ultraviolet radiation and the eye: an epidemiologic study
52
ULTRAVIOLET RADIATION AND THE EYE: AN EPIDEMIOLOGIC STUDY* BY Hugh R. Taylor, MD INTRODUCTION ALL OF US ARE EXPOSED TO SOME DEGREE OF SUNLIGHT. THE AMOUNT OF exposure can vary greatly among different occupations and different recreational activities. The study described here was undertaken to see if sun exposure was harmful to the eye. Specifically, it examined possible associations between levels of exposure to ultraviolet radiation (UVR) and the formation of cataract, macular degeneration, and corneal disease. As a visual organ, the eye is very much affected by light. All day, thousands of molecules of rhodopsin are altered by visible light, but with ordinary exposure these light-induced changes are short-lived and rapidly reversed. However, intense exposure to either the broad band of visible light or to narrower specific bands in the visible spectrum, such as those produced by a laser, can cause permanent ocular damage. For example, the occurrence of retinal burns in eclipse blindness is well known,' and retinal laser photocoagulation is one of the major advances in the treat- ment of eye disease of the last two decades.2 Not all bands of eletromagnetic radiation emanating from the sun are in the visible spectrum, and many of the nonvisible bands can have a serious impact on biological function. While most harmful solar radiation is filtered out by the atmosphere, the sunlight that does reach the earth's surface contains sufficient amounts of UVR to cause sunburn3 and a variety of skin cancers.4 For many years, it has been suggested that exposure to sunlight (or, more specifically, UVR) may be associated with an increased risk of senile cataract5 and possibly even with senile macular degeneration (SMD; now also referred to as age-related or aging-related macular degeneration or maculopathy). 1 Most of the initial suggestions concerning the association between UVR and cataract came from astute observations by experienced physicians5 rather than rigorous epidemiologic studies. More recent field *From the Dana Center for Preventive Ophthalmology, the Wilmer Ophthalmological Institute, the Johns Hopkins University Schools of Medicine and Public Health, Baltimore, Maryland. Supported in part by NEI grant EY-06547 and in part by NIH grant EY04547. TR. AM. OPHTH. Soc. vol. LXXXVII, 1989
Transcript of ultraviolet radiation and the eye: an epidemiologic study
ULTRAVIOLET RADIATION AND THE EYE:AN EPIDEMIOLOGIC STUDY*
BY Hugh R. Taylor, MD
INTRODUCTION
ALL OF US ARE EXPOSED TO SOME DEGREE OF SUNLIGHT. THE AMOUNT OFexposure can vary greatly among different occupations and differentrecreational activities. The study described here was undertaken to see ifsun exposure was harmful to the eye. Specifically, it examined possibleassociations between levels of exposure to ultraviolet radiation (UVR) andthe formation of cataract, macular degeneration, and corneal disease.As a visual organ, the eye is very much affected by light. All day,
thousands of molecules of rhodopsin are altered by visible light, but withordinary exposure these light-induced changes are short-lived and rapidlyreversed. However, intense exposure to either the broad band of visiblelight or to narrower specific bands in the visible spectrum, such as thoseproduced by a laser, can cause permanent ocular damage. For example,the occurrence of retinal burns in eclipse blindness is well known,' andretinal laser photocoagulation is one of the major advances in the treat-ment of eye disease of the last two decades.2Not all bands of eletromagnetic radiation emanating from the sun are in
the visible spectrum, and many of the nonvisible bands can have a seriousimpact on biological function. While most harmful solar radiation isfiltered out by the atmosphere, the sunlight that does reach the earth'ssurface contains sufficient amounts of UVR to cause sunburn3 and avariety of skin cancers.4
For many years, it has been suggested that exposure to sunlight (or,more specifically, UVR) may be associated with an increased risk of senilecataract5 and possibly even with senile macular degeneration (SMD; nowalso referred to as age-related or aging-related macular degeneration ormaculopathy). 1 Most of the initial suggestions concerning the associationbetween UVR and cataract came from astute observations by experiencedphysicians5 rather than rigorous epidemiologic studies. More recent field
*From the Dana Center for Preventive Ophthalmology, the Wilmer OphthalmologicalInstitute, the Johns Hopkins University Schools of Medicine and Public Health, Baltimore,Maryland. Supported in part by NEI grant EY-06547 and in part by NIH grant EY04547.
TR. AM. OPHTH. Soc. vol. LXXXVII, 1989
UV and the Eye
studies, reviewed in greater detail below, also suggest an association.However, all of these studies suffer from a lack of precision both in thedefinition of cataract and in the determination of UVR exposure. Theyhave used a variety of definitions of cataract and often have failed todistinguish between different types of cataract. None has attempted todetermine the exposure of each individual to sunlight or UVR. Instead,they have taken the amount of radiation in the region in which the personlived as the indicator of personal lifetime exposure, assuming that every-one in a given region will have a similar exposure to UVR. This results inan epidemiologic trap known as the "ecology fallacy," since differentpeople in the same environment differ in their individual exposures. As aresult, the suspected relationship between UVR exposure and cataractshas awaited rigorous scientific evaluation. The case for an associationbetween UVR exposure and SMD is even less clear. The following studywas undertaken in an attempt to answer these questions definitively.The following introductory sections review the basis for the notion that
UVR may cause ocular damage. They include a review of the photobiol-ogy of UVR. The biochemical changes associated with cataract are dis-cussed with emphasis on the potential role for UVR. Finally, the epidemi-ologic studies of UVR and cataract are evaluated. This body of evidencesuggests, overall, a physical and biochemical basis for an associationbetween UVR and cataract, although to date, the epidemiologic evidencehas been unconvincing. The review will also examine the possibility of anassociation between UVR and SMD.
DESCRIPTION OF ULTRAVIOLET RADIATION
Physical Definition of UVRThe spectrum of nonionizing radiation ranges from short wavelengthUVR (wavelength 100 nm) through to far infrared radiation (1 mm or100,000 nm).6 Ionizing radiation has wavelengths shorter than 100 nm andincludes x-rays, gamma rays, and cosmic rays. Hertzian radiation haswavelengths greater than 1 mm and includes radar, microwave radiation,and radio waves, which can be up to several kilometers in length. Thevisible spectrum lies between 400 nm (indigo) and 760 nm (red). Abovethe visible spectrum is infrared radiation, and below the visible spectrumare the shorter wavelengths of nonionizing radiation called UVR. Much ofthe nonionizing radiation is absorbed by the earth's atmosphere and doesnot reach the earth's surface.6 Wavelengths below 290 nm are totallyabsorbed by the ozone layer in the stratosphere, and longer wavelengthsare absorbed to a lesser extent. Thus, in nature, one does not encounter
803
Taylor
UVR below 290 nm, although the physical spectrum of UVR ranges from100 nm to 400 nm.UVR has been subdivided into three bands: UV-A (400 to 320 nm), UV-
B (320 to 290 nm), and UV-C (290 to 100 nm). This arbitrary subdivision isbased on the biologic effects ofthe different wavelengths or bands.7 UV-A,or near UV, produces sun tanning (the browning of the skin due to anincrease in the skin content of melanin). UV-A is also responsible forphotosensitivity reactions. UV-A is commonly encountered and is emittedby so-called black lights, which are often used to make objects fluoresceand are also used in tanning salons. UV-B is the sunburn spectrum andcauses sunburn (painful erythema) and tissue damage (blistering). UV-B isassociated with skin cancer. 4-8 UV-C is germicidal and may also cause skincancer. UV-C, or far UV, is not commonly encountered on the earth'ssurface and comes entirely from artificial sources such as germicidal UVlamps or arc welding. Although UVR is only 5% of the sun's energy, it isthe most hazardous portion encountered by man. Furthermore, althoughUV-B is only 3% of the UVR that reaches the earth's surface, it is muchmore biologically active than UV-A.9
Ocular Exposure to UVRThe amount of UVR that reaches the eye can vary enormously. UVR isscattered across the whole sky by the Rayleigh effect, just as blue light isscattered.8 Light or broken clouds do not significantly reduce the level ofUVR, although levels are reduced by heavy cloud cover.8 A sky with aclear horizon for 3600 provides for a maximal exposure; when hills, trees,or buildings obstruct part or all of the horizon, the UVR exposure isreduced proportionally.'0 UVR can also be reflected by the ground, theamount depending greatly on the type of surface. Grass and soil reflectonly 1% to 5% of UV-B, water 3% to 13%, sand and concrete about 7% to18%, and fresh snow up to 88%. 10The eye is protected and shielded from UVR by a number offactors""12
and only receives a small fraction of ambient UV-B under normal circum-stances. The normal horizontal alignment of the eye and the orbit signifi-cantly reduces ocular exposure to whole-sky irradiation. Further anatomicprotection is provided by the brows, the nose, and the cheek. 13 The eye isrelatively unprotected laterally, although the transmission of UVR byinternal reflection in the cornea may lead to a concentration of UVirradiation at the nasal limbus.'4 The eyelids provide protection that isfurther enhanced by squinting, a common reflex in bright sunlight.'3Other factors that can influence ocular UVR exposure in a given environ-ment include wearing a hat and the use of eyeglasses. 1112 Taken together,
804
UV and the Eye
these different factors result in an ocular exposure that is considerably lessthan the ambient UVR level. The most important factors in determiningan individual's exposure in a given environment are whether protectiveglasses or a hat are worn.12
Ocular Transmission of UVRNot all the UVR that reaches the eye passes back to the retina-a fact withimportant photobiological implications. The amount of radiation that isabsorbed determines the potential for damage to the absorbing tissue.Energy from absorbed radiation must be dissipated, and it is this dissipa-tion that results in damage. Radiation that is not absorbed by a superficialtissue will be transmitted and can affect a deeper tissue.The cornea absorbs almost 100% of UV-C radiation (below 290 nm), but
transmission rapidly increases for longer wavelengths, so that, for in-stance, 60% of radiation at 320 nm is transmitted by the cornea. 1&18 Thenormal, young human lens absorbs most UVR below 370 nm. With age,the human lens yellows and absorbs even more UV-A and also absorbsshorter visible wavelengths.18'19 In adults, less than 1% of radiationbetween 320 nm and 340 nm and only 2% of radiation of 360 nm reachesthe retina.20 The pattern of absorption shown in the classic series oftransmittance curves published by Boettner and Wolter17 indicates thatthe lens is exposed to and absorbs most of the UV-B that reaches the eye.
Mechanisms of PhototoxicityThe mechanisms of phototoxicity are complex and not totally understood.All electromagnetic radiation exhibits both wave-like (oscillatory) andparticle-like (photon) characteristics.6 The energy carried by a photon isdirectly proportional to its frequency, thus the shorter the wavelength,the higher the energy. The energy of a photon is absorbed by the atom ormolecule with which it collides. Low-energy infrared photons will carryenough energy to affect the rotational or vibrational state of an atom or amolecule and can produce warming.7 The higher energy UVR photons,however, can alter the energy state of the electrons, making the atom ormolecule electronically excited and, therefore, relatively unstable. Thisinstability can lead to chemical reactions including photo-oxidation. Evenhigher energy photons such as gamma rays can cause an electron to beremoved entirely from the molecule thereby causing ionization.The radiant energy of UVR can be absorbed by nucleic acids, proteins,
or other molecules within the cell. Some energy may be dissipated asheat, but an excited molecule may be structurally altered or cleaved or itmay react with other molecules by forming new bonds. The capacity of agiven atom or molecule to absorb radiant energy is dependent on its
805
Taylor
physicochemical properties, and the characteristics of a tissue are in turndependent on the properties of its constituents. The lens proteins are richin the amino acid residues of tryptophan, tyrosine, and phenylalanine;and these proteins absorb most of the radiant energy below 300 nm.Other chromophores and pigments in the lens appear to absorb most ofthe energy in the 300 nm to 400 nm range.2'
Ocular Action Spectrum for UVRThe eye is much more sensitive to damage by some wavelengths thanothers. The term "action spectrum" can be defined as the amount ofirradiation at a given wavelength or band of wavelengths that is sufficientto cause damage. It is the threshold level for damage and is specific fordifferent tissues. In their classic work, Verhoeff et al22 showed thatrepeated subliminal exposures delivered within minutes or hours to theeye are additive for up to 24 hours. For suprathreshold corneal damage, atleast, there is a period of latency between exposure and evidence ofdamage which varies with dose but can range from 30 minutes to 24hours. The latency period accounts for the delay in presentation of weld-ers with flashburns. For the rabbit lens, a latency period of 5 to 10 dayshas been reported for reversible lesions and 2 to 14 months for irrevers-ible lesions. 16 No data exist for the action spectrum of the human lens orretina. The action spectrum for the human cornea is generally similar tothat of subhuman primates, although the human cornea is more sensitiveto UVR than is the cornea of either monkeys or rabbits.23 The most activewaveband for corneal damage in both monkeys and rabbits is 270 nm.Exposure of rabbit or guinea pig lens to wavebands between 297 nm and365 nm results in cataract, with a peak sensitivity shown at 297 nm; i'nmonkeys, the sensitivity of the lens falls rapidly for radiation above 313nm.16 24The rabbit lens is 100 times more sensitive to 320 nm radiationthan to 365 nm radiation.Y5 Thus, these studies have shown that the lens isparticularly susceptible to damage from UV-B.Ham and co-workers26 have studied the action spectrum for retinal
injury in aphakic primate eyes. They have found that at 325 nm, theshortest waveband they tested, the retina was six times more sensitivethan at 441 nm. UVR produced early and irreparable damage to the rodsand cones with later changes in the retinal pigment epithelium. The laterchanges were similar to those seen with blue light (441 nm), although bluelight did not cause photoreceptor damage.27 These authors emphasizedthe extreme sensitivity of the primate retina to UVR-induced damage.
806
UV and the Eye
BIOCHEMICAL CHANGES IN CATARACT
This section reviews what is known of the biochemistry ofcataract and thenext section shows how these changes could be related to UVR exposure.
Changes in Lens ProteinsThe lens has an extraordinarily high protein content, and changes in thelens proteins result in cataract. Overall, proteins form 35% of the wetweight of the lens, and in the nucleus, they form 65% to 70%.28 In theyoung lens, much of this protein is in a soluble form; but with aging, thereis an increase in the amount of water-insoluble protein.29 With cataract,there is an even more marked increase in the proportion of water-insol-uble protein and a decrease in the amount of water-soluble protein.30
Benedek3l suggested that the opacification seen in cataract was due tothe formation of large protein aggregates. These aggregates are formed bythe cross-linkage of soluble proteins to form larger, irregular, and insolu-ble protein masses which then scatter light and cause the lens to appearopaque. These protein aggregates are stabilized in part by covalent disul-fide bonds32 which result from the oxidation of exposed thiol groups.33.34Some of these aggregates are associated directly with the membranes ofthe lens fiber.28,35There are differences in the types of protein aggregates found in
nuclear and cortical cataracts.28,36 Nuclear cataract is characterized byhigh levels of insoluble protein complexes that are covalently linked to thelens fiber membranes. These protein complexes may be derived fromgamma crystallin.37 In the cortex, however, high molecular-weight aggre-gates of insoluble protein are not found. Spector28 has suggested that incortical cataract there may be a complete rupture of the protein-mem-brane complex and that the protein lumps then disaggregate from theruptured membrane remnants.Most of the changes in lens proteins can be explained either by oxida-
tive28 or by osmotic changes.38 With normal aging, there is a slow oxida-tion of the thiol groups of the cysteine and methionine residues in the lensfiber membranes. In cataract there is a more marked oxidation in themembrane, and the crystallins inside the fiber are also oxidized.39 Oxida-tion of a single thiol group in gamma crystallin causes an unfolding of themolecule, which leads to the exposure of more groups for oxidation and acompounding of the damage.28 The oxidized thiol groups can form cova-lent bonds, which lead to the aggregation of lens proteins to each other orto the cell membranes. Osmotic swelling leads to progressive disruptionof the lens fiber, and this has been extensively studied in the context of"sugar" cataract.38,40 Initially, there is an increase in the intracellular
807
water with a loss of biochemical constituents. This leads to a markedswelling of the lens fiber and then to its disintegration with vacuoleformation and opacification.Changes in the lens proteins can lead to light scattering and opacifica-
tion by a number of different mechanisms.4' Aggregation and the forma-tion of large water-insoluble proteins can cause light scatter. An increasein turbidity or syneresis also leads to increased light scatter, and thismechanism may be important in osmotic cataracts. Other mechanismsinclude membrane degeneration, the disorientation of cytoskeletal ele-ments, and phase separation. The latter is seen in experimental coldcataract. Because there is essentially no turnover of the lens proteins, anyabnormal or denatured protein will remain, and these altered moleculeswill gradually accumulate.
Recently, it has been discovered that lens proteins previously thoughtto be inert and to have only a structural role may, in fact, have importantfunctional significance. Reptilian epsilon crystallin has been found to havelactate dehydrogenase activity and thus may be an important glycolyticenzyme.42 Similarities exist between delta crystallin and arginosuccinatelyase, gamma crystallin and enolase, and Slll crystallin and glutathiones-transferase.43 It is unclear whether these functional roles are importantin lens physiology or what effect UVR damage might have on this activity.
Changes in Lens PigmentationDiurnal animals, including man, have a number of pigments in theirlenses.44 Teleologically, these are thought to provide some protection forthe retina from the potentially harmful effects of UVR and blue light.45Included among these pigments is a series oflow molecular-weight, water-soluble compounds related to kynurenine, and oxidative product of tryp-tophan.46,47 Another is an anthranilic acid derivative that is bonded to thelens proteins and is also possibly an oxidation product of tryptophan.36Both of these pigments increase with age and with the proportion ofinsoluble proteins.2' Another nontryptophan water-soluble pigment,which appears to decrease with age, has also been described.2'
Although much attention has been given to the pigments of the lens inthe biochemical literature of cataract, it is not clear what is the biologicalor visual significance of these pigments. The lenses of older people arebrowner than those of younger people. This is termed "nuclear sclerosis"in the strict sense and can be regarded almost as a normal change seenwith aging.48 This increase of nuclear pigmentation (nuclear sclerosis),however, is independent of nuclear opacification (nuclear cataract).49 Ad-vanced browning of the lens acts as a filter and reduces the amount of
Taylor808
UV and the Eye
visible light reaching the retina, especially at the blue end of the spec-trum. However, the major visual disability associated with cataract is dueto light scatter and opacification that is attributable to changes in lensproteins and not to an increase in lens pigmentation.
ASSOCIATION BETWEEN UVR AND CATARACT
This section examines how UVR could contribute to the biochemicalchanges seen in cataract and then reviews the experimental and epidemi-ological evidence for an association.
Biochemical Basis for an Association Between UVR and CataractThere are good biochemical grounds to believe that UVR may be animportant cause of at least some types of cataract. UVR could directlyaffect the lens and cause cataract by at least four different mechanisms: (1)photo-oxidation of free or protein-bound tryptophan; (2) photosyntheticprocesses involving activated species of oxygen; (3) disruption of themembrane-cation transport system; and (4) damage to nucleic acids inlens epithelial cells.
Photo-oxidation of Tryptophan. Lens proteins contain photosensitiveamino acid residues, most notably those of tryptophan. It has beensuggested that UVR-induced photo-oxidation of tryptophan may be acritical first step that initiates changes in lens proteins.21 In a series ofpioneering experiments, Pirie465'0 and Dilley5l showed that lens proteinsexposed to sunlight turned brown, and these changes were similar tothose found in human lenses. They demonstrated the photo-oxidation oftryptophan to give N-formyl kynurenine, a brown compound. Subse-quently, other species of pigments derived from kynurenine were foundby van Heyningen,52 who also showed that these pigments caused morerapid oxidation of lens proteins.47'53 It has been shown that free tryp-tophan in the lens can be oxidized54 as can at least a portion of theprotein-bound tryptophan.55 The effects of these molecules and otherphotosensitizing compounds on the impact of UVR have been compre-hensively reviewed.2128
However, as Harding and Dilley5' point out, the proteins of the browncataractous nucleus do not appear to have less tryptophan than normallens proteins, and the brown cataract change affects only the nucleus andnot the anterior cortex, which receives the highest levels of UVR.
Activated Species of Oxygen. UVR can generate a series of highlyreactive toxic oxidants by its effect on molecular oxygen.57 These oxidantsinclude singlet oxygen, superoxide, and hydrogen peroxide. Specific
809
Taylor
enzymes that destroy these destructive oxygen species include superox-ide dismutase, which inactivates superoxide, and catalase, which inacti-vates hydrogen peroxide. These enzymes are found in the lens epitheliumand occur in high levels in the retina. However, they are present only invery low levels within the lens itself, mainly in the cortex.5 The activitiesof both catalase and superoxide dismutase decrease with age, and catalaseis inactivated by exposure to UVR.21,59
Other antioxidants are also found within the lens. The most importantis glutathione, although ascorbic acid (vitamin C) and alpha tocopherol(vitamin E) are also present.28'58 Reduced glutathione becomes oxidizedas it repairs oxidative damage. Oxidized glutathione is returned to thereduced state by glutathione reductase. Reduced glutathione is found inhigh levels in the lens epithelium and the cortex but in much lower levelsin the nucleus.57,60 The concentration of glutathione in the lens decreaseswith age and with exposure to UVR.61 Glutathione may have multipleroles in maintaining lens clarity by maintaining lens protein and mem-brane thiol groups in the reduced state as well as scavenging free radicalsand hydrogen peroxide.60
Ascorbate can also repair photo-oxidative damage.57'62 Ascorbate isnormally abundant in the lens, although its levels decrease with age andin the presence of cataract. Ascorbate protects Na/K ATPase againstUVR63 and inhibits the browning of lens proteins.64 Recently, Bron andBrown62 suggested that certain cortical opacities, "retrodots," which areprobably oxalate deposits, may result from the oxidation of ascorbate inthe lens.
Oxidants may be formed not only in the lens but also in the aqueoushumor. They could diffuse from the aqueous into the lens and causeoxidative damage. High levels of hydrogen peroxide have been reportedin the aqueous humor of patients with cataract, and the exposure of thelens in vitro to hydrogen peroxide leads to cortical opacification.65 Hydro-gen peroxide affects membrane transport systems, including Na/K ATPaseactivity. 66
Disruption ofMembrane Cation Transport. Normal Na/K ATPase activ-ity, the so-called sodium pump, is crucial for lens clarity as it maintainsthe osmotic balance within cells. A loss of activity leads to osmoticswelling of lens fibers, as can be seen when the enzyme is inhibited byouabain.38 This mechanism may be important in at least some experimen-tal congenital cataracts. 67 Na/K ATPase is sensitive to damage by UVR butcan be protected by ascorbate in the lens.63'68 This enzyme is found inlarger quantities in the retina, where it is also sensitive to UVR inactiva-tion.21
810
UV and the Eye
Damage to Lens Epithelium. Finally, UVR could damage the lensepithelium by a direct effect on deoxyribonucleic acid (DNA). UVR candamage DNA in the skin.68 UVR exposure of the lens of animals leads tohistologic changes in the lens epithelium that are similar to those seen inskin. 69,70 The lens epithelium shows a lack of differentiation which may bedue to DNA damage. The undifferentiated cells migrate to the posteriorlens surface and cause posterior opacities. These changes are similar tothose seen with ionizing radiation in man and human posterior subcapsu-lar opacities.7' Apart from a direct effect on the differentiation of lensepithelium, UVR damage to the lens epithelium could have indirecteffects on the lens by altering lens nutrition or by altering the metabolicand protective role of the epithelium.
Experimental Basis for an Association Between UVR and CataractExperiments in animals suggest that UVR may cause cataract. Corticaland posterior subcapsular cataracts have been induced by UV irradiationin a number of different experimental animals. Rohrschneider72 exposedguinea pigs to a mercury vapor lamp (293 nm to 303 nm) and producedclouding of the anterior cortex. Bachem'6 confirmed these findings inboth guinea pigs and rabbits, using a number of different light sources,and determined the action spectra. Zigman and co-workers73 reportedsubcapsular and punctate cortical opacities in albino mice that had beenexposed to broadband UVR from 40 W blacklight lamps (300 to 400 nm).The mice were exposed for 12 hours a day. After 35 weeks of exposure,changes were seen on slit lamp examination, and after 60 weeks ofexposure, clear-cut cortical opacities were seen on histologic examination.At this time, the posterior migration of undifferentiated lens epitheliumwas also noted.69 Pitts and co-workers24 produced cortical and posteriorsubcapsular opacities in pigmented rabbits exposed to short-durationexposures to UVR between 295 nm and 315 nm. They commentedspecifically on the low radiant exposures of UV-B needed to produce theselenticular opacities. Keeney and Rapton74 exposed nonpigmented mice todaylight and caused extensive ear damage and corneal changes, but lensopacities were not seen.Permanent lens opacities can be induced in vivo in laboratory animals
with either acute high-dose (suprathreshold) or chronic low-dose (sub-threshold) exposure to UVR, specifically UV-B. The opacities are eithercortical or subcapsular. Nuclear opacities and brunescent changes havenot been induced in these experiments. The lack of brunescent changecould be because these animals do not have pigment (chromophores) intheir lenses.
811
Taylor
Epidemiologic Basis for an Association Between UVR and CataractEpidemiologic and clinical observations also suggest a link between sun-light exposure and cataract. Cataracts occur more commonly in tropicalareas than in more temperate regions. 575 This is often ascribed to greatersun exposure, but few epidemiologic studies have examined, even indi-rectly, the role of sunlight in cataractogenesis. There is a greater preva-lence of cataracts in the sunnier part of Romania,76 and cataracts are morecommon in Israel than in England.77 People having cataract surgery aremore likely to have brunescent cataracts if they live closer to the equatoror work outdoors.78 People in the United States who live more than halftheir lives in areas with high sunlight or UVR levels have a greater risk ofcataract. 79,80 This association holds for cortical cataract but not for nuclearcataract. 81An earlier study in Australian aborigines showed an epidemiologic as-
sociation between the occurrence of senile cataract and resident sunlightexposure and, in particular, local levels of UV-B radiation.82 The associa-tion was specific, consistent, and showed a dose-response relationship.Hollows and Moran83 also confirmed and extended these findings. Theyfound a strong positive correlation between the intensity of UV-B radia-tion in the zone of residence and the presence of cataract when theyanalyzed data from 64,307 aborigines.83 These two studies on Australianaborigines are important for several reasons. First, aborigines receivevery little protection from the environment because they spend virtuallyall of their time living in the open, so their individual exposure is likely tobe more closely correlated with the ambient level. Second, the studiescovered a large geographic area with a wide range of environmentalparameters and ambient UVR levels. Third, the study area was lightlypopulated, and it was possible to examine almost the entire aboriginalpopulation living in the study areas rather than a sample. This avoided thenecessity of sample selection with the attendant potential sources of bias.An association was not found for the Europeans examined by Hollows andMoran.83 This is probably because of selection bias and lack of quantifica-tion of individual exposure.A study of 125,279 Chinese in seven rural areas found that cataract was
more common in areas with more sunlight, and consequently more UV-Bradiation, especially areas at higher altitudes.84 A recent small-scale, case-control study in Tibet showed greater risk of senile cataract in those whoworked outside for more than 6 hours a day.85 A country-wide survey ofNepal in which 30,565 lifelong residents were examined also found apositive correlation between sunlight and cataract.86 In this study, theinvestigators had to contend with the marked influence of neighboring
812
UV and the Eye
mountains on sun exposure, and they came up with a simple instrumentto measure the height of the surrounding mountain mass. An earlier studyin north India had also reported a higher prevalence of cataract in theplains than in the mountains, which had been taken as proof against anassociation between UVR and cataract.87 This earlier study did not at-tempt to ascertain either personal or ambient UVR exposure and wasconfounded by so many other factors that it is hard to interpret.
Although these studies suggest an association between exposure tosunlight, or UVR, and cataract, the studies share several common short-comings. None of them have prospectively taken into account the poten-tial for UVR to preferentially affect one part of the lens. The outcome theyhave used was "cataract," often advanced or mature cataract. Sometimesthe cataracts are referred to as being brunescent, but it is unclear whetherthey were pure brown nuclear cataracts or whether they were maturemixed cataracts which happened to be brown.
Furthermore, each of these major studies was "ecological" in that theexposures of individuals to sunlight or UVR were not ascertained. Rather,the characteristics of the area of residence, such as latitude or morerefined meteorological data, were used to estimate exposure. This gives avery imprecise measure of actual individual exposure. It is also possiblethat the observed geographic or ecological differences in the rate ofcataract might be due to other confounding factors such as genetic charac-teristics,88,89 nutritional status,87,90 other climatic factors such as tem-perature or humidity,82'87 the presence of endemic diseases such aschronic diarrhea,91'92 or even the availability or utilization of healthservices.
In an attempt to control for some of these confounding variables, self-selected samples of Maryland watermen and their wives and Pennsylva-nian underground coal miners and their wives were examined.93 Becauseof intergroup differences, only limited between-group comparisons couldbe made. The watermen could be grouped by their work-related UVRexposure. Cortical opacities were seen more commonly in those with ahigher UVR exposure history than in those with a lower exposure. Noassociation was seen with nuclear opacities. SMD as determined byfundus photography also appeared to be more common in those watermenunder 60 years of age who had a higher UVR exposure, but no trend wasseen in those over the age of 60 years.
In an effort to better quantify personal lifetime UV-B exposure, anotherstudy examined 212 men who had had a skin biopsy taken from the facialarea.94,95 Each biopsy was graded histologically for actinic elastosis, amarker for cumulative UV-B exposure. A positive, but modest, association
813
Taylor
was found between actinic elastosis and cortical opacities. This associationwas strongest in those under age 55. No association between UVR andnuclear opacities was found.
Despite their differences, these epidemiologic studies suggest an asso-ciation may exist between UVR and either mature (brunescent) cataract orcortical cataract in man. None ofthem suggest an association with nuclearcataract as such.
ASSOCIATION BETWEEN UVR AND MACULAR DEGENERATION
Much less is known about the role of chronic UVR exposure and maculardamage. Although the lens filters out most of the radiation below 370 nm,the retina has been shown to be particularly sensitive to any UVR thatdoes reach it.27,9697 Light can damage the retina by thermoacousticdamage (as with YAG laser treatment), by thermal damage or burn (aswith xenon photocoagulation), or by photochemical damage. These mech-anisms have been recently reviewed in detail by Guerry and co-workers. 1Blue light and UVR usually cause retinal damage by photochemicalmeans. 1,96 The processes involved are essentially similar to those outlinedfor damage to the lens. The retina differs from the lens in that it has amore active metabolism. It has much higher levels of oxygen and higherlevels of superoxide dismutase and the other antioxidants (especiallyascorbic acid and alpha tocopherol). Furthermore, in the retina, damagedproteins can be replaced by normal cellular repair mechanisms.
Short, intense exposure to sunlight leads to retinal burns known aseclipse blindness or solar retinopathy-probably the result of photo-chemical damage to the photoreceptors.96 Similar damage may be causedinadvertently by ocular instruments.97,98 Experimentally, the histologicchanges induced by cumulative photic injury in rhesus monkeys resemblethose seen in SMD in man.99
Although much attention has been given to the retinal effects of short,intense light exposures, the effect of long-term sunlight or UV irradiationon the retina is unclear. Animal studies by Ham26 and others96 "00'01 havedemonstrated that longer wavelength UVR and blue light can causeretinal damage at light levels below those that cause photocoagulation.Damage from repetitive exposures may be additive. 102,103 However, epi-demiologic studies have not adequately addressed the question ofwheth-er exposure to high levels ofUVR increase the risk of SMD, although thepossibility of such an association has been suggested. 103104 As mentionedabove, a small study of Chesapeake Bay watermen found a weak associa-tion between UVR exposure and SMD in watermen under the age of 60years but no association in those over this age.93
814
UV and the Eye
Some investigators have found SMD to be associated with light iris andhair color. 105 It has been suggested that this may reflect a lower level ofmelanin and thus less protection against photo-oxidative damage becauseof the direct absorption of light.105 A small case-control study reportedthat the degree ofdermal elastotic degeneration in sun-protected skin waspredictive of exudative maculopathy.106 Such information suggests thatindividuals whose elastic fibers are more susceptible to photic or otherdegenerative stimuli may also have an increased risk of developing SMD.As discussed above, the aging lens becomes increasingly brown and
acts as a blue-light filter to protect the retina from shorter wavelengths.Eyes with nuclear sclerosis have been reported to have less SMD thaneyes without nuclear sclerosis.107 This would support the notion of pro-tection, although it is possible that cases of SMD have been missed ineyes with nuclear sclerosis. In the same analysis, eyes with corticalopacities were at greater risk of having SMD, which could suggest acommon cause for these two conditions. Thus, there is some indirectevidence to suggest a linkage between UVR exposure and SMD.
SUMMARY
The preceding review indicates that an association between UVR andocular damage, including cataract, could be suspected on photobiological,biochemical, experimental, and epidemiologic grounds. There is evi-dence to suggest that sufficient UVR may reach the lens to cause damage.In vitro UV exposure can lead to oxidation and denaturation of lensproteins by a number of different pathways, and the changes induced byUVR are similar to those seen in human cataractous lenses. There isexperimental evidence in animals that in vivo exposure to UVR can causecataracts. Epidemiologic evidence in man also suggests that high levels ofUVR may be associated with cataract. Although intense light exposure isknown to cause retinal damage in animals and man, there is only equivo-cal epidemiologic evidence to suggest an association between maculardisease and UVR.The establishment of an adverse effect on UVR on the eye would have
tremendous public health importance. The ocular diseases attributed toUVR are of major significance in terms of the absolute numbers of peopleinvolved. In the United States alone, over 1 million cataract operationsare performed each year,108 and worldwide, over 17 million people areblind from cataract. 109 Although SMD affects fewer people than cataract,it is the leading cause ofnew cases ofblindness in those over age 65 in theUnited states. 110 Furthermore, blindness from SMD is generally irrevers-ible, in sharp contrast to that caused by cataract.
815
Taylor
Protecting the eye from UVR has become a multimillion-dollar-a-yearindustry with the development of UVR-absorbing spectacles, sunglasses,intraocular lenses, and, most recently, contact lenses. Furthermore, thereare strong reasons to believe that we may be facing significantly higherlevels of UVR because of progressive changes in the earth's atmo-sphere. 111-113 Recent data indicates that chlorofluorocarbon compoundsare causing a significant reduction in the ozone layer in the strato-sphere.14 The ozone layer is the main atmospheric filter of UVR. It istherefore of great importance to examine in detail the association betweenUVR and ocular damage, specifically senile cataract and SMD.We have undertaken a definitive epidemiologic study in which we tried
to determine accurately the cumulative UVR exposure of each individualand correlated this with the presence and severity of the major types ofsenile cataract and SMD.The specific goals of this study were:1. To identify a study population that had a range of occupational
exposure to UV-B radiation.2. To determine the annual UV-B exposure for each year of adult life
for each member of the study population.3. To determine the presence and severity of lens and macular changes
for each member of the study population.4. To conduct a statistical analysis, assessing the association of UV-B
exposure with senile cataract and with SMD.
METHODS
SAMPLE SELECTION
Baseline PopulationThe people enrolled in this study were all watermen who work on theChesapeake Bay. Every commercial waterman who wants to fish or collectseafood legally in the state of Maryland must purchase the appropriatelicense every season through the Maryland Department of Natural Re-sources (DNR). For each license applicant, the DNR records the name,birthdate, address at the time of application, type of license, and date ofapplication. This information has been coded and filed on data tape for thelast 10 years. The DNR provided us with a copy of these data so we coulddefine our baseline population.To be eligible for this study, a subject had to be a male over the age of
30 years who resided in either Somerset County (excluding PrincessAnne) or lower Dorchester County and who had held at least one type of
816
UV and the Eye
professional waterman license within the last 10 years. The original listwas updated and clarified with assistance from the Maryland WatermanAssociation and its county branches, and from telephone listings, localservice clubs, and post office records, together with home visits.A total of 1203 watermen met the criteria for inclusion in our survey
and formed the baseline population.
Study PopulationOf the 1203 watermen we determined were eligible for the survey, 838(70%) were interviewed and examined during three intensive periods ofdata collection. The periods were timed to correspond to the breaksbetween the crabbing and oystering seasons that occur in the early springand the early fall when most watermen spend 1 to 3 weeks repairing andrefitting their boats. We hoped that they would be more likely to partici-pate in the study than if we scheduled the interviews and examinationswhen they were working on the water.The first two periods of data collection were conducted in Somerset
County and Dorchester County, in March and September 1985, respec-tively. Six hundred twenty-one watermen were examined during this timeand are referred to as "primary attenders." Because of concern for possi-ble bias in this group, a random 10% sample of those who were nonat-tenders at that time was chosen to determine if important differencesexisted between those who had been examined and those who had not.
Exhaustive recruitment efforts were mounted to examine the 68 water-men randomly selected who are referred to as the "random samplegroup." Members of the random sample were sought during the thirdperiod of data collection from December 1985 to January 1986. Additionalefforts were also made at that time to improve the overall response rate byactively recruiting more nonattenders to the survey. A total of 176 addi-tional watermen, excluding members of the random sample, were ex-amined at this time, and they are referred to as the "secondary attenders."Of the 68 members of the random sample, 17 (25%) were eventually
found not to meet the inclusion criteria in that they were either nonresi-dents (9), deceased (6), or have given incorrect birthdates at the time ofregistration and were actually less than 30 years of age (2). Of the remain-ing 51, it was possible to contact 46 (90%), and all agreed at least to beinterviewed. Forty-one (80%) also agreed to have the eye and skin exami-nations.
In summary, the baseline population as determined from the DNRrecords consisted of 1203 watermen who met the inclusion criteria. Ofthese, 797 watermen who were either primary or secondary attenders and
817
Taylor
41 in the random sample group had eye and skin examinations; thus thefinal study sample consisted of 838 men who were both interviewed andexamined. They represent 69.7% of the determined baseline population.
DATA COLLECTION
RecruitmentBefore each period of data collection, the survey was widely publicized ineach community. Local watermen and their wives were also hired to assistwith recruitment and field work. Each eligible waterman was contactedby mail and given a suggested appointment. If a waterman did not keepthis appointment, he received telephone calls and home visits to encour-age his participation.
Altogether, 360 members of the baseline population (30%) did not'participate in the study. It was possible to either contact or identify all but72 of these (6% of baseline population) and ascribe a reason for theirnonparticipation. Of 288 who were either contacted or identified, 117(10% of baseline population) refused to participate; a further 101 (8%)were covert refusals as they indicated their willingness to participate but,in fact, did not do so; 18 (2%) agreed to be interviewed but refused to beexamined; 32 (3%) were known to be living at their given address butcould not be contacted; 15 (1%) were away; 3 were hospitalized; and 2 hadpsychiatric disorders.Interview DataAn interview was administered to each individual by a trained inter-viewer who gathered information on the following factors: (a) demograph-ic and background characteristics, including birthdate, education, resi-dence, characteristics offreckling and sunburning, and dietary history; (b)medical history, including use of phototoxic drugs, history of diabetes,hypertension, use of steroids, aspirin, antihypertensive and cardiac medi-cation, and tobacco use; and (c) exposure history, including a detailedoccupational hiistory covering each year of life from the age of 16 years, inwhich daily exposure data was recorded on a monthly basis, and a similarhistory for leisure activities. Both histories included information abouthours spent outside, hat use, glasses use, and history of arc welding.Eye ExaminationThe visual acuity for each eye was tested with correction if the patientwore distance glasses. If the acuity was less than 20/20, a pinhole test wasperformed. If the vision was still less than 20/20, a subjective refractionwas done and the best corrected acuity determined. Intraocular pressurewas measured with either an applanation pneumotonometer or a hand-
818
UV and the Eye
held applanation tonometer. Patients with elevated pressures were checkedwith a Goldmann applanation tonometer.
Clinical Grading of Lens Opacities. The pupils were dilated with 10%phenylephrine and 1% tropicamide. After dilation, lens opacities weregraded by slit-lamp examination using direct and retroillumination.115The examination was considered adequate if the pupil was dilated to atleast 6 mm. Corneal and conjunctival abnormalities were also recorded.The assessment of the lens status was made without the examiner know-ing the patient's visual acuity.
Lens changes were clinically graded according to their anatomicallocation and their estimated severity:
a) Cortical opacity-opacities seen on retroillumination that werein the external 1/3 of the lens. These were graded for severity bythe estimated area of the lens affected by spokes. The area of theopacities was expressed as the cumulative number of 1/8 wedgesof the retroilluminated lens involved with opacities, Grade 0 =no opacity; grade 1 = < 1/8; grade 2 = < 1/4; and so forth.
b) Nuclear opacity-opacities seen in the optical section of theinner 2/3 of the lens. These were graded according to theirexpected impact on visual acuity as follows: grade 0 = no opac-ity; grade 1 = some opacity but consistent with vision 20/20;grade 2 = opacity consistent with vision between 20/20 and20/30; grade 3 = opacity consistent with vision 20/40 to 20/100;grade 4 = opacity consistent with vision 20/200 or less. Standardphotographs were used to assist in this grading. 115 The observerwas specifically not informed of the measured visual acuity tominimize observer bias. This grading scheme was an importantinnovation as it gave an unbiased assessment of nuclear opacity.The bias of knowing the visual acuity has been a major disabilityin many previous studies that have graded cataract.79-81 If theexaminer were aware of the subject's visual acuity, it could in-duce observer bias, as the knowledge of an impairment couldencourage the examiner to look for and identify minimal opac-ities and to consider them as significant.116
c) Posterior subcapsular cataracts (PSC). The overall height andwidth of the opacity were measured with the slit lamp graticule.
d) Aphakia. Any lens that had been operated on, even if lensremnants were present, was regarded as aphakia. There were 18patients with aphakia. The operating ophthalmologist was con-tacted in each case, and the preoperative diagnosis of the type ofcataract was obtained for 17 of them.
819
Taylor
We did not regard the following lens opacities and changes as senilecataract: cortical vacuoles, Mittendorfs dots, small axial embryonal sul-tural opacities, and other small dot opacities of a characteristic congenitalappearance (such as blue dot congenital opacities).Photograding of Lens Opacities. All lenses were photographed in an
attempt to get a completely objective and unbiased assessment of lensopacity. Retroillumination photographs of the anterior and posterior cor-tex ofthe lens ofeach eye were taken using a Neitz cataract camera. 115 Slitphotographs of the nucleus were taken with a Topcon SL-5D photo slitlamp using standard settings.17 One photographer took all the corticalphotographs and another took all the nuclear photographs.Each set of photographs of the lens was graded for the presence and
severity of opacity. Cortical opacities were graded according to criteriasimilar to those described for the clinical examination. Nuclear opacitieswere graded by comparing them to the set of standard photographs ofnuclear opacities that corresponded to the clinical grading.'17The photographs of the lens were graded independently by two grad-
ers. Any disagreement were adjudicated by a third grader. The photo-graphs of the cortex were graded independently of the photographs of thenucleus.
Analysis of the grading data showed good agreement between theclinical grading and the photograding and good intra- and interobserveragreement among graders."15,117,118
Photograding of Macular Changes. Subtle macular changes and earlystages of macular degeneration are often easier to detect on high-qualityfundus photographs than on clinical examination. Stereo fundus photo-graphs centered on the disc and macula of each eye were therefore taken-for each patient using a Topcon FET retinal camera.
Fundus photographs were graded with a new scheme we have devel-oped to grade the presence and severity of macular changes."l9 Thisgrading scheme includes both the earliest fundus changes of maculardegeneration and drusen characteristics thought to be associated with anincreased risk of developing the exudative forms of this disease. Inexamining the fundus photographs, the graders used a template with 3000and 6000 pu circles and a set of standard photographs."19
Macular changes were graded as follows.Grade 1: Drusen present within 3000 pu of the fovea (greater than
standard photo 1).Grade 2: Drusen present within 1500 ,u of the fovea (greater than
standard photo 2).
820
UV and the Eye
Grade 3: Presence ofdrusen within 1500 ,u of the fovea with so-called"high-risk" characteristics (large, soft, confluent, pigment-ed; these features were defined in standard photographs).
Grade 4: Presence of exudative disease or extensive geographic ornongeographic atrophy (greater than a standard photo-graph).
These categories were then combined as follows: SMD 1, grades 1through 4; SMD 2, grades 2 through 4; SMD 3, grades 3 and 4; and SMD4, grade 4 alone.
All fundus photographs were graded independently by two graders.After each grader had read each photograph independently, any disagree-ments were reviewed by the two graders together and the grade estab-lished by consensus. The reliability and reproducibility of this scheme hasbeen assessed, and the interobserver and intraobserver agreement wasgood to excellent."19
Skin ExaminationWe were interested in assessing the relationship of sun-induced skinchanges in both exposure and ocular damage. Each person had a der-matologic examination. Particular attention was paid to the skin of thehead and neck. The degree of elastosis of the periorbital areas, includingthe upper cheek and lower forehead, was graded in four steps from noneto severe according to a grading scheme we had devised.'20
Standard macrophotographs of the periorbital region were also takenand later graded for actinic elastosis. Two graders compared skin photo-graphs to standard photographs and graded each photograph by consen-sus. The definitions were the same as those used in the clinical gradingscheme. Disagreements were adjudicated by a third dermatologist. Again,inter- and intraobserver trials showed a high degree of reproducibility.120The photograding is well correlated with the clinical grading of actinicelastosis and the histologic grading of elastotic change.94The examining dermatologist also recorded the presence of other skin
lesions, especially those due to excessive sun exposure, such as squamouscell carcinoma, basal cell carcinoma, and actinic keratosis. When scarswere found (indicating the surgical removal or biopsy of lesions), thetreating physician was contacted and the diagnosis obtained from themedical records in all cases.
Examination ProceduresThe examinations were conducted in each community at a suitable localbuilding such as a church or fire hall. When a waterman came for theexamination, he underwent the following procedures: (1) his name was
821
Taylor
checked on a master list, informed consent was obtained, and a uniqueidentification number was assigned; (2) visual acuity and intraocular pres-sure were measured, and dilating drops were instilled; (3) the interviewand skin examination with photography were performed while the dilat-ing drops were taking effect; and (4) the eye examination was performed,and lens and fundus photographs were taken. The ocular findings werethen discussed and any questions answered. If further follow-up or treat-ment appeared warranted, appropriate referrals were made to local medi-cal specialists.
Thirty-seven watermen were either unable or unwilling to come to thecentral site; for them, a home visit was arranged. An interview wasobtained and an ophthalmologic examination undertaken. The lens wasexamined with a portable slit lamp and, where possible, fundus photostaken with a portable fundus camera. Skin photographs were also taken,although the detailed skin examination was not done.At each stage of data collection, information in each area was gathered
and recorded independently without knowledge of data from the otherareas in order to avoid bias. Thus, for example, interviews had no knowl-edge of the status of the lens before they interviewed the subject on UVexposure.
DATA ANALYSIS
Data were collected, for the most part, on self-coding forms. Data wereentered on personal computers using customized interactive data entryprograms (Infostar). Data files were transferred to a mainframe computer(IBM 4331). The files were checked and edited. A number of standardstatistical packages were used during the analysis including SAS andSPSS.
Calculation of ExposureThe yearly ocular UV-B exposure was calculated for each individual foreach year of life beyond the age of 15. This was done by combininglaboratory-derived and field-derived data and published data on ambientUV-B with personal exposure histories obtained in interviews (Fig 1).Laboratory investigations, using anatomically correct mannikin models,were conducted to determine the ocular dose as a fraction ofambient UV-B-the ocular ambient exposure ratio or OAER-and the attenuation ofocular exposure by spectacles and hat use. 121 Seasonal variations in OAERwere examined during field studies in which watermen wore UV-B ab-sorbing polysulfone film badges in order to monitor their actual dailydoses of UV-B while they worked on the water, crabbing or oystering,
822
UV and the Eye
12
-xp E xPm [Fwork + Fi.is
m = montheXPm - mean ambient monthly exposure (MSY)Fwork = fraction of monthly ocular exposure acquired at work
Fwork - Hrwork x LOcamb x Splcwork x OAERworks x (workdays)7
Hrwork = fraction of daily ambient exposure during hours workedLocamb = mean annual level at job location (compared to Maryland)Specwork = mean UVR attenuation due to spectacle wear while workingOAERwork = OAER for given work surface, hat use, and seasonWorkdays = number of days worked per week
Fleis = fraction of monthly ocular exposure acquired during leisure
Fbis - Hr1*i5 x LOcamb x Spesqis x OAERi.is x (1 - workdays)7
Hrleis = fraction of daily ambient exposure during leisure hoursLocamb = mean annual level at leisure location (compared to Maryland)SPECleis = mean UVR attenuation due to spectacle wear on days offOAERleis = OAER for given hat use and seasonWorkdays = number of days worked per week
FIGURE 1The factors included in the mathematical model for the calculation of yearly ocular UV-Bexposure (Yexp) for each individual. (Yearly exposure is expressed as a fraction of totalambient UV-B radiation in terms of Maryland Sun Years. See text for a more detailed
description of this model and the different factors.)
with and without hats.'22 Other outdoor workers were also studied toobtain OAER for work over land. Data on the proportion of exposure foreach hour, for each month, and for different localities were available frompublished tables.123124The annual exposure was expressed as a proportion of total ambient
UV-B radiation in terms of Maryland Sun Years (MSY); one MSY is equalto the total amount of ambient UV-B irradiance of a horizontal surface atsea level in Maryland over 1 year. On the basis of readings taken in
823
Taylor
Philadelphia, this is approximately 2500 minimal erythemal doses, or 95Jcm -2.123,124 Once the individual yearly exposures were determined, itwas possible to determine other measures for each waterman, includingcumulative exposure, average annual exposure, maximum annual expo-sure, age of first maximum exposure, number of consecutive or noncon-secutive years at either his maximum annual exposure or a given level ofexposure.
Statistical MethodsA tremendous amount of data was collected during this study, and anordered approach to statistical analysis was followed. Some of the moreimportant statistical tests that were used are outlined.The odds ratio is a test used to assess risk in retrospective or cross-
sectional studies. 125 It gives a general measure of the risk of disease for anindividual exposed to a specific factor in comparison with the risk ofdisease for an individual not exposed. Specifically, it divides the odds thatan individual with the disease has been exposed to the risk factor by theodds that an individual without the disease has been exposed to the riskfactor. An odds ratio of 1 means that there is no increased odds of havingbeen exposed to the risk factor if one has the disease. An odds ratio of 2means that the odds of having been exposed to that factor are twice asgreat in those with the disease. The 95% confidence interval (CI) is usedto assess whether an increased risk is statistically significant. If the CI of agiven odds ratio does not include 1.0 the increase in risk is statisticallysignificant, at least to the 0.05 level. for example, the increased odds ofcortical cataract if cumulative UV-B exposure is doubled is statisticallysignificant, as the derived odds ratio is 1.60 (95% CI, 1.01 to 2.64). Theodds ratio of 1.60 also indicates that people with the higher exposure have60% more cataract than those with a lower exposure.
Data were analyzed using the SAS standard statistical package to calcu-late Mantel-Haenszel summary odds ratios. Odds ratios were also derivedfrom logistic regression models used to analyze the independent contri-bution of exposure to risk of the observed ocular changes.
Various regression analytic methods were also used to study the associ-ation between one dependent variable (cortical opacities, for example)and many independent variables (say age, UV-B exposure, smoking, andhypertension). These sophisticated computer-based statistical techniquescan simultaneously indicate the strength and statistical significance ofmultiple potential associations while controlling for possible confoundingeffects of the independent variables. 125 Results from such an analysis canoften be presented as odds ratios but for continuous variables the regres-sion coefficient with or without a confidence interval is usually presented.
824
UV and the Eye 825
This coefficient gives a measure of the strength of the association for eachunit of that variable, for example, the regression coefficient for age in themultiple logistic regression model of UV-B exposure and cortical opacitiesis 0.16. This can be translated to say that, on average for each additionalyear of life, the risk of cortical cataract increases by 17% (eO 16).A serially additive expected dose model was also used to explore the
relationship between UV-B exposure and lens opacities. 126This method ofanalysis involves calculating the actual yearly exposure for each year of lifefor cases-for example, those with established cortical cataract-and com-paring this with the exposure of age-matched controls who do not havecortical cataract. Cases and controls were matched within 2 years of age.
RESULTS
REPRESENTATIVES OF STUDY POPULATION
The first step of the analysis was to ensure the representativeness of oursample and show that it was not unduly affected by selection biases. Therandom sample appeared to be representative of the sample of all nonat-tenders on the two variables that could be determined from the DNRrecords: age and primary license type (Table I).
TABLE I: COMPARISON OF AVAILABLE BASELINE CHARACTERISTICS OBTAINED FROM LICENSERECORDS (AGE AND LICENSE TYPE) OF PARTICIPANTS (STUDY POPULATION) AND THOSE WHO WERE
ELIGIBLE BUT DID NOT PARTICIPATE (NONATTENDERS)*
STUDY POPULATION
PRIMARY SECONDARY RANDOMATTENDERS ATTENDERS SAMPLEt TOTAL NONATTENDERS
NO * NO % NO % NO % NO %
Age (yrs)30-39 145 23 47 26 12 29 204 24 103 274049 104 17 34 19 10 24 148 18 73 2050-59 130 21 28 16 8 19 166 20 70 1960-69 131 21 42 24 4 10 177 21 53 1570-79 84 14 18 10 5 12 107 13 48 1380+ 27 4 7 4 2 5 36 4 13 4
LicenseCrab 385 62 98 56 25 61 508 60 229 64Oyster 174 28 46 26 8 20 228 27 81 22Limited crab 12 2 15 9 3 7 30 4 17 5Other 50 8 17 10 5 12 72 9 33 9
Total 621 176 41 838 360
*No statistically significant differences were seen between the groups.Age: Random sample vs nonattenders: x2 = 0.95, P = NS.License: random sample vs nonattenders: x2 = 1.04, P = NS.tThe random sample subjects aged less than 30 or who only had interviews are excludedfrom this table.
Taylor
The distribution of several variables between attenders and the randomsample was then examined to see ifthese groups were similar. Again therewere no differences with respect to age and license type (Table I). Fur-ther, no difference was found in general medical background, such as thetendency to freckle (present in 48%), frequency or degree of sun burning(33% usually or always burn), or use of photosensitizing drugs (2%); norwas there a difference in frequency of diabetes (7%), hypertension (34%),reported use of heart or diuretic medication (20%), regular aspirin use(36%), or use of oral steroids (4%). There was no difference in educationalhistory (average, 9.5 grades), smoking history (79% greater than 5 packs intheir lifetime), or the use of glasses outdoors (73%). Those in the randomsample had used arc welding more frequently than those in the other twogroups (49% compared to 26% and 27%). There was also no difference inthe hours spent outside in days off work (the median was 5 hours),although 8% of the random sample did not wear a hat during leisure time,compared to 21% and 20% of the primary and secondary attenders,respectively.Of particular concern would be a difference in the rates of cataract or
UV-B exposure. No difference was observed in either the proportion ofsubjects with nuclear or cortical opacity (Table II) or several indices ofUV-B exposure, including average annual exposure, maximum annual expo-sure, and age at first year of maximum exposure. The groups had similareye examinations. There was no difference in the frequency with whichcorneal opacities occurred (85%), nor were there any differences between
TABLE II: DISTRIBUTION OF LENS OPACITES (CLINICAL EXAM) AMONG AITENDERS ANDRANDOM SAMPLE*
PRIMARY SECONDARY RANDOMATFENDERSt A1ITENDERSt SAMPLE
NO % NO % NO %
Nuclear opacityNone 462 75 116 66 25 631 88 14 34 19 8 202 or more 67 11 25 14 7 17
Cortical opacityNone 533 86 153 88 35 871 60 10 11 6 3 82 or more 24 4 11 6 2 5
*No statistically significant differences in the distribution of lens opacities are seen betweenthe groups.
Nuclear opacity: x2 = 7.26, P = NSCortical opacity: x2 = 3.71, P = NS
tTwo subjects with bilateral congenital cataract, three without clinical examinations, and onewith bilateral aphalda are excluded.
826
UV and the Eye
the frequency of a history of glaucoma (2%) or the presence of pseudoex-foliation (0.4%). Aphakia was equally common in each of these threegroups (3%).These data suggest that, although not all of the baseline population was
examined, the attenders (who represent 70% of this population) and thenonattenders were very similar on all the important characteristics thatcould be assessed, and no bias from this source should be expected in theresults.
DESCRIPTION OF STUDY POPULATION
General and Occupational CharacteristicsOf the 838 watermen examined, 204 (24%) were between 30 and 39 yearsof age and 140 (17%) were over the age of 70 (Table I). The oldest was 94,and the mean age was 53.0 years. There were 24 watermen (3%) who wereblack.
During the interview, a detailed occupational history was obtained.Overall, 75% had spent up to 4 years in military service, but approx-imately 23% of the watermen had not held any other job apart frommilitary service. Less than 25% had held three or more jobs and less than2% had held six or more. Altogether, information was collected on 1717different jobs undertaken by members of the sample during their workinglife. Of all these jobs, 72% were undertaken in Maryland and another 8%in contiguous states.Watermen could be classified according to their "main job." The main
job was defined as the occupation they had pursued for the longestperiod, though not necessarily continuously. The various occupationswere grouped together into nine broad categories (Table III). Watermenwere regarded as working full time if they worked on the water year
TABLE III: CHARACTERISTICS OF OCCUPATIONS DEFINED AS MAIN JOBS
TIME JOB HELD HOURS OUTSIDE
NO (%) YEARS WORK DAYS LEISURE DAYS
Full-time watermen 437 (52.1) 28.2 ± 14.1 11.3 + 1.7 4.6 ± 2.7Part-time watermen 103 (12.3) 25.6 ± 13.6 NA 5.1 ± 2.6Water related 16 (1.9) 26.1 ± 15.1 7.5 ± 3.1 5.4 ± 2.2Outside workers 80 (9.5) 22.7 + 12.0 5.3 ± 3.1 5.6 ± 2.3Laborers 23 (2.7) 20.3 ± 10.8 2.3 ± 3.3 5.3 ± 2.3Farmer 17 (2.0) 27.4 ± 12.5 8.6 ± 2.7 5.5 ± 3.0Army 11 (1.3) 20.2 ± 5.0 3.0 ± 2.9 5.0 ± 3.3Inside workers 108 (12.9) 22.2 ± 10.4 1.9 ± 2.7 5.1 ± 3.0White collar 43 (5.1) 21.7 ± 9.9 2.0 ± 2.7 5.1 ± 2.8
Total 838 25.9 ± 13.3
827
round. Part-time watermen would only work part of the year (the crab-bing season, for example) and had either another job or no job for the restof the year. Water-related jobs included those of sailors and marine police.Outside workers were those who spent most of their working hoursoutside and included construction workers and truck drivers but notfarmers and laborers. The other categories are self-explanatory. The timethe main job had been held was similar for each category (Table III).Although there was the expected variation in the number of workinghours spent outside, the number of leisure hours spent outside wassimilar for each category.The characteristics of the watermen's jobs were examined in detail;
overall, 705 (84%) of those studied had crabbed, 611 (73%) had oystered,92 (11%) had fished, and 37 (4%) had clammed. Whatever occupation awaterman was following, he was likely to be on the water from first light.Those fishing, clamming, and crabbing usually returned during the mid-dle of the day (12 noon to 2 pm), whereas those oystering usually did notreturn until after 4 p.m.The oystering season is set by regulation; it usually runs from October
to April. Most watermen will crab between April and September. Clam-ming could start any time ofthe year, but most clammed for 2 to 4 months,usually between April and June. Similarly, fishing could also be under-taken year round, and 60% ofwatermen who fished did so for more than 6months of the year. When crabbing, three-quarters would work 6 or 7days a week, as would almost half ofthose fishing or clamming. Because ofthe poor weather in winter, two-thirds would oyster only 4 or 5 days aweek.Over three-quarters of watermen always wore a hat while working,on
the water; less than 10% said they never wore a hat on the water. Therewas no difference for the different types ofwatermen jobs. Oystering andfishing are done without a canopy on the boat, although one-fifth ofclammers use a canopy and two-thirds of crabbers use a canopy at leastsome of the time.
Distribution of UV-B ExposureThe annual exposure of the eyes to UV-B was determined for eachwaterman for each year of his life after the age of 15 years. Given thediverse occupational and behavioral background of the watermen, it is notsurprising that there was quite a range in the various parameters calcu-lated. Cumulative exposure, for example, ranged from 0.024 to 3.664MSY with the median being 0.756 MSY (Fig 2). Average annual exposureranged from 0.001 to 0.074 MSY with the median being 0.022 MSY (Fig3). Maximum annual exposure ranged from 0.002 to 0.128 MSY with a
828 Taylor
UV and the Eye82
150
125
100
FREQUENCY 75
50
25
0.1 .5 .9 1.3 1.7 2.1 2.5 2.9 3.3 3.7
CUMULATIVE EXPOSUREFIGURE 2
Frequency distribution of cumulative ocular UV-B exposure of 838 watermen as a proportionof total annual ambient UV-B (in Maryland Sun Year [MSY] units).
150
125 Median
100
FREQUENCY 75lii
25
.002 .012 .022 .032 .042 .052 .062 .072
AVERAGE EXPOSURE
FIGURE 3Frequency distribution of average annual ocular UV-B exposure for 838 watermen as a
proportion of total annual ambient. UV-B (equal to 1 MSY).
829
median of0.038 MSY. For more than halfof the watermen, their first yearof their maximum annual exposure had occurred by the age of 18 years.The maximum possible annual ocular exposure in Maryland is 0.170 MSY.To achieve this exposure, one would have to work on the water all day,every day of the year, and not wear a hat or glasses. Under these circum-stances, the eye would receive 17% of the ambient UV-B.
Distribution of Lens Opacities and CataractThere was no difference in the occurrence of various types or severity ofsenile lens opacities between the right eye and the left eye, and thesubsequent analysis has been performed for each type ofopacity using thegrading in the worst or most severely affected eye.Two watermen had bilateral congenital cataracts (one was aphakic) and
have been excluded from the subsequent analyses of lens opacities. Twowatermen had unilateral congenital lens opacities, and ten watermen hadunilateral traumatic opacities (two were aphakic). These 12 people wereclassified according to the change in their unaffected eye. Seventeen wereaphakic, having had cataract surgery for senile cataract. Nine had uni-lateral aphakia; and of these, four had moderate or severe cataract in thefellow eye (Table IV).
Data on the clinical assessment of lens opacities was available on 835watermen. Photographic data was available on cortical opacities for 749and on nuclear opacities for 729. The reasons photographs were notavailable are shown in Table V.
Overall, 111 (13%) watermen had some cortical opacity on clinicalexamination and 229 (27%) had some nuclear opacity. These figuresinclude those who had had cataract surgery. There was a progressive
TABLE IV: DISTRIBUTION OF CATARACT TYPES IN APHAKIC PATIENTS*
UNILATERAL APHAKIA
FELLOW EYEtBILATERAL OPERATEDAPHAKIA EYE CO NO PSC
Cortical opacity (CO) 2 0Nuclear opacity (NO) 4 3 0 2 0Posterior subcapsular 1 5 0 0 2(PSC)NO and PSC 0 1 0 0 0Unknown 1 0
Total 8 9
*One patient with unilateral aphakia following traumatic cataract is excluded.tPresence of lens opacity grade 3 or greater.
Taylor830
UV and the Eye
TABLE V: REASONS FOR MISSING OR UNREADABLE PHOTOGRAPHS
CORTICAL NUCLEAR MACULARPHOTOS PHOTOS PHOTOS
One eyeAphakic 9 11 2Monocular 4 4 4Inadequate photograph 35 6 0Opaque media 0 0 7No known reason 4 9 2Total 58 30 15
Both eyesAphakic 4 3 4Drops contraindicated 11 14 10Home visit 32 34 27Refusal 7 8 9Equipment failure 24 35 1Subject missed photo 8 2 5Inadequate photograph 0 0 5No known reason 3 13 0Total 89 109 61
increase in the prevalence and severity of cortical and nuclear opacitieswith age. This was true with both the clinical grading and photograding(Figs 4 to 7). The trends are remarkably similar for both types of assess-ment, with the exception that the photograding of nuclear opacitiestended to grade opacities as being more severe than did the clinicalgrading. Only 14 watermen were found to have PSC, including the 7 whohad cataract surgery for PSC (Fig 8), and these numbers are too few toprovide firm age-specific prevalence rates.There was a highly significant statistical correlation between cataract
severity and visual acuity (Table VI). Overall, 83% of those eyes withoutcortical opacities saw 20/20 or better compared to only 58% of those eyeswith cortical opacities. Similarly, 91% of eyes without nuclear opacitiessaw 20/20 or better compared to only 46% of those eyes with nuclearopacities. In this subanalysis, eyes with conditions-other than the partic-ular cataract type-that might reduce best corrected acuity were ex-cluded.
Distribution of Macular ChangesMacular photographic data was available for 777 watermen. The reasonsfor missing photographs are shown in Table V.
Macular changes became increasingly common with increasing age.The overall prevalence of macular changes of any severity (SMD 1)increased with age from 17% in those less than 40 years of age to 50% in
831
Taylor
70
60
50
00LPREVALENCE
40
30
20 .4 .
10 - *30 40 50 60 70 80
AGEFIGURE 4
Prevalence and severity of cortical opacities as determined by clinical grading in the moreseverely affected eye for 838 watermen.
% 40PREVALENCE 330/
20 / S.
0~~~~~~~~~~/**
30 40 50 60 70 80AGE
FIGURE 5Prevalence and severity of cortical opacities as determined by photograding in the moreseverely affected eye for 746 watermen for whom cortical photographs were available.
832
UV and the Eye
100
80
00LPREVALENCE
60
40 1
20/
30 40 50 60 70 80AGE
FIGURE 6Prevalence and severity of nuclear opacities as determined by clinical grading in the more
severely affected eye for 838 watermen.
100
80
% 60PREVALENCE
40
20
0 30 40 50 60AGE
FIGURE 7
Prevalence and severity of nuclear opacities as determined by photograding in the more
severely affected eye for 726 watermen for whom nuclear photographs were available.
70 80
833
Taylor
7 6/1773/3%6 zoclinical psc
5 m aphakic psc
NUMBER 4 3/166 3/105OF CASES 2/2% 30/a
2/20410/
2I02i30-39 50-59 70-79
40-49 60-69 180
AGE GROUPFIGURE 8
The occurrence of PSC as determined by clinical grading in the more severely affected eyefor 838 watermen.
those over age 80 (Fig 9). Grade 3 changes or worse (SMD 3) were presentin 97 (12%) cases. Ten (1%) watermen had frank macular degeneration;that is, disciform degeneration or geographic atrophy (SMD 4).Distribution of Other Ocular AbnormalitiesCorneal opacities were seen in only 17 watermen (Table VII), but pteryg-ium and pinguecula were common. Of particular interest was the fre-quent occurrence of climatic droplet keratopathy (CDK); 162 watermenshowed some degree of this change. One waterman had bilateral Terrein'scorneal degeneration. Two watermen had miscellaneous conjunctival con-ditions; conjunctival dysplasia was found in one and Bowen's disease inanother.
Less than 2% of eyes were found to have pressures of over 21 mm Hg,and only four eyes had pressures of 30 mm Hg or greater.Distribution of Skin DiseaseSkin changes due to sun damage were common. Seven hundred four(89%) of the 788 watermen who had skin examinations had moderate tosevere elastosis on clinical grading, and 540 (66%) of the 819 who had skin
834
UV and the Eye
TABLE VI: CORRELATION BETWEEN SEVERITY OF LENS OPACI AND VISUALACUITY IN INDIVIDUAL EYES*
VISUAL ACUITY
20/20 20/2.20/30 20/40 OR LESS
Cortical opacitytGrade 0 1032 102 14Grade 1 46 28 7Grade 2 or more 7 3 1Total no. of eyes 1240
Nuclear opacityfGrade 0 975 80 14Grade I 110 51 7Grade 2 or more 20 32 31Total no. of eyes 1320
*Eyes with aphkia; congenital, traumatic or PSC lens opacities; SMD 3 or4; or other obvious ocular pathology that would reduce acuity wereexcluded.tEyes with grade 2 nuclear opacity or worse were also excluded (x2 =86.4, P < 0.001. Fisher's exact test [opacity present/absent vs 20/20-20/25or worse] P < 0.001.)*Eyes with worse than grade 2 cortical opacity were also excluded (X2 =413.8, P<0.001).
60
50-
401-
PREVALENCE 30
20 F
10
n I
V
30 40 50 60 70 80AGE
FIGURE 9
The prevalence and severity of macular degeneration in the more severely affect eye as
determined by examination of macular photographs in 777 watermen.
--- SMD I
......SMD 2
--i SMD 3
SMD 4
. 00
- I
835
PI
0
Taylor
TABLE VII: OCCURRENCE OF CORNEAL ABNORMALITIES IN835 WATERMEN
CORNEA UNILATERAL BILATERAL
Axial opacity 3 (0.4%) 0 ( -)Peripheral opacity 13 (1.6%) 1 (0.1%)Pterygium 70 (8.3%) 70 (8.3%)Pinguecula 41 (4.9%) 601 (71.9%)CDK 18 (2.1%) 144 (17.2%)
photography had moderate to severe elastosis on photograding. However,246 showed periorbital sparing due to the wearing of either glasses, a hat,or both. Actinic elastosis, graded either clinically or photographically,showed a progressive increase with age, although there was a tendencyfor some plateauing after the sixth decade (Fig 10). The 24 black water-men were excluded for this comparison.
Actinic elastotic change is assumed to be a function of UV-induceddamage and therefore may provide a measure of cumulative personal UVexposure. When the protective influence of glasses and hats is excludedfrom the calculations of cumulative exposure, exposure is well correlatedwith degree of actinic elastosis (Fig 11). Whether the actinic elastosis isgraded clinically or photographically (data not shown), an increase inmean cumulative exposure is seen, with more severe grades of elastosisfor most decades.
RISK FACTOR ANALYSIS
UV-B Exposure and CataractCataracts are increasingly more common at older ages (Figs 4 to 7) and anyanalysis of association or risk factors must control for the effect of age.Furthermore, because cumulative UV-B exposure and age are so closelyrelated, particular care must also be taken when assessing the effect ofcumulative exposure. Because of the complexity of the following analysisand because similar results were obtained using both the clinical andphotographic grading schemes, only the data for clinical grading will bepresented.
To identify potential confounding factors, age-adjusted bivariate anal-yses were performed (Table VIII). Subsequent logistic regression analysisadjusting for age revealed a statistically significant association betweentotal cumulative UV-B exposure and cortical opacities (regression coeffi-cient = 0.70; 95% CI, 0.01 to 1.40) (Table IX). These data show that, ie,for a given age, a doubling of cumulative UV-B exposure was associated
836
UV and the Eye
100
801-
0VLPREVALENCE
60sF401-
20!F0
30 40 50 60 70 80AGE
FIGURE 10The prevalence and severity of actinic elastosis determined by clinical assessment in 704
watermen. This analysis excludes 24 black watermen.
3.0
2.5
MEANEXPOSURE
2.0
1.5
1.0
.5
0 30-39 50-59 70-7940-49 60-69 P80
AGE GROUPFIGURE 11
The correlation between the severity of clinically determined actinic elastosis and mean
cumulative skin UV-B exposure in 704 watermen. This analysis excludes 24 black watermen.There were no watermen aged 70 to 79 years with mild actinic elastosis.
So*-fft00o- -tmtwwo W
.4.
* *0.- Grade
.-- 1 or worse: --- 2 or worse
...... 3 or worsemm 4
.0.0 _ ._ 4
_._ * * I I
E Mild0 ModerateM Severe
837
II
II
0I
Taylor
TABLE VIII: AGE ADJUSTED ODDS RATIOS (WITH 95% CI) SHOWING THE ASSOCIATIONS BETWEENVARIOUS POTENTIAL RISK FACTORS AND DIFFERENT TYPES OF LENS OPACMES (CLINICAL GRADING)*
ODDS RATIO
CORTICAL NUCLEAR PSCFACTOR NOt (n = 11) (n = 229) (n = 14)
Heart/diuretic medication 163 1.5 (0.9-2.4) 0.9 (0.4-1.4) 2.4 (0.8-7.2)History of hypertension 286 0.9 (0.6-1.4) 0.6 (0.4-0.9)* 1.9 (0.7-5.6)Smoking 660 1.3 (0.8-2.3) 1.6 (0.9-2.9) 0.9 (0.2-3.3)Freckling 402 0.9 (0.5-1.4) 0.8 (0.5-1.3) 1.7 (0.5-5.6)Steroid use 33 0.5 (0.1-2.1) 1.0 (0.4-2.4) 1.5 (0.2-10.8)Tendency to burn 279 1.1 (0.7-1.8) 1.6 (1.0-2.4) 2.4 (0.8-7.2)Aspirin use 301 1.1 (0.7-1.8) 0.9 (0.6-1.4) 0.4 (0.1-1.5)Diabetes 62 1.3 (0.6-2.6) 1.0 (0.5-1.9) 0.7 (0.1-5.6)More than 8 years school 502 1.3 (0.8-2.1) 0.8 (0.5-1.2) 1.0 (0.3-3.0)Arc welding 227 1.0 (0.5-1.8) 0.7 (1.4-1.1) 1.4 (0.4-4.7)Eye color (blue eyes) 480 0.6 (0.4-1.0)t 0.8 (0.5-1.3) 9.0 (1.5-54.0)f:Actinic elastosis 422 0.8 (0.5-1.3) 1.1 (0.7-1.9) 1.3 (0.44.5)Pterygium 140 0.8 (0.5-1.4) 0.8 (0.4-1.5) 3.3 (1.1-9.9)tPinguecula 640 0.8 (0.4-1.3) 1.0 (0.7-1.4) 0.3 (0.1-0.9)tGlaucoma 15 0.5 (0.1-1.9) 0.6 (0.2-1.9) -§
*See Methods section, Data Analysis for a description of odds ratio and its significance.tNumber of watermen having this condition.4Chi-square test gave, P < 0.05.§None of the PSC cases had glaucoma.
TABLE IX: RESULTS OF LOGISTIC REGRESSION ANALYSES OF THE ASSOCIATION BETWEENCUMULATIVE UV-B EXPOSURE AND RISK OF LENS OPACITY (GRADE 2 OR MORE)*
REGRESSION STANDARDVARIABLE COEFFICIENT ERROR P
Cortical opacityIntercept - 14.23 1.93 0.001Age 0.16 0.02 0.001Cumulative UV-B exposuret 0.70 0.35 0.04
Nuclear opacityIntercept -10.88 0.81 0.0001Age 0.17 0.01 0.001Cumulative UV-B exposuret -0.01 0.16 NSHistory of hypertension -0.53 0.22 0.02
*Statistically significant association seen between cumulative UV-B exposure and corticalopacity but not nuclear opacity.tLog transformation.
838
UV and the Eye
TABLE X: ODDS RATIO (WITH 95% CI) DETERMINED BY LOGISTIC REGRESSIONANALYSIS FOR CORTICAL AND NUCLEAR CATARACT (EACH GRADE 2 OR MORE) BY
QUARTILES OF ANNUAL AVERAGE UV-B EXPOSURE*
ODDS RATIOSEXPOSURE DOSE RANGEQUARTILE (MSY) CORTICAL NUCLEAR
1st 0.012 or less 1.00 1.00 (0.51-2.91)2nd 0.013-0.022 2.32 (0.70-7.73) 1.22 (0.51-0.91)3rd 0.023-0.032 3.25 (0.98-10.80) 1.26 (0.52-3.06)4th 0.033 or more 3.30 (0.90-9.97) 0.96 (0.36-2.60)
Age (regression coefficient) 0.16 0.17
*This analysis shows an increased risk of cortical opacity but notnuclear opacity with increased annual UV-B exposure.
with a 1.60 times (95% CI, 1.01 to 2.64) increased risk of cortical opaci-ties. Examined in another way, the risk of cortical cataract increasedmarkedly with increasing annual average UV-B exposure (Table X). Theodds ratio for exposure in the upper quartile compared to the lowestquartile was 3.30 (95% CI, 0.90 to 9.97). No increased risk for nuclearopacities was apparent with increased UV-B exposure, even adjusting forage, tendency to burn, and history of hypertension (regression coefficient= -0.01; 95% CI, -0.32 to 0.31).The UV-B exposure for cases of cortical opacity was significantly higher
than the expected exposure when examined in the serially additive dosemodel (t-test, 2.23; P = 0.03; Fig 12). It is clear that those with corticalopacities have had more UV exposure every year of life after age 15,suggesting that damage is a cumulative phenomenon. On average, thismodel indicates that people with cortical cataract had a 21% higher UV-Bexposure than those without cortical cataract. There is no evidence thatthose with cortical opacities had more exposure at a particular susceptibleperiod of life or that there was an obligatory latency period for develop-ment of this change. Further analysis found no evidence to suggest a safethreshold for either exposure level (annual average UV-B exposure) orduration (the number of years above a given UV-B exposure). Instead, thedata indicate a progressive increase in risk of cortical cataract with in-creased UV-B exposure. No such association was seen between UV-B ex-posure and nuclear opacities in the serially additive dose model (Fig 13).Other Risk Factors for CataractThe association between various other factors and lens opacities deter-mined clinically is shown in Table VIII. Similar results were obtainedwhen photographic grading was used. The prevalence rates of corticalopacities were higher in those with blue eyes. The prevalence rates for
839
840 Taylor
1197
AVERAGE 5DIFFERENCE 3(MSYX103 ) 1 -
-1-3
20 30 40 50 60 70 80
AGEFIGURE 12
The average difference in ocular UV-B exposure at each year of life between 34 watermenwith cortical opacities (grade 2 or worse in the more severely affected eye) and 213 age-matched controls without this degree of cortical opacity as determined by the seriallyadditive expected dose model. (Note: in this model, if there were no difference in exposurebetween the cases and the controls, the line would hover around 0. If the cases had a lowerexposure, the line would be below 0. Here the line is above 0, indicating that those withcortical cataract have a consistently higher exposure at every year of life above age 15. Theannual exposure of cases with cortical opacities is, on average, 21% higher than controls.)
97
AVERAGE 5DIFFERENCE K(MSYx103) 1
-1-3-5
20 30 40 50 60 70 80AGE
FIGURE 13The average difference in ocular UV-B exposure at each year of life between 184 watermenwith nuclear opacities (grade 2 or worse in the more severely affected eye) and 413 age-matched controls without this degree of nuclear opacity as determined by the seriallyadditive expected dose model. (There is no difference in UV-B exposure between the cases
with nuclear opacities and controls, as the line hovers around 0.)
UV and the Eye
nuclear opacity were somewhat lower in those reporting a history ofhypertension. However, because of the large number of subjects report-ing uncertainty over their use of antihypertensive medication and be-cause blood pressure was not actually measured, this finding should beinterpreted with caution. The prevalence of both cortical and nuclearopacities was higher among those who had "ever smoked" than amongthose who had "never smoked," although the difference was not signifi-cant in the initial analyses. There was no correlation between the pres-ence of either basal cell or squamous cell carcinoma and cortical ornuclear opacities.The number of cases of PSC was small, so the analyses for this opacity
were limited. The prevalence rates of PSC were significantly higher inblue-eyed individuals. They were also significantly higher among thosewith severe actinic elastosis as determined by photograding and amongthose with pterygium (compared to those with pinguecula alone or nei-ther disease). The rates ofPSC were higher in steroid users and those whoused heart or diuretic medication, but these did not reach statisticalsignificance.
In contrast to recent reports suggesting a protective effect of aspirin incataract prevention, we found no evidence that aspirin use, duration ofuse, or dose had any impact on opacities.127
UV-B Exposure and Senile Macular DegenerationNo correlation was found between the presence of SMD of any severityand UV-B exposure as expressed by cumulative or annual average expo-sure or by the other measures of UV-B exposure that were outlined in theanalysis performed for cataract (Table XI and Fig 14). Similarly, no associa-tion was found between SMD of any severity and cortical or PSC lensopacities, pterygium, or eye color. The presence of nuclear opacities wasassociated with an increased risk of SMD grade 3, and unexpectedly,smoking appeared to be somewhat protective for SMD. Analysis showedno consistent association between SMD of any severity and any of theother variables collected in the medical history, occupational history, orexamination.
UV-B Exposure and Corneal DiseaseBoth pterygium and CDK were more common in those who had a higherUV-B exposure. This was true for both annual average UV-B exposure(Table XII) and for cumulative exposure (data not shown). No such associa-tion was seen with pinguecula. Because a previous or coexistent pin-guecula is often overlooked in the presence of a pterygium, a further
841
Taylor
TABLE XI: ODDS RATIO (WITH 95% CI) AS DETERMINED BYLOGISTIC REGRESSION ANALYSIS FOR MACULAR
DEGENERATION (SMD 3) BY QUARTILES OF AVERAGEANNUAL UV-B EXPOSURE*
EXPOSUREQUARTILE DOSE RANGE (MSY) SMD 3
1st 0.012 or less 1.002nd 0.013-0.022 1.85 (0.96-3.53)3rd 0.023-0.032 1.34 (0.67-2.67)4th 0.033 or more 1.10 (0.53-2.28)
Age (regression coefficient) 0.45
*This analysis shows no increased risk of maculardegeneration with increased annual UV-B exposure.
11
97
AVERAGE 5DIFFERENCE 3(MSYx1O-3) I
-1
-3
-5
AGEFIGURE 14
The average difference in ocular UV-B exposure at each year of life between 89 watermenwith macular degeneration (SMD 3 or worse in the more severely affected eye) and 670 age-
matched controls without this degree of macular degeneration as determined by the seriallyadditive expected dose model. (There is no difference in UV-B exposure between the cases
with SMD 3 and controls, as the line hovers around 0.)
TABLE XII: ODDS RATIO (95% CI) AS DETERMINED BY LOGISTIC REGRESSION ANALYSIS FORPTERYGIUM, PINGUECULA, AND CDK BY QUARTILES OF AVERAGE ANNUAL UV-B EXPOSURE*
EXPOSUREQUARTILE DOSE RANGE (MSY) PTERYGIUM PINGUECULA CDK
1st 0.012 or less 1.00 1.00 1.002nd 0.013-0.022 1.01 (0.55-1.83) 0.98 (0.63-1.53) 1.78 (0.94-3.35)3rd 0.023-0.032 1.93 (1.09-3.39) 1.17 (0.75-1.85) 3.42 (1.85-6.31)4th 0.033 or more 3.06 (1.77-5.31) 1.40 (0.88-2.23) 6.36 (3.46-11.68)
Age (regression coefficient) 0.05 0.01 0.08
*This analysis shows the increasedd risk of pterygium and CDK but not pinguecula withincreased annual UV-B exposure.
842
UV and the Eye
analysis was undertaken to detect a possible interaction between pin-guecula and pterygium. UV-B exposure continued to show a strongassociation with pterygium but not with pinguecula. Age-adjusted oddsratios were calculated for the risk of developing each of these conditionsfor each quartile of annual average UV-B exposure. A strong associationwas seen for both pterygium and CDK but not for pinguecula (Table XII).
DISCUSSION
In this study, we set out to assess whether there was an associationbetween high UV-B exposure and different types of senile cataract orSMD. To be able to do this, we had to develop methods for quantifyingpersonal UV exposure for each individual in our study. We had to developreproducible grading methods for assessing cortical and nuclear cataractand SMD. In the final analysis, this study shows a clear associationbetween a high UV-B exposure and an increased risk of visually significantcortical cataract (ie, one quarter or more of the cortex involved withopacity). Those with this degree of cortical cataract had 21% greaterexposure to UV-B radiation at each year of life after the age of 15 yearsthan those who did not have cortical cataract; and a doubling of cumula-tive UV-B exposure increased the risk of cortical cataract by 60%. Noassociation was found between UV-B exposure and either nuclear opaci-ties or SMD.
Previous evidence from biochemical, animal, and epidemiologic stud-ies suggesting that UV-B exposure might be associated with the occur-rence of so-called senile cataracts in man was largely circumstantial, aswas weaker evidence to suggest some linkage with SMD. There was aneed for a definitive study relating the actual ocular UV-B exposure ofindividuals with their ocular status.We selected the watermen of Chesapeake Bay as our study population
for a number of reasons. First, and most obviously, watermen wereselected because they work outside all day. Potentially, they are exposedto the maximum UV-B irradiation naturally possible in this region. Theyusually work on an open boat; and because the land around the Chesa-peake Bay is flat, they have an unobstructed horizon. Therefore, they areexposed to scattered UV-B from the whole sky. Further, as they work overwater, they are also exposed to some additional reflected UV-B.
Second, although some watermen may be exposed to the maximumamount of UV-B, there is a range of exposure within this otherwise fairlyhomogeneous and stable population group. Many watermen wear hats,some wear glasses, and others have held other occupations with varying
843
Taylor
UV-B exposure. These factors resulted in a wide range of individual UV-Bexposures within this group, which greatly facilitated our analysis.The third reason for selecting the watermen is perhaps the most
important. Their work habits are, by and large, very stable and predict-able. This is due, in part, to the nature of their work and, in part, to stateregulations. Most watermen are on the water before dawn, and the timethey return to the dock is often set by regulation. Seasons, catches, andequipment are all regulated. The fact that the Chesapeake Bay skipjack isthe last working sailboat in the country attests to this fact. 128 The workinghabits of a waterman today have changed very little from those of 10, 20,or even 50 years ago. This is true for very few other outdoor occupations;one has only to think of the changes that have occurred in farming overthe last 50 years with the use of tractors and then protective cabs.
All of these factors taken together mean that the watermen of theChesapeake Bay form a stable occupational group for whom one couldreasonably hope to determine work habits and, therefore, occupationalUV-B exposure over their working lives with an acceptable degree ofaccuracy and who would have a broad range of personal UV-B exposure.
Before undertaking this study, we undertook sample size calculations toensure that we would examine sufficient numbers ofwatermen to be ableto answer the questions we were asking. Calculations repeated after thedata was collected showed the initial calculations were correct. For nucle-ar opacities, which occurred most commonly (prevalence of 28%), wecould be confident of identifying factors that increased the risk of cataractby as little as 40% (relative risk, 1.40) if they affected 30% of the popula-tion (type 1 error, 0.05; type II error, 0.20). This would include factorssuch as sunburning (33%), hypertension (34%), regular aspirin use (30%),and those who had smoked less than five packs of cigarettes (21%). lorfactors that affected only about 5% of the population (such as diabetes[7%], steroid use [4%r, and glaucoma [2%]), we could detect an 80%increase (relative risk, 1.80). For less common changes such as corticalopacities (prevalence of 13%) and macular changes (SMD 3, prevalence of12%), we could be confident of detecting an increase of approximately65% (relative risk, 1.65) for a factor that affected 30% of the population or140% (relative risk, 2.40) for a factor that affected 5%.Our sample size was therefore large enough to address the major
questions we posed on the effect of UV-B exposure on the occurrence ofcortical and nuclear cataract and SMD. The sample size was not sufficientfor detailed analysis of less common outcomes-in particular, PSC, ofwhich only 14 cases were seen. Similarly, the study was not designed tohave the power to test the association between cataract and relatively
844
UV and the Eye
uncommon factors such as diabetes.The calculation of individual ocular UV-B exposure is unique and goes
far beyond any previous attempt to quantify personal exposure to UVR.129Innovative measurements and approaches allowed the development of aset of values that quantified the way personal habits or characteristicsaltered UV-B exposure. 11,12.121,122 The relatively stable work habits of thewatermen permitted the collection of detailed lifetime occupational infor-mation. The integration of these two data sets in the ocular exposuremodel permitted us to develop an assessment of individual ocular expo-sure to UV-B with much greater precision than previously possible. Thecorrelation between the calculated dermal UV-B exposure and actinicelastosis attests to the validity of our model, as does the distribution andstatistical behavior of the exposures themselves.One of the major stumbling blocks in any study is the lack of a clear
definition of outcome or "a case." This was a major problem facing us atthe start of this study. We eventually had to develop grading schemes forseven separate outcomes: clinical grading schemes for cortical, nuclear,and posterior subcapsular opacities and photographic grading schemes forcortical and nuclear opacities, macular changes, and actinic elasto-sis. 115,117-120 In each instance, the grading scale gave a three- or four-stepgradation from no disease to severe disease. The progression of severityand the proportion of disease at each grade is a good measure of thesoundness or biological plausibility of a scheme. As can be seen from ourdata, there is good distribution of people in each grade and steadyprogression of severity with increasing age for each grading scheme (Figs4 to 9), with the sole exception ofPSC for which too few cases were seen.Another important measure of the soundness of a grading scheme is itsreproducibility. We have also demonstrated high levels of reproducibilityby both inter- and intraobserver reliability testing for each scheme. 115,117-120On the one hand, the grading of photographs would seem to have much
to recommend it over clinical grading. The grading of photographs canmore easily be standardized and would seem to be less subject to observerbias. Photograding readily lends itself to the masking of the observer;multiple observers can be used and observer reproducibility trials can beperformed easily. While these benefits may seem commendable, wefound in this study that these apparent advantages come at some cost.Overall, for one in eight of the watermen, cortical or nuclear photographswere not obtained, most commonly because of equipment failure orinability to transport the cameras on home visits. On the other hand, theparallel analysis of the clinical data and the photographic data gave similarresults. This suggests that for future cross-sectioned field studies of cata-
845
Taylor
ract, the standardized clinical grading methods may be not only sufficientbut also preferable.As discussed in detail in the Introduction, much of the biochemical
literature relating to UV-B exposure and cataract has focused on thechanges that occur in the nuclear pigmentation; and field studies haveoften reported the occurrence of mature cataract. Taken together, theyhave fostered the notion that the association between UV-B and cataractshould relate to nuclear and not cortical cataract. However, the biochemi-cal evidence for UV-induced changes in the proteins of the cortex seemsto be at least as compelling as for changes in nuclear proteins. Theexperimental data from animal studies, also, all point toward UV-B caus-ing cortical changes and not nuclear changes. Furthermore, the threeepidemiologic studies that have separated cataract by type showed anassociation between UV-B exposure and cortical cataract, not nuclearcataract. 81,93,94 In this context, the finding of our study is quite consistentand not unexpected.The lack of an association between UV-B exposure and SMD is also not
altogether unexpected in that the lens absorbs most of the UV-B, and onlyvery small amounts of this waveband can reach the retina. It would be ofconsiderable interest to investigate the association between UV-A expo-sure and SMD, since more UV-A is transmitted by the lens, and thiswaveband also has the potential for retinal toxicity.
It is of interest to note the relative rarity of PSC changes in ourpopulation-based sample. PSC occurred in only 14 watermen whereascortical opacities appeared in 111 and nuclear opacities in 229. However,PSC had led to cataract surgery in 7 watermen (associated with nuclearopacities in 1), while only 10 had cataract surgery as a result ofother typesof cataract. The watermen with PSC were also younger than those withother lens opacities. This suggests that PSC, although relatively uncom-mon, occurs in younger patients, develops more rapidly, affects visionearlier, and therefore leads to earlier surgery than other lens opacities.What is the clinical relevance of the strong epidemiologic and statistical
association we found between ocular exposure to UV-B and cortical cata-ract? At present, we do not understand the causes of senile cataract ingeneral or cortical cataract in particular, even though over 1 millioncataract operations are performed each year,108 and approximately onethird ofthem are for cortical cataract. The cause of cataract now appears tobe clearly multifactorial. This study has for the first time convincinglyidentified one of the important risk factors for cortical cataract. Theassociation between UV-B exposure and cortical cataract was strongest forthose with at least grade 2 cortical opacities-that is, where one-quarter
846
UV and the Eye
or more of the cortex was already opacified. This degree of corticalopacity was frequently associated with 20/30 vision or less. By clinicalexperience, such opacities proceed quite rapidly to cataract surgery in themajority of cases.
Given these findings, what are the implications for the watermen or forthe general population? It would seem prudent to protect the eyes fromunnecessary exposure to UV-B. The amount of ambient UV-B variesmarkedly during the day (being highest in summer between 10 am and 2pm). The periods of high levels of UV-B are usually well recognized, asthis is the time when one is most likely to become sunburned. As a publichealth recommendation, therefore, people should be advised to use ocu-lar protection at those times when they are at risk of getting sunburned.There are two very easy ways to reduce UV-B exposure short of staying
indoors, out of the sun. A hat with a brim will reduce ocular exposure byhalf, and ordinary, close-fitting plastic spectacles can reduce it to about5%.12 The effect of hats and glasses are additive. Although special UV-absorbing lenses can stop all UV-B transmission, a sample of 40 clearspectacle lenses showed that all ofthem significantly reduced ocular UV-Bexposure.12 The shape and position of the glasses were more important inreducing UV-B exposure than the actual lens material. Wrap-aroundglasses gave almost complete protection, while, if the frames were oneinch from the brow, there was only a 25% reduction of the amount of UV-B which reached the eye. Thus, to minimize ocular exposure to UV-Bcheaply and effectively, people should be advised to wear a hat with abrim and close fitting sunglasses at times when they could get sunburned.
SUMMARY
Circumstantial evidence from biochemical, animal, and epidemiologicstudies suggests an association between exposure to UV-B radiation (290nm to 320 nm) and cataract. Such an association had not been provenbecause it had not been possible to quantify ocular UV-B exposure ofindividuals or to reliably grade the type and severity of cataract in fieldstudies. We undertook an epidemiologic survey of cataract among 838watermen who work on the Chesapeake Bay. Their individual ocular UV-B exposure was quantified for each year of life over the age of 16, on thebasis ofa detailed occupational history combined with laboratory and fieldmeasurements of ocular UV-B exposure. Cataracts were graded by bothtype and severity through clinical and photographic means. SMD changeswere ascertained by fundal photography. A general medical history wastaken to discover potentially confounding factors. This study showed that
847
people with cortical lens opacities had a 21% higher UV-B exposure ateach year of life than people without these opacities. A doubling inlifetime UV-B exposure led to a 60% increase in the risk of corticalcataract, and those with a high annual UV-B exposure increased their riskof cortical cataract over threefold. Corneal changes, namely pterygiumand CDK, were also strongly associated with high UV-B exposure. Noassociation was found between nuclear lens opacities or macular degener-ation and UV-B exposure. This study also indicated several simple, practi-cal measures, such as wearing spectacles or a hat, that effectively protectthe eye from UV-B exposure. Thus it is easily within the power ofindividuals to protect their eyes from excessive UV-B exposure and re-duce their risk of cortical cataract. A program of public education in thisarea could be a cost-effective means of reducing this important disease.
ACKNOWLEDGMENTS
The author wishes to thank the many people who assisted with thisarduous and exacting undertaking. Special thanks are due to Drs SheilaWest, Edward Emmett, Helen Abbey, Frank Rosenthal, Stuart Fine, NeilBressler, Susan Bressler, Lorraine Cameron, and Mrs Beatiz Munoz. DrsHenry Newland, Ben Vitasa, and Alex Bakalian assisted with field work asdid Miss Paula Prestia and Messrs David Emmett and John Scrimgeour.Invaluable help and assistance came from members of the MarylandWaterman's Association, especially Mr Wayne "Hon" Lawson of Crisfield.The dedicated assistance of Miss Sue Simmons, Mrs Celeste Wilson, andMrs Alice Flumbaun is acknowledged as well as the editorial assistance ofDr Susan Edmunds and the support and advice of Dr Elizabeth Dax.
REFERENCES
1. Guerry RK, Ham WT, Mueller HA: Light toxicity in the posterior segment, in TDDuane, EA Jaeger (eds): Duane's Clinical Ophthalmology, Vol 3. Philadelphia, Harper& Row, 1986, pp 1-17.
2. American Academy of Ophthalmology: Eye and visual system abnormalities, in EyeCare for the American People, Supplement to Ophthalmology. San Francisco, Ameri-can Academy of Ophthalmology, 1987, Chap 2.
3. Hausser KW, VahleW (translated by F Urbach): Sunburn and suntanning, in F Urbach(ed): Biologic Effects of Ultraviolet Radiation. Oxford, Pergamon Press, 1969, pp 3-21.
4. Jones RR: Ozone depletion and cancer risk. Radiat Res 1987; 2:443-446.5. Duke-Elder S, MacFaul PA: Radiational injuries: Action on the lens, in S Duke-Elder
(ed): System of Ophthalmology. St Louis, CV Mosby, 1972, Vol XIV, Pt 2, pp 928-933.6. Phillips M: Electromagnetic radiation, in Encyclopaedia Brittanica, Vol 6. Chicago,
Encyclopaedia Brittanica, Inc, 1980, pp 644-665.7. Parrish JA, Anderson RR, Urbach F, et al: UV-A: Biological Effects of Ultraviolet
Radiation with Emphasis on Human Responses to Longwave Ultraviolet. New York,Plenum Press, 1978, Chap 1.
848 Taylor
UV and the Eye 849
8. Robertson DF: Solar ultraviolet radiation in relation to sunburn and skin cancer. MedJAust 1968; 2:1123-1132.
9. Fishman GA: Ocular phototoxicity: Guidelines for selecting sunglasses. Surv Ophthal-mol 1986; 31:119-124.
10. Sliney DH: Physical factors in cataractogenesis: Ambient ultraviolet radiation andtemperature. Invest Ophthalmol Vis Sci 1986; 27:781-90.
11. Rosenthal FS, Safran M, Taylor HR: The ocular dose of ultraviolet radiation fromsunlight exposure. Photochem Photobiol 1985; 42:163-171.
12. Rosenthal FS, Bakalian AE, Taylor HR: The effect of prescription eyewear on ocularexposure to ultraviolet radiation. Am J Public Health 1986; 76:1216-1220.
13. Sliney DH: Eye protective techniques for bright light. Ophthalmology 1983; 90:937-944.
14. Coroneo MT: Albedo concentration in the anterior eye and the location of some solardiseases. MS thesis. Sydney, Australia, University of Sydney, 1988.
15. Kinsey VE: Spectral transmission of the eye to ultraviolet radiations. Arch Ophthalmol1948; 39:508-513.
16. Bachem A: Ophthalmic ultraviolet action spectrum. Am J Ophthalmol 1956; 41:969-975.
17. Boettner EA, Wolter JR: Transmission of the ocular media. Invest Ophthalmol Vis Sci1962; 1:776-783.
18. Cooper G, Robson J: The yellow colour of the lens of man and other primates. J Physiol(Lond) 1969; 203:411-417.
19. Lerman S: Human ultraviolet radiation cataracts. Ophthalmic Res 1980; 12:303-314.20. Rosen ES: Filtration of non-ionizing radiation by the ocular media, in J Cronly-Dillon,
ES Rosen, J Marshall (eds): Hazards of Light: Myths and Realities of Eye and Skin.Oxford, Pergamon Press, 1986, pp 145-152.
21. Zigman S: Photobiology of the lens, in H Maisel (ed): The Ocular Lens: Structure,Function, and Pathobiology. New York, Marcel Dekker, 1985, pp 301-347.
22. VerhoeffFH, Bell L, Walker CB: The pathological effects of radiant energy on the eye:An experimental investigation with a systematic review on the literature. Proc AmAcad Arts Sci 1916; 51:630-818.
23. Pitts DG: The human ultraviolet action spectrum. Am J Optom Physiol Optics 1974;51:946-960.
24. Pitts DG, Cullen AP, Parr WH: Ocular ultraviolet effects from 295nm to 335nm in therabbit eye. Washington, DC, U.S. Department of Health, Education, and Welfare(NIOSH), 1976, pp 1-55.
25. Parrish JA, Anderson RR, Urbach F, et al: UV-A: Biological Effects of UltravioletRadiation with Emphasis on Human Responses to Longwave Ultraviolet. New York,Plenum Press, 1978, Chap 9.
26. Ham WT Jr, Mueller HA, Ruffolo JJ Jr, et al: Action spectrum for retinal injury fromnear-ultraviolet radiation in aphakic monkey. Am J Ophthalmol 1982; 93:299-306.
27. Ham WT Jr, Ruffolo JJ Jr, Mueller HA, et al: Histologic analysis of photochemicallesions produced in rhesus retina by short wavelength light. Invest Ophthalmol Vis Sci1978; 17:1029-1035.
28. Spector A: The search for a solution to senile cataracts (Proctor Lecture). InvestOphthalmol Vis Sci 1984; 25:130-146.
29. Garner WH, Spector A: A preliminary study of the dynamic aspects of the agedependent changes in the abundances of human lens polypeptides. Doc Ophthalmol1979; 18:91-99.
30. : Racemization in human lens: Evidence of rapid insolubilizatioa of specificpolypeptides in cataract formation. Proc Natl Acad Sci USA 1978; 75:3618-3620.
31. Benedek GB: Theory of transparency of the eye. Appl Optics 1971; 10:459.32. Spector A, Roy D: Disulfide-linked high molecular weight protein associated with
human cataract. Proc Natl Acad Sci USA 1978; 75:3244-3348.33. Dische Z, Zil H: Studies on the oxidation of cysteine to cystine in lens proteins during
850 Taylor
cataract formation. Am J Ophthalmol 1951; 34:104-113.34. Harding JJ: The nature and origin ofthe urea insoluble protein ofhuman lens. Exp Eye
Res 1972; 13:3340.35. Farnsworth PN, Spector A, Lozier JR, et al: The localization of a 43k polypeptide in
normal and cataractous lenses by immunofluorescence. Exp Eye Res 1981; 32:257-264.36. Truscott R, Faull K, Augusteyn R: The identification of anthranilic acid in proteolytic
digests of cataractous human lens protein. Ophthalmic Res 1977; 9:263-268.37. Garner WH, Garner MH, Spector A: Gamma-crystallin, a major cytoplasmic polypep-
tide disulfide linked to membrane proteins in human cataract. Biochem Biophys ResCommun 1981; 98:439-447.
38. Kinoshita JH: Mechanisms initiating cataract formation (Proctor Lecture). Invest Oph-thalmol Vis Sci 1974; 13:713-724.
39. Garner MH, Spector A: Selective oxidation of cysteine and methionine in normal andsenile cataractous lenses. Proc Natl Acad Sci USA 1980; 72:1274-1277.
40. Kador PF, Kinoshita JH: Diabetic and galactosaemic cataracts, in J Nugent, J Whelan(eds): Human Cataract Formation, Ciba Foundation Symposium 106. London, Pit-man, 1984, pp 110-131.
41. Bettelheim FA: Physical basis of lens transparency, in H Maisel (ed): The Ocular Lens:Structure, Function, and Pathology. New York, Marcel Dekker, 1985, pp 265-300.
42. Wistow GJ, Mulders JWM, de Jong WW: The enzyme lactate dehydrogenase as astructural protein in avian and crocodilian lenses. Nature 1987; 326:622-624.
43. Wistow G, Piatigorsky J: Recruitment of enzymes as lens structural proteins. Science1987; 236:1554-1556.
44. Walls G, Judd H: The intraocular colour filters of vertebrates. BrJ Ophthalmol 1933;17:641-654.
45. Duke-Elder S: General considerations: Normal age changes, in S Duke-Elder (ed):System of Ophthalmology. St Louis, CV Mosby, 1976, Vol XI, pp 10-16.
46. Pirie A: Formation of N-formylkynurenine in proteins from lens and other sources byexposure to sunlight. Biochem J 1971; 125:203-208.
47. van Heyningen R: The glucoside of 3-OH-kynurenine and other fluorescent com-pounds in human lens, in The Human Lens in Relation to Cataract, Ciba FoundationSymposium 19. Amsterdam, Associated Scientific Publishers, 1973, pp 151-168.
48. Duke-Elder S: Cataract: The pathology of cataract, in S Duke-Elder (ed): System ofOphthalmology. St Louis, CV Mosby, 1976, Vol XI, pp 125-142.
49. Chylack LT, Ransil BJ, White 0: Classification of human senile cataractous change bythe American Cooperative Cataract Research Group (CCRG) method. III: The associa-tion of nuclear color (sclerosis) with extent of cataract formation, age, and visual acuity.Invest Ophthalmol Vis Sci 1984; 25:174-180.
50. Pirie A: Colour and solubility of the proteins of human cataracts. Invest Ophthalmol1968; 7:634-650.
51. Dilley KJ: Ultraviolet light and human cataract. Nature 1975; 257:71-72.52. van Heyningen R: Fluorescent glucoside in the human lens. Nature 1971; 230:393.53. : Experimental studies on cataract (Proctor Lecture). Invest Ophthalmol 1976;
15:685-697.54. Dillon J: Photolytic changes in lens proteins. Curr Eye Res 1984; 3:145-150.55. Lerman S: Lens transparency and aging, in F Regnault, 0 Hockwin, Y Courtois (eds):
Aging of the Lens. Elsevier, Biomedical Press, 1980, pp 263-279.56. Harding JJ, Dilley KJ: Structural proteins of the mammalian lens: A review with
emphasis on changes in development, aging, and cataract. Exp Eye Res 1976; 22:1-73.57. Augusteyn RC: Protein modification in cataract: Possible oxidative mechanisms, in G
Duncan (ed): Mechanisms of Cataract Fornation in the Human Lens. London, Aca-demic Press, 1981, pp 71-82.
58. Spector A: Aspects of the biochemistry of cataract, in H Maisel (ed): The Ocular Lens:Structure, Function, and Pathology. New York, Marcel Dekker, 1985, pp 405-438.
59. Zigman S, Yulo T, Griess G: Inactivation of catalase by near-UV light. Mol CeU
UV and the Eye 851
Biochem 1976; 11:149-154.60. Reddy VN, Giblin FJ: Metabolism and function of glutathione in the lens, in J Nugent,
J Whelan (eds): Human Cataract Formation. Ciba Foundation Symposium 106, 1984,pp 65-87.
61. Kalustian A, Zigman S, Sun M: Near-UV light sensitized inactivation of glutathionereductase. Proc Am Soc Photobiol 1978, pp 112-113.
62. Bron AJ, Brown NAP: Perinuclear retrodots: A role for ascorbate in cataractogenesis.Br J Ophthalmol 1987; 71:86-95.
63. Varma SD, Kumar S, Richards RD: Light-induced damage to ocular lens cation pump:Prevention by vitamin C. Proc Natl Acad Sci USA 1979; 76:3504-3506.
64. Zigman S, Griess G, Yulo T, et al: Ocular protein alterations by near UV light. Exp EyeRes 1973; 15:255-264.
65. Spector A, Garner W: Hydrogen peroxide and human cataract. Exp Eye Res 1981;33:673-681.
66. Garner WH, Garner MH, Spector A: H202-induced uncoupling of bovine lens Na+,K+-ATPase. Proc Natl Acad Sci USA 1983; 80:2044-2048.
67. Iwata S, Kinoshita JH: Mechanism of development of hereditary cataract in mice.Invest Ophthalmol 1971; 10:504-512.
68. Pathak MA, Kraemer DM, Guengerich U: Formation ofthymine dimers in mammalianskin by UV radiation in vivo. Photochem Photobiol 1972; 15:177-185.
69. Zigman S, Schultz J, Yulo T: Possible roles of near UV light in the cataractous process.Exp Eye Res 1974; 13:462-465.
70. Pitts DG, Cullen AP, Hacker PD, et al: Ocular ultraviolet effects from 295nm to 400nmin the rabbit eye. Washington, DC, US Department of Health, Education, andWelfare (NIOSH), 1977, pp 1-82.
71. Harding CV Jr, Susan SR, Lo W-K, et al: The strucure of the human cataractous lens,in H Maisel (ed): The Ocular Lens: Structure, Function, and Pathology. New York,Marcel Dekker, 1985, pp 367-404.
72. Rohrschneider W: Linsenschadigung durch ultraviolette Strahlen im Tierversuch.Arch Ophthalmol 1936; 135:282-292.
73. Zigman S, Yulo T, Schultz J: Cataract induction in mice exposed to near UV light.Ophthalmic Res 1974; 6:259-270.
74. Keeney AH, Rampton DV: Solar irradiation and ocular concerns. Ophthalmology(Suppl) 1986; 93:109.
75. Wilson J: The six main causes of blindness, in International Agency for the Preventionof Blindness, J Wilson (eds): World Blindness and Its Prevention. Oxford, OxfordUniversity Press, 1980, pp 1-13.
76. Pacurariu I, Marin C: Changes in the incidence of ocular disease in children and oldpeople. Ophthalmologica 1973; 17:289-308.
77. van Heyningen R: The human lens: I. A comparison of cataracts extracted in Oxford(England) and Shikarpur (W Pakistan). Exp Eye Res 1972; 13:136-147.
78. Zigman S, Datiles M, Torczynski E: Sunlight and human cataracts. Invest OphthalmolVis Sci 1979; 18:462-467.
79. Hiller R, Giacometti L, Yuen K: Sunlight and cataract: An epidemiologic investigation.Am J Epidemiol 1977; 105:450-459.
80. Hiller R, Sperduto RD, Ederer F: Epidemiologic associations with cataract in the1971-72 National Health and Nutrition Examination Survey. Am J Epidemiol 1983;118:239-249.
81. : Epidemiologic associations with nuclear, cortical, and posterior subcapsularcataracts. Am J Epidemiol 1986; 124:916-925.
82. Taylor HR: The environment and the lens. Br J Ophthalmol 1980; 64:303-310.83. Hollows F, Moran D: Cataract-the ultraviolet risk factor. Lancet 1981; 2:1249-1250.84. Mao WS, Hu TS: An epidemiologic survey of senile cataract in China. Chin Med J
1982; 95:813-818.85. Xu J, Mao W. Zhu S, et al: A case-control study of senile cataract in lhasa, Tibet,
852 Taylor
China. Invest Ophthalmol Vis Sci (Suppl) 1987; 28:396.86. Brilliant LB, Grasset NC, Pokhrel RP, et al: Associations among cataract prevalence,
sunlight hours, and altitude in the Himalayas. AmJ Epidemiol 1983; 118:250-264.87. Chatterjee A: Cataract in Punjab, in The Human Lens in Relation to Cataract, Ciba
Foundation Symposium 19. Amsterdam, Associated Scientific Publishers, 1973, pp265-279.
88. van Heyningen R: What happens to the human lens in cataract. Sci Am 1975; 233:70-81.
89. Mann I: Culture, Race, Climate and Eye Disease. Springfield, Charles C Thomas,1966, pp 533-534.
90. HardingJJ: Possible causes of the unfolding of proteins in cataract and a new hypothe-sis to explain the high prevalence of cataract in some countries, in F Regnault, 0Hockwin, Y Courtois (eds): Aging of the Lens. Elsevier, Biomedical Press, 1980.
91. HardingJJ, Rixon KC: Is diarrhoea a major cause of cataract in some tropical countries?Metab Pediatr Ophthalmol 1981; 5:161-166.
92. Harding JJ: Cataract: Sanitation or sunglasses? Lancet 1982; 1:39.93. Cameron LL, Auer CL, McCormick PA, et al: Association of sunlight with senile
macular and lens changes. Invest Ophthalmol Vis Sci (Suppl) 1983; 24:202.94. Cameron LL: Association of Senile Lens and Dermal Changeswith Cumulative Ultra-
violet Exposure. PhD Dissertation. Baltimore, Johns Hopkins University, 1985.95. Cameron LL, Emmett EA, Abbey H, et al: Association of senile lens opacities with UV
and other factors. Invest Ophthalmol Vis Sci (Suppl) 1986; 27:45.96. Tso MOM, LaPiana FG: The human fovea after sungazing. Trans AmAcad Ophthalmol
Otolaryngol 1975; 79:788-795.97. Calkins JL, Hochheimer BF: Retinal light exposure from operation microscopes. Arch
Ophthalmol 1979; 97:2363-2367.98. Hochheimer BF, DAnna SA, Calkins JL: Retinal damage from light. AmJ Ophthalmol
1979; 88:1029-1044.99. Borges JM, Li ZY, Tso MOM: The cumulative effects of repeated photic exposures on
the monkey macula. Invest Ophthalmol Vis Sci (Suppl) 1987; 28:47.100. Noell WK, Walker VS, Kang BS, et al: Retinal damage by light in rats. Invest
Ophthalmol 1966; 5:450.101. Kuwabara T, Gom RA: Retinal damage by visible light: An electron microscopic study.
Am J Ophthalmol 1968; 79:69-78.102. Lawwill T, Crockett S, Currier G: Retinal damage secondary to chronic light exposure.
Doc Ophthalmol 1977; 44:379402.103. Mainster MA: Light and macular degeneration: A biophysical and clinical perspective.
Eye 1987; 1:304-310.104. Heriot WJ: Light and the retinal pigment epithelium: The link in senile macular
degeneration, in J Cronly-Dillon, ES Rosen, J Marshall (eds): Hazards of Light,Oxford, Pergamon Press, 1985, Vol 1, pp 187-196.
105. Weiter JJ, Delori FC, Wing GL, et al: Relationship of senile macular deeneration toocular pigmentation. Am J Ophthalmol 1985; 99:158-187.
106. Blumenkranz MS, Russell SR, Robey MG, et al: Risk factors in age-related maculopa-thy complicated by choroidal neovascularization. Ophthalmology 1986; 93:552-558.
107. Sperduto RD, Hiller R, Seigel D: Lens opacities and senile maculopathy. ArchOphthalmol 1981; 99:1004-1008.
108. Pizzarello LD: The dimensions of the problem of eye disease among the elderly.Ophthalmology 1987; 94:1191-1195.
109. Kupfer C: Six main causes of blindness, in International Agency for the Prevention ofBlindness, Sir J Wilson (eds): World Blindness and Its Prevention. Oxford, OxfordUniversity Press, 1984, Vol 2, pp 4-14.
110. US Department of Health and Human Services: Vision Research-A National Plan:1983-1987, Vol 2/Pt 2. Bethesda, National Institutes of Health, 1983 (NIH PublicationNo 83-2471).
UV and the Eye 853
111. Maddox J: The great ozone controversy. Nature 1987; 329:101.112. Garelik G: A breath of fresh air. Time 1987; 28:35.113. Bowie L: The politics of ozone: Balancing interests. The Baltimore Sun Paper, Septem-
ber 27, 1987.114. Farmer CB, Toon GC, Schaper PW, et al: Stratospheric trace gases in the spring 1986
Antarctic atmosphere. Nature 1987; 329:126-130.115. Taylor HR, West SK: A simple system for the clinical grading of lens opacities. Lens
Res 1988; 5:175-181.116. Sommer A: Diabetes and senile cataract. Am J Ophthalmol 1981; 91:134-135.117. West SK, Rosenthal F, Newland HS, et al: Use of photographic techniques to grade
nuclear cataracts. Invest Ophthalmol Vis Sci 1988; 29:73-77.118. Taylor HR, West SK: The clinical grading of lens opacities. Aust J Ophthalmol 1989;
17:81-86.119. Bressler NM, Bressler SB, West S, et al: Senile eye changes: The grading and
prevalence of macular degeneration. Arch Ophthalmol 1989; 107:847-852.120. Cameron LL, Vitasa BC, Lewis PG, et al: Visual assessment of facial elastosis using
photographs as a measure of cumulative ultraviolet exposure. Photodernatol 1988; pp277-282.
121. Rosenthal FS, Bakalian AE, Phoon C, et al: Senile eye changes: Determination ofocular exposure to ultraviolet light. Invest Ophthalmol Vis Sci (Suppl) 1987; 28:397.
122. Rosenthal FS, Phoon C, Bakalian AE, et al: The ocular dose of ultraviolet radiation inoutdoor workers. Invest Ophthalmol Vis Sci 1988; 29:649-656.
123. Cotton J: National Oceanographic and Atmospheric Agency. Personal communication.124. Scotto J, Fears TR, Gori G: Measurements of Ultraviolet Radiation in the United States
and Comparisons with Skin Cancer Data. Bethesda, US Department of Health,Education, and Welfare, National Cancer Institute, 1977.
125. Riegelman RK: Studying a Study and Testing a Test: How to Read the MedicalLiterature. Boston, Little, Brown & Co, 1981, pp 223-242.
126. Smith AH, Waxweiler RJ, Tyroler HA: Epidemiologic investigation of occupationalcarcinogenesis using a serially additive expected dose model. Am J Epidemiol 1980;112:787-797.
127. West SK, Taylor HR: Lack of evidence for aspirin use and prevention of cataracts. ArchOphthalmol 1987; 105:1229-1231.
128. Peffer RS: Waterrnen. Baltimore, Johns Hopkins University Press, 1979.129. Tucker MA, Shields JA, Hartge P, et al: Sunlight exposure as risk factor for intraocular
malignant melanoma. N Engl J Med 1985; 313:789-792.
![[PPT]Infrared Radiation, Microwave, Ultraviolet . · Web viewInfrared Radiation, Microwave, Ultraviolet Radiation. Infrared Infrared lamps emits electromagnetic radiation within frequency](https://static.fdocuments.net/doc/165x107/5aa9b1b37f8b9a90188d2f50/pptinfrared-radiation-microwave-ultraviolet-viewinfrared-radiation-microwave.jpg)
