Ординатура / Офтальмология / Английские материалы / Glaucoma Identification and Co-management_Edgar, Rudnicka_2007

The origins of Glaucoma Identification and Comanagement can be traced back to the introduction in 1996 of the first two Certificate courses for registered Optometrists run jointly by City University and Moorfields Eye Hospital: Diabetic Shared Care and Glaucoma Shared Care. In 1999 Diabetic Eye Disease Identification and Comanagement was published with chapters written by contributors to the Diabetic Shared Care course, and it is with great pleasure that we introduce the sister book written by contributors to the Glaucoma course. This course is now run annually by City University.

There are approximately 250,000 sufferers from Primary Open Angle Glaucoma (POAG) in the UK, with possibly a similar number remaining undiagnosed in the community. POAG patients now represent 25–30% of the outpatient load of ophthalmology departments in the UK, and this outpatient burden will increase as life expectancy increases and as our methods of detection of glaucoma become more sensitive.

A general finding from population based surveys is that approximately 50% of people found to have glaucoma were previously undiagnosed, hence the role of general practitioners, optometrists and technicians as primary screeners has been investigated. Consensus is yet to be reached on the most effective way to screen for glaucoma, and at present there is no satisfactory test that would be suitable for mass screening for glaucoma. Evidence on the efficacy of treatments to prevent further deterioration of visual function in glaucoma is only just emerging in the literature. For these reasons population screening for POAG is probably unjustified in Westernised populations.

Glaucoma will place demands on the NHS that will require innovative approaches to patient management, including the development and refinement of co-management/shared-care schemes.

Glaucoma Identification and Co-management aims to provide the background knowledge needed by optometrists embarking on co-management/ shared-care of POAG and to reinforce the knowledge of those already involved in co-management/ shared-care practice. While the majority of readers will be registered optometrists, the book will also serve as a valuable reference work for students of optometry. The book provides detailed methods of clinical examination techniques and their interpretation together with a detailed description of the histopathology, physiology and visual functional changes in glaucoma. Therefore, it may be of use to general practitioners and medical students with an interest in glaucoma, as well as other healthcare professionals with an interest in the identification and co-management of glaucoma.

Co-management/shared-care schemes require a combination of skills from several disciplines – notably ophthalmology and optometry – and these professions are well represented among our authors. We also have a contribution from a pharmacist as pharmacy is another profession with a key role to play in the management of patients suffering from glaucoma. We are most grateful to all our authors, who have worked together so diligently to produce this book.

Christopher Bentley

Visiting Professor of Ophthalmology, Middlesex

University; Honorary Senior Lecturer, Imperial

College, London; Consultant Ophthalmic Surgeon,

Central Middlesex Hospital, London, UK

Jill Bloom

Medicines Information Pharmacist, Department of

Pharmacology, Moorfields Eye Hospital, London,

UK

Philip Bloom

Visiting Professor of Ophthalmology, Middlesex

University; Honorary Senior Lecturer, Imperial

College, London; Consultant Ophthalmic Surgeon,

Western Eye Hospital and Hillingdon Hospital,

London, UK

Yvonne Delaney

Ophthalmologist, Eye Department, Mater

Misericordiae Hospital, Dublin, Ireland

David F Edgar

Professor of Clinical Optometry, Department of

Optometry and Visual Science, City University,

London, UK

John G Flanagan

Professor, School of Optometry, University of Waterloo; Professor, Department of Ophthalmology and Vision Sciences, University of Toronto; Senior Scientist, Toronto Western Research Institute, University Health Network, Ontario, Canada

Robert Harper

Consultant Optometrist, Manchester Royal Eye

Hospital; Honorary Senior Lecturer, University of

Manchester, Manchester, UK

David B Henson

Professor of Ophthalmology and Vision Sciences,

University of Manchester, Manchester, UK

Peng T Khaw

Professor of Glaucoma and Ocular Healing,

Paediatric Glaucoma Unit, Moorfields Eye Hospital

and Wound Healing Research Unit, Institute of

Ophthalmology, London, UK

John G Lawrenson

Professor of Clinical Visual Science, Department of

Optometry and Visual Science, City University,

London, UK

Colm O’Brien

Professor of Ophthalmology, University

College Dublin, Mater Hospital, Dublin,

Ireland

Christopher G Owen

Senior Lecturer in Epidemiology, Division of

Community Health Sciences, St. George’s,

University of London, London, UK

C Lisa Prokopich

Lecturer, School of Optometry, University of

Waterloo; Head, Ocular Health Clinic, School of

Optometry, University of Waterloo; Head, Freeport

Hospital Vision Centre, Kitchener, Ontario,

Canada

Simon J A Rankin

Consultant Ophthalmic Surgeon, Ophthalmology

Department, Royal Hospitals, Belfast, Northern

Ireland, UK

CHAPTER CONTENTS

General epidemiological principles 1

1.1General definitions of the glaucomas 2

1.2Prevalence of primary open angle glaucoma 3

1.2.1Geographical and ethnic distribution of primary glaucoma 4

1.3Incidence of primary open angle glaucoma 4

1.4Risk factors for primary open angle glaucoma 6

1.4.1Ocular risk factors 6

1.4.2Demographic and genetic risk factors 7

1.4.3Systemic disease risk factors in glaucoma 9

1.5Screening 10

References 12

GENERAL EPIDEMIOLOGICAL PRINCIPLES

Epidemiology is the study of the incidence, distribution and determinants of disease in human populations with a view to identifying their causes and bringing about their prevention.

A cause of a disease is a factor that is associated with the disease so that if the intensity or prevalence of the factor in a population is changed, the incidence of the disease also changes.

Wald (2004)1

Epidemiology is concerned with examining groups of individuals with the intention of identifying risk factors that are present before the disease is clinically manifest and thereby identify a cause (or causes) for the disease. Once a cause is identified it may then be possible to bring about prevention of disease by removal or modification of the causal factor. An example of a study to investigate the epidemiology of a disease would involve examining a population sample of people who do not yet have the disease of interest and measuring various risk factors over time (such as age, social class, smoking status, alcohol consumption, blood pressure) and then waiting to see who develops the disease in later life.

The method of analysis is concerned with examining differences in the pattern of the risk factors in those who develop and those who do not develop the disease of interest. This study design is called a cohort study, from which we can also quantify the

burden (e.g. prevalence and incidence—see below) of the disease. A simpler form of population study is a cross-sectional study (i.e. a survey or prevalence study), which involves measuring risk factors and disease outcomes at the same point in time; there is no long-term follow-up of the sample. However, unlike a cohort design, disease incidence cannot be ascertained, and one cannot be certain whether a risk factor associated with a disease caused the disease or occurred as a consequence of the disease. Another type of epidemiological study identifies people who already have the disease (i.e. cases) and a suitable control group (i.e. people who do not have the disease but are representative of the population from which cases of the disease have arisen) and involves comparing risk factors of interest between both groups. This is called a case–control study, and although this design does not give a measure of disease burden, and cannot always distinguish whether a risk factor(s) was present before the disease developed, case–control studies are useful in the study of rare diseases, such as glaucoma. These different epidemiological study designs have advantages and disadvantages that are not within the scope of this chapter. However, the reason for describing these study designs is to highlight some of the different types of epidemiological study used in this chapter to assimilate the evidence concerning the burden of glaucoma and potential risk factors for glaucoma.

Prevalence (also referred to as point prevalence) is the proportion of people in a defined population who have the disease of interest in a defined time period. It is simply a proportion or a percentage, e.g. disease A has a prevalence of 1% in persons aged 45–55 years of age, and an alternative way to express this is 10 per 1000 population aged 45–55 years of age.

Incidence is the number of new cases of a disease occurring in a defined population over a specified period of time. Incidence rate is the rate of disease, e.g. disease A has an incidence of 1 per 10 000 per year in persons over 40 years of age.

Risk factor is any factor measured either in an individual or in a group of individuals that is associated with the risk of a disease.

1.1 GENERAL DEFINITIONS OF

THE GLAUCOMAS

The glaucomas are a group of ocular diseases that may cause characteristic progressive changes in the optic nerve head, visual field loss, or both.2 Glaucomas can be subdivided into primary conditions in which the mechanism for the disease is unknown, and secondary conditions where the glaucoma is secondary to another ocular or systemic disease. Secondary glaucoma typically results in raised intraocular pressure (IOP) secondary to, for example, cataract, trauma, uveitis and disorders affecting the drainage and structure of the anterior chamber angle.

Primary and secondary glaucomas can be further subdivided into open angle and angle closure (also called closed or narrow angle glaucoma), which directly relates to whether the anterior chamber angle and the region for aqueous drainage is open or narrowed. Chapter 2 describes in detail aqueous production and drainage and Chapter 4 describes the clinical examination of the anterior chamber angle and quantification of its structure.

Primary open angle glaucoma (POAG) has an adult onset, is usually bilateral and produces characteristic changes in the optic nerve head or visual field (see Chapters 3, 5, 7 and 9) and these changes may be in the presence or absence of elevated IOP. In more advanced stages of POAG, patients become aware of the visual deficits. Although IOP can be raised in POAG it is not a prerequisite of POAG. Historically there was a great deal of emphasis on IOP in the glaucoma literature and this led to a misunderstanding that heightened IOP was synonymous with POAG. There is considerable overlap in the levels of IOP in people with and without glaucomatous optic neuropathy. The clinical definition of POAG does not depend on the eye having an eye pressure above a given IOP, for example, 21 mmHg, but treatment of POAG is primarily concerned with reducing IOP (see

Fig. 1.1 Classification of the glaucomas.

Chapters 10–12). Chapter 8 provides more detailed information on the measurement of and factors that influence the variability of IOP in normal and glaucomatous populations and gives guidelines for referral of patients.

A large proportion of the glaucoma literature is focused on IOP and this has led to further subgroups, defined on the basis of IOP (see Fig 1.1).

■POAG, which is subdivided into:

●normal-tension glaucoma (formerly called low-tension glaucoma), which includes those with glaucomatous optic neuropathy but with IOP within the ‘normal range’

●‘high-tension’ or ‘classical’ glaucoma, being POAG with raised IOP.

■Ocular hypertension; those with raised IOP (usually IOP above 21 mmHg) but no optic nerve damage or visual field loss.

In American and European populations between 2% and 10% of people will have IOP above 21 mmHg, and prospective studies suggest that of these only 1–3% per year develop glau- coma.3–7 Therefore most patients with ocular hypertension do not go on to develop glaucoma. However, very high IOPs require treatment because of the risk of central retinal vein occlusion.

These subgroups of POAG are attempts to split the population into specific groups when in reality there is a continuous spectrum of risk factors in people. The correlation between IOP and POAG is analogous to the relationship between blood pressure and cardiovascular disease; there is a great deal of overlap in the distribution of blood pres-

sure values of people who have cardiovascular disease and those who do not. There is no real lower safe limit below which cardiovascular disease never occurs. The overlap in blood pressure levels between affected and unaffected individuals is one of the main reasons why screening for cardiovascular disease by measuring blood pressure is not an effective screening test. The same problem arises in screening the population for glaucoma by the measurement of IOP alone.

This chapter focuses on the epidemiology of POAG, since in the UK and other European populations it accounts for the vast majority of the glaucomas.

1.2 PREVALENCE OF PRIMARY OPEN

ANGLE GLAUCOMA

There are many population-based surveys on the prevalence of glaucoma. Unfortunately many of the older publications did not differentiate between POAG and primary angle closure glaucoma (PACG). However, the latter is far less common than POAG in white populations and those of European descent8–13 and therefore the estimates are likely to reflect mainly cases of POAG. In white people 75–95% of primary glaucoma is open angle whereas in Asians the findings are more variable with 30–90% of primary glaucoma being angle closure. The population sampling procedures in the prevalence studies were of reasonable quality but few studies conducted visual field examination on all subjects. Visual field testing was typically performed on ‘high-risk’ individuals such as those with suspicious optic discs or raised IOP. Unfortunately this leads to biased estimates of the numbers of subjects with glaucoma because it is now generally accepted that approximately half of patients with clinically defined glaucoma have IOP in the ‘normal’ range and, in addition, the IOP can vary considerably within an individual. Hence such study designs were likely to have missed cases of glaucoma that had IOPs within what would have arbitrarily been defined as the ‘normal range’ and so underestimated the number with glaucoma. An interesting observation in nearly all the population surveys is that about

half of the cases of POAG detected at the time of survey were previously undiagnosed.

1.2.1 GEOGRAPHICAL AND ETHNIC DISTRIBUTION OF PRIMARY GLAUCOMA

Table 1.1 summarises the prevalence of POAG and PACG from some of the larger population-based studies9,10,12,14–42. Although the methods of testing and sampling vary from one study to another they give an idea of the relative prevalence in different populations. The prevalence for POAG ranges from 0.03% in China to 8.76% in St Lucia; most of the studies in Table 1.1 are in people aged 30 years or more. The relative prevalence of PACG and POAG differs dramatically according to race and age. In Europeans, Africans and North Americans POAG is the most predominant form of glaucoma.

The prevalence of POAG in those aged over 40 years in white people from Europe, America and Australia of comparable age groups is of the same order (approximately 1–3%), whereas black populations in the Caribbean and the USA have higher prevalence in similar age groups. Currently the highest prevalence of POAG is reported in black populations of the Caribbean, particularly St Lucia and Barbados, ( 7–9%), with slightly lower prevalence (3–4%) in black Africans from Baltimore, London and other parts of Africa.12,14–18 The Baltimore Eye Study directly compared the prevalence in white and black people from the same geographical location, and the age-adjusted rates were 4.3 times higher in Black Americans compared with White Americans.12 The age of onset of POAG appears to be earlier in Africans than in white Europeans and seems to progress more rapidly and may be more resistant to IOP reduction therapy. Interestingly, primary glaucoma was not found in pure-blooded New Zealand Maoris and was uncommon in Australians of aboriginal origin;43,44 an explanation for these findings remains unclear. A recent systematic review and meta-analysis of 46 cross-sectional studies, that included 2509 cases of POAG, found that Blacks had the highest prevalence of POAG at all ages compared to Whites and Asians.45 The prevalence of POAG in those aged 50–59 years was estimated to be 4.6% in Blacks, 0.8% in Whites and 1% in Asians; in those aged 60–69 years the estimates were respectively 7.2%,

1.6% and 1.6%; and over 70 years of age the estimates were 16%, 6% and 3% respectively.

Variability in the relative prevalence of PACG and POAG in studies conducted in Chinese and Asian (Mongoloid) communities exists, although most of these studies show a higher prevalence of PACG compared with studies carried out in European, American and African populations (Table 1.1). Japan appears to be the exception, where the prevalence of PACG is extremely low (0.08%), and much lower than the prevalence of POAG (2.53%).21 Japan is also unusual because the majority of the POAG cases have IOPs within the ‘normal’ range (2% with ‘normal’ IOP and 0.53% with raised IOP).21 A recent survey in Japan found 92% of patients with POAG had IOP below 21 mmHg.27 Also, mean levels of IOP in Japan have been shown to be lower than in European populations.21 Conversely, in India the prevalence of PACG has been shown to be far greater than the prevalence of POAG (4.3% versus 0.4%, respectively).23 The Mamre in South Africa are a mixed racial group with ancestors from south-east Asia and later migrants who came from east Africa and western Europe, and the prevalences of POAG and PACG are similar in the Mamre population.33

Across different ethnic groups there are marked variations in glaucoma prevalence. This may partly be explained by differences in survey methodology, but may also allude to different mechanisms for glaucoma or genetic susceptibility.

1.3 INCIDENCE OF PRIMARY OPEN

ANGLE GLAUCOMA

There are fewer studies of glaucoma incidence. Extrapolations from the Framingham and Ferndale prevalence studies gave a 5-year incidence of 0.2% at age 55 years, increasing to 1% at 75 years (equivalent to 4 per 10 000 per year and 20 per 10 000 per year respectively).13,30 Bengtsson46 reported 24 per 10 000 per year in Sweden in those over 55 years of age. In the Melbourne Visual Impairment study the incidence was reported as 12 per 10 000 per year in those aged 60–69, 28 per 10 000 per year in the 70–79 age group and 82 per 10 000 per year in those aged over 80 years.7 Longitudinal follow-up of the Barbados Eye Study6 showed a

Table 1.2 Prevalence estimates of POAG

according to intraocular pressure (IOP)

higher incidence in Black Caribbeans. The 4-year risk of open angle glaucoma in black participants was 2.2%, which is equivalent to 55 per 10 000 people per year. The rates were 1.2% per 4 years (30 per 10 000 per year) in those aged 40–49 years rising to 4.2% (105 per 10 000 per year) at ages 70 years or more. In the Barbados and Melbourne studies, subjects with higher IOPs at baseline were more likely to develop POAG at follow-up.6,7

1.4 RISK FACTORS FOR PRIMARY

OPEN ANGLE GLAUCOMA

Currently several risk factors have been identified for primary open angle glaucoma but as yet the underlying cause is not known. It has been suggested that a combination of risk factors such as decreased blood flow to the optic nerve head and IOP levels that are too high in an individual may contribute to ganglion cell death. Autoimmune reactions such as increased levels of glutamate and nitric oxide have been implicated with ganglion cell death47 but these factors have not been demonstrated to be associated with POAG in prospective epidemiological studies and so it cannot be ruled out that these factors are a consequence of rather than a cause of the disease.

1.4.1 OCULAR RISK FACTORS

Intraocular pressure

Epidemiological studies have shown that as IOP increases there is a corresponding increase in the prevalence of glaucomatous optic nerve atrophy and visual field loss.12,48 Apart from the mechanical

1000 people 40+ years

Fig. 1.2 Hypothetical example illustrating how it is possible in patients with primary open angle glaucoma (POAG) to have roughly half with raised intraocular pressure (IOP) and half with ‘normal’ IOP, assuming a prevalence of 10% of POAG in those with IOP above 21 mmHg and 1% in those with IOP ≤ 21 mmHg.

effect of raised IOP on the retinal nerve fibre layer and optic nerve head, other contributing factors including perfusion to the optic nerve and structural support within the lamina cribrosa have been implicated in the pathogenesis of POAG. Table 1.2 gives the prevalence estimates from two large studies according to level of IOP.

Comparing the lowest and middle IOP groups the increase in POAG prevalence with increasing IOP is approximately six-fold, and is about 16–40- fold comparing the lowest and highest IOP groups. Among patients with asymmetrical IOP, usually the eye with the higher pressure has the greater degree of cupping or visual field loss. Glaucoma is rare in eyes with IOP less than 10 mmHg. The arbitrary cut-off at 21 mmHg to define elevated IOP is a statistical concept based on the mean value (16 mmHg) plus 2 standard deviations (2 × 2.5 mmHg), and if the distribution of IOP followed a Gaussian distribution we would expect 2.5% of the population to have IOPs above 21mmHg. However, the distribution of IOP is not Gaussian but positively skewed, meaning that there is a higher proportion of high IOPs than expected for a Gaussian distribution; indeed, up to approximately 10% of people have IOPs above 21 mmHg. In population-based surveys it has been found that between one-third and two-thirds of those with POAG have IOPs below 21 mmHg at screening and 20–30% of POAG patients have IOP consistently less than or equal to 21 mmHg.10,13,30,34,35,37,48–50 Figure 1.2 is a hypo-