Continuing Education

The deleterious effects of sunlight on the eye have been recorded since antiquity. ¹ As early as 360 BC, Socrates was reported stating: ‘People may injure their bodily eye by observing and gazing on the sun during an eclipse, unless they take the precaution of only looking at the image reflected in the water, or in some similar medium.’ (Plato 360 BC, 11 99d-e).²

It is well established that ultraviolet (UV) light is a major causative factor in the development of human skin cancer.³ The evidence that UV radiation (UVR) may cause ocular pathology shares many similarities with the evidence associating UV exposure to skin disease.⁴ In both cases, years will have lapsed between exposure and clinical effects.⁴

Nevertheless, the concept that UVR causes skin cancer is much more widely accepted than the notion that UVR is associated with eye disease.⁴

UV light is one of the best-characterised environmental carcinogens, acting both as a tumour initiator and a tumour promoter.³ UV light acts also as a potent modulator of cell growth and differentiation and some of its actions are important in normal physiological activity, such as in melanogenesis.³ It can also be efficiently used as a therapy for certain skin conditions, such as psoriasis and atopic dermatitis.³ However, in excessive amounts, ultraviolet light can be toxic.³ Indeed, UV light phototoxicity has been implicated in causing or accelerating the progression of several diseases of the eyes and its supporting structures.⁵

This article discusses the mechanisms of UV-induced ocular damage, the recent evidence of UV damage to the eye, and the acute and chronic ocular pathologies caused or exacerbated by exposure to UV light.

Light is a form of energy produced naturally by the sun and artificially by incandescence, fluorescence, lasing and other means.⁵

The spectrum of light comprises visible light, necessary for sight, as well as UV and infrared lights.5 UVR encompasses wavelengths between 100nm and 400nm and includes UVA (315nm to 400nm), UVB (280nm to 315nm), UVC (200nm to 280nm), and UVvacuum (100nm to 200nm).⁴ UVC and UVvacuum are blocked from reaching the earth by the ozone in the stratosphere⁴ (Figure 1).

The amount of solar radiation reaching the earth’s surface depends on the location, altitude, sky cover, time of day, and time of year⁴ and is measured by the UV index (Table 1).

Due to ozone depletion, there has been an increase in the amount of UVR reaching the earth over recent years:

Light Absorption Mechanisms of The Eye

The eyes are the principal route of exposure to ultraviolet radiation (9) (Figure 2). The cornea absorbs most of the radiation below 300 nm (UVB) and the lens absorbs most of the radiation below 370 nm (UVA) (9) (Figure 3).

Short-wavelength light is demonstrably hazardous and has great potential to induce phototoxic injury in ocular cells (13)

Indeed, the shorter the wavelength, the greater the energy and therefore the greater the potential for biological damage (14).

Solar radiation is radiant energy and when a photon of radiant energy is absorbed, its energy is transferred to the molecule that absorbed it (15). The larger the packet of energy, the higher is the risk of damage to the molecule (15).

The absorption of UV light by chromophores (molecules absorbing solar energy) present in the eye cells and tissues, leads to changes that can eventually result in a biologic effect (9) (Figure 4). The chromophores absorb light energy from the various wavelengths with differing efficiencies (9). This pattern of absorption is called an absorption spectrum and is characteristic of the type of molecule involved (9).

The thermal and biochemical response to UV light absorption can be toxic and damaging to the eye if the amount of response is beyond the reparative processes (5).

Mechanisms of Ocular Phototoxicity

Aside from the skin, the organ most susceptible to sunlight-induced damage is the eye (14), with the three critical structures affected by UV exposure being the cornea, the lens, and the retina (12). Light-induced ocular damage occurs either through an inflammatory response or a photo-oxidation reaction (14):

• Inflammatory response: an initial injury to the tissue provokes a cascade of events that eventually result in wider tissue damage.

• Photo-oxidation reactions: a sensitizing compound in the eye absorbs light, is excited to a singlet, then a triplet state, and from the triplet produces free radicals and reactive oxygen species that in turn damage the ocular tissues.

Corneal Damage

Corneal exposure to short UV light leads to an inflammation reaction (17). Human corneal stromal cells exposed to low doses radiation in vitro or in situ show significant increases in the production of cytokines (biologically active chemicals) (9). The identified cytokines, interleukin-1 (IL-1), IL-2, IL-8, and tumor necrosis factor alpha (TNFa), are pro-inflammatory and may be responsible for the inflammation accompanying photokeratitis (9).

Corneal UVB exposure causes morphological signs of apoptosis (cell death) (10) that are wavelength-dependent (18). In corneas exposed to 280-nm UVR, apoptosis is detected in the epithelial cells and superficial keratocytes only(18). In contrast, in corneas exposed to 310-nm UVR showed a more extensive damage, with apoptosis detected in the epithelial cells, in the keratocytes (throughout the entire thickness of the stroma), and in the endothelial cells (18).

Under normal physiological conditions, the cornea is protected from UV radiation by a pro-oxidant/antioxidant balance (10). However, during exposure to increased UV irradiation (mainly short UV light), the antioxidant protective mechanisms of the eye are overwhelmed, resulting in a prooxidant/antioxidant imbalance (10) and photo-oxidation reactions.

Lens Damage

Both UVA and UVB radiations are known to damage the lens (19). This damage is painless, accumulative, permanent, and can lead to cataracts (17). Because UVA radiation readily penetrates the cornea (20), lenticular exposure to UVA is three times greater than exposure to UVB (19). However, even small amounts of UVB incident for extended periods of time can cause chemical and biochemical damage to the constituents of the lens (21).

UVA and UVB radiation involve different photochemical mechanisms (19):

• n UVB radiation induces the formation of pyrimidine dimers (DNA damage);

• n UVA light causes photo-oxidative damage.

The major species responsible for lenticular absorption of UV radiation between 300 and 400 nm are tryptophan metabolites, also called UV filters (19). When an electron in tryptophan absorbs a UV photon, the extra energy in the electron can be passed to oxygen, producing singlet oxygen, which can set off a chain of free-radical effects, leaving a trail of oxidized, denatured molecules in its wake (15).

The oxidized lens proteins become structurally altered (8) and accumulate in the centre of the lens, as only the epithelial layer of the lens is capable of renewal and repair (15). This oxidation is a defining feature of age-related nuclear cataract, with the oxidative modifications resulting in protein aggregation (19).

The oxidative damage to the lens is further promoted by a covalent attachment of tryptophan-derived UV filters to the lens proteins (19,22). These UV filter adducts increase in amount with age and appear to be mainly responsible for the yellowing of the lens (22).

Furthermore, protein oxidation at the centre of the lens may be facilitated by the development of a lens barrier in the aged normal human lenses that prevents the ready transport of glutathione (GSH) (a water-soluble antioxidant) from the cortex to the nucleus (19). Indeed, cataract lenses exhibit decreased levels of antioxidants, such as glutathione and ascorbic acid (19).

The oxidative modifications induced by UV light and promoted by decreased antioxidants, result in protein aggregation and yellowing of the lens (19,22).

Retinal Damage

The lens plays a significant role in absorbing UV radiation, which would otherwise induce photooxidative damage to the retina (19). In youth, a very small amount of UV A reaches the retina, but the lens becomes more absorbing with age (12). The intraocular filters effectively filter different parts of the UV spectrum and allow only about 1 % or less to actually reach the retina (12). Nevertheless, this small fraction of energy, if toxic, could still be of concern (12).

Whether UV radiation reaches the retina in sufficient quantities to cause acute or chronic trauma is still a subject of debate (4).

• n Experimental studies on primates suggest that high intensity light may cause acute retinal trauma, with a wavelength dependent response (4).

• n Recently, shorter wavelength light, especially UVR, has been shown to cause the most intense shedding of photoreceptors, resulting in retinal injury (23).

Ocular Disease associated with uv exposure

Photokeratitis

The ocular effect most directly attributable to environmental UV radiation exposure is photokeratitis (9), an acute and reversible injury of the corneal epithelium (24). The ocular equivalent of sunburn, photokeratitis occurs after short-term exposure (9), usually within 8 to 24 hours (25).

A threshold photokeratitis can be caused by a one-hour exposure to UV reflected off snow and by a 6 to 8-hour exposure to UV reflected off light sand around midday (24).

Clinically, photokeratitis is characterized by an inflammation of the cornea, severe pain, lacrimation, photophobia, and blepharospasm (9). It frequently occurs in skiers ("snowblindness"), beach-goers, and in outdoor recreationists (9).

Pterygium

Pterygium is a fleshy wing-like thickening of the conjunctiva and cornea (figure 6) that may progress to cover the cornea, resulting in

Pterygium formation has been linked to corneal and conjunctival microtrauma from exposure to sunlight, especially UV radiation, and to particulate matter, such as smoke, sand, and dust particles (26). Studies have shown a higher prevalence of pterygium among outdoor workers (26), thus suggesting an association between pterygium and chronic exposure to sunlight (26).

Pterygium also occurs more frequently in Eskimos living in Greenland, further indicating that increased UV exposure has an effect on the development of this lesion (27).

Pinguecula

Pingueculae, from the latin ‘pingueculus’ meaning fatty (14), is a raised opaque mass just adjacent to the cornea (9) that consists of a fibro-fatty degeneration of the intrapalpebral conjunctiva (24).

The pathological changes that occur in Pinguecula are similar to actinic elastosis of the skin, a condition thought to be linked to sunlight exposure (24).

The predominant location of pinguecula in the nasal interpalpebral fissure is related to reflection of light from the nose onto the nasal conjunctiva (27). The prevalence of pinguecula is high in populations living near the Red Sea (24) and in Greenland (27), thus suggesting an association with sunlight exposure.

Furthermore, a significant relationship has been found between occupational motorcycle driving and the prevalence of pinguecula (28).

Climatic Droplet Keratopathy (CDK)

CDK is a degeneration of the fibrous layer of the cornea with the accumulation of droplet-shaped deposits (9). These deposits consists of altered proteins and can lead to corneal opacification (29). CDK usually affects both eyes symmetrically and is restricted to the intrapalpebral band of the cornea (24).

Histologically, the material deposited in the superficial corneal stroma as spheroidal droplets is most likely to be derived from a mixture of altered plasma proteins, including fibrinogen, albumin, and immunoglobulins (24).

CDK occurs around the world, but is more common(24,29) : - in areas where snowfall persists late into the summer (northern hemisphere), - in areas of sand and desert, - on sea coasts where there is coral or salt-impregnated sand, - in outdoor workers (six-fold increased risk). All of these findings concur to suggest an association between CDK and sunlight exposure.

Squamous Cell Carcinoma (SCC) of the cornea and conjunctiva

SCC is a malignant neoplasm similar to those found in sun-exposed skin (9). It can affect not only the eyelid, but also the cornea and conjunctiva (30). • It is the second most common eyelid tumour and generally affects fair-skinned elderly individuals (30). Chronic sunlight exposure appears to be the leading predisposing factor, even if the exposure occurred decades prior to the development of the lesion (30). Clinically, SCC of the eyelid can be nodular, papillomatous, cystic, placoid, or ulcerated (30).

SCC frequently begins at the limbus in the intrapalpebral area, but may also occur on the palpebral conjunctiva and on the cornea (30). It appears gelatinous and papillomatous and may be covered by a keratin-producing leukoplakic lesion (30). The growth of SCC is slow, but the tumor may expand through the conjunctival basement membrane into the substantia propria, rarely extending deeper and usually not invading Bowman’s layer (30).

Ocular Melanoma

Compared to melanomas of the skin, non-cutaneous melanomas are rare (31). From 1996 to 2000, ocular melanomas accounted for 3.7 % of the 133,209-melanoma cases reported in the United State , with a 1.29 male-to-female rate ratio (31). • Most ocular melanomas occur in the uveal tract (82.5 %), of which 86.3 % occur in the choroid (31).

In the United States, the rates of ocular melanomas are (31) :

- 8 to 10 times higher in whites than in blacks

- - higher in the southern and coastal regions.

Together, these findings suggest that cutaneous and ocular melanoma may share a common environmetal risk factor : UV radiation (31).

Lenticular pathologies

Cataract

Cataract is the leading cause of blindness in the world (32) and UV radiation is regarded as one of the widespread risk factors contributing to its formation (33). Cataract is a clinical syndrome involving the opacification of the crystalline lens (30) due to the accumulation of oxidized lens proteins (9).

Cataract symptoms usually include cloudy vision, glare, reading difficulties, faded colors, monocular diplopia, and frequent prescription changes (30). • A cataract can form in the cortical, nuclear, anterior and posterior capsular regions of the lens (30). •

A high ambient solar radiation is associated with a 2.5-fold and a 4.0-fold increased risk of cortical and mixed cataracts, respectively (32). Professional exposure to solar radiation has also been shown to be associated with a 1.6-fold increased risk of posterior subcapsular (PSC) cataract (32).

Retinal pathologies

Age-Related Macular Degeneration (ARMD)

Exposure to sunlight has long been suggested to play a role in the aetiology of ARMD, but epidemiological studies have yielded inconsistent results (34). While most studies have found no associations between sunlight exposure and ARMD (34), recent evidence strongly suggests such an association (23).

The results of a recent study support the concept of solar radiation having an effect on the development of ARMD (28). The Beaver Dam Eye Study found significant associations between extended exposure to the summer sun and the 10-year incidence of early Age-Related Maculopathy (35).

The Chamonix Study: A Higher Prevalence of Light-Related Ocular Pathologies (36)

The objective of the Chamonix study was to document the clinical repercussions of phototoxicity in an exposed population (mountain guides ; n = 40) versus a control group of unexposed factory workers (n = 40). The outcome is summarised in figure 7.

U V L i g h t : A Crucial Need for Eye Protection

Because of the aging of the population and the thinning of the ozone layer, we receive today a greater lifetime UV radiation exposure (4). As a consequence, eye care practitioners may encounter the ocular effects of this increased UVR exposure in more and more patients (4). Today, there is enough evidence to assume that chronic sunlight exposure contributes to ocular disease and to institute preventive measures (37).

Some sceptics may still question the hypothesis that UV sunlight is an etiological factor in cataract, droplet keratopathies, or pterygium (38). However, from a public health and preventive medicine point of view, we really must consider it as a likely factor (12).

Indeed, the association of sunlight with a number of ocular disease has major public health implications(37). Although the etiology of these disease is multifactorial, there is enough evidence to implicate sunlight(37). Thus, it’s prudent to protect the eyes from unecessary solar radiation(37).

Preventive measures are even more important when one considers that: n

- a 10-year delay in cataract onset could reduce the need for cataract surgery by as much as half (38), n

- ocular protection against light may delay or eliminate most blinding disorders in the elderly (14).

-

Eye care practitioners can educate their patients on the dangers of UV radiation and offer them various options for UV protection (4).

An easy and important strategy is to wear UV protection in the form of eyewear (30).

- Acute UV effects on the eyes are easily preventable by appropriate eyewear (24).

- The frequent use of sunglasses is associated with a 40 % decreased risk of PSC cataract (32).

-

There is widespread scientific agreement that the use of eyewear with lenses that preferentially absorb the high-energy components of the solar spectrum substantially reduce the risk of sunlight-related eye diseases (39). Certain lens treatment and coatings may help reduce harmful radiation (30). Variable tint lenses, developed by companies such as Transitions Optical, offer 100 % UV protection (30).

Photochromic Lenses

Photochromic (i.e. coloured by light) lenses represent the ideal solution for UV protection. Not only do they block 100 % of UVA and UVB, but they also provide an on-demand light modulation by (40):

- decreasing incident light when levels are too high, n allowing sufficient light into the eyes when levels are lower. Photochromic lenses rely on chemical reactions induced by ultraviolet radiation (figure 8) to produce darkening upon exposure to light and clearing when the light stimulus is removed (figure 9). Benefits of Photochromic Lenses

- Visual acuity n Long-term vision protection: they block 100 % of UV light

- Visual comfort: they modulate the illuminance extremes the eye is exposed to

- Maximized visual function: they do not unnecessarily decrease illuminance when light is low, contrary to fixed tinted glasses

- Visual convenience: a single pair of lenses that performs well under various illumination conditions

References

1. Cullen AP, Perera SC. Sunlight and Human Conjunctival Action

Spectrum. The 1995 Sun Conference.

http://alep.unibase.com/sunconf/papers/cullen/cullen.html

n 2. Glickman RD. Phototoxicity to the retina: mechanisms of

damage. Int J Toxicol.2002 ; 21:473-90.

n 3. Heck DE and al. Solar ultraviolet radiation as a trigger of cell

signal transduction. Toxicol Appl Pharmacol. 2004 ;195:288-97.

n 4. Bergmanson JP, Sheldon TM. Ultraviolet radiation revisited.

CLAO J. 1997 Jul;23(3):196-204.

n 5. Canadian Ophtalmological Society. Policy Statements and

Guidelines. Ultraviolet Radiation and the Eye. 2004 Canadian

Ophtalmological Society

n 6. WHO. Global Solar UV Index : A Practical Guide.

World Health Organization 2002. ISBN 92 4 159007 6.

n 7. Understanding science. Reporting on Climate Change. Chapter

5. Ozone Depletion: When Less is Not Enough.

n 8. Leaf A. 1993. Loss of Stratosphoric Ozone and Health Effects

of Increased Ultraviolet Radiation. In Critical Condition :

Human Health and Environment, ed. E. Chivian, M. McCally,

H . Hu, and A. Haines, 139-50. Cambridge, MA : The MIT Press.

n 9. Longstreth J and al. Health risks. J Photochem Photobiol B.

1998;46:20-39.

n 10. Cejkova J and al. UV Rays, the prooxidant/antioxidant

imbalance in the cornea and oxidative eye damage. Physiol

Res. 2004; 53:1-10.

n 11. de Gruijl FR, Van der Leun JC. Environment and Health: 3.

Ozone depletion and ultraviolet radiation.

CMAJ 2000; 163: 851-55

n 12. Sliney DH. How light reaches the eye and its components. Int

J Toxicol. 2002; 21:501-9.

n 13. Kwok LS and al. Prevention of the adverse photic effects of

peripheral light-focusing using UV-blocking contact lenses.

Invest Ophthalmol Vis Sci. 2003; 44:1501-7.

n 14. Roberts JE. Ocular phototoxicity. J Photochem Photobiol B.

2001; 64:136-43.

n 15. Young RW. The family of sunlight-related eye diseases.

Optom Vis Sci. 1994; 71:125-44.

n 16. Rayonnement Solaire et prevention Oculaire. Les Cahiers

d’Ophtalmologie. Cahier N°2: Supplément au N°22.

n 17. Roberts JE. Screening for ocular phototoxicity. Int J Toxicol.

2002; 21:491-500.

n 18. Podskochy A and al. Apoptosis in UV-exposed rabbit corneas.

Cornea. 2000; 19:99-103.

n 19. Parker NR and al. Protein-bound kynurenine is a

photosensitizer of oxidative damage. Free Radical Biology &

Medicine 2004; 37: 1479-89.

n 20. Zigman S. Lens UVA photobiology. J Ocul Pharmacol Ther.

2000;16:161-5.

n 21. Balasubramanian D. Photodynamics of Cataract: An Update

on Endogenous Chromophores and Antioxidants. Photochem

Photobiol. 2004; [Epub ahead of print]

22. Takikawa O and al. Age-related nuclear cataract and

indoleamine 2,3-dioxygenase-initiated tryptophan

metabolism in the human lens. Adv Exp Med Biol.

2003;527:277-85.

n 23. Sheedy JE, Edlich RF. Ultraviolet eye radiation: the problem

and solutions. J Long Term Eff Med Implants. 2004;14:67-71.

n 24. International Programme on Chemical Safety. Ultraviolet

radiation. EHC 160. 1994. 2nd edition.

n 25. Borderie V. Clinical aspects of corneal burns. J Fr Ophtalmol.

2004; 27:1170-4.

n 26. Khoo J and al. Outdoor work and the risk of pterygia: a casecontrol

study. Int Ophthalmol. 1998; 22:293-8.

n 27. Loeffler KU and al. Is age-related macular degeneration

associated with pinguecula or scleral plaque formation?

Curr Eye Res. 2001; 23:33-7.

n 28. Nakaishi H and al. Pingueculae and pterygia in motorcycle

policemen. Ind Health. 1997; 35:325-9.

n 29. Diffey B. L. Solar ultraviolet radiation on biological systems.

Physics in Medicine and Biology 1991; 36: 299-328.

n 30. Marc B, Taub OD. Ocular effects of UV radiation. UV special.

OT 2004; 34-38

n 31. McLaughlin CC and al. Incidence of noncutaneous

melanomas in the U.S. Cancer. 2005;103:1000-7.

n 32. Delcourt C and al. Light exposure and the risk of cortical,

nuclear, and posterior subcapsular cataracts: the Pathologies

Oculaires Liees a l’Age (POLA) study. Arch Ophthalmol. 2000;

118:385-92.

n 33. Wegener A and al. Experimental evidence for interactive

effects of chronic UV irradiation and nutritional deficiencies

in the lens. Dev Ophthalmol. 2002; 35:113-24.

n 34. Delcourt C and al. Light exposure and the risk of age-related

macular degeneration: the Pathologies Oculaires Liees a l’Age

(POLA) study. Arch Ophthalmol. 2001; 119:1463-8.

n 35. Tomany SC and al. Sunlight and the 10-year incidence of

age-related maculopathy: the Beaver Dam Eye Study. Arch

Ophthalmol. 2004;122: 750-7.

n 36. Le Bail B, Phung F, Corbe Ch. Répercussion clinique de la

photo-toxicité dans une population exposée.

http://www.ssco.asso.fr/symposiums/1996/repercussion_clini

que.htm

n 37. Roh S, Weiter JJ. Light damage to the eye. J Fla Med Assoc.

1994; 81:248-51.

n 38. Congdon NG. Prevention strategies for age related cataract:

present limitations and future possibilities. Br J Ophthalmol.

2001; 85:516-20.

n 39. Young RW. The Charles F. Prentice Medal Award Lecture

1992: Optometry and the Preservation of Visual Health.

Optometry and Vision Science 1998; 7: 255-62

n 40. Stenton S, Fisk D. Contrast Sensitivity, Glare, and Quality of

Vision. Beyond 20/20. Transitions Optical 2004.

n 41. Light, Sight, and Photochromics. Transitions Optical 2002.