than five million blind from glaucoma. (2)

Shared care of glaucoma by ophthalmologists and optometrists, has been internationally postulated by many learned bodies as a mechanism of reducing the high cost of glaucoma management and increasing the quality of patient care. (2,3,4)

The prevalence of primary open angle glaucoma (POAG) is estimated as being from 1.1-3 % of Western populations, over the age of 40 years, in both past and more recent population surveys.

These surveys all use differing diagnostic criteria (1) - however, the inescapable conclusion is that POAG is an increasingly common disease in our ageing population. (1,4,5,6,7,8,9 ) The prevalence of POAG is commonly thought of higher in men than in women (although some studies do not support this). (8)

A recent study from the Netherlands found overall prevalence of POAG was 1.10% (95% confidence interval [CI]: 1.09, 1.11). Age-specific prevalence figures increased from 0.2%in the age group of 55 to 59 years to 3.3% in the age group of 85 to 89 years. Men had a more than three times higher risk of having POAG than women (odds ratio, 3.6). In 8.8% of the eyes (2.9% of patients), visual acuity was 6/ 60 or less due to POAG. (7 )

The Blue Mountains Eye Study provided detailed age and sex-specific prevalence rates for open-angle glaucoma and ocular hypertension in an older Australian population found a prevalence of 3.0% for POAG. Ocular hypertension, defined as an intraocular pressure in either eye greater than 21 mmHg, without matching disc and field changes, was present in 3.7% of this population (95% CI, 3.1-4.3), but there was no significant age-related increase in prevalence. ( 8 ) This correlates with the original Framingham Eye Study (1977) which found a prevalence of POAG in an aged population of 3.3%. (5)

Ethnicity affects both the chance of an individual developing glaucoma and the prognosis of his or her disease. The Barbados Eye Study highlighted the public health importance of POAG in the Afro-Caribbean region and has implications for other populations. The prevalence of POAG by self-reported race was 7.0% in black, 3.3% in mixed-race, and 0.8% (1/133) in white or other participants. In black and mixed-race participants, the prevalence reached 12% at age 60 years and older and was higher in men (8.3%) than in women (5.7%), with an age-adjusted male-female ratio of 1.4. Among participants 50 years old or older, one in 11 had POAG, and prevalence increased to one in six at age 70 years or older. (10 )

Glaucoma is still considered to be under- diagnosed. In the United Kingdom it was recently concluded that glaucoma screening of people over age 40 years is economically justifiable, and should now form part of the standard optometric examination. (1,4) Estimates infer that approximately 50% of patients who suffer from glaucoma still remain undiagnosed. (1,2)

Hitchings noted that in the United Kingdom optometric screening is the principal

modality of glaucoma diagnosis and the trend in Europe and the United States is that

optometrists are becoming far more directly involved in the care of their patients. (1)

Ophthalmologists for the interaction between ophthalmologists and optometrists in

glaucoma management is that of ‘shared care’, namely the optometrist refers the

patient to an ophthalmologist for confirmation of the diagnosis and initiation of

The optometrist then takes over the subsequent care of the patent serially evaluating

intraocular pressures and visual fields and monitoring the progression of the disease.

ophthalmologist for another opinion. (3) Studies undertaken in Bristol showed this to

The aqueous humour is produced by non- pigmented epithelium of the ciliary processes of the ciliary body. The aqueous flows through the pupil from the posterior chamber to the anterior chamber and leaves the eye via the trabecular meshwork, Schlemm’s canal and episcleral veins. (12,13) IOP is determined by the rate of aqueous production, the rate of aqueous outflow and the episcleral venous pressure. Many factors affect the IOP, these include age, systemic blood pressure, genetic factors and topical or systemic medications.(13,12)

Factors that affect the level of recorded IOP include the time of day, season, respiration and method of measurement. Recent studies have indicated that IOP can be lowered by regular aerobic exercise. (12)

The measurement of IOP ( tonometry ) can be performed using one of several instruments. Commonly used devices are the Goldmann applanation tonometer (used in conjunction with a slit lamp biomicroscope), the Perkins tonometer (a hand-held applanation tonometer) and the non-contact air-puff. There are inaccuracies inherent with all methods of tonometry that may contribute to the varying IOP measurements seen in individual patients. Most optometrists will already be familiar with the advantages and disadvantages of these methods so that it is not felt necessary to present a detailed overview of the various techniques currently employed. (13)

The mean IOP is 16mm Hg; the arbitrary “normal” range is 10-21 mm Hg. IOP must be evaluated in a clinical context. (1,13) Approximately 6.6% % of the population have an IOP above 21mmHg.

There is no clearly defined level of safe IOP; some individuals may develop optic nerve damage with an IOP of 12mm Hg whilst others may not develop damage with an IOP of 30mm Hg. (13)

Elevation of IOP is regarded as a very important risk factor for the development of glaucoma. However, it is only a risk factor and is present in about 80% of patients with POAG (so-called “high tension” glaucoma in contrast to “normal tension” glaucoma ).(14)

Ocular hypertension can be defined as IOP greater than 21mmHg where the optic disc and visual field are normal. (8) ( The Baltimore Eye Survey, found 6.6% of people had an intraocular pressure greater than 22mmHg in one or both eyes.[15] )

A useful clinical concept is that each eye treated for glaucoma has a target pressure, this is based upon a general assessment of each individual patient’s disease burden. (13,14)

The optic disc and nerve fibre layer are examined for signs of glaucoma damage. The slit lamp biomicroscope offers a far superior view compared with the direct ophthalmoscope because of stereo-visualisation, favourable illumination and high magnification. (13)

The normal optic disc is round or slightly oval. It contains a central physiological cup which is devoid of optic nerve fibres and of a different colour. The ratio of optic cup diameter to optic disc diameter (cup to disc ratio, CDR) is usually 0.3A CDR of greater than 0.5 is seen in 6% of the normal population. (13)

Progressive enlargement of the optic cups documented with periodic follow-up is a most important sign of uncontrolled glaucoma ( table ).

Notching of neuroretinal rim, Pallor, Splinter haemorrhage, Progressive enlargement , vertical elongation, Asymmetry (between the left & right eyes), Nasal displacement of central retinal vessels, baring of lamina cribrosa. (21)

Atrophy of the Retinal Nerve Fibre Layer may be detectable using the green ( red-free) light of the slit lamp biomicroscope. (13)

A so-called splinter haemorrhage located at the optic disc margin is characteristic of glaucoma. It is more commonly seen in normal tension glaucoma. (21)

Other conditions that may mimic glaucomatous optic neuropathy include a large physiological cup and congenital optic disc abnormalities such as coloboma. (13)

Recent scientific work has been devoted to determining the role of optic disc perfusion in glaucoma. Most authorities now agree that there are abnormalities of the ocular circulation which contribute to the pathogenesis of the disease although the precise significance of these abnormalities is not understood and there are some inconsistencies of results between major research centres. There are as yet no drugs available which have been consistently shown to aid optic nerve perfusion. (16-20)

Visual field examination is important in glaucoma management in order to detect and quantify any deficits of the patient’s peripheral vision and to quantify any progressive changes seen with repeated follow-up. (1,21) Several perimeter machines are available, the Humphrey 24-2 Fastpac being currently the most popular method of field analysis. (22,23) Others include the Octopus, the Henson and the Dicon. The machines basically test the patient’s ability to detect a target stimulus against a darker background. Testing conditions that can be varied include the number, duration and light intensity of the target stimulus. (21-23)

Factors that can affect the result include patient fatigue or lack of concentration, the spectacle frame, miosis ( from pilocarpine drops) and opacities of the ocular media (such as cataract). (21-23)

Static perimetry is the basis of computerised supra-threshold perimetry, a stationary target is presented and its intensity varied to determine retinal sensitivity. (21-23)

Blue target against a yellow background help to identify damage to the larger ganglion cells (magnocellular loss).

In kinetic ( isopter ) perimetry a moving target of differing sizes is presented. (21-23) This article discuss the many techniques and types of perimetery and their relative advantages and disadvantages but rather presents a photographic atlas of common glaucoma defects.

Hitchings notes that motion detection perimetry, performed on a laptop computer may be of help to optometrists undertaking glaucoma screening. (1) Blue on yellow perimetry has recently been shown to detect nerve fibre defect s significantly earlier then conventional suprathreshold perimetry.

Examination of the anterior chamber angle with a gonioscopic contact lens (gonioscopy) is also very important in determining the aetiology of glaucoma, for example- chronic angle closure glaucoma versus POAG. (13)

to avoid the problem of total internal reflection which normally makes all angle

structures invisible. ( The large difference in refractive index between the cornea and air has to be minimised. )

to be filled with about 3 drops of normal saline or hypromellose before application

It is best to ask the patient to look down whilst the lens is applied to prevent spillage.

Each quadrant of angle can be examined by rotating the lens. Typically the upper quadrant is narrowest.

Illustration courtesy of Dr. Robert Harvey FRCSE, from Practical Ophthalmology CD ROM, 2002 Palmtrees Publishing. (13)

The most common type of glaucoma in Western societies is primary open angle glaucoma. The resistance of the trabecular meshwork increases, typically as an ageing or involutional change leading to increased IOP. It is now recognised that intrinsic factors within the optic nerve are also important in the development of POAG as are genetic factors. Older definitions of the disease have often put undue stress in the role of raised intraocular pressure ( IOP ) in the pathogenesis of open angle glaucoma. Recent scientific studies have revealed the situation to be more complex and that other factors, both vascular and biochemical, are likely involved in the pathogenesis of glaucomatous optic neuropathy.

In glaucomatous optic neuropathy there is optic disc cupping and atrophy and apoptosis of retinal ganglion cells and their axons, and possibly other retinal elements, leading to irreversible visual field loss. The intraocular pressure (IOP) is usually elevated. Glaucoma can thus be considered a generic name for a group of diseases causing optic neuropathy ( disc cupping ) and visual field loss usually, but not always, in the presence of raised IOP, other factors- such as optic nerve head perfusion, are concomitantly responsible for optic neuropathy in adult glaucoma. Some authors postulate a disturbance of the mechanism of autoregulation of blood flow to the optic nerve whilst head other authors describe glaucomatous optic neuropathy as an intrinsic optic neuropathy due to localised vascular disease and to other biochemical mechanisms which have yet to be fully elucidated.(1,16-20)

Increased IOP may cause glaucomatous damage by a mechanical and/or ischaemic effect upon the optic nerve. There may be direct mechanical compression of optic nerve fibres from the increased IOP. Increased IOP may also interrupt the blood supply of the optic nerve fibres. (16-20)

Glaucomatous optic neuropathy usually has an insidious onset. It is often bilateral; it may be highly asymmetrical. It is more prevalent and more severe in black individuals. It is about 5 times more prevalent in individuals whose close relatives have POAG. Corticosteroid eye drops may cause glaucomatous damage by producing an elevation of IOP as a side effect. This side effect of IOP elevation, known as steroid response, is more common in patients with POAG. (13)

Elevated IOP is a major risk factor for the development of glaucoma. However, 20% of patients do not have an elevated IOP. This is referred to as normal tension glaucoma. It is commoner in females. In normal tension glaucoma optic nerve damage and visual field loss occur despite a “normal” IOP. (24) A CT scan should performed before a diagnosis of NTG is made to exclude possible optic nerve compression by a tumour. (13)

20% of newly diagnosed glaucoma patients have IOPs less than 21 mm Hg at presentation.

NON PROGRESSIVE-Due to transient vascular shock (single event of systemic hypotension)

Resolved secondary glaucoma (non-progressive) steroid related, pigmentary, intermittent ACG

History of CVS disease, diabetes, hypertension / hypotension, steroid use, vasospastic disease (Raynaud’s, migraine)

CVS- BP, carotids, ECG, FBC (anaemia), ESR (GCA), cholesterol and triglyceride, BSL

3. Reduce IOP maximally, aim for 10 mmHg (medical and laser treatment have only a limited role)Often come to surgery:- trabeculectomy + 5FU, Or Scheie thermosclerostomy, rarely a seton.Treat one eye as a therapeutic trial as there is no definite evidence that reducing IOP prevents progression.

Other factors which may contribute to the development of glaucoma include diabetes,

cardiovascular disease, myopia and a positive family history of glaucoma. There may be at least two primary open-angle glaucoma genes, the GLC1A gene on chromosome 1q and other genes located elsewhere in the genome. The TIGR gene is responsible for the phenomenon of steroid response. ( 6, 25-28 ) In all, about seventeen candidate genes have been identified as possible associates in POAG. The ongoing elucidation of the genetic mechanism responsible for POAG and the possibilities of detecting glaucoma early in phenotypes predisposed to POAG and tailoring therapy based upon genetic information is one of the most exciting areas of ongoing research.

from other conditions such as corticosteroid administration, pigmentary glaucoma or phacolytic glaucoma, or neovascularication of the iris ( rubeotic glaucoma ) (13).

Paediatric glaucoma can be congenital or develop during infancy or later childhood.

It is most commonly primary (i.e. isolated). Secondary glaucoma can be associated with ocular conditions (such as aniridia, trauma or ocular tumour) or with systemic conditions (such as rubella). A neonate or young child with glaucoma may present with epiphora, photophobia, blepharospasm, enlargement of the cornea or of the globe. Bupthalmos, enlargement of the globe, is not uncommon.

IOP can be measured in infants and young children using a Perkins tonometer or Tono-Pen. In older children a Goldmann applanation tonometer can be used. Many types of paediatric glaucoma are genetically determined. (25,26,27,28 )

Conditions that can mimic glaucoma include carotid artery stenosis and optic nerve compressive lesions. The need for ophthalmic evaluation should be considered particularly for patients with atypical features (such as unilateral optic

It can be difficult to distinguish clinically between the patient with early glaucoma and the patient with no glaucoma, experience is clearly needed in deciding when to treat. Issues in the management of glaucoma include both the indications for treatment and the type of treatment. (13)

This difficulty leads to the dilemma of determining which patients should be treated . Patients that do not have glaucoma may be subjected to the inconvenience, expense and possible toxicity of treatment. The unfortunate corollary is that treatment may be withheld from patients who have early glaucoma or who may develop glaucoma. (13)

The ultimate goal in glaucoma management is the preservation of vision. Factors to be considered include the initial IOP, the patient’s life expectancy and the degree of optic nerve damage. (13)

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A target IOP should be determined. This represents the IOP aimed for following therapy. For example, a patient with advanced glaucomatous optic neuropathy may require a target IOP of 12 mmHg. A patient with an initial IOP of 45 mmHg may possibly preserve vision with a target IOP of 25 mmHg.

A patient with a long life expectancy may require more frequent follow-up and more aggressive therapy. More aggressive therapy may be similarly required for patients with extensive optic nerve damage.

Table- Compliance is a very important issue in glaucoma management. Patients may be have no symptoms from glaucoma. Medication may cause various side effects. It may be difficult to comply with treatment regimes, for example, forgetting to administer midday doses of eye drops or falling asleep before taking the evening dose. (3)

Eye drops (and gel preparations) are the most common form of therapy to treat glaucoma. They are often prescribed to prevent glaucoma in patients who are regarded as being glaucoma suspects.

The choice of medication depends on how well the eye drop reduces the IOP and how well the medication is tolerated. Many possible ocular and systemic side effects can occur. Compliance is a very common and often overlooked source of failure of medical therapy. (1,13)

Side effects include asthma, bradycardia, reduction in exercise tolerance, altered mentation, impotence, drowsiness and fatigue. A topical beta blocker is usually the first line therapy in patients over the age of 40 years unless there are systemic contraindications such as asthma or bradycardia. (13,13 29-31)

thereby improving compliance and safety. In view of the diurnal variation in IOP with the peak occurring in the morning, instillation of the eye drop after awakening is advisable. . (13 29-31)

This was designed for once-daily administration. It appears to be very similar in efficacy to twice-daily administration of Timoptol 0.5% drops. (13 29-31)

Carteolol 1%- A non-selective beta blocker with intrinsic sympathetomimetic activity.

This is a selective beta blocker. It can cause side effects seen with other beta blockers although less frequently and less severely.

Betaxalol is a popular cost effective choice as a first line drug in POAG. (13 29-31)

This agent is an alpha 2-agonist. It appears to be as effective as timolol in controlling glaucoma but does not cause a significant reduction in heart rate.

Side effects include dry mouth ( 10% of patients ), allergy (seen in 10% of patients in 1 year trial), drowsiness, depression and fatigue. (32)

f more than one type of eye drop is being prescribed the patient should be instructed to wait 5 minutes between the instillation of eye drops in order to maximise ocular absorption. The eyelids should be gently closed after instillation. Patients may also find administration easier in front of a mirror. (3)

Dorzolamide requires three times a day instillation whether prescribed alone or twice daily in combination. (29)

Latanaprost is a prostaglandin analogue. Its action is increases aqueous drainage vie the uveoscleral route. It is effective with once daily instillation; it is about as effective as Timolol. (24)

Muscarinic agonists derived from the pilocarpus plant have been in use in ophthalmology for over a century and are still efficacious in the treatment of acute and chronic glaucoma. (11,13, 31)

Side effects are common and include brow ache, blurred vision (from spasm of accommodation) and decreased night vision (from miosis).

This is a pro-drug, converted to adrenaline inside the eye. Ocular side effects are common, including redness and stinging. If a patient is already using a topical beta blocker then adding propine usually does not significantly lower the IOP further. (13)

Long term therapy with topical medication can cause histological damage to the conjunctiva. This secondary change may be responsible for failure of trabeculectomy surgery performed at a future stage. (33,34)

It is well justified that medical practitioners and optometrists routinely perform pupil dilation (mydriasis) provided patients are instructed on the risks and benefits of the procedure.

Encourage patients to seek urgent ophthalmic care if they develop a red painful eye. It may be worthwhile medico-legally giving written advice detailing symptoms of angle closure and giving a contact number or alternately, detailing the address of the nearest ophthalmic casualty.

The risks of provoking angle closure glaucoma are, in fact, very small (15) Of 4,870 subjects whose eyes were dilated on screening examination ( many of whom had previously diagnosed open angle glaucoma) none developed acute angle-closure glaucoma.(15) It has been recommended that the depth of the anterior chamber depth be estimated on the slit lamp prior to mydriasis. ( 15 )

Guttae tropicamide 0.5 %, which lasts 4-6 hours, is the preferred mydriatic for routine examinations.

Be careful in elderly patients, especially with cataracts.(15) Females are more prone to PACG. Patients should be instructed not to drive home. (15)

This treatment involves the application of laser energy (usually argon green) to the trabecular meshwork, thereby improving the rate of outflow of aqueous humour. Laser therapy and surgical therapy for glaucoma have an advantage over

medical therapy by sometimes obviating the problem of compliance. Several weeks may be required before the effects of argon laser trabeculoplasty (ALT) become evident. Complications include transient IOP elevation in the first few hours postoperatively and also permanent IOP elevation. The IOP is usually reduced by 25%. 80% of patients show an initial beneficial effect. In at least 50% of these patients the effect is lost in the first 5 years. (13,35)

In black patients the benefit is lost earlier (35) another study yielded a success rate for ALT of 46% for 3-year follow-up.. ALT is less successful following cataract surgery. Re-treatment in general is associated with a low success rate.(35) ALT is not useful in certain types of glaucoma, for example paediatric glaucoma.

Topical medication is the conventionally initial type of therapy for POAG. There is increasing evidence, particularly from studies undertaken at Moorfields Eye Hospital (Moorfields Primary Treatment Trial ) that initial or early therapy in the form of surgery may have significant advantages over initial medical therapy even when the patient presents with early glaucoma. (1,33,34)

The most common surgical procedure for glaucoma is trabeculectomy. In trabeculectomy an ostium is made in the inner sclera, a fistula covered by a flap fashioned in the outer sclera, thereby providing an alternative drainage site for aqueous humour. (13,33,34,36,37)

Trabeculectomy lowers the intraocular pressure more consistently than anti-glaucoma eye drops or laser trabeculoplasty. Some authorities consider performing trabeculectomy as primary therapy . (13,33,34,36, 37)

However, glaucoma surgery may also be associated with complications. The trabeculectomy fails usually because of scarring around the scleral flap or due to closure of the internal ostium. (33 )

Cataracts may progress rapidly after trabeculectomy. Age 61 years or older, exfoliative glaucoma, postoperative hypotony, and IOP peaks were identified as risk factors for accelerated cataract progression after trabeculectomy. (36)

Topical antimetabolites, such as 5-fluorouracil and mitomycin, can be used intraoperatively or immediately postoperatively in order to increase the success rate of the trabeculectomy procedure. Antimetabolite use, however, may increase the risk of complications such as ocular hypotony, wound leakage and infection. (37,38)

Microtrabeculectomy, usually performed under local anaesthesia, is a less invasive variant of the trabeculectomy procedure which is gaining popularity. Reverse trabeculectomy, deep sclerectomy and viscocanalostomy are also other novel procedures which are currently being evaluated in the treatment of POAG. (38,39,40,41)

Increased community awareness of glaucoma, and earlier detection of the condition, will doubtless result in decreased morbidity due to glaucoma. (1,4,8) Shared care has been postulated as a model for interaction between optometrists and ophthalmologists by the Royal College of Ophthalmologists and will result in a more comprehensive, efficient and cost effective service for patients. (3,13)

Recent scientific advances include elucidation of the genetic mechanism behind the disease (6,27-29) and the study of haemodynamic and biochemical co-factors in the development of glaucomatous optic neuropathy, particularly in relation to the pathogenesis of normal tension glaucoma. (16-20,42) Several new types of topical medication have recently developed for therapy of glaucoma (24,29-32) and both the impact of these therapies and their cost effectiveness remains to be evaluated. (41)

All methods of current glaucoma treatment rely on the reduction of intraocular pressure- as yet there is no medication which has been proven as neuro-protective or will favourably influence optic nerve perfusion.

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Authors :

David A. Infeld FRCSE

John G. O'Shea MD

Illustrations: Robert Harvey FRCSEd (from Practical Ophthalmology, 2002 Palmtrees Publishing)

Webmaster: David Kinschuck FRCS

Rob Harvey FRCSE

E-mail Address : rob_harvey@msn.com

Correspondence-

Birmingham and Midland Eye Centre, Dudley Rd, Birmingham B18 7QH, U.K.