ULTRAVIOLET RADIATION

10.1  Introduction

         Since the early part of this century ophthalmologists have
    suggested an association between sunlight exposure and UV and the
    development of cataracts and other ocular effects (Widmark 1889,
    1901; Hess 1907; Martin 1912; Birch-Hirschfeld, 1914; Verhoeff and
    Bell, 1916; Duke-Elder, 1926b); however, only in the past twenty
    years have epidemiological studies provided a scientific link. UV is
    probably one of a number of factors associated with the development
    of cataract. Despite the number of animal and human studies, many
    questions remain as to the validity of interpretations of past data
    and the biological and physical factors that influence the outcome
    of UV exposure of the eye.

    10.2  The Eye

         The eyeball is deeply set in a bony orbital cavity, and the
    upper bony ridge provides not only protection from mechanical injury
    but also serves as a shield from overhead sky light. The upper and
    lower eyelids (figure 10.1) also provide considerable protection by
    serving as “ shutters” against bright light. The eyeball consists
    of three layers of tissue: (a) an outer protective layer, the sclera
    and cornea; (b) a middle layer of blood vessels, pigment cells and
    muscle fibres called the uvea; and (c) an inner, light sensitive
    layer called the retina.

         The sclera, the outer posterior layer, is a tough, thick,
    opaque tissue formed of collagen fibres. The cornea, the anterior
    transparent part of the eyeball, consists of multiple layers. The
    surface epithelium continues with the surface epithelium of the
    conjunctiva. The epithelial cells are known to be constantly
    changing and the basal layer overlies the Bowman layer. The
    outermost epithelial cells undergo rapid turnover, having a lifetime
    at the surface of approximately 48 hours.

         The main bulk of the cornea, the stroma, consists of highly
    organized collagen fibres in a pattern that makes the cornea
    transparent. The innermost layer, the endothelium, is a single layer
    of an active ion pump (Na-K) that maintains the hydration state of
    the stroma, an important factor for corneal transparency.

         The middle layer of the eyeball consists of the iris
    anteriorly, the ciliary body, and the choroid. The iris is a
    diaphragm that adapts by changing the pupillary size according to
    ambient light level. The iris is formed of mainly pigmented cells of
    various densities, blood vessels and smooth muscle fibres that are
    attached to the anterior part of the ciliary body. The smooth muscle
    fibres form the sphincter and dilator of the pupil.

   

         As part of the middle layer lining the sclera, the choroid
    consists of a meshwork of blood vessels, nerves and pigment cells
    that contribute to the nutrition of the retina and support the
    function of the innermost layer, the retina, that contains the
    photoreceptors and the neuronal network.

         The lens, embryologically of ectodermal (skin) in origin,
    consists of closely and orderly packed transparent elongated lens
    cells that are enclosed in a capsule. New lens cells are constantly
    formed at the so-called lens equator and old ones are displaced
    towards the centre of the lens. The lens is suspended to the ciliary
    body by fine ligaments. The lens shape can be changed by contraction
    or relaxation of the ciliary muscles. This change provides a
    focusing power to the eye that is called accommodation and is made
    possible by the elasticity of the young lens. The lens is avascular
    and obtains its nutrient from the aqueous fluid in front of it and
    the vitreous body that fills the posterior cavity behind it.
    Notably, the lens proteins cannot be renewed and therefore
    accumulate lesions inflicted on them throughout life.

         The photoreceptors, the rods and cones of the retina,
    constitute the primary light receptor with rods functioning at low
    light levels (scotopic vision) and cones operating at high light
    levels (photopic vision). Thus the rod system subserves the function
    of retinal sensitivity, whereas cones provide colour vision, high
    resolution visual acuity and motion perception. The retinal pigment
    epithelium is essential for the maintenance of photoreceptor
    metabolism including, the transport, storage and regeneration of the
    visual pigments.

         Visible light (400-760 nm) incident upon the eye is strongly
    refracted at the cornea, then transmitted through the aqueous humour
    in the anterior chamber to the lens where it is refracted further.
    After transmission through the vitreous gel-like structure, it
    finally reaches the light-sensitive receptors in the retina. It is
    these structures that are primarily damaged by UV and visible
    radiations. The neuronal layers perform the complex task of
    information processing. The primary visual signal is transformed and
    ultimately transmitted to the visual cortex in the brain, thus
    providing the image seen by the eye.

         Most of the UV incident on the eye is absorbed in the tear
    film, the cornea and the lens. The lens and the tissues in the
    anterior part of the eye may however, be exposed to UV at
    wavelengths above 295 nm and the retina is exposed to a fraction of
    the incident UVA. Absorption of UV in the ocular media is given in
    Fig 10.2 (Sliney & Wolbarsht, 1980). Boettner & Wolter (1962)
    measured the transmission of direct forward scattering UV in the
    cornea, aqueous humour, lens and vitreous humour from freshly
    enucleated normal human eyes. The cornea absorbed all UV with
    wavelengths <300 nm, while above 300 nm some UV was transmitted

    through the cornea. About 60% of UV at 320 nm and 80% at 380 nm was
    transmitted through the cornea. The aqueous humour transmitted most
    incident UV (90% transmission at 400 nm) with no evidence of
    scattering.

         Recently Barker and Brainard (1993) quantified the change in UV
    transmittance of the human lens with age. All of these studies
    clearly show the steady decrease in UV transmittance of the lens
    age. At birth there is a small window of transmission to the retina
    at 320 nm. This window almost disappears by the second decade due to
    an age-related yellowing of the human lens. As shown in Fig 10.3 the
    lens absorption is strongest in the 340-380 nm band with somewhat
    less absorption in the 310-320 nm range (Rosen, 1986; Barker and
    Brainard 1993). The human lens is unique in that it contains a UVA
    absorbing filter (O-beta of 3-hydroxykynurenine) which protects the
    retina.

    10.3  Study Design

         This chapter reviews the epidemiological evidence for a causal
    association between exposure to UV and development of specific eye
    diseases which have at some point been linked with exposure to UV.
    Two distinctive types of UV exposure assessments have been used in
    the epidemiological studies. Some studies have related the
    occurrence of eye disease to non-personal factors associated with
    place of residence, such as meteorological data on average annual UV
    dose or average annual hours of sunlight. Other studies have
    obtained estimates of exposure at the individual level (e.g. hours
    of sunshine exposure, lifetime exposure to UV) and related these to
    disease occurrence.

         Three types of epidemiological studies have been used to
    investigate an association with UV exposure: geographical
    correlation studies, cross-sectional studies, and case-control
    studies. In the geographical correlation studies the prevalence of
    eye disease in different areas has been related to non-personal
    factors associated with place of residence. These studies are useful
    for generating hypotheses but of limited value in testing a
    particular hypothesis because observed correlations may result from
    confounding by other factors which also vary geographically, and
    because the level of exposure for persons with the disease is not
    known.

   

   

         The second, and most common type of study design, has been the
    cross-sectional study in which a population or occupational group is
    surveyed and disease prevalence measured. Cross-sectional surveys
    identify all persons with the disease, some of which are new cases
    while other persons may have had the disease for a period of time.
    Some cross-sectional studies have related non-personal factors
    associated with place of residence to disease status. Other studies
    have collected detailed information from each study participant on
    personal exposure to UV or indices of exposure (e.g. hours of
    exposure to sunshine, occupation) and related these exposures to
    disease status.

         The third type of study design has been the case-control study,
    where differences in UV exposure between persons with the disease
    and those without have been compared. Cases have usually been drawn
    from a hospital or clinic. Controls have been drawn from other
    hospital or clinic patients or from the general population and have
    usually only included persons with good visual acuity, without the
    disease of interest, and without a disease that is associated with
    UV exposure. Some case-control studies have related disease status
    to non-personal factors associated with place of residence while
    others have used personal exposure information.

         Data from both cross-sectional and case-control studies can be
    useful in confirming a hypothesis, but have a number of limitations.
    If there is an excess risk of death associated with the disease, as
    has been suggested for cataract (Minassian et al., 1992; Vitale
    et al., 1992), both types of study will be biased towards the
    survivors. In addition, disease status and prior exposure indices
    are measured at the same time and it may not be possible to
    differentiate between cause and effect, especially if the disease
    has a long latency period.

    10.4  Diseases of the External Eye

    10.4.1  Photokeratitis and photoconjunctivitis

         Cases of photokeratitis and photoconjunctivitis have occurred
    between 0.5 and 24 hours after prolonged exposure to intense solar
    radiation, often in highly reflective environments (Wittenberg,
    1986). The most severe cases are usually manifested as snow
    blindness, suggesting that UV is the cause of this condition.

         The action spectrum for UV photokeratitis produced in the
    rabbit was first measured by Cogan and Kinsey (1946). Pitts (1974,
    1978) in a series of laboratory studies on humans estimated the mean
    threshold of UVB (290-315 nm) for photokeratitis at 3500 J m-2.
    These laboratory data are supported by Blumthaler et al. (1987),
    who estimated that the radiant exposures in clinically observed
    cases of photokeratitis ranged from 1200 to 5600 J m-2. It is
    estimated that 100 to 200 seconds of direct, unattenuated exposure

    to 295-315 nm solar radiation will result in photokeratitis (Sliney,
    1987; Wittenberg, 1986). Blotting out the solar disc would remove
    around 40% of the UV, still leaving a threshold of around 5.5
    minutes. Sliney (1986) has estimated that the reflected levels of UV
    from light sand should be sufficient to cause a threshold
    photokeratitis within exposure periods of 6-8 hours centred around
    midday, and within 1 hour for UV reflected from snow.

         Experimental data shows photokeratitis can be induced in
    animals by UVB exposure and that use of UVB absorbing contact lens
    or chromophores can prevent UVB induced photokeratitis in laboratory
    animals. Collectively, there is sufficient experimental and
    epidemiological evidence that exposure to intense UVB radiation
    causes photokeratitis and photoconjunctivitis.

    10.4.2  Climatic droplet keratopathy

         Climatic droplet keratopathy, among a variety of other names
    (Gray et al., 1992), is also known as spheroidal degeneration from
    its histological appearance. It is a degenerative condition usually
    affecting both eyes symmetrically, and restricted to the exposed
    interpalpebral band of the cornea. This condition is of major
    significance for vision in some parts of the world, reducing vision
    to blindness levels in older people. For example, in Mongolia it has
    been found in an initial survey to be the third cause of blindness
    (Baasanhu et al., in press).

         Climatic droplet keratopathy occurs throughout the world, but
    is more common in areas with snowfall persisting late into the
    summer in the northern hemisphere, such as parts of northern Canada,
    Siberia and Mongolia, and in areas of sand and desert in other
    latitudes, including Somalia, the Arabian peninsula, Iran, and
    Australia. It is also particularly common on sea coasts where there
    is coral sand or the sand is impregnated with salt, such as the
    islands of the Red Sea (Gray el al., 1992).

         In a cross-sectional study of Australian aborigines Taylor
    (1980a) found no correlation between the prevalence of climatic
    droplet keratopathy and ambient UVB levels, although the condition
    was more common among those working as stockmen. Johnson (1981)
    reported a geographical correlation with the calculated flux of
    reflected UV from snow and ice throughout the year in the eastern
    coast of Newfoundland and Labrador and the eastern Arctic of Canada.

         In a cross-sectional study of Chesapeake Bay waterman study
    Taylor et al. (1989) examined the risk of climatic droplet
    keratopathy with chronic UVB exposure. Although a positive
    association was found (RR= 6.4, 95%CI=2.5-11.7) for those in the
    highest quarter of exposure compared to those with the bottom
    quarter, further analyses of this data (Taylor et al., 1992)

    showed the risk of climatic droplet keratopathy was also related to
    UVA.

         There is strong evidence that the corneal degeneration is due
    to environmental factors. Circumstantial evidence exists that it is
    caused by solar UV, mainly reflected from ground surfaces such as
    snow and sand which are particularly reflective of UV.
    Histologically, the material deposited in the superficial corneal
    stroma as spheroidal droplets is most likely to be derived from a
    mixture of altered plasma proteins, including fibrinogen, albumin,
    and immunoglobulins (Johnson & Overall, 1978).

         Other proposed aetiological agents such as low atmospheric
    humidity, low temperature or high temperature have been excluded. It
    is possible that particulate injury by wind-blown ice or snow or
    sand particles may contribute to the development of the condition by
    causing inflammation and therefore outpouring of additional plasma
    proteins from the blood vessels of the limbs.

    10.4.3  Pinguecula

         Pinguecula is a fibro-fatty degeneration of the interpalpebral
    conjunctiva. The pathological changes that occur in pinguecula are
    similar to actinic elastosis of the skin, a condition thought to be
    linked to sunlight exposure. This indirect evidence suggests that
    exposure to sunlight may be a risk factor for pinguecula.

         Geographical variation in the occurrence of pinguecula has been
    reported, with higher prevalence in Arabs living near the Red Sea
    than in Eskimos from Greenland or Caucasians in Copenhagen (Norn,
    1982). Johnson et al. (1981) in a study of pinguecula in Labrador
    found the size of pinguecula was correlated with the severity of
    climatic droplet keratopathy. Taylor et al. (1989) in the study of
    Chesapeake Bay watermen found a weak association for the presence or
    absence of pinguecula with exposure to UVA and UVB. The relative
    risk for the top quartile of exposure was 1.4 (95%CI=0.9-2.2), less
    than for climatic droplet keratopathy or pterygium. Karai &
    Horiguchi (1984) in a study of 191 Japanese welders found no
    difference in the occurrence of pinguecula between welders and
    controls.

         It is concluded that there is currently insufficient
    epidemiological or experimental data for an assessment of the risk
    of pinguecula with exposure to UV.

    10.4.4  Pterygium

         Pterygium is a triangular shaped degeneration and hyperplastic
    process in which the bulbar conjunctiva encroaches on the cornea.

         A geographical association between variation in the occurrence
    of pterygium and variation in sunlight exposure was first suggested
    by Talbot (1948). Based on observation of pterygium in New Zealand
    and South Pacific Islands Elliott (1961) suggested pterygium in
    these locations resulted from UV exposure.

         Studies of non-personal factors associated with place of
         residence

         In a study of pterygium patients in US Veterans Administration
    hospitals during 1957-59 Darrell & Bachrach (1963) related mean
    daily UV (319nm) levels to the ratio of pterygium to all hospital
    discharges. A trend was found between UV level and pterygium ratio
    for persons born in rural counties. A similar association with UV
    level was seen for persons residing in a rural county at the time of
    the hospital discharge. Cameron (1965) examined the global pattern
    of pterygium and reported an inverse gradient with latitude. In a
    study of Australian aborigines Taylor (1980a) found pterygium was
    correlated with ambient UVB level and hours of sunshine at place of
    residence. Data from Canada indicates that pterygium is also common
    in arctic and sub-arctic environments (Johnson et al., 1981).
    Moran & Hollows (1984) found a nonsignificant increase in the
    prevalence of pterygium among Australian aborigines residing in
    areas with higher ambient UV levels.

         Studies with personal exposure measurements

         Four studies have related occurrence of pterygium to personal
    measurements. Karai & Horiguchi (1984) examined 191 Japanese welders
    for the presence of pterygium. A trend of increasing risk of
    pterygium was found with years of employment as a welder, an
    indirect measure of cumulative occupational exposure to UV.

         Booth (1985) undertook a hospital-base case-control study of
    pterygium in Sydney. No difference between cases and controls was
    found in subjective assessment of exposure to sunlight in work or
    sport. However, a family history of pterygium was found to be a
    strong risk factor.

         Among Chesapeake Bay watermen, Taylor et al. (1989) found a
    dose-response relationship between risk of pterygium and exposure to
    UVA and UVB. The relative risk for the top quarter of UVB exposure
    was 3.1 (95%CI=1.8-5.3) compared to the lowest quarter. However, it
    is noted that pterygium was equally associated with ocular exposure
    to UVA and visible light.

         Mackenzie et al. (1992) undertook a hospital-based
    case-control study of pterygium in Queensland. A strong
    dose-response relationship was found with closeness of place of
    residence to the equator, type of outdoor work environment (e.g.
    sandy) and amount of time spend outdoors. The most striking finding

    was the magnitude of risk associated with spending most of the time
    outdoors was stronger when related to childhood exposure (RR=17.2,
    95%CI=6.2-47.6) than to adult exposure (RR=5.7, 95%CI=3.1-10.6). The
    risk associated with working at ages 20-29 in an outdoors
    environment of mainly sand or concrete was associated with a
    relative risk of 11.3 compared with indoor workers. Corneo (1993)
    has suggested that the cornea is acting as a side on lens focusing
    light and also UV across the anterior chamber to the nasal limbus.
    This hypothesis may explain why pterygia usually commence on the
    nasal side of the eye.

         Evaluation of epidemiological evidence

         While several geographical studies have reported an inverse
    trend with latitude, the common occurrence of pterygium in arctic
    and subarctic locations suggest that closeness to the equator does
    not fully explain the distribution of this disease.

         The strength of the association with time spent outdoors
    reported by Mackenzie et al. (1992) suggests that the association
    may be causal. However, there is insufficient evidence to show that
    the observed association with UV exposure is not, in part, due to
    confounding. The findings from three of the studies lend support to
    a hypothesis that irritation by particulate matter is associated
    with pterygium. The Australian aborigines live in a dry, dusty
    environment and welders are occupationally exposed to a range of
    particles. Similarly, the Queensland study found highest risk among
    those who worked in sandy locations. The particulate matter
    hypothesis is also supported by a report (Dhir et al., 1967) of
    higher prevalence of pterygium among Punjabi Indians working in
    sawmills (an indoor occupation) in New Delhi and British Columbia
    than Punjabi farmers (an outdoor occupation). Similar findings of
    increased risk of pterygium among sawmill workers in Thailand and
    Taiwan have been reported (Detels & Dhir, 1967). The evidence of
    possible confounding by particulate matter is inconsistent, with the
    Chesapeake Bay watermen study finding an association with sunlight
    exposure in a location that was neither hot, dry or dusty.

         It is not possible, based on available epidemiological data, to
    assess the risk of pterygium with exposure to UV because of possible
    confounding of observed associations by exposure to particulate
    matter or other factors.

    10.4.5  Hyperkeratosis, carcinoma-in-situ, and squamous cell
            carcinoma of the conjunctiva

         These conditions probably form a gradation of development and
    cannot necessarily be distinguished clinically. Invasive squamous
    cell carcinoma is often said to arise from a pre-cancerous lesion.
    Epithelial dysplasia and carcinoma-in-situ look the same, and are
    sometimes keratinized and present as leucoplakia in which case the

    term actinic keratosis may be applied (Naumann & Apple, 1986;
    Garner, 1989). The main argument for an actinic causation is that
    these tumours usually present in the exposed area of the eye between
    the lids (the interpalpebral fissure) and under conditions where
    they may be expected to be exposed to solar radiation.

         Xeroderma pigmentosum is a recessively inherited syndrome
    characterized by clinical and cellular hypersensitivity to solar
    radiation and a defect in the capacity to repair UV-induced damage
    in DNA (Fitzpatrick, et al., 1963). Among reports of 337 patients
    with xeroderma pigmentosum for whom ocular findings had been
    described, Kraemer et al. (1987) identified 88 ocular tumours of
    which 73 were specific to the corneal-scleral limbus (34), the
    cornea (24) or the conjunctiva (15). Of the non- melanomas for which
    histopathological type was specified, 28 were squamous cell
    carcinomas and 12 were basal cell carcinomas. Among 64 patients with
    ocular neoplasms whose age was stated, half the neoplasms had
    occurred before 11 years of age. While the eyelids are a site of
    preference for basal cell carcinoma, this tumour rarely, if ever,
    arises in the conjunctiva in otherwise normal individuals.

         Squamous cell carcinoma of the conjunctiva is an uncommon
    tumour. Garner (1989) reviewed all cases of tumours at the limbus
    sent over a 40 year period for examination to the Institute of
    Ophthalmology, London. The total was only 636 tumours, of which 73
    were squamous carcinomas. This amounts to less than 2 cases per year
    coming to the Pathology Laboratory, even though Moorfields Eye
    Hospital which the Laboratory serves, attracts patients from all
    over the country and from overseas.

         Lee & Hirst (1992) attempted to provide population-based
    figures and estimate the incidence of these tumours in metropolitan
    Brisbane (latitude 30° south). They surveyed the histological
    records of all ocular surface tumours examined in the pathological
    laboratories over the previous 10 years, serving a population of
    more than 745,000 in 1989. There were 139 cases of which 79 were
    corneal epithelial dysplasia, 28 carcinomas-in-situ and 32 were
    squamous cell carcinomas. There was a strong male preponderance. The
    incidence ranged from 1 per 100,000 in 1980 to 2.8 per 100,000 in
    1982. This is well below the rate for squamous cell carcinoma of the
    skin and melanoma of the skin in Queensland as a whole. On the other
    hand, it is a substantially higher rate than that recorded in London
    where the pathological laboratory referred to also covers a much
    larger population.

         Squamous cell carcinoma of the conjunctiva has been reported to
    form a greater proportion of eye tumours in Africans living in areas
    close to the equator (Templeton, 1967) than in the south of Africa
    (Higginson & Oettlé, 1959), and much higher than in Baltimore
    (39°N). The incidence (0.3 per 100,000) in Uganda (0°) has been

    reported to be twice that in Denmark (55°N) despite the potential
    underascertainment in Africa (Templeton, 1967).

         It is extremely rare for a neoplasm to arise de novo in the
    corneal epithelium, where it may be called a corneal intra-
    epithelial neoplasm. Most such intra-epithelial sheets are connected
    at the corneo-scleral limbus to a conjunctival lesion, such as a
    papilloma or a leucoplakia over a pterygium or pinguecula (Waring
    et al., 1984). The only available evidence for an UV aetiology is
    the location of the lesion within the interpalpebral fissure, and
    the fact that it may arise from a lesion which is itself associated
    with UV. Three cases of corneal intra-epithelial neoplasia have been
    recently reported in people aged 31 to 38 who wore contact lenses
    and were considered to have had substantial exposure to artificial
    and solar UV (Guex-Crosier & Herbort, 1993).

    10.5  Diseases of the Lens

    10.5.1  Cataract

         For the purpose of this review, a cataract is defined as an
    opacity of the lens of the eye. The three major types of cataract
    are cortical, nuclear and posterior subcapsular (PSC). When a lens
    opacity interferes with vision, a clinically significant cataract is
    present. If left untreated, cataract will often progress to
    blindness. Cataract causes half of the world’s blindness.

         Definitions of cataract and methods used to assess the presence
    and severity of cataract have not been uniform in epidemiological
    studies of cataract. Many studies include lens opacities that are
    not necessarily accompanied by a decrease in visual acuity. Some
    have combined all three major types of lens opacities into a single
    “cataract” category, while others have investigated associations for
    specific types of opacity. Methods of assessing the presence and
    sometimes the severity of opacities range from reviews of existing
    charts to clinical examinations using written definitions of
    cataract, and the use of standardized grading systems that have been
    found to be highly reliable.

         Occupational case series

         When cataracts result from occupational exposure to UV, it may
    be difficult to differentiate between the contribution of
    occupational and non-occupational factors to the development of the
    disease. Lerman (1980) described the onset of lens opacities in
    three persons who worked in a dental clinic and were exposed to UV
    (300-400 nm) from a dental curing unit. The lens damage varied from
    posterior subcapsular cataract in the dentist, who was reported to
    have received the highest dose, to zonular type opacities in one of
    the dental assistants. However, any retrospective reconstruction of

    the actual ocular exposure has a large degree of uncertainty, and
    the results from such an exercise must be interpreted with caution.

         Studies in which UV exposure was inferred from place of residence

         Selected studies of humans exposed to solar UV are presented in
    tables 10.1 and 10.2. Studies were selected for inclusion in the
    tables on the basis of the scientific quality of the published
    report and the overall contribution of the paper to the evaluation
    of the UV-cataract hypothesis. The tables do not include the
    relative risks for other factors, which in some instances are higher
    than for sunlight or UV exposure.

         Hiller et al. (1977) investigated sunlight and cataracts
    using data from the large sources (blindness registries in 14 states
    and the cross-sectional Health and Nutrition Examination Survey
    (HANES) of 35 geographic areas of the US) and US Weather Bureau
    geographical data on annual hours of sunlight in each geographical
    area. Above the age of 65 the prevalence of cataract increased with
    annual hours of sunlight, with the highest prevalence found in
    locations with 3000+ annual hours of sunshine. At ages 45-64 there
    was some evidence of an association with hours of sunshine but the
    gradient was weaker. Below age 45 there was little association
    between annual hours of sunshine and prevalence of cataract. In a
    further analysis of HANES data Hiller et al. (1983) reported a
    correlation between average daily UVB levels and prevalence of
    cataract. Analysis of HANES data by type of cataract (Hiller et
    al., 1986) revealed UVB levels at location of residence were
    associated with pure cortical cataract but not with pure nuclear or
    posterior subcapsular cataract.

         The prevalence of cataract among Australian aborigines was
    found to be correlated with annual ambient UVB level at place of
    residence (Taylor et al., 1980b). Hollows & Moran (1981) found the
    prevalence of cataract was highest among aborigines living in the
    north of Australia, an area with high average daily UVB radiation.
    Mao & Hu (1982) studied age related cataract in seven rural areas of
    China and found the prevalence of cataract was correlated with
    annual direct solar radiation.

         Residents of rural villages in Nepal had a prevalence of
    cataract related in different zones of the country to average hours
    of sunshine (Brilliant et al., 1983). The prevalence was higher in
    the plains where there were 12 hours of direct sunshine compared to
    the mountains with 7-9 hours per day. Factors such as use of glasses
    and hats modify personal ocular exposure to UV and should be
    assessed.

   
    TABLE 10.1  SELECTED HUMAN CATARACT STUDIES WITH SUNLIGHT OR UV EXPOSURE BASED ON RESIDENCE
                                                                                                                                              
    AUTHOR           POPULATION             MEASURE OF            MEASURE OF               ASSOCIATIONS OBSERVED      COMMENTS
                                            OUTCOME               SUNLIGHT EXPOSURE
                                                                                                                                              

    Hiller et al.    MRA: 9110 persons      Blind from cataract,  Average hours of         RR= 3.3 (age 65-74)        Adjusted for age and
    (1977, 1983,     registered as blind    visual acuity (VA)    sunlight < 2400 vs                                  sex; blind registry data
    1986)            in 14 US States;       6/60                  3000+
                     whites;

                     NHANES: 3580 persons;  Lens opacity and VA   Average hours of         RR= 2.7 (age 65.74)        Adjusted for age and sex
                     probability sample of  < 6/7.5               sunlight < 2400 vs
                     US population;                               3000+

                     NHANES data            Lens opacity and VA   Average daily UVB        RR= 1.58 (age 45-74,       Adjusted analysis
                                            < 6/9                 count in area of         p<.05)
                                                                  residency 6000 vs 2600

                     NHANES data            Nuclear and cortical  Average daily UVB        RR= 3.6 for cortical       Adjusted analyses; pure
                                            opacity               count in area of         opacity; no association    opacity types only
                                                                  residency 6000 vs 2600   with nuclear opacity

    Taylor (1980b)   Survey of 350          Lens opacity with     Average daily sunlight   RR= 4.2 (95% CI=0.9-18.91  Unadjusted for age or
                     Australian Aborigines  good vision, poor     hours in area of                                    potential confounding
                                            vision or blindness   residence: 9.5+ vs < 8                              factors

                                                                  Annual mean UVB          RR= 1.8 (95%ci=0.9-3.4)1
                                                                  radiation level for
                                                                  area of residence:       1 95%CI estimated from
                                                                  3000 vs 2000             published data

    Hollows & Moran  Survey of 64,307       Lens opacity and VA   Average daily UVB        Significant positive       Wide age bands;
    (1981)           Aborigines and 41,254  < 6/6                 count in 5 zones of      correlation between        unadjusted analyses
                     non-Aborigines,                              Australia: 3000 vs       prevalence of lens
                     Australia                                    1000                     opacity and UVB counts
                                                                                           in Aborigines; no
                                                                                           association in
                                                                                           non-Aborigines

    TABLE 10.1 (contd).
                                                                                                                                              
    AUTHOR           POPULATION             MEASURE OF            MEASURE OF               ASSOCIATIONS OBSERVED      COMMENTS
                                            OUTCOME               SUNLIGHT EXPOSURE
                                                                                                                                              

    Brilliant et     Survey of 27,785       Lens opacities or     Average daily sunlight   RR= 3.8 (p<.001)           Adjusted for age and
    al. (1983)       Nepalese; national     aphakia               hours: 12 vs 712 vs                                 sex; RR decreased with
                     probability sample;                          7-9                                                 increasing altitude; sun
                     lifelong residents;                                                                              blocked by mountains at
                                                                                                                      high elevations

                                                                  12 vs 712 vs 7-9         RR= 2.6 (p<.005)

    Cruickshanks et  Cross-sectional        Nuclear, cortical     Average annual ambient   UVB exposure associated    Adjusted for other risk
    al. (1993)       survey of 4926         and PSC opacities     UVB exposure             with cortical opacities    factors; measure of
                     persons, Wisconsin,                                                   in men (RR=1.36,           exposure represents
                     USA                                                                   95%CI=1.02-1.79) but not   average potential
                                                                                           women, not associated      exposure at residency;
                                                                                           with nuclear or PSC        also Table 9.2
                                                                                           opacities
                                                                                                                                              

    TABLE 10.2  SELECTED HUMAN CATARACT STUDIES WITH INDIVIDUAL UV EXPOSURE ASSESSMENT
                                                                                                                                              
    AUTHOR        POPULATION             MEASURE OF         MEASURE OF SUNLIGHT          ASSOCIATIONS OBSERVED               COMMENTS
                                         OUTCOME            EXPOSURE
                                                                                                                                              

    Collmann et   Clinic-based case      Nuclear, cortical  Average annual sunlight      No significant association with     Low power to
    al. (1988)    control study of 113   and PSC opacities  exposure, based on           any type of opacity                 detect
                  cases and 168                             residential history and                                          association;
                  controls, North                           amount of time spent in sun                                      matched on age
                  Carolina, USA; whites                                                                                      and sex

    Taylor et     Cross-sectional        Nuclear and        Cumulative ocular exposure   Dose-response relationship in       High exposure
    al. (1988)    survey of 838          cortical           to UV since age 16, based    which a doubling of cumulative UVR  study population;
                  watermen, Maryland,    opacities          on life history and ocular   exposure increased risk of          detailed ocular
                  USA                                       exposure model               cortical opacity by 1.60            exposure model
                                                                                         (95%CI=1.01-2.64). RR= 3.30
                                                                                         (95%CI=0.90-9.97) for highest vs
                                                                                         lowest quartile. No association
                                                                                         between ocular exposure to UVR and
                                                                                         nuclear opacity

    Bochow et     Clinic-based           PSC cataract       Cumulative ocular exposure   Increased levels of UVB exposure    Adjusted analyses;
    al. (1989)    case-control study of  (surgical          since age 16, based on life  associated with increased risk of   association
                  168 cases and 168      patients)          history and exposure model   PSC cataract                        present when
                  controls, Maryland,                                                                                        adjusted for
                  USA                                                                                                        cortical cataract

    Dolezal et    Clinic-based           Cataract           Lifetime sunlight exposure,  No association between lifetime     Only partially
    al. (1989)    case-control study of  (scheduled for     based on life history,       sunlight exposure and risk of       adjusted for
                  160 cases and 160      surgery)           amount of time in sun and    cataract; use of head covering      potential
                  controls, Iowa, USA                       use of glasses and hat       reduced risk of cataract in males   confounding
                                                                                         (RR=0.48, 95%CI=0.25-0.94)          factors; crude
                                                                                                                             index of exposure,
                                                                                                                             low power

    TABLE 10.2 (contd).
                                                                                                                                              
    AUTHOR        POPULATION             MEASURE OF         MEASURE OF SUNLIGHT          ASSOCIATIONS OBSERVED               COMMENTS
                                         OUTCOME            EXPOSURE
                                                                                                                                              

    Italian-Am.   Clinical-based         Nuclear,           Work location in the         Cortical and mixed opacities        Adjusted for other
    study (1991)  case-control study of  cortical, PSC and  sunlight; leisure time in    associated with work location in    risk factors;
                  1008 cases and 469     mixed opacities    the sunlight; use of         sunlight (RR=1.75,                  crude indices of
                  controls, Italy                           glasses and hat              95%CI=1.15-2.65), leisure time in   exposure; also
                                                                                         sunlight (RR=1.45,                  Table 9.1
                                                                                         95%CI=1.09-1.93). Cortical, PSC
                                                                                         and mixed opacities associated
                                                                                         with use of a hat in summer
                                                                                         (RR=1.80, 95%CI=1.17-2.47). No
                                                                                         association between sun exposure
                                                                                         indices and nuclear opacities

    Leske et al.  Clinical-based         Nuclear, cortical  Work in sunlight; leisure    Work in sunlight significantly      Analyses adjusted
    (1991)        case-control study of  and PSC mixed      time in sun; residence and   reduced risk of nuclear opacity     for other risk
                  945 cases and 435      opacities          travel to areas of high sun  (RR=0.61, 95%CI=0.37-0.99); no      factor
                  controls,                                 exposure, use of hat and     significant associations between
                  Massachusetts, USA                        sunglasses                   exposure and cortical or PSC
                                                                                         opacities

    Cruikshanks   Cross-sectional        Nuclear, cortical  Leisure and work time        No associations with cortical       Adjusted for other
    et al.        survey of 4926         and PSC opacities  outside; use of glasses and  opacities; reduced risk of nuclear  factors; crude
    (1993)        persons, Wisconsin,                       hat                          and PSC opacities amount men for    indices of
                  USA                                                                    outdoor leisure time in winter;     exposure; also
                                                                                         use of hats and sunglasses          Table 9.1
                                                                                         significantly increased risk of
                                                                                         PSC opacity in women
                                                                                                                                              

   
         Age and sex adjusted prevalence for all types of cataract in
    persons aged 40 years and older was found to be 60% greater in Tibet
    than in Beijing (14.6% versus 9.1%, p>0.001) (Hu et al., 1989).
    The authors suggested a relationship with higher UV at the higher
    altitudes of Tibet, but confounding factors could not be excluded
    and prevalences were higher in women than men.

         Studies with personal exposure measurements

         A number of studies have collected information from each study
    participant and estimated personal exposure to either sunlight or
    UV. Factors such as use of glasses and hats should be assessed. The
    characteristics of selected studies are outlined in Table 10.2.

         In a cross-sectional study of cataract in the Punjab related
    prevalence of cataract to work environment Chatterjee et al.
    (1982) found a suggestion of lower cataract incidence among men
    whose main work location was outdoors (RR=0.7, 95%CI=0.5-1.1).

         Collman et al. (1988) examined lifetime exposure to sunlight
    in a clinic-based case-control study of cortical, nuclear or PSC.
    Lifetime exposure to sunlight was estimated from intensity of solar
    radiation in area of residence, years of residence and average
    amount of time spent outdoors during daylight hours. A
    non-significant risk (RR=1.1) of cataract was found for the highest
    category of lifetime exposure to sunlight.

         Personal exposure history and ambient UVB data were combined to
    estimate an individual’s lifetime annual ocular exposure to UVB
    after age 15 in a cross-sectional study of Chesapeake Bay watermen
    (Taylor et al., 1988). This included information on occupational
    and leisure exposures, type of work surfaces, seasons, and use of
    head wear and eyewear. A moderate association with a trend of
    increasing risk with exposure to UVB was seen for cortical cataract,
    with a RR of 3.3 (95%CI=0.9-10.0) for the top quarter of exposure
    relative to the bottom quarter. A nonsignificant association was
    also found between exposure to UVA (320 -340 nm) and prevalence of
    cortical cataract. Little evidence was found for an association
    between UVA or UVB exposure and nuclear cataract. It is noted that
    UVA and UVB exposures were highly correlated and that the study
    would not have been able to differentiate between the effects of UVA
    and UVB. Further analyses suggested a significant difference between
    the cumulative lifetime ocular exposure among cases of cortical
    cataract compared to non- cataract controls. No threshold or latency
    period was observed.

         In a clinic-based study of PSC cataracts in Maryland, cases
    were persons who underwent PSC extraction in an ophthalmic practice
    (Bochow et al., 1989). Controls, matched on age, sex, and type of
    referral were chosen from other patients on the appointment book of

    the same ophthalmic practice who did not have a PSC cataract or a
    previous cataract extraction. Annual and cumulative ocular UVB
    exposures were estimated for each individual using the same method
    as the studies of Chesapeake Bay watermen. Thirty-nine percent of
    cases had a pure PSC cataract, the remaining 61% had mixed PSC and
    other cataracts. Almost half the controls had a non PSC cataract
    (nuclear, cortical or other lens opacity). UVB exposure was
    significantly associated with PSC cataracts. Both the average
    cumulative exposure and average annual exposure were higher in cases
    than controls, after adjusting for steroid use, eye colour,
    education, diabetes and presence of cortical cataracts.

         In a hospital-based study of cataract patients in Iowa Dolezal
    et al. (1989) found little evidence of an association between
    individual lifetime sunlight exposure and cataract. Mohan et al.
    (1989) in a similar study of cataract in New Delhi examined a range
    of environmental factors, including occupation. An increase in cloud
    cover was significantly associated (RR=0.8, 95%CI=0.7-0.9) with
    cataract when adjusted for each of the other environmental
    variables. The study did not quantify individual lifetime exposure
    to sunlight or UV.

         In a study of cataract patients in a Massachussetts hospital,
    Leske et al. (1991) investigated occupational exposure to
    sunshine. No association was found for PSC cataract (RR=1.3,
    95%CI=0.7-2.3), cortical cataract (RR=0.9, 95%CI=0.6-1.3), or mixed
    cataract (RR=0.8, 95%CI=0.6-1.1) among those with at least 2 hours
    of exposure to bright sunshine per day for at least 2 months. The
    risk of nuclear cataract was reduced (RR=0.5, 95%CI=0.3-0.9).

         A hospital-based study from Italy (Italian-American Cataract
    Study Group, 1991) found an excess of pure cortical and mixed
    cataract (RR=1.8, 95%CI=1.2-2.6) and a nonsignificant deficit of
    nuclear (RR=0.6) and PSC cataract (RR=0.8) among those with a work
    location in the sunlight. Leisure time spent in the sunlight was
    associated with an excess of cortical and mixed cataract (RR=1.4,
    95%CI=1.1-1.9) and a nonsignificant deficit of posterior subcapsular
    cataract (RR=0.6).

         In an Indian clinic-based study of cataract and history of
    severe diarrhoeal diseases Bhatnagar et al. (1991) found an
    elevated risk of cataract (RR=2.1, 95%CI=1.2-3.6) for outdoor
    occupations compare with indoor occupations. However Zaunuddin &
    Saski (1991) found no relationship between hours of exposure to
    sunshine and prevalence of nuclear or cortical cataract in Sumatra
    (0° latitude). In Beaver Dam, Wisconsin, Cruickshanks et al.
    (1993) found no association between average annual exposure to UVB
    and cortical, PSC or nuclear cataract. Wong et al. (1993) surveyed
    fishermen in Hong Kong. A sun exposure score was calculated based on
    daily sunlight exposure, and protection from use of a canopy, hat,
    and glasses. The highest grades of cataract of all types considered

    together were more common in subjects with the highest sun exposure
    scores, but none of these associations was significant at the 5%
    level. A population-based case-control study (Shibati et al.,
    1993) reported an increased risk of cortical cataract among men aged
    40-50 years who spent 5 or more hours per day outdoors compared with
    those who spent less time outdoors (RR = 6.89; 95%CI = 1.22-39).

    Evaluation of epidemiological evidence

         An association has been demonstrated between prevalence of
    cataract and residence in areas at low latitudes, with long hours of
    sunlight or high ambient UV radiance in several studies undertaken
    in different parts of the world. However, in each study, the
    observed association may be confounded by other possibly causal
    factors. Certain of the earlier studies did not classify the lens
    opacities into types of cataract.

         Cortical cataract was examined separately in four studies. Only
    one study assessed individual exposure. Taylor et al. (1988) found
    a dose-response relationship with exposure to UVB radiation. The
    relative risk for the highest exposure category was three times that
    for the lowest exposure category. It is unlikely that the exposure
    assessment was able to distinguish between UVA and UVB exposure. The
    other two used simple measures of sun-related behaviour. Leske et
    al. (1991) found no association between exposure to bright
    sunshine and cortical cataract, while in the Italian-American
    Cataract Study (1991), a work location in the sunlight was related
    to cortical and mixed cataract. The Italian study also found an
    association between leisure time outdoors and cortical and mixed
    cataract. The other two studies showed non-significant trends in
    opposite directions. More recently, Cruickshanks et al. (1993)
    found annual UVB exposure was associated with cortical opacities
    among men, but no association was found for women.

         Four studies report risk estimates for posterior subcapsular
    (PSC) cataracts. Bochow et al. (1989) measured individual exposure
    and found PSC cataract patients had higher annual and cumulative
    exposures to UVB than controls, even after allowing for the effects
    of several other factors. The other two studies used simple measures
    of sun-related behaviour and showed non-significant trends in
    opposite directions. Leske et al. (1991) found elevated risk for
    pure PSC cataract patients compared to controls. However, the
    Italian-American Cataract Study (1991) reported reduced risk for
    pure PSC cataract patients with a work location in the sunlight or
    who spent leisure time in the sunlight. Cruickshanks et al. (1993)
    found no association between annual UVB exposure and risk of PSC
    cataract.

         Five studies provide risk estimates separately for nuclear
    cataracts. These studies are consistent in showing no association
    between UV exposure and nuclear cataract (Taylor et al., 1988;

    Dolezal et al., 1989; Leske et al., 1991; The Italian-American
    Cataract Study, 1991; and Cruickshanks et al., 1993). Collectively
    these studies are consistent in showing no association between UV
    exposure and nuclear cataract.

         All of the published epidemiological studies of UV and cataract
    have been challenged by the enormous difficulty of determining
    ocular exposure in different climates. As noted previously, the
    cornea and lens are seldom directly exposed to light rays from much
    of the sky; hence the sunlight scattered from the ground and the
    horizon determine the actual accumulated UV dose.

         These studies clearly demonstrate that UV is at least one
    aetiologic factor in cataractogenesis. However, extrapolation of
    strong associations found in a mid-latitude population where no
    serious nutritional problems are present (e.g. Taylor, et al.,
    1988) to a tropical population in less developed regions, may not be
    valid, since the contribution of UV relative to other factors such
    as malnutrition and dehydration may be far more important.

    10.5.2  Exfoliation syndrome

         The exfoliation syndrome (pseudoexfoliation of lens capsule)
    consists of abnormal material deposited on or arising from various
    parts of the anterior eye. This condition was originally described
    from Finland by Lindberg (1917). In the Nordic countries it
    contributes to a high proportion of glaucoma in the older
    population. This appears as a round area in the centre of the
    anterior lens capsule, corresponding to normal pupil size, on which
    bluish-grey flakes are deposited. This is surrounded by a clear
    zone, which in turn is surrounded by a peripheral band of
    involvement as well. On the border of the pupil it looks like
    “dandruff”. Similar material is trapped in the pores of the
    trabecula meshwork and may be seen on the ciliary processes, on the
    zonulas, surrounding the conjunctival vessels and in retro-orbital
    tissues. It is a basement membrane material, akin to amyloid in some
    respects, although many histochemical studies do not support this
    identification.

         The prevalence varies enormously from country to country, and
    even within countries. The highest prevalence was found in the
    Navajo Indians of New Mexico, in which 38% were over 60 years of
    age. At the other extreme, only 2 cases have ever been recorded in
    Eskimos, and these were two Greenlanders, possibly of mixed
    ancestry, aged over 70 years (Ostenfeld-Åkerblom, 1988). The average
    prevalence in central Europe is around 2% on the basis of figures
    from several authors (Forsius, 1988).

         The possibility of environmental factors was proposed by Taylor
    (1979) based on observations of exfoliation in Australian

    aborigines. The distribution of exfoliation was linked to annual
    global radiation and to climatic droplet keratopathy.

         Exfoliation syndrome sometimes occurs in other areas of high
    UV, and high prevalence of climatic keratopathy. Examples include
    Somalia, Djibouti and Saudi Arabia. There is, however, considerable
    evidence to suggest that UV is not the main factor associated with
    the development of exfoliation. The geographic distribution does not
    consistently correspond with that of climatic keratopathy. There may
    be wide differences in prevalence of exfoliation syndrome at similar
    latitudes. For example, it is frequent in parts of East Africa, but
    rare in West Africa. Similarly it may be seen at high prevalence in
    the Lapps of Finland and Sweden, but not in Eskimos at the same
    latitude. The prevalence may vary within the same country. A total
    of 4,042 patients aged over 50 were examined in clinics in 6 areas
    in different parts of France over a 2 week period. The prevalence
    was high in Brittany (20.6% in those over 60 years) and extremely
    rare in Picardy at a similar latitude (Colin et al., 1985).
    Exfoliation is usually more frequent in females than males. It is
    found in parts of the eye, such as the ciliary body and in the
    orbit, remote from the influence of light. Forsius (1988) has
    reviewed the evidence for genetic aetiology for the condition.

         The present conclusion is that environment, at least in the
    form of UV, is not the primary cause. There is not a consistent
    direct relationship with solar radiation. There is at least a major
    racial or genetic predisposition, but it is possible that light or
    some other environmental factor activates or induces the development
    of the exfoliation syndrome in those who are genetically
    predisposed.

    10.5.3  Anterior lens capsule

         In 1989 a previously unrecorded condition was reported from
    Somalia (Johnson et al., 1989). This consisted of alterations of
    the pupillary area of the anterior capsule of the lens. The first
    stage appeared to be an opalescence of the capsule, which then
    became a plateau-shaped elevation above the surrounding contour of
    the anterior lens. In its most developed form it was a bagging of
    the anterior lens capsule and contents through the pupil, appearing
    like a hernia. This condition was invariably associated with
    climatic droplet keratopathy, but not necessarily with cataract. In
    fact, there appeared to be an inverse relation with cataract.

         The absolute association with climatic keratopathy suggests
    that it also may be due to excessive UV exposure. Attempts to secure
    histology on extracted lenses with this condition were difficult
    because the lens capsule so frequently tore from the rest of the
    lens as it was extracted by the cryoprobe. The capsules examined
    showed thinning and splitting of the layers, and death of many of
    the nuclei of the epithelial cells. However, there were no controls

    from the same geographical and ethnic area of the same ages for
    comparison.

    10.6  Diseases of the Choroid and Retina

         Among adults, only extremely small amounts of UVA and UVB at
    wavelengths below 380 nm reach the retina, because of the very
    strong absorption by the cornea and lens. Less than 1% of radiation
    below 340 nm and 2% of radiation between 340 and 360 nm reaches the
    retina (Barker and Brainard, 1993). Even in early childhood the
    highest spectral transmittance reaches about 4% in the UVB and is
    generally of the order of 1%. However, because of the biological
    activity of the shorter wavelengths of UVB, the biological
    importance of the small amount of this radiation that does reach the
    retina cannot be completely neglected. As children age, UV is
    increasingly absorbed by the cornea and lens, and the proportion
    reaching the retina decreases. This suggests firstly, that exposure
    to UV during childhood may be of more importance than exposure to UV
    during adult life, and secondly, that exposure to longer wavelength
    radiation (e.g. visible light) may be of more importance in
    adulthood.

    10.6.1  Uveal melanoma

         Exposure to solar radiation is considered to be causally
    associated with the development of cutaneous malignant melanoma
    (IARC, 1993). There is a possibility that exposure to UV may also
    cause melanoma of the uveal tract. There is no separate ICD code for
    intra-ocular melanoma, so descriptive studies have generally been
    based on cancer of the eye (ICD-9 190), of which it has been
    estimated that 80% are intra-ocular melanomas (Osterlind, 1987). In
    the case-control studies cases of uveal-tract melanomas were
    confirmed histologically, but also included tumours of iris and
    ciliary body with those of the choroid.

         The incidence of cancer of the eye is higher among white than
    black or Asian populations residing at the same latitude. For
    example, in US whites the incidence rates are 0.7 per 100 000 person
    years in males and 0.6 in females compared with 0.2 in both sexes in
    blacks (Parkin et al., 1992). Among people of European ancestry,
    risk of ocular melanoma was observed to be least in those of
    southern European ethnic origin; for example, in comparison with an
    RR of 1.0 in those of southern European origin, the RR in people of
    northern European origin was 6.5 (95% CI 1.9-22.4; Seddon et al.,
    1990). Risk of ocular melanoma was observed to be increased in those
    with light eye colour, with RRs of 1.7 to 2.1 (Gallagher et al.,
    1985; Tucker et al., 1985c; Holly et al., 1990), but not when
    ethnicity was taken into account (Seddon et al., 1990). Kraemer
    (1987) found five cases of ocular melanoma among reports of 337
    patients with xeroderma pigmentosum for whom ocular findings had

    been described. The defect in this condition is failure to repair
    DNA after damage by UV.

         There is no evident latitude gradient in incidence of ocular
    melanoma in white populations of the northern hemisphere or
    Australia (IARC, 1992) and, within the USA, its risks in those born
    in southern parts of the country, where ambient solar radiation is
    highest, has variously been reported to be more (Tucker et al.,
    1985c), less (Seddon et al., 1990) or the same (Schwartz & Weiss,
    1988; Mack & Floderus, 1991) as that in those born elsewhere in the
    country. Similarly Gallagher et al. (1985) in Canada found no
    association with latitude of residence.

         Two studies have examined place of birth and risk of uveal
    melanoma, but the findings are inconsistent. Tucker et al. (1985)
    found an excess of cases were born south of latitude 40°N, whereas
    Seddon et al. (1990) found a deficit.

         Indicators of personal sun exposure have been inconsistently
    associated with risk of cancer of the eye or ocular melanoma. A
    small rural excess in incidence of cancer of the eye has been
    reported (Doll, 1991). Two descriptive studies reported an
    association with farming (Saftlas et al., 1987; Gallagher, 1988)
    but this was not found in several other such studies (Milham, 1983;
    Office of Population, Censuses and Surveys, 1986; Vågerö et al.,
    1990) or two case-control studies of ocular melanoma (Gallagher et
    al., 1985; Seddon et al., 1990). Some high exposure activities
    such as gardening (RR 1.6, 95% CI 0.7-1.6) and taking sunny
    vacations (RR 1.5, 95% CI 1.0-2.3, for highest category) were
    significantly associated with increased risks of ocular melanoma in
    one case-control study (Tucker et al., 1985c) but no similar
    associations with personal sun exposure at work in leisure time, or
    in vacation were found in three other studies (Gallagher et al.,
    1985; Holly et al., 1990; Seddon et al., 1990). Indeed,
    Gallagher et al., (1985) found an elevated risk for government
    workers, a predominantly indoor managerial group. The lack of use of
    protective eyewear (sunglasses, visors, headgear) was associated
    with an increased risk of ocular melanoma in one study (Tucker et
    al., 1985c) with an RR for infrequent or rare use of 1.6 (95% CI
    1.2-2.2). Weak evidence of a similar effect was found by Seddon et
    al. (1990).

         No statistically significant association has been observed
    between ocular melanoma and a personal history of skin cancer in
    several studies of cancer registry or other data (Osterlind et al.,
    1985; Tucker et al., 1985a; Holly et al., 1991; Lischko et al.,
    1989; Turner et al., 1989).

         There is evidence of associations between exposure to sunlamps
    and some other artificial sources of UV and risk of ocular melanoma
    in the three case-control studies in which they have been examined.

    Tucker et al. (1985c) found a relative risk of 2.1 (95% CI
    0.3-17.9) for frequent use of sunlamps compared with no use (p=0.10
    for trend over four categories of use); Holly et al. (1990) found
    a relative risk of 3.7 (95% CI 1.6-8.7) for ever having an exposure
    to “artificial UV or black light” and with welding burn, sunburn to
    eyelids, or snow-blindness, RR 7.2 (95% CI 2.5-20.6); and Seddon et
    al. (1990) found a relative risk of 3.4 (95% CI 1.1-10.3) for
    frequent or occasional use of sunlamps compared with never used. In
    one of these studies, there was also a strong association with
    employment as a welder (RR 10.9, 95% CI 2.1-56.5; Tucker et al.,
    1985c). No similar association was found by Seddon et al. (1990)
    but an increased risk in welders (RR 8.3, 95% CI 2.5-27.1) was found
    in an occupational study of French Canadians (Siemiatycki, 1991).

         Overall, the epidemiological studies do not provide convincing
    evidence of an association between exposure to solar UV and uveal
    melanoma. None of the studies has developed a practical assessment
    of individual cumulative ocular exposure to UVB. They have all used
    various simple estimates of sun-related behaviour.

         On the other hand, the use of a sunlamp, an artificial source
    of UV, was significantly associated with uveal melanoma in the two
    case-control studies that examined their use. Another study found
    elevated risk of uveal melanoma with exposure to UV or black lights.
    Collectively, these studies suggest frequent use of a sunlamp may be
    associated with a 2-4 fold increase in risk of developing uveal
    melanoma. Sunlamp use can produce over five-fold more DNA damage per
    unit of erythema than the sun (Nachtwey & Rundel, 1981).

         The large number of ocular melanomas in xeroderma pigmentosum
    patients also means that exposure to UV cannot be ruled out as a
    causative factor.

    10.6.2  Age-related macular degeneration

         Age-related macular degeneration (AMD) is one of the leading
    causes of blindness in the industrialized world. Visual loss can
    occur because of the development of geographic atrophy (loss of the
    outer retinal segments and retinal pigment epithelium), retinal
    pigment epithelial detachment or sub-retinal neovascularization
    (exudative AMD). Prior to visual loss AMD is characterized by the
    presence of drusen (lipofuscin and other material deposited between
    the retinal pigment epithelial cells and Bruch’s membrane and
    appearing as yellow-white nodules with distinct and indistinct edges
    on retinal examination).

         There is evidence for association of AMD with UV exposure.
    Photochemical retinal damage can occur from prolonged exposure to
    high intensity light. Whether such damage is directly related to AMD
    is unknown. Although aged Rhesus monkeys have drusenoid deposits, no
    good experimental animal models for AMD currently exist.

         In a case control study, Hyman et al. (1983) found no
    association of AMD and light exposure based on residential history.
    They also found no association of AMD to occupational light
    exposure.

         In studies based on individual exposure data; the results are
    equivocal. The initial evaluation of the association of AMD and UV
    exposure in the cross-sectional study of Chesapeake Bay watermen
    revealed no statistically significant association (West et al.,
    1989). However, a reanalysis based on the small number of cases of
    AMD with exudative disease or geographic atrophy suggested an
    association with 20 year exposure to blue light but not UVA or UVB
    (Taylor, 1992).

         The Beaver Dam Eye Study found an association of late stage AMD
    (exudative AMD or geographic atrophy) and summer leisure time
    outdoors (RR=2.2 CI=1.1-4.2). It was also suggested that an
    association existed in men only between early stage AMD and summer
    leisure time outdoors. The magnitude of the risk estimates were
    unchanged after adjusting for numerous possible confounding factors
    (Cruickshanks et.al. 1993).

         It can be concluded that there are very limited data
    demonstrating an association of AMD with UV exposure. The finding of
    an association with blue light exposure is consistent with the
    wavelengths of visible light reaching the retina and needs further
    investigation.

    10.7  Conclusion

         The causal links between UVB exposure and various ocular
    conditions were evaluated on the basis of the following definitions:

    Sufficient evidence for a causal association indicates that
    positive associations have been observed between human exposure to
    UV and the effect in which chance, bias and confounding could be
    ruled out with reasonable confidence.

    Limited evidence for a causal association indicates that positive
    associations have been observed between exposure to UV and the
    effect for which a causal interpretation is considered to be
    credible, but chance, bias or confounding could not be ruled out
    with reasonable confidence.

    Inadequate evidence for a causal association indicates that the
    available studies are of insufficient quality, consistency, or
    statistical power to permit a conclusion regarding the presence or
    absence of a causal association between UV and the effect, or no
    data were available.

    Evidence for lack of causal association indicates that there are
    several adequate studies covering the range of exposure that humans
    are known to encounter which are consistent in not showing a
    positive association between UV and the effect.

         There is sufficient evidence to link photokeratitis to acute
    ocular exposure to UVB.

         Sufficient evidence exists to link the production of cortical
    and PSC cataracts to UVB exposure in animals. There is limited
    evidence to link cortical and PSC cataract in humans to chronic
    ocular exposure to UVB. Inadequate evidence is available to link PSC
    cataract in humans to chronic UVB exposure. Insufficient data have
    been collected upon which to evaluate the risk of cataract
    associated with childhood exposure to UVB. Half the world’s
    35-million blind people are blind because of cataract. The
    proportion of cataract that results from UVB exposure is unknown,
    but may be as high as 20%.

         There is limited evidence to link sunlight exposure of the eye
    to the development of pterygium. It is unclear whether the observed
    association is specific for UV. The contribution from other
    environmental factors remains unclear.

         There is limited evidence to associate climatic droplet
    keratopathy with UV exposure and insufficient to link pinguecular
    and cancers of the anterior ocular structures. Insufficient evidence
    exists to link uveal melanoma to ocular exposure to solar UV
    radiation. However, several epidemiological studies have suggested
    that the use of sunbeds (an artificial source of UV) is associated
    with uveal melanoma.

         There is inadequate evidence of an association between ocular
    UV exposure and acute solar retinitis, age-related macular
    degeneration, acceleration of pigmentary retinopathies and
    exfoliation syndrome.

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