- Email: [email protected]
Ocular hazards of blue-light therapy in dermatology
Ocular hazards of blue-light therapy in dermatology Daniel P. Walker, BS,a Heidi R. Vollmer-Snarr, PhD,b and Cheryl Lee D. Eberting, MDc Dallas, Texas; and Provo and Alpine, Utah Blue-light phototherapy has become important in the treatment of many dermatologic conditions and as a result continue to be developed. Although blue-light therapy is successful, research shows that excessive ocular blue-light exposure may contribute to age-related macular degeneration and other vision problems. As blue-light therapy becomes increasingly more popular for clinical and at-home use, patients and operators of blue-light devices should be aware of its associated ocular hazards. Protective eyewear should be carefully selected and implemented with each therapy session to guard against the development of retinal disease. ( J Am Acad Dermatol 2012;66:130-5.) Key words: age-related macular degeneration; blue light; blue-light phototherapy; photodynamic therapy; phototherapy; retinopathy.
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lue-light phototherapy is used in the treatment of many skin conditions. Currently, blue light is widely used in the treatment of actinic keratoses,1-4 basal cell carcinoma,5-8 and acne.9-12 Because of its distinct mechanism of action, relative convenience, cost-effectiveness, and overall efficacy, blue-light phototherapy continues to be studied for its use as a novel treatment for many other dermatologic disorders. Blue-light devices are not only used in the dermatology clinic, but are now available for over-the-counter use. Although bluelight phototherapy is widely accepted and thought to be harmless, research shows that excessive bluelight exposure may cause age-related macular degeneration (AMD)13-17 and other ocular problems. Dermatologists and patients alike should be advised of the safe handling and ocular risks associated with these blue-light devices.
THE EFFECTS OF BLUE LIGHT ON THE RETINA Research has long suggested that different wavelength ranges of light cause damage to the skin and eye. Ultraviolet light (180-400 nm) causes erythema and carcinogenesis, corneal photokeratitis, and lens From the University of Texas Southwestern Medical Centera; Department of Chemistry and Biochemistry, Brigham Young University, Provob; and Alpine Dermatology.c Funding sources: None. Conflicts of interest: None declared. Reprint requests: Cheryl Lee D. Eberting, MD, Alpine Dermatology PC, 144 S Main St, Suite 100, Alpine, UT 84004. E-mail: [email protected]. Published online May 3, 2011. 0190-9622/$36.00 Ó 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.11.040
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Abbreviations used: ALA: AMD: PDT: RPE:
aminolevulinic acid age-related macular degeneration photodynamic therapy retinal pigmented epithelium
cataracts.18 Infrared radiation (2-50 m) is primarily responsible for thermal hazards to the cornea and lens and contributes to their opacities. Blue light (400-480 nm), part of the visible spectrum, causes retinal damage (photoretinitis)18,19 and is implicated in the pathogenesis of AMD, the leading cause of blindness in developed countries. Studies have demonstrated blue-light damage to retinal photoreceptors directly through the photosensitive molecule, rhodopsin.20 These blue-lightsensitive photoreceptors send vital information to nonvisual brain centers that mediate circadian rhythms, neuroendocrine and neurobehavioral responses, metabolic homeostasis, stress response, and production of serotonin and melatonin.21-25 Irreversible damage to photoreceptive cells may disrupt these biological systems, resulting in associated problems including insomnia, memory loss, and depression.26 Moreover, several studies have shown that the retinal pigmented epithelium (RPE), a cellular layer attached to the retina and responsible for its nourishment, is damaged or destroyed by excessive blue-light exposure.27-33 Research has implicated the accumulation of RPE lipofuscin, granules composed of proteins, lipids, and retinoids, to this damage.34-36 The most documented retinoid component in lipofuscin that has demonstrated phototoxicity is A2E.31,32,37,38 Photoirradiation of this bisretinoid generates singlet
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and triplet oxygen, thus forming harmful oxidized A2E application for blue light is in photodynamic therapy derivatives that cause DNA damage37,39,40 and apo(PDT). The mechanism of action of PDT mirrors a ptosis.15,31,32,38-40 Research suggests that A2E slowly damage process observed in photoretinopathy.11,60 Light activates biological or chemical photosensitizing accumulates in the RPE over a lifetime and individual agents in the skin or retinal tissues to form cytotoxic doses of blue light each contribute to the cumulative intermediates, including singlet oxygen. These cytoformation of cytotoxic photoproducts.41,42 Individuals who are chronically exposed to blue light may be toxic species promote cell death in nearby target cells. at higher risk of developBlue-light PDT is commonly ing AMD.13,14,16,36,41,43-50 A used in combination with the CAPSULE SUMMARY number of epidemiologic topical photosensitizer aminostudies have found associalevulinic acid (ALA) or less Blue-light phototherapy has become an tions between increased light commonly, with its counterimportant tool in treating many exposure over a lifetime and part methylaminolevulinic dermatologic conditions, and it is critical AMD.14,16,41,49-53 However, acid. to understand its proper use and there are inherent difficulties Blue-light PDT is freassociated hazards. in accurately measuring cuquently used in the treatEven small amounts of blue-light mulative ocular exposure to ment of actinic keratoses1-4 irradiation can contribute to age-related and basal cell carcinoma.5-8 light over a number of years. macular degeneration and other ocular Blue light alone or in comEstimates are difficult to do problems. bination with ALA also efretrospectively and some fectively treats acne by studies54-57 have been less The proper protective eyewear should conclusive about the risks asreducing the number of inbe selected and used by both patient sociated with chronic light flammatory and comedonal and operator during blue-light exposure and development lesionseproviding a safer phototherapy sessions. of AMD. alternative to retinoid drugs The amount of irreversiand their associated teratoble damage sustained by the retina depends on both genicities.9-12 Other studies report the efficacy of blue-light PDT in the treatment of sebaceous the intensity and the duration of blue light transmithyperplasia,61 warts,62,63 and roseacea.64,65 PDT is ted.40 Blue-light injury can result from viewing either an extremely bright light for a short period of time or also used for improvement in overall cosmesis,9,66 including decreased skin wrinkling,67 improvement from a low-dose exposure for an extended period of 18,32 Most manufacturers of blue-light devices in hyperpigmentation,9,67 and reduction of telantime. follow guidelines for light exposure based on acute gectasias.9 This list is not exhaustive, and the number of skin conditions treated with blue light or subacute retinal phototoxicity. Although the loss continues to expand as studies further explore the of a minimal number of RPE cells associated with a benefits of this relatively new technology.11 single dose may not severely impair vision, the cumulative loss of these postmitotic cells may eventually lead to irreversible vision loss. Individuals with BLUE-LIGHT DEVICES frequent exposure to moderate amounts of blue light As the clinical use for blue light increases, so does from occupational devices should be aware that the variety and availability of blue-light devices. The although acute threshold damage is often avoided most commonly used light sources for blue-light because of manufacturer compliance with published PDT are the BLU-U (DUSA Pharmaceuticals, safety guidelines, long-term damage, not immediWilmington, MA), ClearLight (Lumenis, Santa Clara, ately apparent, may appear over time.58 Similar CA), and Omnilux Blue (Photo Therapeutics Inc, studies59 have suggested that prolonged effects of Carlsbad, CA) photosystems. These devices provide blue light on the retina can result from intensities light near 417 nm, the maximum absorption peak for well below accepted safety levels. Thus, excessive ALA therapeutics.9,11 These systems are freeblue-light exposure, regardless of intensity, should standing, stationary units that require the patient be be avoided to prevent retinal disease. brought close to the light source while a large area of skin is illuminated. BLU-U (DUSA Pharmaceuticals) BLUE-LIGHT PHOTOTHERAPY IN and ClearLight (Lumenis) use narrowband fluoresDERMATOLOGY cent tubes that produce incoherent light, and In recent years, blue-light phototherapy has become Omnilux Blue (Photo Therapeutics Inc) uses a an essential tool for treating a growing number of skin light-emitting diode array. Blue-light devices have conditions. The most common and clinically proven also been developed for nondermatologic dental d
d
d
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use, including photobleaching of dental stains68 and photocuring of fillings. Over-the-counter blue-light devices are becoming popular for at-home use for dermatologic and other medical conditions. These devices include stationary and hand-held units for the treatment of acne, and stationary tabletop panels for photorejuvenation therapy. Blue-light panels are available over the counter for the treatment of winter depression or seasonal affective disorder,69 and sleep disorders, such as insomnia and hypersomnia. The seasonal affective disorder and sleep-disorder devices are recommended for daily use to artificially stimulate blue-light photoreceptors in the eye and the consumer intentionally looks directly into the blue-light source. All these over-the-counter bluelight devices are readily available to the public with no regulation over their frequency of use and exposure time.
PROTECTION FOR BLUE-LIGHT USE In the clinic, patients undergoing therapy are easily protected from the damaging effects of blue light by opaque, protective goggles. If worn correctly, these goggles prevent the potentially hazardous light from affecting the retina. If worn incorrectly, or not at all, the retina will be exposed to blue light. Dermatologists and other personnel who are operating the blue-light devices, however, may be less likely to wear protective goggles because of a perception of low risk from exposure to moderate amounts of indirect blue light. These operators may be at higher risk to the cumulative damage of blue light because of their frequent exposure during multiple treatment sessions. Operators often assist patients during treatments and are thus frequently exposed to scattered blue light. It is not possible for the dermatologist or system operator to wear completely opaque lenses because they need some visible light to operate equipment, make adjustments to device settings if the patient experiences discomfort during a procedure, or to adjust the light source so it is treating the appropriate area on the patient. The best option for these operators is protective eyewear that will selectively block both direct and scattered blue light, and still maintain functional vision. Eyewear with yellow-orange lenses will absorb most light in the blue spectrum. Lenses are available to absorb the specific wavelengths used in any given blue-light therapy. The most effective eyewear should contain a short-wavelength filtering lens with a transmission cutoff around 500 nm. The wearer will experience some short-term alteration
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in color perception but will otherwise retain functional vision. Safety eyewear should have sufficient wraparound protection to avoid blue-light scatter. These products are typically labeled as ‘‘laser safety goggles’’ and are available commercially through a number of online vendors (eg, NoIR, South Lyon, MI; Philips Safety, Middlesex, NJ; Kentek, Pittsfield, NH). Goggles are ideal, as opposed to spectacles or wraps, as they fit tightly to the face and shield the eyes completely from scattered light. Eyewear without adequate wrap-around coverage does not protect against this reflected and scattered light in treatment rooms and may even increase peripheral or ground exposure because of increased eye opening.70 Most manufacturers provide information on optical density for each lens that describes which wavelength range the given lens absorbs. The buyer should select a lens with sufficient optical density (optical density $ 4) to transmit a negligible amount of light with wavelengths less than 500 nm. Studies have shown that these blue-blocking lenses block nearly all blue-light transmission.71,72 Other studies73 have provided a quantitative assessment of the blue-light hazard in relation to the use of blue-filtering lenses. Similar eyewear recommendations have been given to dentists using blue-light systems.68 Blue-blocking glasses are also prescribed to aphakic patients because the lens provides some inherent protection against blue light. Moreover, patients with cataract and AMD use blue-blocking intraocular lenses to prevent further damage associated with AMD.19,44,48 Blue-light exposure guidelines are maintained by organizations such as the International Commission on Non-Ionizing Radiation Protection74 and are available to direct users in their selection of protective eyewear. Although these precautions may be relatively simple to implement in clinical settings, patients using at-home blue-light devices also need to be advised of risks. At-home dermatologic treatments are not designed to provide blue light to the eyes, so protective goggles can be worn. Warning labels should be prominently displayed on all blue-light devices, so that patients are alerted to the possible ocular harm associated with blue-light exposure. Where appropriate, these devices should also come with opaque or filtering lenses. More complicated are the blue-light devices designed for the treatment of seasonal affective disorder, insomnia, or sleep therapy, because intentional ocular exposure is part of the treatment plan. When undergoing PDT in a dermatology office, it is also important to inform patients not to touch or rub their eyes once ALA or methylaminolevulinic
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acid have been applied to a treatment area, as this may transfer the photosensitizer to the eye itself, making it photosensitized. The author (C. L. D. E.) has encountered this when a patient presumably touched her eyes after the application of ALA and experienced photosensitivity during and for 2 days after blue-light treatment, despite wearing occlusive metal eye shields during the treatment.
CONCLUSION Blue-light phototherapy has become a conventional treatment for many skin conditions. It is efficient, easy to administer, noninvasive, and highly effective in treating many of these conditions. Patients, physicians, and any system operators should avoid the cumulative effects of chronic ocular blue-light exposure by using eyewear that protects against direct and indirect exposure to blue light. As new uses for blue-light therapy are discovered, those who are developing them should be alerted to the possible ocular damage associated with cumulative low intensity and short duration blue-light exposure, so they may provide proper warnings for the use of their devices. There is still a need for additional wellcontrolled studies of the blue-light hazard in dermatology. But although it is difficult to definitively measure the long-term risks of blue-light exposure in human beings and their contribution to AMD, research is mounting in support of blue light as a contributing factor in this disease. The use of blueblocking goggles provides a simple way to avoid this vision loss later in life. The authors would like to thank David Sliney, PhD, for his direction in regard to the safety standards for blue-light devices. The authors would also like to thank David Glabe, BS, for his guidance on blue-blocking eyewear recommendations. REFERENCES 1. Jeffes EW, McCullough JL, Weinstein GD, Fergin PE, Nelson JS, Shull TF, et al. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid: a pilot dose-ranging study. Arch Dermatol 1997;133:727-32. 2. Szeimies RM, Karrer S, Sauerwald A, Landthaler M. Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study. Dermatology 1996;192:246-51. 3. Dijkstra AT, Majoie IM, van Dongen JW, van Weelden H, van Vloten WA. Photodynamic therapy with violet light and topical 6-aminolaevulinic acid in the treatment of actinic keratosis, Bowen’s disease and basal cell carcinoma. J Eur Acad Dermatol Venereol 2001;15:550-4. 4. Goldman M, Atkin D. ALA/PDT in the treatment of actinic keratosis: spot versus confluent therapy. J Cosmet Laser Ther 2003;5:107-10.
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5. Soler AM, Warloe T, Tausjo J, Berner A. Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study. Acta Derm Venereol 1999;79:204-6. 6. Horn M, Wolf P, Wulf HC, Warloe T, Fritsch C, Rhodes LE, et al. Topical methyl aminolevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment. Br J Dermatol 2003;149:1242-9. 7. Fijan S, Honigsmann H, Ortel B. Photodynamic therapy of epithelial skin tumors using delta-aminolevulinic acid and desferrioxamine. Br J Dermatol 1995;133:282-8. 8. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 1992;14:275-92. 9. Gilbert DJ. Incorporating photodynamic therapy into a medical and cosmetic dermatology practice. Dermatol Clin 2007; 25:111-8. 10. Kawada A, Aragane Y, Kameyama H, Sangen Y, Tezuka T. Acne phototherapy with a high-intensity, enhanced, narrow-band, blue light source: an open study and in vitro investigation. J Dermatol Sci 2002;30:129-35. 11. MacCormack MA. Photodynamic therapy in dermatology: an update on applications and outcomes. Semin Cutan Med Surg 2008;27:52-62. 12. Tzung TY, Wu KH, Huang ML. Blue light phototherapy in the treatment of acne. Photodermatol Photoimmunol Photomed 2004;20:266-9. 13. Algvere PV, Marshall J, Seregard S. Age-related maculopathy and the impact of blue light hazard. Acta Ophthalmol Scand 2006;84:4-15. 14. Cruickshanks KJ, Klein R, Klein BE, Nondahl DM. Sunlight and the 5-year incidence of early age-related maculopathy: the Beaver Dam eye study. Arch Ophthalmol 2001;119:246-50. 15. Suter M, Reme C, Grimm C, Wenzel A, Jaattela M, Esser P, et al. Age-related macular degeneration: the lipofusion component Nretinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells. J Biol Chem 2000;275:39625-30. 16. Taylor HR, Munoz B, West S, Bressler NM, Bressler SB, Rosenthal FS. Visible light and risk of age-related macular degeneration. Trans Am Ophthalmol Soc 1990;88:163-78. 17. Holz FG, Pauleikhoff D, Klein R, Bird AC. Pathogenesis of lesions in late age-related macular disease. Am J Ophthalmol 2004;137:504-10. 18. Sliney DH. Ocular hazards of light. In: Tibbits T, editor. International lighting in controlled environments workshop. Madison (WI):NASA-CP-95-3309, 1994. p. 183-9. 19. Ham WT Jr, Mueller HA, Sliney DH. Retinal sensitivity to damage from short wavelength light. Nature 1976;260:153-5. 20. Grimm C, Wenzel A, Williams T, Rol P, Hafezi F, Reme C. Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching. Invest Ophthalmol Vis Sci 2001;42:497-505. 21. Hanifin JP, Brainard GC. Photoreception for circadian, neuroendocrine, and neurobehavioral regulation. J Physiol Anthropol 2007;26:87-94. 22. Hankins MW, Peirson SN, Foster RG. Melanopsin: an exciting photopigment. Trends Neurosci 2008;31:27-36. 23. Mainster MA. Violet and blue light blocking intraocular lenses: photoprotection versus photoreception. Br J Ophthalmol 2006;90:784-92. 24. Mainster MA, Turner P. Intraocular lens spectral filtering. In: Steinert RF, ed. Cataract Surgery, 3rd Edition, London: Elsevier Ltd; 2007.
134 Walker, Vollmer-Snarr, and Eberting
25. Mainster MA, Turner PL. Blue-blocking intraocular lenses: myth or reality? Am J Ophthalmol 2009;147:8-10. 26. Van Someren EJ, Riemersma RF, Swaab DF. Functional plasticity of the circadian timing system in old age: light exposure. Prog Brain Res 2002;138:205-31. 27. Busch EM, Gorgels TG, van Norren D. Temporal sequence of changes in rat retina after UV-A and blue light exposure. Vision Res 1999;39:1233-47. 28. Ham WT Jr, Allen RG, Feeney-Burns L, Masmor MF, Parver LM, Proctor PH, et al. The involvement of the retinal pigment epithelium. Boca Raton (FL): CRC Press; 1986. 29. Ham WT Jr, Mueller HA, Ruffolo JJ Jr, Millen JE, Cleary SF, Guerry RK, et al. Basic mechanisms underlying the production of photochemical lesions in the mammalian retina. Curr Eye Res 1984;3:165-74. 30. Ham WT Jr, Ruffolo JJ Jr, Mueller HA, Clarke AM, Moon ME. Histologic analysis of photochemical lesions produced in rhesus retina by short-wave-length light. Invest Ophthalmol Vis Sci 1978;17:1029-35. 31. Sparrow JR, Nakanishi K, Parish CA. The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci 2000;41: 1981-9. 32. Sparrow JR, Zhou J, Ben-Shabat S, Vollmer H, Itagaki Y, Nakanishi K. Involvement of oxidative mechanisms in bluelight-induced damage to A2E-laden RPE. Invest Ophthalmol Vis Sci 2002;43:1222-7. 33. Tso MO, Fine BS. Repair and late degeneration of the primate foveola after injury by argon laser. Invest Ophthalmol Vis Sci 1979;18:447-61. 34. Kim SR, Jang YP, Jockusch S, Fishkin NE, Turro NJ, Sparrow JR. The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model. Proc Natl Acad Sci U S A 2007;104:19273-8. 35. Kim SR, Nakanishi K, Itagaki Y, Sparrow JR. Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin. Exp Eye Res 2006;82: 828-39. 36. Young RW. Solar radiation and age-related macular degeneration. Surv Ophthalmol 1988;32:252-69. 37. Ben-Shabat S, Itagaki Y, Jockusch S, Sparrow JR, Turro NJ, Nakanishi K. Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Angew Chem Int Ed Engl 2002;41:814-7. 38. Schutt F, Davies S, Kopitz J, Holz FG, Boulton ME. Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci 2000;41:2303-8. 39. Hammer M, Richter S, Guehrs KH, Schweitzer D. Retinal pigment epithelium cell damage by A2-E and its photoderivatives. Mol Vis 2006;12:1348-54. 40. Sparrow JR, Vollmer-Snarr HR, Zhou J, Jang YP, Jockusch S, Itagaki Y, et al. A2E-epoxides damage DNA in retinal pigment epithelial cells: vitamin E and other antioxidants inhibit A2Eepoxide formation. J Biol Chem 2003;278:18207-13. 41. Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, et al. Sunlight exposure, antioxidants, and age-related macular degeneration. Arch Ophthalmol 2008;126: 1396-403. 42. Wu J, Seregard S, Algvere PV. Photochemical damage of the retina. Surv Ophthalmol 2006;51:461-81. 43. Andley UP, Chylack LT Jr. Recent studies on photodamage to the eye with special reference to clinical phototherapeutic procedures. Photodermatol Photoimmunol Photomed 1990;7: 98-105.
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JANUARY 2012
44. Braunstein RE, Sparrow JR. A blue-blocking intraocular lens should be used in cataract surgery. Arch Ophthalmol 2005; 123:547-9. 45. Cuthbertson FM, Peirson SN, Wulff K, Foster RG, Downes SM. Blue light-filtering intraocular lenses: review of potential benefits and side effects. J Cataract Refract Surg 2009;35: 1281-97. 46. Ham WT Jr, Mueller HA, Ruffolo JJ Jr, Guerry D III, Guerry RK. Action spectrum for retinal injury from near-ultraviolet radiation in the aphakic monkey. Am J Ophthalmol 1982;93: 299-306. 47. Hui S, Yi L, Fengling QL. Effects of light exposure and use of intraocular lens on retinal pigment epithelial cells in vitro. Photochem Photobiol 2009;85:966-9. 48. Mainster MA, Sparrow JR. How much blue light should an IOL transmit? Br J Ophthalmol 2003;87:1523-9. 49. Taylor HR, West S, Munoz B, Rosenthal FS, Bressler SB, Bressler NM. The long-term effects of visible light on the eye. Arch Ophthalmol 1992;110:99-104. 50. Tomany SC, Cruickshanks KJ, Klein R, Klein BE, Knudtson MD. Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam eye study. Arch Ophthalmol 2004;122: 750-7. 51. Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al. Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology 2001;108: 697-704. 52. Simons K. Artificial light and early-life exposure in age-related macular degeneration and in cataractogenic phototoxicity. Arch Ophthalmol 1993;111:297-8. 53. Blumenkranz MS, Russell SR, Robey MG, Kott-Blumenkranz R, Penneys N. Risk factors in age-related maculopathy complicated by choroidal neovascularization. Ophthalmology 1986; 93:552-8. 54. Darzins P, Mitchell P, Heller RF. Sun exposure and age-related macular degeneration: an Australian case-control study. Ophthalmology 1997;104:770-6. 55. McCarty CA, Mukesh BN, Fu CL, Mitchell P, Wang JJ, Taylor HR. Risk factors for age-related maculopathy: the visual impairment project. Arch Ophthalmol 2001;119:1455-62. 56. Delcourt C, Carriere I, Ponton-Sanchez A, Fourrey S, Lacroux A, Papoz L. 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. 57. Hirvela H, Luukinen H, Laara E, Sc L, Laatikainen L. Risk factors of age-related maculopathy in a population 70 years of age or older. Ophthalmology 1996;103:871-7. 58. Lawwill T, Crockett S, Currier G. Retinal damage secondary to chronic light exposure, thresholds and mechanisms. Doc Ophthalmol 1977;44:379-402. 59. Berninger TA, Canning CR, Gunduz K, Strong N, Arden GB. Using argon laser blue light reduces ophthalmologists’ color contrast sensitivity: argon blue and surgeons’ vision. Arch Ophthalmol 1989;107:1453-8. 60. Zeitouni NC, Oseroff AR, Shieh S. Photodynamic therapy for nonmelanoma skin cancers: current review and update. Mol Immunol 2003;39:1133-6. 61. Richey DF. Aminolevulinic acid photodynamic therapy for sebaceous gland hyperplasia. Dermatol Clin 2007;25:59-65. 62. Schroeter CA, Pleunis J, van Nispen tot Pannerden C, Reineke T, Neumann HA. Photodynamic therapy: new treatment for therapy-resistant plantar warts. Dermatol Surg 2005;31:71-5. 63. Nestor MS, Gold MH, Kauvar AN, Taub AF, Geronemus RG, Ritvo EC, et al. The use of photodynamic therapy in
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64. 65. 66.
67.
68.
69.
dermatology: results of a consensus conference. J Drugs Dermatol 2006;5:140-54. Bryld LE, Jemec GB. Photodynamic therapy in a series of rosacea patients. J Eur Acad Dermatol Venereol 2007;21:1199-202. Nybaek H, Jemec GB. Photodynamic therapy in the treatment of rosacea. Dermatology 2005;211:135-8. Itkin A, Gilchrest BA. delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome. Dermatol Surg 2004;30:1054-61. Touma D, Yaar M, Whitehead S, Konnikov N, Gilchrest BA. A trial of short incubation, broad-area photodynamic therapy for facial actinic keratoses and diffuse photodamage. Arch Dermatol 2004;140:33-40. Council on Dental Materials I, and Equipment. The effects of blue light on the retina and the use of protective filtering lenses. J Am Dent Assoc 1986;112:533-5. Glickman G, Byrne B, Pineda C, Hauck WW, Brainard GC. Light therapy for seasonal affective disorder with blue
70. 71.
72.
73.
74.
narrow-band light-emitting diodes (LEDs). Biol Psychiatry 2006;59:502-7. Sliney DH. How light reaches the eye and its components. Int J Toxicol 2002;21:501-9. Sasseville A, Paquet N, Sevigny J, Hebert M. Blue blocker glasses impede the capacity of bright light to suppress melatonin production. J Pineal Res 2006;41:73-8. Lee C, Smith MR, Eastman CI. A compromise phase position for permanent night shift workers: circadian phase after two night shifts with scheduled sleep and light/dark exposure. Chronobiol Int 2006;23:859-75. Bradnam MS, Montgomery DM, Moseley H, Dutton GN. Quantitative assessment of the blue-light hazard during indirect ophthalmoscopy and the increase in the ‘‘safe’’ operating period achieved using a yellow lens. Ophthalmology 1995;102:799-804. The International Commission on Non-Ionizing Radiation Protection. Guidelines in limits of exposure to broad-band incoherent optical radiation (0.38 to 3 m). Health Physics 1997;73:539-52.
B
lue-light phototherapy is used in the treatment of many skin conditions. Currently, blue light is widely used in the treatment of actinic keratoses,1-4 basal cell carcinoma,5-8 and acne.9-12 Because of its distinct mechanism of action, relative convenience, cost-effectiveness, and overall efficacy, blue-light phototherapy continues to be studied for its use as a novel treatment for many other dermatologic disorders. Blue-light devices are not only used in the dermatology clinic, but are now available for over-the-counter use. Although bluelight phototherapy is widely accepted and thought to be harmless, research shows that excessive bluelight exposure may cause age-related macular degeneration (AMD)13-17 and other ocular problems. Dermatologists and patients alike should be advised of the safe handling and ocular risks associated with these blue-light devices.
THE EFFECTS OF BLUE LIGHT ON THE RETINA Research has long suggested that different wavelength ranges of light cause damage to the skin and eye. Ultraviolet light (180-400 nm) causes erythema and carcinogenesis, corneal photokeratitis, and lens From the University of Texas Southwestern Medical Centera; Department of Chemistry and Biochemistry, Brigham Young University, Provob; and Alpine Dermatology.c Funding sources: None. Conflicts of interest: None declared. Reprint requests: Cheryl Lee D. Eberting, MD, Alpine Dermatology PC, 144 S Main St, Suite 100, Alpine, UT 84004. E-mail: [email protected]. Published online May 3, 2011. 0190-9622/$36.00 Ó 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.11.040
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Abbreviations used: ALA: AMD: PDT: RPE:
aminolevulinic acid age-related macular degeneration photodynamic therapy retinal pigmented epithelium
cataracts.18 Infrared radiation (2-50 m) is primarily responsible for thermal hazards to the cornea and lens and contributes to their opacities. Blue light (400-480 nm), part of the visible spectrum, causes retinal damage (photoretinitis)18,19 and is implicated in the pathogenesis of AMD, the leading cause of blindness in developed countries. Studies have demonstrated blue-light damage to retinal photoreceptors directly through the photosensitive molecule, rhodopsin.20 These blue-lightsensitive photoreceptors send vital information to nonvisual brain centers that mediate circadian rhythms, neuroendocrine and neurobehavioral responses, metabolic homeostasis, stress response, and production of serotonin and melatonin.21-25 Irreversible damage to photoreceptive cells may disrupt these biological systems, resulting in associated problems including insomnia, memory loss, and depression.26 Moreover, several studies have shown that the retinal pigmented epithelium (RPE), a cellular layer attached to the retina and responsible for its nourishment, is damaged or destroyed by excessive blue-light exposure.27-33 Research has implicated the accumulation of RPE lipofuscin, granules composed of proteins, lipids, and retinoids, to this damage.34-36 The most documented retinoid component in lipofuscin that has demonstrated phototoxicity is A2E.31,32,37,38 Photoirradiation of this bisretinoid generates singlet
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and triplet oxygen, thus forming harmful oxidized A2E application for blue light is in photodynamic therapy derivatives that cause DNA damage37,39,40 and apo(PDT). The mechanism of action of PDT mirrors a ptosis.15,31,32,38-40 Research suggests that A2E slowly damage process observed in photoretinopathy.11,60 Light activates biological or chemical photosensitizing accumulates in the RPE over a lifetime and individual agents in the skin or retinal tissues to form cytotoxic doses of blue light each contribute to the cumulative intermediates, including singlet oxygen. These cytoformation of cytotoxic photoproducts.41,42 Individuals who are chronically exposed to blue light may be toxic species promote cell death in nearby target cells. at higher risk of developBlue-light PDT is commonly ing AMD.13,14,16,36,41,43-50 A used in combination with the CAPSULE SUMMARY number of epidemiologic topical photosensitizer aminostudies have found associalevulinic acid (ALA) or less Blue-light phototherapy has become an tions between increased light commonly, with its counterimportant tool in treating many exposure over a lifetime and part methylaminolevulinic dermatologic conditions, and it is critical AMD.14,16,41,49-53 However, acid. to understand its proper use and there are inherent difficulties Blue-light PDT is freassociated hazards. in accurately measuring cuquently used in the treatEven small amounts of blue-light mulative ocular exposure to ment of actinic keratoses1-4 irradiation can contribute to age-related and basal cell carcinoma.5-8 light over a number of years. macular degeneration and other ocular Blue light alone or in comEstimates are difficult to do problems. bination with ALA also efretrospectively and some fectively treats acne by studies54-57 have been less The proper protective eyewear should conclusive about the risks asreducing the number of inbe selected and used by both patient sociated with chronic light flammatory and comedonal and operator during blue-light exposure and development lesionseproviding a safer phototherapy sessions. of AMD. alternative to retinoid drugs The amount of irreversiand their associated teratoble damage sustained by the retina depends on both genicities.9-12 Other studies report the efficacy of blue-light PDT in the treatment of sebaceous the intensity and the duration of blue light transmithyperplasia,61 warts,62,63 and roseacea.64,65 PDT is ted.40 Blue-light injury can result from viewing either an extremely bright light for a short period of time or also used for improvement in overall cosmesis,9,66 including decreased skin wrinkling,67 improvement from a low-dose exposure for an extended period of 18,32 Most manufacturers of blue-light devices in hyperpigmentation,9,67 and reduction of telantime. follow guidelines for light exposure based on acute gectasias.9 This list is not exhaustive, and the number of skin conditions treated with blue light or subacute retinal phototoxicity. Although the loss continues to expand as studies further explore the of a minimal number of RPE cells associated with a benefits of this relatively new technology.11 single dose may not severely impair vision, the cumulative loss of these postmitotic cells may eventually lead to irreversible vision loss. Individuals with BLUE-LIGHT DEVICES frequent exposure to moderate amounts of blue light As the clinical use for blue light increases, so does from occupational devices should be aware that the variety and availability of blue-light devices. The although acute threshold damage is often avoided most commonly used light sources for blue-light because of manufacturer compliance with published PDT are the BLU-U (DUSA Pharmaceuticals, safety guidelines, long-term damage, not immediWilmington, MA), ClearLight (Lumenis, Santa Clara, ately apparent, may appear over time.58 Similar CA), and Omnilux Blue (Photo Therapeutics Inc, studies59 have suggested that prolonged effects of Carlsbad, CA) photosystems. These devices provide blue light on the retina can result from intensities light near 417 nm, the maximum absorption peak for well below accepted safety levels. Thus, excessive ALA therapeutics.9,11 These systems are freeblue-light exposure, regardless of intensity, should standing, stationary units that require the patient be be avoided to prevent retinal disease. brought close to the light source while a large area of skin is illuminated. BLU-U (DUSA Pharmaceuticals) BLUE-LIGHT PHOTOTHERAPY IN and ClearLight (Lumenis) use narrowband fluoresDERMATOLOGY cent tubes that produce incoherent light, and In recent years, blue-light phototherapy has become Omnilux Blue (Photo Therapeutics Inc) uses a an essential tool for treating a growing number of skin light-emitting diode array. Blue-light devices have conditions. The most common and clinically proven also been developed for nondermatologic dental d
d
d
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use, including photobleaching of dental stains68 and photocuring of fillings. Over-the-counter blue-light devices are becoming popular for at-home use for dermatologic and other medical conditions. These devices include stationary and hand-held units for the treatment of acne, and stationary tabletop panels for photorejuvenation therapy. Blue-light panels are available over the counter for the treatment of winter depression or seasonal affective disorder,69 and sleep disorders, such as insomnia and hypersomnia. The seasonal affective disorder and sleep-disorder devices are recommended for daily use to artificially stimulate blue-light photoreceptors in the eye and the consumer intentionally looks directly into the blue-light source. All these over-the-counter bluelight devices are readily available to the public with no regulation over their frequency of use and exposure time.
PROTECTION FOR BLUE-LIGHT USE In the clinic, patients undergoing therapy are easily protected from the damaging effects of blue light by opaque, protective goggles. If worn correctly, these goggles prevent the potentially hazardous light from affecting the retina. If worn incorrectly, or not at all, the retina will be exposed to blue light. Dermatologists and other personnel who are operating the blue-light devices, however, may be less likely to wear protective goggles because of a perception of low risk from exposure to moderate amounts of indirect blue light. These operators may be at higher risk to the cumulative damage of blue light because of their frequent exposure during multiple treatment sessions. Operators often assist patients during treatments and are thus frequently exposed to scattered blue light. It is not possible for the dermatologist or system operator to wear completely opaque lenses because they need some visible light to operate equipment, make adjustments to device settings if the patient experiences discomfort during a procedure, or to adjust the light source so it is treating the appropriate area on the patient. The best option for these operators is protective eyewear that will selectively block both direct and scattered blue light, and still maintain functional vision. Eyewear with yellow-orange lenses will absorb most light in the blue spectrum. Lenses are available to absorb the specific wavelengths used in any given blue-light therapy. The most effective eyewear should contain a short-wavelength filtering lens with a transmission cutoff around 500 nm. The wearer will experience some short-term alteration
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in color perception but will otherwise retain functional vision. Safety eyewear should have sufficient wraparound protection to avoid blue-light scatter. These products are typically labeled as ‘‘laser safety goggles’’ and are available commercially through a number of online vendors (eg, NoIR, South Lyon, MI; Philips Safety, Middlesex, NJ; Kentek, Pittsfield, NH). Goggles are ideal, as opposed to spectacles or wraps, as they fit tightly to the face and shield the eyes completely from scattered light. Eyewear without adequate wrap-around coverage does not protect against this reflected and scattered light in treatment rooms and may even increase peripheral or ground exposure because of increased eye opening.70 Most manufacturers provide information on optical density for each lens that describes which wavelength range the given lens absorbs. The buyer should select a lens with sufficient optical density (optical density $ 4) to transmit a negligible amount of light with wavelengths less than 500 nm. Studies have shown that these blue-blocking lenses block nearly all blue-light transmission.71,72 Other studies73 have provided a quantitative assessment of the blue-light hazard in relation to the use of blue-filtering lenses. Similar eyewear recommendations have been given to dentists using blue-light systems.68 Blue-blocking glasses are also prescribed to aphakic patients because the lens provides some inherent protection against blue light. Moreover, patients with cataract and AMD use blue-blocking intraocular lenses to prevent further damage associated with AMD.19,44,48 Blue-light exposure guidelines are maintained by organizations such as the International Commission on Non-Ionizing Radiation Protection74 and are available to direct users in their selection of protective eyewear. Although these precautions may be relatively simple to implement in clinical settings, patients using at-home blue-light devices also need to be advised of risks. At-home dermatologic treatments are not designed to provide blue light to the eyes, so protective goggles can be worn. Warning labels should be prominently displayed on all blue-light devices, so that patients are alerted to the possible ocular harm associated with blue-light exposure. Where appropriate, these devices should also come with opaque or filtering lenses. More complicated are the blue-light devices designed for the treatment of seasonal affective disorder, insomnia, or sleep therapy, because intentional ocular exposure is part of the treatment plan. When undergoing PDT in a dermatology office, it is also important to inform patients not to touch or rub their eyes once ALA or methylaminolevulinic
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acid have been applied to a treatment area, as this may transfer the photosensitizer to the eye itself, making it photosensitized. The author (C. L. D. E.) has encountered this when a patient presumably touched her eyes after the application of ALA and experienced photosensitivity during and for 2 days after blue-light treatment, despite wearing occlusive metal eye shields during the treatment.
CONCLUSION Blue-light phototherapy has become a conventional treatment for many skin conditions. It is efficient, easy to administer, noninvasive, and highly effective in treating many of these conditions. Patients, physicians, and any system operators should avoid the cumulative effects of chronic ocular blue-light exposure by using eyewear that protects against direct and indirect exposure to blue light. As new uses for blue-light therapy are discovered, those who are developing them should be alerted to the possible ocular damage associated with cumulative low intensity and short duration blue-light exposure, so they may provide proper warnings for the use of their devices. There is still a need for additional wellcontrolled studies of the blue-light hazard in dermatology. But although it is difficult to definitively measure the long-term risks of blue-light exposure in human beings and their contribution to AMD, research is mounting in support of blue light as a contributing factor in this disease. The use of blueblocking goggles provides a simple way to avoid this vision loss later in life. The authors would like to thank David Sliney, PhD, for his direction in regard to the safety standards for blue-light devices. The authors would also like to thank David Glabe, BS, for his guidance on blue-blocking eyewear recommendations. REFERENCES 1. Jeffes EW, McCullough JL, Weinstein GD, Fergin PE, Nelson JS, Shull TF, et al. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid: a pilot dose-ranging study. Arch Dermatol 1997;133:727-32. 2. Szeimies RM, Karrer S, Sauerwald A, Landthaler M. Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study. Dermatology 1996;192:246-51. 3. Dijkstra AT, Majoie IM, van Dongen JW, van Weelden H, van Vloten WA. Photodynamic therapy with violet light and topical 6-aminolaevulinic acid in the treatment of actinic keratosis, Bowen’s disease and basal cell carcinoma. J Eur Acad Dermatol Venereol 2001;15:550-4. 4. Goldman M, Atkin D. ALA/PDT in the treatment of actinic keratosis: spot versus confluent therapy. J Cosmet Laser Ther 2003;5:107-10.
Walker, Vollmer-Snarr, and Eberting 133
5. Soler AM, Warloe T, Tausjo J, Berner A. Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study. Acta Derm Venereol 1999;79:204-6. 6. Horn M, Wolf P, Wulf HC, Warloe T, Fritsch C, Rhodes LE, et al. Topical methyl aminolevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment. Br J Dermatol 2003;149:1242-9. 7. Fijan S, Honigsmann H, Ortel B. Photodynamic therapy of epithelial skin tumors using delta-aminolevulinic acid and desferrioxamine. Br J Dermatol 1995;133:282-8. 8. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 1992;14:275-92. 9. Gilbert DJ. Incorporating photodynamic therapy into a medical and cosmetic dermatology practice. Dermatol Clin 2007; 25:111-8. 10. Kawada A, Aragane Y, Kameyama H, Sangen Y, Tezuka T. Acne phototherapy with a high-intensity, enhanced, narrow-band, blue light source: an open study and in vitro investigation. J Dermatol Sci 2002;30:129-35. 11. MacCormack MA. Photodynamic therapy in dermatology: an update on applications and outcomes. Semin Cutan Med Surg 2008;27:52-62. 12. Tzung TY, Wu KH, Huang ML. Blue light phototherapy in the treatment of acne. Photodermatol Photoimmunol Photomed 2004;20:266-9. 13. Algvere PV, Marshall J, Seregard S. Age-related maculopathy and the impact of blue light hazard. Acta Ophthalmol Scand 2006;84:4-15. 14. Cruickshanks KJ, Klein R, Klein BE, Nondahl DM. Sunlight and the 5-year incidence of early age-related maculopathy: the Beaver Dam eye study. Arch Ophthalmol 2001;119:246-50. 15. Suter M, Reme C, Grimm C, Wenzel A, Jaattela M, Esser P, et al. Age-related macular degeneration: the lipofusion component Nretinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells. J Biol Chem 2000;275:39625-30. 16. Taylor HR, Munoz B, West S, Bressler NM, Bressler SB, Rosenthal FS. Visible light and risk of age-related macular degeneration. Trans Am Ophthalmol Soc 1990;88:163-78. 17. Holz FG, Pauleikhoff D, Klein R, Bird AC. Pathogenesis of lesions in late age-related macular disease. Am J Ophthalmol 2004;137:504-10. 18. Sliney DH. Ocular hazards of light. In: Tibbits T, editor. International lighting in controlled environments workshop. Madison (WI):NASA-CP-95-3309, 1994. p. 183-9. 19. Ham WT Jr, Mueller HA, Sliney DH. Retinal sensitivity to damage from short wavelength light. Nature 1976;260:153-5. 20. Grimm C, Wenzel A, Williams T, Rol P, Hafezi F, Reme C. Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching. Invest Ophthalmol Vis Sci 2001;42:497-505. 21. Hanifin JP, Brainard GC. Photoreception for circadian, neuroendocrine, and neurobehavioral regulation. J Physiol Anthropol 2007;26:87-94. 22. Hankins MW, Peirson SN, Foster RG. Melanopsin: an exciting photopigment. Trends Neurosci 2008;31:27-36. 23. Mainster MA. Violet and blue light blocking intraocular lenses: photoprotection versus photoreception. Br J Ophthalmol 2006;90:784-92. 24. Mainster MA, Turner P. Intraocular lens spectral filtering. In: Steinert RF, ed. Cataract Surgery, 3rd Edition, London: Elsevier Ltd; 2007.
134 Walker, Vollmer-Snarr, and Eberting
25. Mainster MA, Turner PL. Blue-blocking intraocular lenses: myth or reality? Am J Ophthalmol 2009;147:8-10. 26. Van Someren EJ, Riemersma RF, Swaab DF. Functional plasticity of the circadian timing system in old age: light exposure. Prog Brain Res 2002;138:205-31. 27. Busch EM, Gorgels TG, van Norren D. Temporal sequence of changes in rat retina after UV-A and blue light exposure. Vision Res 1999;39:1233-47. 28. Ham WT Jr, Allen RG, Feeney-Burns L, Masmor MF, Parver LM, Proctor PH, et al. The involvement of the retinal pigment epithelium. Boca Raton (FL): CRC Press; 1986. 29. Ham WT Jr, Mueller HA, Ruffolo JJ Jr, Millen JE, Cleary SF, Guerry RK, et al. Basic mechanisms underlying the production of photochemical lesions in the mammalian retina. Curr Eye Res 1984;3:165-74. 30. Ham WT Jr, Ruffolo JJ Jr, Mueller HA, Clarke AM, Moon ME. Histologic analysis of photochemical lesions produced in rhesus retina by short-wave-length light. Invest Ophthalmol Vis Sci 1978;17:1029-35. 31. Sparrow JR, Nakanishi K, Parish CA. The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci 2000;41: 1981-9. 32. Sparrow JR, Zhou J, Ben-Shabat S, Vollmer H, Itagaki Y, Nakanishi K. Involvement of oxidative mechanisms in bluelight-induced damage to A2E-laden RPE. Invest Ophthalmol Vis Sci 2002;43:1222-7. 33. Tso MO, Fine BS. Repair and late degeneration of the primate foveola after injury by argon laser. Invest Ophthalmol Vis Sci 1979;18:447-61. 34. Kim SR, Jang YP, Jockusch S, Fishkin NE, Turro NJ, Sparrow JR. The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model. Proc Natl Acad Sci U S A 2007;104:19273-8. 35. Kim SR, Nakanishi K, Itagaki Y, Sparrow JR. Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin. Exp Eye Res 2006;82: 828-39. 36. Young RW. Solar radiation and age-related macular degeneration. Surv Ophthalmol 1988;32:252-69. 37. Ben-Shabat S, Itagaki Y, Jockusch S, Sparrow JR, Turro NJ, Nakanishi K. Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Angew Chem Int Ed Engl 2002;41:814-7. 38. Schutt F, Davies S, Kopitz J, Holz FG, Boulton ME. Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci 2000;41:2303-8. 39. Hammer M, Richter S, Guehrs KH, Schweitzer D. Retinal pigment epithelium cell damage by A2-E and its photoderivatives. Mol Vis 2006;12:1348-54. 40. Sparrow JR, Vollmer-Snarr HR, Zhou J, Jang YP, Jockusch S, Itagaki Y, et al. A2E-epoxides damage DNA in retinal pigment epithelial cells: vitamin E and other antioxidants inhibit A2Eepoxide formation. J Biol Chem 2003;278:18207-13. 41. Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, et al. Sunlight exposure, antioxidants, and age-related macular degeneration. Arch Ophthalmol 2008;126: 1396-403. 42. Wu J, Seregard S, Algvere PV. Photochemical damage of the retina. Surv Ophthalmol 2006;51:461-81. 43. Andley UP, Chylack LT Jr. Recent studies on photodamage to the eye with special reference to clinical phototherapeutic procedures. Photodermatol Photoimmunol Photomed 1990;7: 98-105.
J AM ACAD DERMATOL
JANUARY 2012
44. Braunstein RE, Sparrow JR. A blue-blocking intraocular lens should be used in cataract surgery. Arch Ophthalmol 2005; 123:547-9. 45. Cuthbertson FM, Peirson SN, Wulff K, Foster RG, Downes SM. Blue light-filtering intraocular lenses: review of potential benefits and side effects. J Cataract Refract Surg 2009;35: 1281-97. 46. Ham WT Jr, Mueller HA, Ruffolo JJ Jr, Guerry D III, Guerry RK. Action spectrum for retinal injury from near-ultraviolet radiation in the aphakic monkey. Am J Ophthalmol 1982;93: 299-306. 47. Hui S, Yi L, Fengling QL. Effects of light exposure and use of intraocular lens on retinal pigment epithelial cells in vitro. Photochem Photobiol 2009;85:966-9. 48. Mainster MA, Sparrow JR. How much blue light should an IOL transmit? Br J Ophthalmol 2003;87:1523-9. 49. Taylor HR, West S, Munoz B, Rosenthal FS, Bressler SB, Bressler NM. The long-term effects of visible light on the eye. Arch Ophthalmol 1992;110:99-104. 50. Tomany SC, Cruickshanks KJ, Klein R, Klein BE, Knudtson MD. Sunlight and the 10-year incidence of age-related maculopathy: the Beaver Dam eye study. Arch Ophthalmol 2004;122: 750-7. 51. Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al. Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology 2001;108: 697-704. 52. Simons K. Artificial light and early-life exposure in age-related macular degeneration and in cataractogenic phototoxicity. Arch Ophthalmol 1993;111:297-8. 53. Blumenkranz MS, Russell SR, Robey MG, Kott-Blumenkranz R, Penneys N. Risk factors in age-related maculopathy complicated by choroidal neovascularization. Ophthalmology 1986; 93:552-8. 54. Darzins P, Mitchell P, Heller RF. Sun exposure and age-related macular degeneration: an Australian case-control study. Ophthalmology 1997;104:770-6. 55. McCarty CA, Mukesh BN, Fu CL, Mitchell P, Wang JJ, Taylor HR. Risk factors for age-related maculopathy: the visual impairment project. Arch Ophthalmol 2001;119:1455-62. 56. Delcourt C, Carriere I, Ponton-Sanchez A, Fourrey S, Lacroux A, Papoz L. 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. 57. Hirvela H, Luukinen H, Laara E, Sc L, Laatikainen L. Risk factors of age-related maculopathy in a population 70 years of age or older. Ophthalmology 1996;103:871-7. 58. Lawwill T, Crockett S, Currier G. Retinal damage secondary to chronic light exposure, thresholds and mechanisms. Doc Ophthalmol 1977;44:379-402. 59. Berninger TA, Canning CR, Gunduz K, Strong N, Arden GB. Using argon laser blue light reduces ophthalmologists’ color contrast sensitivity: argon blue and surgeons’ vision. Arch Ophthalmol 1989;107:1453-8. 60. Zeitouni NC, Oseroff AR, Shieh S. Photodynamic therapy for nonmelanoma skin cancers: current review and update. Mol Immunol 2003;39:1133-6. 61. Richey DF. Aminolevulinic acid photodynamic therapy for sebaceous gland hyperplasia. Dermatol Clin 2007;25:59-65. 62. Schroeter CA, Pleunis J, van Nispen tot Pannerden C, Reineke T, Neumann HA. Photodynamic therapy: new treatment for therapy-resistant plantar warts. Dermatol Surg 2005;31:71-5. 63. Nestor MS, Gold MH, Kauvar AN, Taub AF, Geronemus RG, Ritvo EC, et al. The use of photodynamic therapy in
J AM ACAD DERMATOL
Walker, Vollmer-Snarr, and Eberting 135
VOLUME 66, NUMBER 1
64. 65. 66.
67.
68.
69.
dermatology: results of a consensus conference. J Drugs Dermatol 2006;5:140-54. Bryld LE, Jemec GB. Photodynamic therapy in a series of rosacea patients. J Eur Acad Dermatol Venereol 2007;21:1199-202. Nybaek H, Jemec GB. Photodynamic therapy in the treatment of rosacea. Dermatology 2005;211:135-8. Itkin A, Gilchrest BA. delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome. Dermatol Surg 2004;30:1054-61. Touma D, Yaar M, Whitehead S, Konnikov N, Gilchrest BA. A trial of short incubation, broad-area photodynamic therapy for facial actinic keratoses and diffuse photodamage. Arch Dermatol 2004;140:33-40. Council on Dental Materials I, and Equipment. The effects of blue light on the retina and the use of protective filtering lenses. J Am Dent Assoc 1986;112:533-5. Glickman G, Byrne B, Pineda C, Hauck WW, Brainard GC. Light therapy for seasonal affective disorder with blue
70. 71.
72.
73.
74.
narrow-band light-emitting diodes (LEDs). Biol Psychiatry 2006;59:502-7. Sliney DH. How light reaches the eye and its components. Int J Toxicol 2002;21:501-9. Sasseville A, Paquet N, Sevigny J, Hebert M. Blue blocker glasses impede the capacity of bright light to suppress melatonin production. J Pineal Res 2006;41:73-8. Lee C, Smith MR, Eastman CI. A compromise phase position for permanent night shift workers: circadian phase after two night shifts with scheduled sleep and light/dark exposure. Chronobiol Int 2006;23:859-75. Bradnam MS, Montgomery DM, Moseley H, Dutton GN. Quantitative assessment of the blue-light hazard during indirect ophthalmoscopy and the increase in the ‘‘safe’’ operating period achieved using a yellow lens. Ophthalmology 1995;102:799-804. The International Commission on Non-Ionizing Radiation Protection. Guidelines in limits of exposure to broad-band incoherent optical radiation (0.38 to 3 m). Health Physics 1997;73:539-52.