Hyperguides

Ophthalmology / Clinical ophthalmology

Retinal Disease and Light Exposure

P. Kumar Rao, MD Justis P. Ehlers, BS
Article


Introduction

Although ocular exposure to light is an obvious necessity for sight, it has been implicated as a causative element in a host of disorders of the human eye, involving structures including the cornea and ocular surface, crystalline lens, and retina. As the retina and choroid are the last structures of the eye to interact with light, they have unique risks. The composition of the light spectrum to which the retina is exposed has been altered not only by the extraocular environment, but also by reflection from the cornea and absorption and filtering by the cornea, aqueous, crystalline lens, and vitreous. Several retinal diseases have been associated with light-induced injury and light has been proposed as a causative element in others, including photic retinopathy, retinopathy of prematurity, and age-related macular degeneration.1,2,3

Natural Protection from Light Injury

Nature has provided the eye with several mechanisms of protection. The atmosphere is the first line of defense. It acts as a filtration system for many of the shorter wavelengths, particularly during times of day when the sun is at a low angle, such as sunset.1 Other protective mechanisms include the shading of the eyebrows, squinting, aversion reflex, and the papillary light response. Additionally, the lens filters out a significant amount of the ultraviolet (UV) and blue light.2 Finally, the geometry of light exposure also provides an inherent limit to the exposure of our eyes to direct sunlight. At midday, the intensity and exposure to the shortest wavelengths are 10 times greater than 3 hours earlier or later. However, the overhead position of the midday sun results in increased shadowing of the eyes by the brows, as well as causing a significant percentage of the rays to be reflected off the cornea, minimizing the transmission of the harmful short wavelength rays. These protective mechanisms allow individuals to be outside during periods of high-intensity sunlight without experiencing injury. The exception to this occurs when a person is in an environmental situation where incident rays are almost parallel to the visual axis, such as when one stares at the sun or when one is surrounded by fresh, white snow. In fact, snow reflects more than 80% of the incident short wavelengths of sunlight, compared to only 1% to 2% reflected by grass.1 Skiing without protective eyewear is almost as bad as looking directly at the sun.

At the cellular and molecular levels, other mechanisms help to prevent damage from light. Photoreceptor shedding helps prevent further damage. Antioxidants help to quench singlet oxygen molecules. Melanin absorbs some of the excess light, limiting the generation of free radicals. Carotenoids have also been implicated as a protective element in the retina. In fact, the yellow color in the center of the macula is made up of two carotenoids: lutein and zeaxanthin. This yellow pigment interferes with free radicals in two ways. First, it absorbs a significant amount of blue light, reducing the initial production of free radicals. Secondly, the carotenoids absorb and quench free radicals after they are created. Carotenoids are dietary in origin, found particularly in fruits and vegetables. It appears there is an efficient transport mechanism in the retina that selectively transports and accumulates zeaxanthin and lutein. More interesting, the most abundant carotenoids in the plasma, lycopene and beta-carotene, have not been documented to exist in the retina. The Eye Disease and Case Control Study showed through logistic regression analysis that higher carotenoid dietary intake had a statistically protective effect for age-related macular degeneration.4

Mechanisms of Light Injury

Three mechanisms for light injury to the retina, particularly in regard to photic retinopathy, have been proposed: photochemical, photothermal, and mechanical. Retinal damage from intense light applied in short-duration exposures appears to be a result, more likely, of photothermal and mechanical effects in a focal area than of photochemical effects. Photochemical injury, on the other hand, typically requires a more protracted exposure time.2

The major determining factor in the type of damage caused by a particular insult is energy confinement. The wavelength of the particular light source will dictate its absorption and penetration within the retinal tissues. The light energy absorbed is dispersed at various rates. In cases where the rate of absorption is faster than the rate of diffusion, the temperature of the tissue begins to rise, a concept known as thermal confinement. Thermal damage typically begins when the temperature of the tissue rises 10° C above the baseline. Similarly, stress confinement occurs when energy is absorbed at a rate above maximal mechanical relaxation rate of the surrounding tissues, resulting in mechanical damage. This mechanical damage results from tissue disruption by shear forces generated by a thermoelastic pressure wave.16

Free radicals are believed to play a major role in photochemical damage in the retina. Lipid peroxidation and disruption of organelle and cellular membranes occur as a result of these free radicals. There are likely many sources for the free radicals, but the pigments of the retina, including melanin and lipofuscin, are considered prime candidates. Although melanin is usually thought of as a protective pigment, studies have shown that as light exposure increases, the lipid peroxidation from melanin increases as well.5 The photoreceptors appear to be the most sensitive of the retinal layers to this damage, and particularly the outer segments. In fact, as long as the inner segment has not been damaged, recovery from the injury is possible.

Lipofuscin accumulation is generally thought to be a result of aging. Its presence in the retinal pigment epithelium (RPE) appears to be secondary to phagocytosis of the outer segments of photoreceptors. 5,6 Studies on the effect of light in the generation of free radicals by lipofuscin have produced conflicting results. Some have shown that the oxidative potential of lipofuscin is relatively high even in darkness and increases slightly on exposure to light.5 Others have shown a wavelength-dependent mechanism in which lipofuscin causes cytotoxicity. The wavelengths between 390 nm and 550 nm appear to be the most damaging. One study showed a reduction in the viability of RPE cells of 51.3% at 24 hours and 66.2% at 48 hours, after exposure of RPE cells to these wavelengths. The cells had cytoplasmic vacuolation, membrane blebbing, and overall alterations in gross morphology.6 Lipofuscin has many chromophores within its structure, as one might expect if it is a product of outer segment phagocytosis. A2E is a chromophore that has been implicated in free radical formation and cellular toxicity.6,7 Studies have demonstrated a clear relationship between elevated cellular A2E levels and cell toxicity after exposure to short wavelength light.7 However, other studies of lipofuscin have shown cytotoxicity even when the A2E content of these cells is not as elevated,6 implying other factors are also working to cause the damage. Further research must be performed to identify all of the agents responsible for free radical production in lipofuscin.

Clinical Manifestations

The clinical manifestations of retinal light injury vary. In the mildest form, excessive retinal illumination results in erythropsia and reduced night vision,1 both of which are usually transient. More serious injuries, such as photic retinopathy, have been clearly linked to light exposure. Other diseases such as age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and cystoid macular edema (CME) have been postulated to be due to light injury, at least in part, but the research is underway to confirm this postulate.

Photic Retinopathy
Photic retinopathy is a direct result of retinal injury from light exposure. It has been called by many names. Solar retinitis is a form of photic retinopathy particularly linked to excessive exposure to sunlight, typically requiring more than 1.5 minutes of staring at the sun. Its main clinical feature is a scotoma.1 In addition to natural sunlight, other sources can be the cause of photic damage, including high-intensity industrial lights and iatrogenic exposure to light.2

Iatrogenic Photic Retinopathy. Although a significant source of iatrogenic exposure, operating microscopes have been found to have little emission of below 400 nm. However, there is a significant output in the infrared spectrum. Ocular surgery presents a unique risk to the patient, during which both corneal and retinal irradiation may be high. This is a result of the high emission from the microscope bulb, the immobility of the eye, the dilated pupil, and the potentially long duration of exposure. If the patient is aphakic, the risk of retinal injury is even greater, secondary to the absence of the lenticular filter. It is thought that aging increases an individual's risk of developing photic retinopathy. Increased levels of lipofuscin, compounded with a decreased reserve, seems to lead to this increased susceptibility.2

The incidence of iatrogenic photic retinopathy from ocular surgery has been evaluated in four studies. Two retrospective studies showed an incidence of 3% and 7%.2,8,9 Two prospective studies had disparate results; one reported an incidence of 28%, whereas the other reported 0%. In the study without cases of photic retinopathy, the irradiance and duration of surgery was significantly less than in the other studies.2,11,12

Clinically, no visible signs are present for the first 24 to 48 hours after exposure. The characteristics of the lesions that subsequently develop depend on the light source. The typical operating microscope light lesions are sharply defined and relatively small, usually no more than 1 to 2 disc diameters. Endoilluminator-induced lesions are usually larger with less defined margins. Most lesions are circumscribed with some outer retinal whitening. Functional impairment can actually be seen without clinically visible lesions. Over the course of a few days, pigmentary changes begin to develop and, during the following 1 to 2 weeks, the pigment tends to become coarse, with a more targetoid appearance. After a month, the lesions tend to regress and become smaller. It is at this time that epiretinal membrane formation may occur. By 3 to 6 months, the only visible sign of injury may be a white plaque. In addition, other late sequelae such as CME and choroidal neovascularization may be found.2

Fluorescein angiography can show early mottling, hyperfluorescence, and late staining. Dye leakage is not usually seen. However, the complications of photic retinopathy including choroidal neovascular membranes and CME may be visualized on fluorescein angiography. Pathology shows focal necrosis with loss of apical villi and organelles, disruption of plasma membranes, and extrusion of RPE granules. Typically edema of the inner segments of the photoreceptors occurs, with disruption of the outer segments.2

The prognosis is variable, but usually favorable. There are no clearly beneficial treatments at this time. Experimental methods of treatment have included dexamethasone, ascorbate, flunarizine, and dimethylothiourea. Prevention would seem to be a better approach. It is usually recommended that patients stop any photosensitizing drug before ocular surgery. Other strategies include the use of a UV-filtering lens in the microscope, UV-blocking chromophores in IOLs, a cooled infusion fluid, prophylactic dexamethasone, and decreasing the inspired pO2 during surgery.2

Cystoid Macular Edema. An association between CME and phototoxic retinopathy has been reported. Two studies have actually looked at how UV-absorbing chromophores in lenses impact the incidence of CME. One study showed a 9.5% incidence of CME in patients with UV-absorbing lenses compared to 18.8% without.2,12 However, a second study did not find a statistically significant difference, with a 17.3% incidence of CME in the group with UV-absorbing chromophores and 21% in those without.2

Further research. Several questions regarding photic retinopathy are unanswered. These include determining the most harmful wavelength(s), the actual pathogenesis and mechanism of the injury, and whether use of UV-absorbing chromophores in intraocular lenses has a role in preventing injury. Additionally, the true effectiveness of many of the treatments and preventative measures must be evaluated.2

Retinopathy of Prematurity
Development of the visual system and retina. Improving technology has pushed the limits of viability of an infant to 23 to 24 weeks of gestation. At this stage of development, the visual system is still very immature. Not until 28 weeks can a visual evoked potential be recorded. Anatomical studies indicate the photoreceptors begin to approach the ora serrata at the same time. And, it is not until approximately 40 weeks that the retinal vascular system is in place. Prior to this time, all of the oxygen supply is obtained by diffusion from the choroidal circulation. In utero, the development of the retinal vasculature and the increased metabolism of the photoreceptors are coordinated.3

The Oxygen Toxicity Theory. For years, we have known from research that increased blood oxygen levels are a risk factor for the development of ROP. Increased oxygen levels were thought to lead to an increase in free radicals in the retina. Nevertheless, infants who did not receive supplemental oxygen have developed ROP, indicating other factors may play a role.3

Premature infants are often exposed to a tremendous amount of light in the neonatal intensive care unit, including bilirubin lights, heat lamps, and background room lighting. The theory of light involvement in the pathogenesis of ROP was initially discounted since some early studies showed that patching the eyes of infants did not change the incidence of ROP.3 However, these studies were conducted at a time when oxygen was still used liberally and the ambient light exposure in the neonatal intensive care unit was lower.3 More recently, a prospective nonrandomized study demonstrated an association between unprotected exposure and the development of ROP. Within this study, a subgroup analysis showed a significant association of ROP with sun exposure from a window. In fact, nearly 80% of the infants who developed ROP had been near the window, compared to 10% of the non-ROP infants having a crib next to the window. These numbers were matched by birth weight to controls.3,13

Clinically, ROP is characterized by vascular changes in the periphery of the retina. The increase in oxygen tension in the inner retinal tissues is thought to be a major predisposing factor for ROP. Exposure to light decreases oxygen consumption and increases the partial pressure of oxygen. Any damage to the retina would also compound the decreased oxygen consumption, thus raising the oxygen tension.

Mueller cells are thought to be important for providing a structural framework for the formation of the retinal vasculature. It has been postulated that in cases of ROP the Mueller cells may close off the undamaged retina, contributing to the characteristic clinical appearance. Retinal detachments are seen in advanced ROP. Excess light may exacerbate these detachments, since exposure to light may induce an inflammatory reaction which would increase subretinal exudation. Retinal edema secondary to light exposure may play a role in altering retinal blood flow.3

At this time the role of light in ROP needs to be explored further. The data are insufficient to make clear recommendations to neonatologists and pediatric ophthalmologists. Some research suggests that cycled, rather than continuous, light exposure may be somewhat protective and, until the data is clearer, it seems reasonable to protect infants from light in general.

Age-Related Macular Degeneration
Macular degeneration is an important cause of irreversible visual loss in persons older than 50. One study reported the prevalence to be as high as 8.8% in individuals older than 51. Clinically, AMD is a complex disease manifested on ocular examination by drusen and/or choroidal neovascular membranes. Research in this area has been a particular challenge due to the lack of a good animal model. However, recent studies have indicated that AMD may be in part caused by excess solar radiation exposure and/or an autoimmune mechanism.4

Pathophysiology. The retinal architecture is designed such that the RPE is able to phagocytose the outer segments of retinal receptors as they are shed. Over the lifetime of an individual, this constant phagocytosis leads to accumulation of lipofuscin. If the amount accumulated within the RPE becomes too great, the excess is released through Bruch's membrane toward the external blood supply. This debris can build up toward the other layers of the retina resulting in drusen formation and contributing to neovascularization.4

Role of light in AMD. Chronic sun exposure has long been thought to contribute to AMD. A recent reanalysis of the study of Chesapeake Bay watermen showed a significant association between blue light exposure and exudative AMD.4,15

Prevention and treatment of AMD. The treatment of AMD is currently limited and unsatisfactory. Prevention may be the best way to reduce visual loss from AMD. Carotenoids and antioxidants may prove useful in preventing AMD. A clinical trial of the treatment of AMD patients for 7 to 12 years with a combination of vitamins C and E, beta-carotene, and selenium stopped the progression or even improved the changes in 60% of patients.4 Again, further research is needed. The National Eye Institute has an ongoing project to evaluate the role of antioxidant supplementation and AMD.4

Summary

Light has been associated with multiple retinal diseases, ranging from photic retinopathy to AMD. More research is needed in many areas from pathogenesis to treatment to prevention. Through that research, the questions may be answered of whether protecting the eyes from sun exposure can help and whether dietary supplementation with antioxidants and carotenoids will play a role in disease management.

References

  1. Sliney D. Ocular injury due to light toxicity. International Ophthalmology Clinics. 1988;23(3):246-250.

  2. Verma L, Venkatesh P, Tewari H. Phototoxic retinopathy. Ophthalmology Clinics of North America. 2001;14(4): 601-609.

  3. Glass P. Light and the developing retina. Documenta Ophthalmologica. 1990;74(3):195-203.

  4. Schalch W. Carotenoids in the retina - A review of their possible role in preventing or limiting damage caused by light and oxygen. Free Radicals and Aging. 1992;62:280-298.

  5. Dontsov A, Glickman R, Ostrovsky M. Retinal pigment epithelium pigment granules stimulate the photo-oxidation of unsaturated fatty acids. Free Radical Biology and Medicine. 1999;26(11):1436-1446.

  6. Davies S, Elliott M, Floor E, et al. Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells. Free Radical Biology and Medicine. 2001;31(2):256-265.

  7. Schutt F, Davies S, Kopitz J, Holz F, Boulton M. Photodamage to human RPE cells by A2E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci. 2000;41(8):2303-2308.

  8. Gomolin J, Koenekoop R. Presumed photic retinopathy after cataract surgery: An angiographic study. Can J Ophthalmol. 1993;28(5):221-224.

  9. Khwarg S, Linstone F, Daniels S, Isenberg S, Hanscom T, Geoghegan M, Straatsma B. Incidence, risk factors, and morphology in operating microscope light retinopathy. Am J Ophthalmol. 1987;103:255-263.

  10. Byrnes G, Anstoszyk A, Maxur D, Kao T, Miller S. Photic maculopathy after extracapsular cataract surgery. A prospective study. Ophthalmology. 1992;99(5):731-737.

  11. Byrnes G, Chang B, Loose I, Miller S, Benson W. Prospective incidence of photic maculopathy after cataract surgery. Am J Ophthalmol. 119(2): 231-2.

  12. Kraff M, Sanders D, Jampol L, Lieberman H. Effect of an ultraviolet-filtering intraocular lens on cystoid macular edema. Ophthalmology. 1985;92(3):366-369.

  13. Glass P, Avergy G, Subramanian K, Keys M, Sostek A, Friendly D. Effect of bright light in the hospital nursery on the incidence of retinopathy of prematurity. New Engl J Med. 1985;313(7):401-404.

  14. Kini M, Leibowitz H, Colton T, Nickerson R, Ganley J, Dawber T. Prevalence of senile cataract, diabetic retinopathy, senile macular degeneration, and open-angle glaucoma in the Framingham eye study. Am J Ophthalmol. 1978;85(1):28-34.

  15. West S, Rosenthal F, Bressler N, Bressler S, Munoz B, Fine S, Taylor H. Exposure to sunlight and other risk factors for age-related macular degeneration. Arch Ophthalmol. 1989;107(6):875-879.

  16. Glickman R. Phototoxicity to the retina: Mechanisms of damage. International Journal of Toxicology. 2002;21(6):473-490.

Posted April 2004