Eye Disease and Blindness Worldwide

The World Health Organization estimates that in 2002 therewere over 161 million people who had significantly reduced vision (designated "moderate visual impairment"). Of this number, 37 million were blind. Despite the advances in eye surgery that have been made in many countries over the last few decades, cataract remains the leading cause of vision problems in all regions of the world, except in the most developed countries of Western Europe, America and Australasia. Other major causes of visual impairment are, in order of importance: glaucoma, age-related macular degeneration, diabetic retinopathy and trachoma [Resnikoff 2004].

EPIC and Eye Disease in the UK

A study carried out in North London found that a third of people aged 65 years and over, had visual impairment (visual acuity less than 6/12) that would prevent them from holding a driving licence [Reidy 1998]. Figures from the registration of cases of blindness and visual impairment in the UK have identified age-related macular degeneration (AMD) and glaucoma as the leading causes of vision loss in the UK, accounting for 57% and 11% respectively of all blindness registered with social services. The number of people affected has increased since 1990, both as a consequence of greater longevity and increasing proportion of visual impairment [Bunce 2006]. In EPIC, we have concentrated our future research on tackling these two leading causes of blindness and visual impairment in the Western World. It is our aim to produce information about the factors that increase risk or help to protect people from common eye diseases in the UK.

An Ipsos MORI poll commissioned by the Government's Medical Research Council found that preventing ill-health is the public's single most valued area for research into ageing. More than twice as many study participants chose research into prevention over research into cure. Research focused on managing conditions and how best to support and care for people who have ill health came second to prevention ahead of cure ['Public consultation on Ageing: Research into Public Attitudes Towards BBSRC- and MRC-Funded Research on Ageing': www.ipsos-mori.com].áThe Office for National Statistics projects that the total number of people aged 60 years and older will rise from 12 million in 2001 to 18.6 million in 2031 and the number of individuals suffering with chronic diseases and disabilities will see a three-fold increase in those 30 years. With one in twelve Britons over 75 currently visually impaired, and one in fifty blind as a consequence of age-related macular degeneration [Evans 2002], the magnitude of the problem will increase considerably with increasing longevity.

Macular Degeneration

Macular degeneration is a condition in which part of the light sensitive layer of the eye (the retina) degenerates, causing a reduction in vision. The macula is the part of the retina which provides the most detailed, central vision that we use for reading, driving, watching TV and for recognising people's faces.

Eye specialists divide AMD into "dry" and "wet" forms of the disease. Most cases are categorized as "dry" macular degeneration where fatty tissue, known as drusen, slowly builds up underneath the retina. Cases of wet AMD result from the growth of abnormal blood vessels under the retina, leading to leakage of blood and other fluid which damages the retina. Wet macular degeneration usually begins as the dry form. If allowed to continue without treatment it may cause very severe damage to the macula, and lead to blindness.

Risk factors:

• Ageing: The disease becomes more common as age increases. It is uncommon before the age of 65.
  

• Smoking: The only behaviour proven to increase the risk of macular degeneration is smoking.
  

• Family history: The risk of developing severe macular degeneration over someone's lifetime is around 50% for people who have a relative with macular degeneration compared with 12% for people who do not have relatives with macular degeneration, i.e. a four times higher risk. This is probably explained by the discovery of genetic mutations that are linked with AMD.
  

• Macular Degeneration Gene: Complement factor H (CFH) and complement factor B (CFB) genes have been found to be strongly associated with a person's risk for developing AMD. It is not yet clear exactly what triggers the disease in people who carry abnormal versions of disease, but it seems likely there is an environmental "trigger".
  

• Cardiovascular Risk Factors: it seems plausible that factors such as high blood pressure, high cholesterol, and obesity increases the risk of AMD, but conclusive proof that reducing any of these will reduce the risk of disease is not yet available.

• Diet: There has been much interest in dietary risk factors for AMD in the last decade. A high fat diet is linked with an increased risk of macular degeneration in both women and men. However, a high fat diet is also linked with other risk factors listed above, and hence it is uncertain whether the relationship is one of cause and effect.

• Vitamins and Minerals: A research study in the United States has suggested that vitamin and mineral supplements are beneficial in people who have moderately advanced AMD. They identified a 30% reduction in risk of progression to advanced AMD from antioxidant (beta-carotene, vitamin C and vitamin E) and zinc supplementation. However, these results have not been greeted with universal enthusiasm as Beta-carotene has been found to increase the risk of lung cancer in smokers and vitamin E has been associated with an increased risk of heart failure in people with vascular disease or diabetes. It is widely agreed that more research in this field is necessary before use of vitamin supplements can be widely recommended.

• Race: Macular degeneration seems to be more common in people of European ancestry than in people whose families originate in Africa. It is not yet clear whether other groups are more or less affected.

• Exposure to sunlight: There is conflicting evidence as to whether exposure to sunlight contributes to the development of macular degeneration.

Glaucoma

Glaucoma is a degenerative condition affecting the optic nerve that may cause blindness as a consequence of loss of nerve fibres that lead from the retina to the brain. It is statistically linked with higher eye pressure (intraocular pressure or IOP), although there is no level of IOP that is safe and normal for all people. In cases of glaucoma which are progressive (i.e. getting worse), reduction of IOP is currently the only proven method of preventing further deterioration of established glaucoma. It is important to recognize that when vision is damaged by glaucoma, the lost vision cannot be restored. Hence identifying the disease in its early stages, and preventing deterioration, are the keys to preventing problems.

There are four categories of disease, based on the age at which the disease is recognised (congenital glaucoma affects children in the first year of life) and the mechanisms that cause increases in intraocular pressure (secondary glaucoma, primary angle-closure glaucoma and primary open-angle glaucoma affect adults predominantly). Primary open-angle glaucoma (POAG) is the most common form of disease in Europe and North America. In Asia primary angle-closure glaucoma (PACG) is also common. Secondary glaucoma may be caused by either open angle or angle-closure mechanisms.

Fluid (aqueous) circulates inside the eye and supplies oxygen and nutrients to the tissues at the front of the eye. The aqueous is produced by the ciliary body behind the iris, circulates through the pupil, and drains out through the trabecular meshwork, which runs in a ring in the white sclera where it joins the cornea (the clear covering at the front for the eye). In some cases the gap between the iris and the cornea becomes closed, either as a consequence of pressure from behind pushing the iris forwards, or more rarely, diseases causing the iris to be pulled forwards. This phenomenon is called angle-closure. Primary angle-closure occurs in the absence of other diseases, just as a consequence of the size and shape of the eye. Smaller eyes are at the highest risk. If rises in eye pressure cause damage to the optic nerve head, the condition is termed primary angle-closure glaucoma (PACG). Secondary angle-closure glaucoma can be caused by diseases such as diabetes or inflammation inside the eye, but this is relatively uncommon. In the past, angle-closure glaucoma was seen as synonymous with "acute glaucoma" where the IOP rose very quickly causing pain, sudden loss of vision, occasionally combined with nausea and vomiting. This is now known to be partly incorrect. Many cases of angle-closure glaucoma (possibly half) occur without the typical symptoms of acute glaucoma. Furthermore, having a rise in IOP which causes symptoms is probably beneficial in the long-term, as it leads to detection and treatment of the condition at an earlier stage than if the person had angle-closure which did not cause symptoms. In asymptomatic cases of glaucoma, without regular check-ups, the individual may not be aware there is a problem until the go blind in one eye. Typically, the other eye will be badly affected by the time the condition is diagnosed.

If the drainage channels are not blocked by the iris, but the pressure is high and/or there is glaucomatous damage to the optic nerve, the condition is termed either ocular hypertension or open angle glaucoma respectively. Open angle glaucoma, which occurs without other diseases that cause a rise in eye pressure is called primary open angle glaucoma (POAG).

Risk factors:

• Older age: Both POAG and PACG forms of glaucoma become progressively more common with increasing age. Both are uncommon before the age of 40

• Higher eye pressure: The higher the intra-ocular pressure (IOP) the more likely an individual is to suffer glaucoma. Normal eye pressure is defined statistically as around 21 mm Hg (the average is 15-16 mm Hg), but between 30 and 50% of all cases of glaucoma occur with pressure consistently within the normal range. Glaucoma is more common among the small number of people who have high IOP. It is unclear exactly how IOP is controlled by the body, but higher blood pressure seems to cause higher IOP.

• Family history: having a family member with glaucoma increases the risk of developing the disease; estimates of increased risk if a parent or sibling has the condition range from 2 fold to nine-fold.
  Genetic abnormalities: there are now known to be several genetic abnormalities that lead to a dramatically increased risk of developing glaucoma. It seems likely that many more will be discovered in the future.

• Race: being from an African family increases the risk of POAG. Having an Asian family background increases the risk of PACG.

• Refractive error: being short-sighted (myopic) increases risk of POAG. People who are long-sighted have a higher risk of angle-closure.

• Diet: there are no particular feature of diet or lifestyle that is known to increase or decrease risk of glaucoma

EYE EXAMINATIONS USED IN EPIC

Visual Acuity

Vision is a complex sense, and it is impossible to measure and describe all of the many facets that make up "normal" vision. However, the most commonly used measure of vision is visual acuity, which describes the ability to recognise fine detail. Typically, visual acuity is measured with a Snellen chart- the tall, narrow illuminated chart that is used in opticians' shops and hospitals to measure vision when assessing whether or not to prescribe glasses. The test is usually carried out at a distance between 2 to 6 metres, depending on the size of the chart, although 6 metres is the standard. Results are expressed as a fraction of normal vision, relative to the ability to see at 6 metres. Normal vision is 6/6 (or 20/20 in America whether they still use imperial measures of feet and inches). If someone could only see an object at 6 metres that most normal people could see at a distance of 12 metres, this would be described as 6/12, and is said by some to represent a 50% reduction in vision, although many people feel this level of vision is perfectly adequate for most normal tasks. Vision of around 6/12 is approximately equal to the main vision requirement for holding a driving licence for a car or motorbike. The actual requirement is to be able to see number plate letters in good light at a distance of 20 metres (DVLA). The World Health Organization defined moderate visual impairment as vision of less than 6/18, and blindness as less than 3/60 (cannot see at 3 metres what a normally sighted person should be able to see at 60 metres). The definition of blindness is intended to indicate the level of vision at which a person cannot walk about unaided.

In EPIC, we decided not to use a Snellen chart to measure peoples' vision. Instead we are using a LogMAR chart, which has several scientific advantages for getting more accurate measures of vision, and being able to perform more sophisticated statistical tests on the results.

Refractive error

We are measuring the amount of short- or long-sightedness in all participants using an auto-refractor, which gives accurate measures of the amount and type of refractive error. This is needed to calibrate several of the machines we use for other measurements, and to correct for the amount of magnification that occurs from the various refracting surfaces of the eye when internal structures are photographed.

Ocular biometry

We are making very precise measurements of the eye from front to back (called the axial length), and the depth of the front chamber of the eye (called anterior chamber depth). These are also needed to calibrate some of the machines we use for other measurements, and to correct for the amount of magnification that occurs from the various refracting surfaces of the eye when internal structures are photographed. This can be used to test for glaucoma as shorter dimensions are associated with PACG.

Intraocular Pressure (IOP)

Eye pressure is an important risk factor for glaucoma. Previous research has shown that measurements routinely made in hospitals and eye clinics can be affected by the rigidity of the eye tissues, and the thickness of the cornea (the clear front "window" of the eye). In order to make the most accurate measurements possible of IOP, and to understand the influence of rigidity of eye tissue on the measurements we make, we are using an advanced device called an Ocular Response Analyzer to measure IOP. It works in a very similar manner to a conventional air-puff device used by many opticians, but uses a computer to collect a large amount of extra information.

Retinal nerve fibre layer thickness

The thickness of the layer of nerve fibres on the surface of the retina is reduced in glaucoma. Measurements of this very fine structure can be made using a device called a Scanning Laser Polarimeter. This computerised device contains data gathered from a large number of people with and without glaucoma. By comparing individual results with the database of measurements, the figures can be used to identify people who may have glaucoma. The device we use incorporates a new piece of software called the VCC or variable corneal compensator, which makes measurements more accurate.

Optic nerve topography

The appearance of the optic nerve head changes when glaucoma develops. This can be detected by a trained eye specialist. However, as glaucoma is typically a progressive condition, changes in the appearance need to be measured. Making precise measurements is impossible, even for very experienced observers. Devices called Scanning Laser Ophthalmoscopes (SLO) use precision laser beams to measure structures inside the eye. They can be used to make measurements of the size and shape of the optic nerve. We use an SLO to measure the surface contour of the optic nerve as another measure of whether people have glaucoma. This computerised device contains data gathered from a large number of people with and without glaucoma. By comparing individual results with the database of measurements, the figures can be used to identify people who may have glaucoma.

Retinal photography

Detailed photographs are taken of the retina and the optic nerve on the back of the eye using a special ophthalmic camera. These photographs can be used to identify cases of age-related macular degeneration, diabetic retinopathy and help in the identification of glaucoma if abnormalities are seen.

Visual fields

The visual field is the amount of the external environment visible to an individual at any one time. Visual field tests are used to measure whether there has been any loss of more peripheral vision than is measured by visual acuity. In glaucoma, there is constriction of the visual field that is typically not noticed by the sufferer until it is very advanced. In EPIC we will be offering a visual field test to anyone who may have glaucoma, and to some other participants who have normal test results as a double check on our methods.

Care of Participants with abnormal test results

All results are reviewed by a consultant ophthalmologist from Moorfields Eye Hospital in London, Mr Paul Foster. If anyone is found to have abnormal results, their GP is contacted, and advised to make a referral to Mr David Broadway, consultant ophthalmologist at the Norfolk and Norwich University Hospital. Systems are in place to make urgent referrals direct to hospital if any test results are found to be very abnormal on the day of examination.

REFERENCES

1.Global data on visual impairment in the year 2002. Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP. Bulletin World Health Organization 2004;82:844-851.
2.Fraser S, Bunce C, Wormald R, Brunner E. Deprivation and late presentation of glaucoma: case control study. BMJ 2001;322(7282):639-643.
3.Evans JR, Fletcher AE, Wormald RP, Ng ES, Stirling S, Smeeth L, Breeze E, Bulpitt CJ, Nunes M, Jones D, Tulloch A. Prevalence of visual impairment in people aged 75 years and older in Britain: results from the MRC trial of assessment and management of older people in the community. Br J Ophthalmol 2002 Jul;86(7):795-800
4.Evans JR, Fletcher AE, Wormald RPL. Age-Related Macular Degeneration Causing Visual Impairment in People 75 Years or Older in Britain. An Add-on Study to the Medical Research Council Trial of Assessment and Management of Older People in the Community. Ophthalmology 2004;111:513-7.
5.Bunce C, Wormald R. Leading causes of certification for blindness and partial sight in England & Wales. BMC Public Health. 2006 Mar 8;6:58.
6.Viswanathan AC, Hitchings RA, Indar A, Mitchell P, Healey PR, McGuffin P, Sham PC. Commingling analysis of intraocular pressure and glaucoma in an older Australian population. Ann Hum Genet. 2004;68:489-97.
7.Yip JL, Machin D, Aung T, Khaw PT, Wong TY, Khaw KT, Seah SK, Foster PJ. Socio-economic status and intraocular pressure: The Tanjong Pagar Study. Br J Ophthalmol 2006