Glaucoma is a term used to describe a group of progressive diseases of the optic nerve head. It is the second leading cause of blindness worldwide.1 Including congenital and juvenile glaucomas, 60 million people are estimated to have glaucomatous vision loss,2 a figure which is set to rise to 111.8 million by 2040.3
Similarly, in the UK, glaucoma is the second leading cause of vision loss after age-related macular degeneration4 and is responsible for approximately 10 per cent of blind and partial sight registrations. Nationally, the prevalence of glaucoma is estimated to be 2 per cent,5 varying in the white population from 0.4 per cent for those aged 40-49, to 3.3 per cent in those aged 70-79.6 Over 300,000 people have been diagnosed with glaucoma in Britain, though it is thought that approximately 50 per cent of those living with the disease are yet to be diagnosed.7,8
For the NHS, the cost of drug therapy alone for glaucoma and ocular hypertension reached over £100m in 2012 – a cost which more than doubled in a decade.9 Beyond the financial burden of glaucoma is the impact of disability and suffering to patients themselves. Glaucoma can cause a loss of wellbeing, independence and mobility.10 When compared to a control group with similar systemic conditions, Haymes et al11 estimated that those with glaucoma are three times more likely to have fallen within the prior 12 months. The likelihood of depression also increases as the severity of glaucoma increases.12
On average, more than one million ganglion cell axons make up a healthy optic nerve. Ageing causes physiological dropout of approximately 6,000 ganglion cells each year, a feature which is accelerated in glaucoma. Although the exact pathogenesis of glaucoma is not entirely understood, it is generally agreed that injury to the retinal ganglion cells (RGCs) results in their subsequent death by apoptosis (programmed cell death).13,14 Glaucomatous damage is initially characterised by retinal nerve fibre loss. Damage to the optic nerve head may include optic disc cupping/excavation resulting from loss of neural tissue, disc notching, disc haemorrhage, nerve head pallor and vessel calibre changes (Figure 1). Once enough cells are lost, those with glaucoma manifest a clinically measurable loss of their peripheral vision.15
[CaptionComponent="2887"]
[CaptionComponent="2888"]
How is glaucoma classified?
Glaucoma is classified into two major categories according to the appearance and/or obstruction of the drainage pathway at the iridocorneal angle trabecular meshwork (Figure 2). In open-angle glaucoma, despite the normal clinical appearance, aqueous outflow is restricted. Contrastingly, in closed-angle glaucoma, tissue physically obstructs the angle.
[CaptionComponent="2889"]
[CaptionComponent="2890"]
Glaucoma can also be classified according to whether it is primary idiopathic; the most common type or secondary associated with detectable comorbidity. Such comorbidities include pseudoexfoliation, rubeosis associated with ocular ischaemia due to vascular occlusion or diabetes, uveitis or complications of ocular surgery, such as retinal detachment surgery. Globally, primary glaucoma is more common than secondary, with secondary glaucoma estimated to account for just 20 per cent of all cases.16 Of the entire primary glaucoma population, two-thirds are thought to have open-angle glaucoma,17 on which this article will primarily be focused.
Primary Glaucoma
Primary open-angle glaucoma (POAG)
POAG typically develops slowly, with glaucomatous optic nerve head damage and gradual loss of visual field. It is most commonly associated with elevated IOP over 21mmHg caused by increased resistance to aqueous outflow in the trabecular meshwork. Major glaucoma treatment studies have also identified advancing age (most cases are detected after the age of 65 years),18,19,20 male gender,18,19 and thinner central corneal thickness 18 as risk factors. As such, current NICE guidance takes into consideration a patient’s age, central corneal thickness and untreated IOP in its treatment recommendation. In addition, POAG is more common, and indeed more severe, in certain ethnic groups such as Afro-Caribbeans. Moderate to high myopia is another risk factor for the development of POAG due to possible increased susceptibility of the optic nerve head to damage caused by increased IOP. Finally, individuals with a history of open-angle glaucoma in a first-degree relative are thought to be four times more likely to develop the disease themselves than somebody who does not.21 In POAG, the only modifiable risk factor is IOP.
Glaucoma can exist in those with an IOP falling within the statistically normal range (mean IOP equal to, or less than 21mmHg), when it is commonly referred to as normal tension glaucoma (NTG), or low tension glaucoma.22 People with vascular dysregulation characterised by excessive arteriolar constriction vasospasm or inappropriate vessel dilation are more likely to develop NTG. When vascular dysregulation involves multiple organ systems, it may be termed vasospastic syndrome, of which Raynaud’s syndrome is an example. Migraine is often associated with vasospastic syndrome and has been linked with an increased risk of NTG.23,24. Individuals who exhibit a nocturnal dip in blood pressure are also at risk of developing NTG.
Pathophysiology of glaucoma
The biological basis for glaucoma is still not fully clear. Three non-mutually exclusive theories of glaucomatous optic nerve injury have been proposed, being the mechanical, biochemical and vascular theories. Current evidence does not strongly favour one theory over another; in fact, it is likely that in many instances, the loss of RGCs leading to glaucoma is multifactorial. Both focal and diffuse damage in the optic nerve head can generate the characteristic patterns of RGC death. The shape and structure of any given optic nerve may increase its vulnerability to damage, where stress/strain and mechanical factors at the level of the lamina cribrosa will influence the initiation of RGC death. Vascular factors such as systemic hypotension or vasospasm may exacerbate RGC death. Other elements within the retina may influence the pattern of RGC death, for example the presence of immune cells in the optic nerve head and retina microglia, and the possible involvement of the immune system in glaucoma.
Mechanical theory
The mechanical theory focuses on the role of IOP. Increased IOP is common and thought to be caused by increased resistance to aqueous outflow at the trabecular meshwork. Its elevation causes an increase in mechanical stress and strain, thus an elongation and stretching of the lamina cribrosa connective tissue. Ganglion cell axons are damaged directly as a result of increased IOP or indirectly, by distortion of the lamina cribrosa through which they pass.25 The degree to which the lamina cribrosa can be distorted varies with age; in younger eyes it has greater elasticity, whereas with ageing, the elasticity of the tissue is reduced, with less of a tendency for deformation to resolve with resolution of the imposed pressure.26 It is perhaps more likely that glaucoma patients who present with significantly elevated IOP have a greater contribution from the mechanical theory.
Biochemical theory
The biochemical theory suggests that glaucoma arises due to an autoimmune response in the patient. The role of optic nerve glia is central to the biochemical theory, whereby it is thought that mechanical stress produces a glial reactivity leading to the release of neurotoxic factors such as nitric oxide and tumour necrosis factor a.27 These and other neurotoxic factors can trigger pro-apoptotic factors, leading to ganglion cell death.28 In post-mortem examination of glaucomatous eyes, auto-immune biomarkers have been found in ocular structures such as the vitreous adjacent to the optic nerve head.
Vascular theory
Perfusion pressure (the driving force of blood flow) and autoregulation (the capacity to maintain a constant level of blood flow in the face of changes in perfusion pressure) are central to the vascular theory of glaucoma. The vascular theory is based upon insufficient ocular blood flow, which may be due to unstable ocular perfusion as a result of disturbed autoregulation or IOP fluctuation or vascular tone, leading to a mild ischaemia-reperfusion injury.29
In the case of the eye, low ocular perfusion pressure is dependent upon arterial pressure and IOP. Ocular blood flow may be reduced due to elevated IOP, whereby compression of the capillaries supplying the optic nerve head causes localised ischaemic axonal damage.30,31 In support of this, previous research points to a reduction of ocular blood flow in glaucoma.32,33,34,35,36 Low blood pressure or raised IOP are able to reduce blood flow. This correlates with clinical observations that low systemic blood pressure, and patients with conditions such as Raynaud’s syndrome, appear to be at increased risk of developing glaucoma. There is evidence that patients with low-tension glaucoma may demonstrate abnormalities in the peripheral circulation in response to changes in temperature.37
Primary angle closure glaucoma (PACG)
The glaucomatous optic neuropathy that occurs in PACG occurs due to elevated IOP caused by obstruction of aqueous outflow, or degenerative changes in the trabecular meshwork due to iridotrabecular contact (Figure 3).
[CaptionComponent="2891"]
It is this which is the primary event, occurring as the result of anatomical disproportion of the anterior segment. On the other hand, secondary angle closure, which is less common, most often occurs as a consequence of a pre-existing ocular or systemic condition such as uveitis, central retinal vein occlusion, diabetes, anterior uveitis, or trauma. Pupil block is the predominant component responsible for angle closure. Plateau iris and peripheral iris crowding have a role in non-pupil block mechanisms. Lens induced and ciliolenticular block are less common mechanisms.
PACG is seen in anatomically pre-disposed eyes which include a shallow anterior chamber and narrow entrance to the angle. The latter may result from a short axial length, a small corneal diameter, or the crystalline lens which may be thicker or more anteriorly positioned or vaulted. Patients presenting with PACG are typically hypermetropic females aged 60 years and above. This glaucoma is relatively more common in South East Asians, and is rarely identified in those of Afro-Caribbean descent. Patients with PACG are more likely to present in optometric practice with the subacute phase, whereby pupillary block and subsequent IOP elevation occurs intermittently. Such patients may complain of blurred vision and haloes around lights due to corneal oedema or frontal headaches, particularly in the evening when mesopic conditions cause pupillary dilation. In the acute phase of the disease, which is most commonly unilateral, patients typically present with unilateral loss of vision in a red and painful eye. Signs include a particularly elevated IOP >50mmHg, ciliary flush around the limbus, corneal oedema, aqueous cells and flare (though this may not be visible due to corneal oedema), dilated iris vessels and a fixed, mid-dilated pupil.
There are several different approaches to the classification of angle closure, including the use of mechanisms, symptoms or an approach based on the natural history of angle closure (Table 1).
Secondary glaucoma
There are a multitude of causes of secondary glaucomas, both open-angle and closed-angle, which occur secondary to another ocular or systemic disease. Secondary glaucomas share the feature that the IOP is elevated due to impaired outflow of aqueous. Detailed descriptions of all types of secondary glaucomas lie beyond the remit of this article.
Secondary open-angle glaucoma
A relatively common cause of secondary open-angle glaucoma is pseudoexfoliation syndrome (PXF) (Figure 4), whereby grey-white material produced by ageing epithelial cells is deposited on structures throughout the eye.
[CaptionComponent="2892"]
In addition to deposition on anterior chamber structures such as the anterior lens capsule, ciliary body and conjunctiva, there is a tendency for pseudoexfoliative material to collect in the trabecular meshwork, thus leading to obstruction. Common clinical features include pseudoexfoliative material on the endothelium, iris pupillary margin and anterior lens surface, and iris sphincter atrophy causing trans-illumination defects. Females are more likely to present with PXF, though males appear to be at higher risk of developing glaucoma. Risk factors for pseudoexfoliative glaucoma include age, IOP elevation and ethnicity. PXF is a common cause of glaucoma in Scandinavian countries.
Pigment dispersion syndrome (PDS) is another common cause of secondary open-angle glaucoma. In this condition, pigment from the iris pigment epithelium is deposited throughout the anterior segment – usually bilaterally – due to mechanical rubbing between the posterior iris and lens zonules. Classically, a Krukenberg spindle of pigment cells forming a vertical linear pattern on the corneal endothelium is visualised (Figure 5a), and iris transillumination (Figure 5b) is often noted.
[CaptionComponent="2893"]
Males are more likely to develop PDS, as are myopes and people of Caucasian descent. Approximately one third of people with PDS are thought to go on to develop ocular hypertension or pigmentary glaucoma due to obstruction of the trabelcuar meshwork by pigment cells. Glaucoma usually presents much earlier than pseudoexfoliative glaucoma, generally in the third of fourth decade of life.
Other secondary glaucomas
Some of the other causes of secondary glaucoma are listed in Table 2, with a brief description of the more commonly encountered provided herein.
Neovascular glaucoma
The principal underlying aetiology of neovascular glaucoma is that of retinal ischaemia and hypoxia, which results in a pro-angiogenic cascade, and the production of vascular endothelial growth factor VEGF. The pathophysiology of this glaucoma involves the formation of new blood vessels on the surface of the iris and angle, with the growth of a fibrovascular membrane over the trabecular meshwork. This initially impedes aqueous outflow, but later contracts to cause a secondary angle-closure form of glaucoma.
Neovascular glaucoma is more prevalent in patients with significant cardiovascular risk factors such as hypertension, diabetes, dyslipidaemia and a history of smoking. The most common conditions associated with neovascular glaucoma are retinal vein and arterial occlusions (central, branch), proliferative diabetic retinopathy and other conditions such as ocular ischaemic syndrome, and carotid artery obstruction. Ocular inflammatory diseases and tumours are other predisposing factors.
Uveitis
The term uveitic glaucoma encompasses a diverse range of clinical entities with IOP elevation resulting from obstruction of aqueous outflow. Obstruction may be caused macroscopically due to iris seclusion pupillae, secondary pupil block or synechial angle closure; or microscopically as seen in secondary open-angle glaucoma or steroid induced IOP elevation.
Glaucoma in uveitis is distinguished by its often episodic nature with high IOPs that if left untreated, may result in more rapid glaucomatous progression than is seen in POAG. Most patients are younger than the typical glaucoma patient and are of working age. Late presentation of glaucoma secondary to uveitis is relatively uncommon as uveitis is usually sufficiently symptomatic to result in presentation to an eye care practitioner.
Management of uveitic glaucoma requires careful evaluation and management of both uveitis and glaucoma. Those with uveitis develop high eye pressure through inflammation itself or the treatments for inflammation (steroids). To make things more complex, inflammation sometimes also lowers IOP, so eye pressure can flip from high to low in an unpredictable way. Many inflammatory diseases can lead to uveitic glaucoma, including juvenile rheumatoid arthritis, sarcoidosis and other similar disorders. Medical and surgical glaucoma treatments are used, but are often more difficult to implement.
Lens induced
The crystalline lens can be involved in both open-angle, and angle-closure glaucoma, of which the latter has previously been mentioned.
There are three main forms of lens induced open-angle glaucomas:
- Phacolytic – leakage of lens proteins through an intact lens capsule in an eye with a mature or hypermature cataract
- Phacoanaphylactic – immune complex formation following sensitisation to lens proteins after lens trauma or surgical lens disruption resulting in a granulomatous uveitis
- Lens particle glaucoma – trabecular obstruction from retained lens material and inflammatory cells as a result of lens trauma or surgical disruption of the lens.
The mechanisms for IOP elevation differs in each but all ultimately result in obstruction of the trabecular meshwork with impairment of aqueous outflow facility.
Iridocorneal endothelial syndrome
A group of disorders characterised by abnormal physiology of the corneal endothelium, leading to varying degrees of progressive iris atrophy, corneal oedema and/or synechial angle closure. Variations of the disorder include progressive iris atrophy, Chandler’s syndrome and Cogan Reese syndrome.
The common feature in the variants of this syndrome is a hammered, silver/gray appearance to the corneal endothelial layer. The abnormal endothelial cells proliferate and migrate over the anterior chamber angle and onto the iris surface leading to peripheral anterior synechiae formation.
Corticosteroid induced
Approximately one third of patients treated with topical steroids exhibit an increase in IOP of 6-15mmHg. Reported predisposing risk factors include POAG and age (children in particular).38 The mechanism of corticosteroid induced increased resistance to aqueous outflow is not clearly understood but several studies have implicated glucorticoide induced changes in the trabecular meshwork and suggest a genetic predisposition.39
Patients receiving corticosteroid therapy should be closely monitored. It may be prudent to avoid depot forms of steroid administration such as sub-Tenon’s or intravitreal depots or injections. If clinically significant corticosteroid induced IOP elevation occurs, alternative anti-inflammatory agents, immunosuppressive agents, or IOP lowering medications may be necessary, and perhaps even glaucoma surgery.
Elevated episcleral venous pressure
Elevated episcleral venous pressure is an important cause of elevated IOP and secondary glaucoma. It should be considered in the differential diagnosis of ocular injection with elevated IOP.
The Goldmann equation explains the effect of elevated episcleral venous pressure on IOP:
P = F/C + Pe
IOP (P) depends upon the rate of aqueous formation (F), which is normally 2-3µL/min; the outflow facility (C), which is nomally 0.2-0.3µL/min/mmHg, and the episcleral venous pressure (Pe), which is normally 8-10mmHg. In the acute situation, outflow facility is not affected by increased episcleral venous pressure, and a normalisation of episcleral venous pressure should result in normalisation of IOP. However, with chronically increased episcleral venous pressure, outflow facility may be adversely affected and may not return to normal with normalisation of episcleral venous pressure.
Although the clinical picture depends upon the cause, consistent features of elevated episcleral venous pressure are dilated, tortuous episcleral vessels and elevation of IOP. Additional signs may include chemosis, proptosis, or orbital bruit. Increased ocular pulse amplitude may be observed during tonometry and gonioscopy may reveal blood in Schlemm’s canal.
Causes of increased episcleral venous pressure include:
- Venous obstruction – thyroid ophthalmopathy, superior vena cava syndrome, retrobulbar tumours, cavernous sinus thrombosis
- Arteriovenous abnormalities – carotid-cavernous sinus fistula, orbital varix, Sturge Weber syndrome.
Traumatic glaucoma
Ocular injury is not uncommon, and trauma related glaucoma may present acutely or may develop later in an individual’s lifetime. It is important to take a history of penetrating or non-penetrating injury with thorough evaluation of the anterior segment as well as careful follow-up, which is necessary to detect the predilection for glaucoma.
Childhood glaucoma
Both primary and secondary forms of glaucoma can occur congenitally and in childhood, and may or may not be associated with systemic features or syndromes. There are numerous causes for childhood glaucoma which is beyond the scope of this article. Examples include anterior segment dysgenesis such as Axenfeld-Rieger syndrome, aniridia, phakomatoses and Peter’s anomaly. Understandably, the evaluation and management of congenital and paediatric glaucoma differs from the evaluation and management of adult forms of glaucoma; it is normally conducted in conjunction with a paediatric ophthalmologist and glaucoma specialist in larger ophthalmology units. Lifelong follow-up for children with glaucoma is essential.
Causes of secondary glaucoma
- Neovascular
- Uveitis Fuch’s heterochromic cyclitis, Posner
Schlossman
- Lens induced phacolytic, phacoanaphylactic, lens
particle induced
- Trauma related
- Iatrogenic Corticosteroid induced, ocular surgery or
laser
- Intraocular tumours
- Elevated episcleral venous pressure
- Iridocorneal endothelial syndrome
- Chandler’s and Cogan Reese
Summary
Glaucoma is a group of progressive disorders of the optic nerve head, in which damage to the RGCs causes retinal nerve fibre dropout and clinically measurable changes to the optic nerve head and visual field. Three non-mutually exclusive theories exist to explain the pathogenesis of glaucoma; the mechanical, biochemical and vascular theories. Glaucoma may be classified as open-angle or closed-angle, of which there are multiple primary and secondary causes for both. The risk factors and likely progression of the disease differ for each form of glaucoma; in POAG, the most common type, risk factors include raised IOP >21mmHg, age over 40 years, male gender, family history, race Afro-Caribbean ethnicity, and corneal thickness. Glaucoma in all its forms is the second most common form of visual loss both in the UK and globally and is reported to cause an increasing considerable financial burden to the economy and loss of wellbeing to the patient.
Model answers
Correct answers are in bold italic
1 Which of the following is not a known risk factor for primary open angle glaucoma?
A Age
B Female gender
C Myopia
D Ethnicity
2 Which of the following may result from pigment dispersion syndrome?
A Primary open angle glaucoma
B Secondary open angle glaucoma
C Primary closed angle glaucoma
D Secondary closed angle glaucoma
3 Which of the following has not been associated with normal tension glaucoma?
A Sleep apnoea
B Migraine
C Raynaud's syndrome
D Pseudoexfoliation
4 Which of the following is most likely to result in the greatest ocular blood perfusion pressure?
A High IOP, high systemic blood pressure
B Low IOP, low systemic blood pressure
C High IOP, low systemic blood pressure
D Low IOP, high systemic blood pressure
5 Which of the following is least likely to be associated with neovascular glaucoma?
A Retinal vein occlusion
B Retinal artery occlusion
C Chorioretinitis
D Diabetes
6 Which of the following statements regarding topical steroid use is true?
A Half of patients using topicaal steroids show an elevation in IOP
B Existing glaucoma increases the risk of IOP elevation
C Steroid induced IOP is more likely with increasing age
D IOP elevation is the only potential adverse response
References
1 Quigley H. Number of people with glaucoma worldwide. Br J Ophthalmol, 1996; 80, 389-93.
2 Quigley H, Glaucoma. Lancet, 2011; 377, 1367-77.
3 Tham et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology, 2014 121, 2081-90.
4 Bunce et al. Causes of blind and partial sight certifications in England and Wales: April 2007-March 2008. Eye Lond, 2010; 24, 1692-9.
5 Burr et al. The clinical effectiveness and cost-effectiveness of screening for open-angle glaucoma: a systematic review and economic evaluation. Health Technol Assess, 2007; 11, iii-iv, ix-x, 1-190.
6 Rudnicka et al. Variations in primary open-angle glaucoma prevalence by age, gender, and race: a Bayesian meta-analysis. Invest Ophthalmol Vis Sci, 2006; 47, 4254-61.
7 Weih et al. Prevalence and predictors of open-angle glaucoma: results from the visual impairment project. Ophthalmology, 2001 108, 1966-72.
8 Mitchell et al. Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology, 1996; 103, 1661-9
9 Connor and Fraser, Glaucoma prescribing trends in England 2000 to 2012. Eye Lond, 2014; 28, 863-9.
10 Varma et al. An assessment of the health and economic burdens of glaucoma. Am J Ophthalmol, 2011; 152, 515-22.
11 Haymes et al. 2007 Risk of falls and motor vehicle collisions in glaucoma. Invest Ophthalmol Vis Sci, 48, 1149-55.
12 Skalicky and Goldberg. Depression and quality of life in patients with glaucoma: a cross-sectional analysis using the Geriatric Depression Scale-15, assessment of function related to vision, and the Glaucoma Quality of Life-15. J Glaucoma, 2008; 17, 546-51.
13 Berkelaar et al. Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J Neurosci, 1994; 14, 4368-74.
14 Quigley et al. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci, 1995; 36, 774-86.
15 Weinreb and Khaw, Primary open-angle glaucoma. Lancet, 2004; 363, 1711-20.
16 Foster et al. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol, 2002; 86, 238-42.
17 Quigley and Broman. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 2006; 90, 262-7.
18 Gordon et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol, 2002; 120, 714-20; discussion 829-30.
19 Blackwell et al. The Advanced Glaucoma Intervention Study AGIS: 12. Baseline risk factors for sustained loss of visual field and visual acuity in patients with advanced glaucoma. American Journal of Ophthalmology, 2002; 134, 499-512.
20 Leske et al. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol, 2003; 121, 48-56.
21 Tielsch et al. Blindness and visual impairment in an American urban population. The Baltimore Eye Survey. Arch Ophthalmol, 1990; 108, 286-90.
22 Anderson, Collaborative normal tension glaucoma study. Curr Opin Ophthalmol, 2003; 14, 86-90.
23 Drance et al. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol, 2001 131, 699-708.
24 Phelps and Corbett. Migraine and low-tension glaucoma. A case-control study. Invest Ophthalmol Vis Sci, 1985; 26, 1105-8.
25 Morgan et al. Axon deviation in the human lamina cribrosa. Br J Ophthalmol, 1998; 82, 680-3.
26 Albon J, Purslow PP et al. Age related compliance of the lamina cribrosa in human eyes. Br J Ophthalmol, 2000; 84: 318-323.
27 Neufeld et al. Nitric oxide synthase in the human glaucomatous optic nerve head. Arch Ophthalmol, 1997; 115, 497-503.
28 Qu et al. Mechanisms of retinal ganglion cell injury and defense in glaucoma. Exp Eye Res, 2010; 91, 48-53.
29 Flammer and Mozaffarieh. What is the present pathogenetic concept of glaucomatous optic neuropathy? Surv Ophthalmol, 2007; 52 Suppl 2, S162-73.
30 Findl et al. , Effects of changes in intraocular pressure on human ocular haemodynamics. Curr Eye Res, 1997; 16, 1024-9.
31 Pillunat et al. Autoregulation of human optic nerve head circulation in response to increased intraocular pressure. Exp Eye Res, 1997; 64, 737-44.
32 Weigert et al. Effects of moderate changes in intraocular pressure on ocular hemodynamics in patients with primary open-angle glaucoma and healthy controls. Ophthalmology, 2005; 112, 1337-42.
33 Hosking et al. Ocular haemodynamic responses to induced hypercapnia and hyperoxia in glaucoma. Br J Ophthalmol, 2004; 88, 406-11.
34 Feke and Pasquale. Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects. Ophthalmology, 2008; 115, 246-52.
35 Gherghel et al. Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients: a case for autonomic failure? Invest Ophthalmol Vis Sci, 2004; 45, 3546-54.
36 Riva et al. Flicker-evoked response measured at the optic disc rim is reduced in ocular hypertension and early glaucoma. Invest Ophthalmol Vis Sci, 2004; 45, 3662-8.
37 Drance et al. Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am J Ophthalmol, 2001; 131, 699-708.
38 Lam et al. Ocular hypertensive and anti-inflammatory responses to different dosages of topical dexamethasone in children: a randomized trial. Clin Experiment Ophthalmol, 2005;33:252-258.
39 Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye, 2006;20:407-16.
Rachael O’Connell is an optometrist at the Countess of Chester Hospital NHS Foundation Trust and a locum for independent practices in Cheshire. Mr Dan Nguyen is a consultant ophthalmologist and the lead clinician for glaucoma at Mid-Cheshire Hospitals NHS Foundation Trust. He is a consultant ophthalmologist at Optegra Manchester Eye Hospital where he also collaborates with Optegra’s Eye Sciences associates