Glaucoma Learning Zone

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Glaucoma overview

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Read time: 50 mins

Last updated:8th Jun 2022

Published:8th Jun 2022

Glaucoma is a disease of global concern, with cases expected to rise to 112 million worldwide over the coming decades^1,2. Explore our Learning Zone to:

Discover the prevalence and burden of glaucoma
Learn about the risk factors for glaucoma from an expert
Understand why glaucoma is difficult to detect

Prevalence and burden of glaucoma

In this video, Professor Anthony King describes the prevalence of glaucoma and explains why it is difficult to estimate. He also highlights major glaucoma risk factors and the burden of glaucoma on patients, health services and society.

Introduction to glaucoma

Glaucoma, known as the ‘silent thief of sight’, is the principal cause of irreversible blindness and visual disability globally, affecting over 60 million people^{3, 4}

Glaucoma is a complex disease with multiple causes⁵. It occurs when the optic nerve – the conduit between the eye and the brain – becomes damaged⁶. It is a common eye condition⁶ characterised by cupping of the optic nerve head, leading to progressive loss of the visual field. At first, peripheral vision is affected with central visual field being unaffected, detection typically occurring only as the disease progresses⁴. Left untreated, glaucoma can lead to irreversible visual field loss and blindness⁷. Chronic glaucoma is often not noticed by the patient as it is usually painless and progresses slowly – it is usually only detected once visual field loss becomes apparent. For these reasons, glaucoma is known as the ‘silent thief of sight’^{3, 8}.

Loss of retinal ganglion cells (RGCs) is the key pathological feature of glaucoma; however, the underlying causes of RGC loss are not yet fully understood⁴. Increased intraocular pressure (IOP) is characteristic of glaucoma and may contribute to loss of RGCs^{4, 9}. IOP becomes elevated when aqueous humour is overproduced or cannot drain properly through the trabecular meshwork where the iris and cornea meet¹⁰. However, only around 50% of glaucoma cases exhibit IOP above reference values^{2, 9}. Further, cases of ‘normotensive glaucoma’ have rapidly increased in recent years, with these patients having a higher likelihood of being underdiagnosed^{2, 9}.

Glaucoma comprises two major types, open angle and closed angle. A third type, childhood glaucoma, also exists. Differentiation between open angle and angle closure depends on the appearance of the iridocorneal angle through which aqueous humour drains from the eye – that is, the drainage angle formed by the iris and cornea^{4, 10}.

Open angle glaucoma^{4, 6, 11, 12}

Iridocorneal drainage angle remains open but with partial blockage of the trabecular meshwork
Slow progression of visual field loss over time
May be considered as high pressure primary open angle glaucoma (POAG) where the IOP is elevated above the population reference range, damaging the optic nerve
May be considered as normal tension glaucoma (NTG) where damage to the optic nerve is present despite IOP being in the normal reference range

Figure 1 depicts the difference in vision between people with normal vision and those with open angle glaucoma.

Figure 1. Open angle glaucoma and depiction of vision in normal versus glaucomatous vision. Depiction of vision for a glaucoma patient is licensed under CC BY-SA 4.0 / Detail added.

Angle closure glaucoma^{2, 4, 6, 11, 12}

Also known as closed angle or narrow angle glaucoma
Defined by presence of irido-trabecular contact
Iridocorneal drainage angle is blocked or narrowed when the iris bulges forward
Angle closure may prevent aqueous draining through the trabecular meshwork, increasing IOP, and may lead to glaucomatous optic neuropathy
Can be acute or chronic, acute being a medical emergency

Childhood glaucoma^{4, 6, 11, 12}

Also known as congenital or paediatric glaucoma
Present at birth or develops over first few years of life
Damage to the optic nerve from drainage blockages

Open angle and angle closure glaucoma may be further differentiated into primary and secondary subtypes, primary being where optic nerve damage occurs in the absence of an identifiable, secondary cause where other conditions or injuries are responsible for changes in the angle leading to elevated IOP. Trauma, inflammation, pigment dispersion and pseudoexfoliation can account for secondary open angle glaucoma⁴, while neovascularisation associated with retinal vascular disease is the main cause of secondary closed angle glaucoma^13-15.

Key features of the major types and subtypes of glaucoma are outlined in Table 1.

Table 1. Key features of the major types and subtypes of glaucoma². IOP, intraocular pressure; RNFL, retinal nerve fibre layer; VF, visual field.

Sub-type	Key features
Open angle glaucoma
Primary open angle	· Normally asymptomatic · Chronic · Progressive · Potentially blinding · Irreversible · Normal angle appearance · Optic nerve cupping/rim notching and RNFL loss with related VF defects · May be subdivided into ‘high pressure’ and ‘normal-pressure’ disease · Early diagnosis and treatment may prevent visual disability
Secondary open angle	· Heterogenous group of conditions (e.g., pseudoexfoliative glaucoma, pigment dispersion, trauma) · Raised IOP
Angle closure glaucoma
Primary angle closure	· Mostly asymptomatic · Aqueous outflow may be impaired by angle closure due to simple obstruction of trabecular meshwork or via irreversible degeneration and damage of the trabecular meshwork
Secondary angle closure	· Many causes (e.g., in iritis the pupil may become secluded, leading to pupillary block and forward bowing of the iris; in neovascular glaucoma a neovascular membrane grows over the angle occluding it) · Clinical signs vary according to underlying condition

While there are treatment options that may help slow glaucoma disease progression and protect the vision that remains, diagnosis is often made late, once irreversible functional loss has already occurred⁴.

Learn about treatment

Current research indicates that the glaucoma disease process begins up to 20 years before diagnosis is possible⁴

Glaucoma prevalence

It is projected that by 2040, there will be 112 million cases of glaucoma globally^{1, 2}

In adults aged 40–80 years, the estimated prevalence of open angle glaucoma is 3.5% globally, and 0.5% for angle closure glaucoma². Primary open angle glaucoma (POAG) is the most common glaucoma subtype, with an estimated 52.68 million cases in adults aged 40–80 years in 2020, and 79.76 million cases projected for 2040^{1, 16}.

Although open angle glaucoma is more prevalent than angle closure glaucoma, blindness is more likely to occur in people with angle closure glaucoma, estimated to be 25% in angle closure glaucoma and 10% in open angle glaucoma over the patient’s lifetime². Furthermore, primary angle closure glaucoma is correlated with a 300% increase in the risk of bilateral vision impairment, compared with primary open angle glaucoma¹⁷. Angle closure glaucoma is more prevalent in East Asian populations, while open angle glaucoma is more prevalent in Black populations².

A meta-analysis and systematic review were conducted to better understand the prevalence of primary open angle glaucoma globally. The study analysed cohort or population-based cross-sectional studies published in 2000–2020, with key findings summarised in Table 2.

Table 2. Global prevalence of primary open angle glaucoma, according to a meta-analysis and systematic review of data published in 2000–2020¹⁶. *Data from Ghana, Nigeria, Tanzania and South Africa. †Data from Australia. CI, confidence interval; df, degrees of freedom; POAG, primary open angle glaucoma.

Prevalence category	Data point	Additional information
Overall global prevalence	Prevalence: 2.4% (95% CI, 2.0–2.8%)	· Prevalence data slightly overestimated for POAG · No change observed in global prevalence between 2000–2009 and 2010–2020
Gender	Relative risk men compared with women: 1.28 (95% CI, 1.12–1.45; P<0.01)	· Prevalence higher for men in 84.4% of studies
Age	· People aged 40–49 years, prevalence: 1.1% (95% CI, 0.8–1.7%; P<0.01) · People aged over 80 years, prevalence: 9.2% (95% CI, 7.0–12.1%; P<0.01)	· Statistically significant difference between age groups (Q = 122.90; df = 6; P<0.001; random effective model)
Geographical location	· Prevalence in Africa*: 4.0% (95% CI, 2.6–6.1%; P<0.01) · Prevalence in Oceania†: 1.8% (95% CI, 1.5–2.3%; P<0.01)	· Africa* has the highest prevalence of POAG of all continents, while Oceania† has the lowest · Statistically significant difference between continents (Q = 15.65; df = 5; P<0.001)
Habitation area vegetation	No statistical difference between urban versus rural environments (Q = 4.82; df = 2; P=0.089)	N/A

According to the results of this meta-analysis, the prevalence of POAG in 2020 may have been as high as 68.56 million cases globally, with over 53% being in Asia¹⁶.

It is estimated that across all geographic regions globally, over half of all glaucoma cases are undetected on average³

The global prevalence of undetected glaucoma is difficult to quantify, with estimates ranging from 33–98%³. Nevertheless, research has been conducted which attempts to estimate the extent of undetected glaucoma. In a meta-analysis and systematic review that analysed data from population-based studies published between 1990–2010, 43.78 million cases of primary open angle glaucoma were projected to be undiagnosed in 2020, with 76.7% of those cases in Africa and Asia³.

Given that the risk of vision impairment increases when glaucoma remains undetected, and vision impairment leads to negative impacts on quality of life and socioeconomic outcomes³, these data suggest that the global burden of glaucoma is indeed very high. Furthermore, glaucoma cases are predicted to rise in the decades to come³, highlighting the urgency in diagnosing and treating this condition.

Burden of glaucoma

The health burden of glaucoma has continuously increased in the 25 years to 2015, and is unequally distributed¹⁸

Vision is the most dominant sensory function^19-23. Over 30% of the human brain is involved in visual information processing and, in one study in the US, vision loss was ranked as the most feared disability²³.

The effects of vision loss on a person’s quality of life and wellbeing differ depending on a range of factors, including the stage of their disease². Early-to-moderate glaucoma tends to have a moderate impact, while advanced visual field loss in both eyes may reduce quality of life substantially². Impaired vision can affect a person’s access to and achievement in education and the workplace, with considerable financial costs borne by individuals, families and communities who are affected²².

Vision impairment is associated with mobility reduction, greater need for social care, increased road traffic accidents, fall risk and dementia risk, and leads to greater rates of mortality²²

Vision impairment impacts physical, social, cognitive and psychological functions, affecting wellbeing and overall quality of life²². For those affected by glaucoma, its impact on quality of life, autonomy and socioeconomic wellbeing can be detrimental^{3, 9}. For the 25 years to 2015, the health burden of glaucoma has increased, with the disability-adjusted life year (DALY) number due to glaucoma increasing by 122%, and the age-standardised DALY rate increasing by 15%¹⁸. For the same period, the health burden of glaucoma was unequally distributed, being significantly associated with¹⁸:

older age
female gender
lower socio-economic level
higher air pollution levels
higher ambient ultraviolet radiation

People with glaucoma experience a variety of impacts on their everyday lives, including²⁴:

vision defects in tasks that involve central and near vision (e.g. reading)
facial recognition
mobility
walking difficulties
climbing stairs
driving

In addition, glaucoma is a significant predictor of depression, with prevalence being estimated at 10% for people with glaucoma²⁴.

There are numerous costs associated with glaucoma. These costs include direct and indirect costs and they are borne by individuals, healthcare systems and society²⁴.

Medications, diagnostic tests, clinic visits and surgery are examples of short-term, direct costs to people or healthcare systems, and these examples also represent costs to people and society in terms of loss of productivity/income and long-term costs associated with loss of vision. Direct costs associated with glaucoma include medical bills, medication costs and transportation, while days missed from work and low workplace productivity are examples of indirect costs. In addition to these costs, the burden of glaucoma extends to the families and carers of those with the condition²⁴.

It has been estimated that people with glaucoma have a greater chance than those without glaucoma, of being admitted to hospital for a fall. This in turn has an impact on a hospital’s operational and financial running costs, and the ability for that hospital to have beds available for other patients who may need them²⁴.

Several research studies indicate that a relationship exists between socioeconomic factors and glaucoma^{16, 25-27}. According to a study of the global health burden of glaucoma, which used disability-adjusted life years (DALY) to investigate its impact, lower socioeconomic level was significantly associated with greater glaucoma burden¹⁸. Research has revealed that people with a poverty income ratio <1.5 were less likely to have received appropriate eye care in the previous year, compared with those with a poverty income ratio of >5²⁴.

With the global population ageing and life expectancy increasing, it is expected that glaucoma cases will continue to rise¹⁸, along with its associated burden.

Risk factors for glaucoma

Within their lifetime, over 10% of people with glaucoma experience serious visual field loss or become blind in both eyes²

Left untreated, glaucoma can lead to moderate-to-severe vision loss. This highlights the need to be aware of the risk factors for glaucoma, so that people at higher risk can be screened, diagnosed and treated as early as possible, early detection being vital to prevention of disease progression²⁴ and irreversible vision loss. Figure 2 illustrates the major risk factors for the development of open angle glaucoma, the most common form of glaucoma².

Figure 2. The major risk factors for development of open angle glaucoma². IOP, intraocular pressure.

Table 3 outlines the risk factors for the more common forms of glaucoma. Of all risk factors, intraocular pressure is the only risk factor known to be modifiable²⁸. Risk factors for secondary subtypes have been excluded from the table, as the risks vary depending on the underlying cause.

Table 3. Risk factors for common forms of glaucoma (Adapted²). BP, blood pressure; CCT, central corneal thickness; IOP, intraocular pressure. *Thinner CCT: not an independent prognostic risk factor for onset/progression of open angle glaucoma in univariate analyses.

Type	Risk factors
Primary open angle glaucoma	Onset: · Higher IOP · Older age · Race/ethnicity: highest prevalence in people of Black race · First-degree relative with confirmed open angle glaucoma · Moderate-to-high myopia · Low diastolic BP · Thinner CCT* Progression: · Higher IOP · Older age · Presence of disc haemorrhages · Thinner CCT*
Primary angle closure glaucoma	· Older age · Race/ethnicity: higher prevalence in South and East Asians · Family history · Female sex · Hypermetropia

The major risk factors for glaucoma blindness are bilateral disease, age and severity of disease at presentation². Taken together, a young person with mild bilateral damage has a greater risk of experiencing visual disability in their lifetime, compared with a person aged 80 years with moderate unilateral damage². Therefore, a person’s rate of disease progression and individual needs should be considered when selecting the most appropriate treatment for their glaucoma².

According to a review, systemic medications such as anticholinergics, corticosteroids, topiramate and some antidepressants can predispose people to glaucoma²⁸.

Signs and symptoms of glaucoma

Glaucoma symptoms are almost undetectable in the early stages – even once the disease process is underway and nerve fibres have already been damaged^{3, 9}

Early detection of glaucoma is key to early treatment and the prevention of further loss of visual function⁴.

The signs and symptoms of glaucoma vary depending on the type and stage of the disease. Below are the common signs and symptoms of glaucoma.

Open angle glaucoma symptoms

In the early stages, there are no obvious symptoms of open angle glaucoma. Blind spots, also known as scotomas, usually develop in the peripheral vision although central visual field is affected in some individuals as the disease progresses. Often, changes to vision generally go unnoticed until substantial damage has already occurred and may be masked by a good visual field in the fellow eye^{6, 8, 10, 28} .

Secondary open angle glaucoma

Being a heterogenous group of conditions, symptoms will vary depending on the underlying cause, although raised IOP is the leading cause². The signs and symptoms are generally similar although in cases of pseudoexfoliation and pigment dispersion syndrome, specific changes will be noted in the anterior chamber on examination²⁹.

Normal tension glaucoma symptoms

Intraocular pressure is within normal ranges, but signs of glaucoma are present, such as optic nerve damage and blind spots in the field of vision⁸.

Angle closure glaucoma symptoms

Most commonly, people with angle closure glaucoma are asymptomatic. Sub-acute episodes of increased IOP due to angle closure may occur in some patients and can result in symptoms including blurred vision, haloes, pain and redness. However, the sensitivity and specificity of these symptoms as a means of identifying angle closure is very low². Given that acute angle closure glaucoma is a medical emergency, it is important that if symptoms develop suddenly – namely red eye, nausea, intense eye pain or blurry vision – the patient seeks immediate treatment. Left untreated, acute angle closure glaucoma can lead to blindness within days^{6, 12}.

Secondary angle closure glaucoma

The clinical signs of secondary angle closure glaucoma vary, depending on the underlying cause².

Progression of disease

In glaucoma, visual field loss usually begins in the periphery, advancing towards central fixation during disease progression²⁸. However, central loss may be experienced earlier in the disease course²⁸. Typically, rates of glaucoma disease progression are evaluated by measuring structural or functional changes to the optic nerve³⁰. When part of the optic nerve head or retinal nerve fibre layer (RNFL) are affected by structural damage, functional loss is often observed in the corresponding visual field location on perimetry²⁸.

Event analyses compare baseline to follow-up measurements, indicating whether the measurement has worsened, and trend analyses determine the rate of progression by using serial measurements. Trend analyses supplements event analyses in that it helps the clinician understand the velocity of vision loss, and whether this may impact the patient’s vision-related quality of life³⁰.

Using standard automated perimetry for visual field testing is the gold standard for measuring glaucoma progression, despite being patient-dependent and carrying high test-retest variability. Other tests that are used for qualitative and quantitative assessment of rate of structural change include spectral domain and swept-source optical coherence tomography³⁰.

Comparison of sequential perimetry results can indicate whether increases in visual field loss have occurred, which can help inform whether further IOP-lowering treatments may be required²⁸. Disease progression and the need for further IOP-lowering treatment may also be indicated when optical nerve head cupping has expanded, or when increased thinning of RNFL tissue on sequential optical coherence tomography (OCT) tests has been observed²⁸.

One example of a functional tool used to detect visual loss is the Amsler grid (also known as the Amsler chart). It is a simple and rapid qualitative test commonly used for people at risk of macula degeneration. It helps identify and locate defects in the central field of vision: specifically, in the central 10 degrees around a fixation point^{31, 32}.

Figure 3 illustrates how the Amsler grid appears when viewed by a person with normal central vision or with central visual field abnormalities associated with macula degeneration.

Figure 3. Examples of the Amsler grid, when viewed by people with varying functional vision. A) indicates what a patient with normal central vision sees, B) and C) indicate how the Amsler grid appears to people experiencing a problem with their central visual field. B) demonstrates a small scotoma below central fixation with surrounding distortion. C) demonstrates a large scotoma encroaching central fixation with some distortion. Figure by Broadway, D. is licensed under CC BY-NC 3.0 / Figure redrawn, notations removed.

The Amsler grid has been tested for its usefulness as a tool to screen for moderate-to-severe visual field loss in glaucoma³³. In a prospective cross-sectional study, people with glaucoma underwent an Amsler grid test for each of their eligible eyes, in which they were asked to identify any scotomas (areas on the grid with abnormal grid lines), and to describe in their own words their perception of those scotomas. In total, 88 eyes from 50 glaucoma patients were included (10–2 visual field mean deviation, −11.75 ± 8.86 dB; mean age 67 ± 11 [range 34–89] years; 17 males and 33 females), with 44 descriptions offered by patients. These descriptions were later categorised into four overarching descriptor categories³⁴:

Missing/White
Blurry/Grey
Black
Not Aware

Seventy-one eyes had Amsler grid scotomas, and those that reported two descriptor categories had worse visual field mean deviation than those who reported one (10–2 visual field mean deviation = −21.26 ± 9.37 in eyes with three descriptor categories, −13.21 ± 8.06 dB in eyes with two descriptor categories, and -11.74 ± 7.80 dB in eyes with one descriptor category; P=0.004 by analysis of variance). These results indicate an association between glaucoma severity, and the perception of scotomas and the breadth of terms used to describe them. These findings suggest that people with glaucoma perceive paracentral vision loss, and highlight the importance of listening to patient’s subjective descriptions of their glaucomatous visual field loss, as they may help inform the severity of their disease³⁴.

Although both eyes are usually affected by glaucoma, the damage may be worse in one eye^{6, 10}. This can cause a barrier to early diagnosis, because when a person has asymmetrical field loss but has both eyes open, they do not see a defect³¹.

When evaluating whether the rate of vision loss is clinically important, there are three factors to consider³⁰:

Current severity of disease in both eyes
The patient’s life expectancy
The stage of disease at which vision-related quality of life would be impacted

It has been difficult to study the natural progression of glaucoma because of the established benefit of IOP-lowering medicines to treat it. However, several trials have provided data on the natural course of open angle glaucoma. Results from the Early Manifest Glaucoma Trial revealed the overall natural rate of progression in the visual field being 1.08 dB/year. In addition, results indicate different rates of progression for participants with different disease phenotypes, being²:

31 dB/year in high tension glaucoma
36 dB/year in normal tension glaucoma
13 dB/year in pseudoexfoliative glaucoma

Modelling techniques utilising machine-learning are being explored to help identify glaucoma patients who are at higher risk of disease progression. They are also being used to help identify an appropriate target IOP level for disease stabilisation, and to predict future visual field loss²⁸. For example, the findings of a cohort study suggest that the machine learning algorithm known as ‘Kalman filtering’ can accurately predict the IOP values, mean deviation and pattern standard deviation in five years for people with ocular hypertension. Such techniques can help clinicians identify patients with ocular hypertension who are more likely to progress to open angle glaucoma and may therefore benefit from early treatment and more frequent monitoring³⁵.

When treated early and successfully, the prognosis for people with glaucoma is good. However, the lack of obvious symptoms in the early stages and the corresponding high rates of undetected glaucoma increase the risk of vision impairment, resulting in negative impacts on the socioeconomic wellbeing and quality of life for those affected by the disease³.

Glaucoma leads to blindness if left untreated. However, approximately 15% of people with glaucoma will become blind in at least one eye within 20 years despite receiving treatment¹⁰

Watch our patient case study videos and test your knowledge

Treating glaucoma

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