Clinics in Dermatology (2015) 33, 247–255

Phototherapy-related ophthalmologic disorders☆ Jennifer DePry, DO a,⁎, Jennifer Brescoll b , Loretta Szczotka-Flynn, OD, PhD c,1 , Pranita Rambhatla, MD d , Henry W. Lim, MD d,2 , Kevin Cooper, MD a,e,3 a

Department of Dermatology University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH b Wayne State University School of Medicine, Detroit, MI c Department of Ophthalmology & Visual Sciences Case Western Reserve University School of Medicine; University Hospitals Eye Institute, University Hospitals Case Medical Center, Cleveland, OH d Department of Dermatology, Henry Ford Hospital, Detroit, MI e Louis Stokes VA Medical Center, Cleveland, OH

Abstract Phototherapy is an effective treatment option for a variety of dermatologic disorders, and the list of indications for its use continues to grow with advances in technology and our understanding of disease processes. Commonly used types of phototherapy include PUVA, broadband UVB, narrowband UVB, photodynamic therapy, and intense pulsed light therapy. Each therapeutic modality can have adverse acute and chronic effects on periocular and ocular structures, including the conjunctiva, cornea, crystalline lens, and retina. There are many types of protective eyewear options available, including goggles and contact lenses that can be used to prevent damage to ocular structures during phototherapy, particularly if eyelid closure is incomplete. © 2015 Elsevier Inc. All rights reserved.

Introduction Phototherapy has been an important part of the treatment of dermatologic diseases for more than 3500 years, when ancient Egyptian and Indian healers used the combination of ☆

Disclosures: Loretta Szczotka-Flynn: Alcon Laboratories: Research funding, Contact Lens and Solution Advisory Board, and speaking/writing honoraria. Johnson & Johnson Vision Care Inc. research funding. ⁎ Corresponding author. E-mail address: [email protected] (J. DePry). 1 Alcon laboratories research funding, Contact Lens and Scare Solution Advisory Board, and speaking/writing honoraria. Johnson & Johnson Vision Care Inc. research funding. Bausch & Lomb Advisory Panel. 2 Consultant for La Roche-Posay/L’Oreal, Ferndale, Pierre Favre, Uriage, Palatin. Investigator for Clinuvel and Estee Lauder. 3 Officer of Fluence Therapeutics, patent holder for Pc4 topical delivery for PDT, research grants from Estee Lauder and L’Oreal, Consultant for Anacor and GSK. http://dx.doi.org/10.1016/j.clindermatol.2014.10.017 0738-081X/© 2015 Elsevier Inc. All rights reserved.

sunlight (heliotherapy) and ingestion of plant extracts for this purpose.1 In 1903, Niels Finsen received the Nobel Prize for his use of phototherapy to treat cutaneous tuberculosis. Artificial light sources continued to be an important tool in dermatology, particularly with the development of Goeckerman therapy in the 1920s, which uses tar in combination with UVB to treat psoriasis.2 In the mid-1970s, psoralen and UVA were used as a treatment for psoriasis, a procedure commonly known as PUVA photochemotherapy.3 In the 1980s, Parrish and Jaenicke showed that monochromatic UVB therapy that eliminated wavelengths less than 296 nm was less erythemogenic and more effective than broadband sources.4 Narrowband UVB (NB-UVB) phototherapy was subsequently developed and shown to be an effective treatment for psoriasis and a variety of other dermatoses. In addition to the UV waveband, several other types of radiation are used to treat dermatologic diseases. Photodynamic

248 therapy combines the use of topical or systemic photosensitizers and light sources that emit the excitation wavelength of the photosensitizer; the most common clinically used photosensitizer is the porphyrin precursor alpha-aminolevulinic acid (ALA). Intense pulsed light treatment uses a broad spectrum of radiation to target a variety of chromophores in the skin. Although phototherapy is an effective therapeutic option for several dermatologic conditions, treatment can result in both acute and chronic damage to ocular and cutaneous structures. Providers must, therefore, regularly monitor patients for unintended side effects and adjust treatment as needed.

UVB phototherapy Broadband UVB radiation (280-320 nm), either alone or in combination with topical tar has been used to treat psoriasis for many years. In the 1980s, NB-UVB (311-312 nm) was found to be more effective than broadband UVB radiation, and it has now become the most widely used form of phototherapy.4 UVB phototherapy is used to prevent polymorphous light eruption and to treat a large range of dermatoses including moderate to severe psoriasis, severe atopic dermatitis, vitiligo, pruritus, parapsoriasis, cutaneous T-cell lymphomas such as mycosis fungoides, pityriasis lichenoides, lymphomatoid papulosis, seborrheic dermatitis, and HIV-associated pruritic eruptions. UVB radiation’s effect on the skin is principally via absorption by chromophores, including DNA and urocanic acid, in the epidermis and dermis. These chromophores stimulate signal transduction pathways and cause decreased keratinocyte proliferation, depletion of Langerhans cells, induction of skin macrophages, immunosuppression, and T-cell apoptosis. This results in therapeutic suppression of the inflammation and lymphoproliferation that occurs in cutaneous disorders. Short-term adverse effects of UVB phototherapy include erythema, xerosis, pruritus, blistering, and reactivation of herpes simplex. Long-term adverse effects include freckling, more advanced photoaging, and skin cancer. There is strong evidence that eyelid malignancies such as basal cell carcinoma and squamous cell carcinoma are associated with UV radiation.5 A 2012 literature review of the carcinogenic risks of NB-UVB shows that no increased risk of skin cancer was detected in four studies, although the lack of prospective studies on patients treated with NB-UVB makes it difficult to truly assess its carcinogenic risks.6 Ocular photodamage from UVB radiation is also an important concern. Toxicity from UVB radiation is mainly due to the induction of cyclobutane pyrimidine dimers (CPD).7 The anterior ocular structures provide a protective barrier from UVB-induced CPDs, and evidence of the association between ocular cancers, such as ocular melanoma and ocular surface squamous neoplasia, and UV radiation remain limited.5,8 Nonetheless, UV radiation can cause deleterious effects to the eye and ultimately affect vision by damaging the cornea, conjunctiva, lens, and retina, resulting in several types of ocular

J. DePry et al. toxicities (to be discussed in the following section). A recent study used manikin heads to quantitatively measure ocular exposure to solar UV radiation at different times throughout the day. This study showed that the time when the maximum UV irradiance occurred differed for direct versus ambient light.9 This illustrates the importance of ocular photoprotection at all times of the day, with both direct and peripheral light, and in every season.9 Due to the known side effects of UV radiation on the eyes, it is common practice that patients must wear UV-blocking goggles for ocular protection during phototherapy. In situations where periocular lesions need to be treated, such as vitiligo, patients need to be instructed to close their eyes for the entire duration of UV exposure. Protective contact lenses may be worn to further protect against ocular damage, particularly when eyelid closure is incomplete.10 Because NB-UVB is the most commonly used phototherapy, the effect of NB-UVB on the eye will be described in detail.

Ocular effects of narrowband UVB phototherapy Although only a negligible amount of UV radiation is transmitted through the eyelid, damage to the cornea, crystalline lens, conjunctiva, and retina can occur if these structures are exposed during phototherapy.11 Photodamage to the eye depends on wavelength, duration, intensity, and size of the radiation source as well as each structure’s absorption potential and ability for self-repair (Figure 1).12,13 The action spectrum for each structure of the eye represents the waveband of radiation that causes the greatest damage.13 The action spectra for the conjunctiva, cornea, crystalline lens, and retina have been determined by performing studies in humans, rabbits, and rhesus monkeys (see later).13–23 NBUVB bulbs have a peak irradiance between 311 nm and 312 nm and produce low levels of radiation in the remaining UVB waveband. These wavelengths are within the action spectra for the cornea, conjunctiva, crystalline lens, and retina are therefore able to induce ocular damage.13–15,21–23

Cornea The cornea is the transparent, dome-shaped window covering the front of the eye. It is a powerful refracting surface, providing two thirds of the eye's focusing power. The cornea absorbs the majority of UVB with only 3% to 8% of radiation being transmitted to deeper structures of the eye.24,25 The action spectrum for the corneal damage occurs between 210 nm and 320 nm with the 270 nm wavelength being the most effective wavelength. 13,15 Without eye protection, an 11.98 mJ/cm2 dose of radiation in the 250 nm and 320 nm waveband can begin to induce corneal damage during NB-UVB phototherapy.10 Although the action spectrum for the cornea includes wavelengths below 250 nm, this waveband is assumed to contribute very little to

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Fig. 1 UV absorption of ocular structures. (From Pitts DG. Prescription absorptive lenses. In: Benjamin WJ, ed. Borish's Clinical Refraction. Butterworth Hinemann; 2006:1177–1198; with permission.)

the total irradiance within an NB phototherapy unit and was therefore not used in the dose calculation.10 The cornea is only about 0.5 mL thick and is classically divided into five layers: epithelium, Bowman membrane, stroma, Descemet membrane, and endothelium. The epithelium is about 5 to 6 cell layers thick and quickly regenerates when the cornea is injured. The Bowman membrane lies just beneath the epithelium and is an acellular, nonregenerating layer between the epithelial basement membrane and the anterior corneal stroma. The stroma is the thickest layer just beneath Bowman, composed of tiny collagen fibrils and keratocytes. The Descemet membrane lies between the stroma and the endothelium. The endothelium is the posterior-most layer, is only one cell layer thick, and functions to pump water from the cornea, keeping it clear. The depth of the UVB-induced cell damage depends on the wavelength of UVB, with wavelengths less than 290 nm causing more damage to epithelial cells and superficial keratocytes and wavelengths between 290 nm and 315 nm (which include wavelengths emitted by NB-UVB bulbs) having more potential to cause stromal and endothelial cell damage13,26,27; that is, there is a wavelength and radiant exposure effect as the deeper corneal layers are more involved at longer wavelengths and higher exposure. In general, radiant exposure beyond 320 nm is not considered part of the action spectrum of the cornea because the levels of exposure required to induce damage are quite high, yet these wavelengths can still induce damage if the radiant energy was produced from a therapeutic instrument with high exposure levels. Threshold doses of UV exposure cause epithelial cell apoptosis and shedding as well as granule formation (breakdown of the primary lysosome membrane) in the columnar cell and wing cell layers of the epithelium.16,27,28 Higher doses can cause loss of cells down to the basement membrane zone, but as long as this structure remains intact, the epithelium can repair itself.16,29 UVB-induced damage to

the corneal endothelium, which lacks the ability to regenerate, may cause formation of guttae (fibrillar collagen formed by dystrophic endothelial cells), resulting in bulging of the Descemet membrane that lies between the endothelial and stromal layers of the cornea.16 The wavelength responsible for endothelial damage lies between 300 nm and 315 nm, which includes the radiance issued by NB-UVB bulbs.13 Higher dosages can also lead to swelling and opacities of the corneal stroma that cause light to scatter and clinically presents as visual blurring.13,16,22,29 Flare and cell in the aqueous of the eye’s anterior chamber (anterior uveitis) is also possible, which leads to symptoms of lacrimation and photophobia. Photokeratitis (welder’s flash) is caused by inflammation of the cornea and is the most common acute condition of the cornea after UVB exposure.30 Clinically, it presents as ocular pain, blurring of vision, erythema of the eye and surrounding skin, photophobia, lacrimation, foreign body sensation, and blepharospasm (abnormal, involuntary blinking or spasm of the eyelids).15,16,29,31 The loss of the epithelium and exposure of corneal nerve fiber endings cause significant ocular pain and photophobia.29 Photokeratitis generally develops from 30 minutes to 24 hours after UVB exposure, with the period of latency being inversely proportional to the intensity of exposure.15,29,31,32 Peak sensitivity generally occurs approximately 1¾ hours after exposure, and the acute symptoms generally disappear within 48 hours without any residual clinical signs.15,29,31 After desquamation, re-epithelialization generally occurs within 36 to 72 hours.16 Unlike the skin, the eye does not develop a tolerance to UV exposure.13 Chronic solar UVR exposure to the cornea is associated with climatic droplet keratopathy (accumulation of material in the superficial corneal stroma within the interpalpebral strip) and possible endothelial dystrophy (edema of the cornea caused by formation of guttae lesions between the corneal endothelium and Descemet membrane).29,31 Electromagnetic radiation incident from the temporal side of the face can be focused

250 through the dome of cornea and concentrated on the nasal and inferonasal crystalline lens, the nasal limbus, and the nasal bulbar conjunctiva next to the limbus. This has been called the Coroneo effect and is one factor in the development of nasal cortical cataracts, pterygia, and pinguecula discussed later.23

Conjunctiva Relatively few studies have examined UVR effects on the conjunctiva. In a study of the conjunctiva, 64 young adults’ conjunctiva were irradiated at 10 nm wavebands between 250 nm and 330 nm, and damage was measured by inflammatory changes, capillary injection, and chemosis or swelling of the conjunctiva.14 Their study found that the peak sensitivity of the conjunctiva occurred at the 270 nm to 280 nm waveband and wavelengths 330 nm and above failed to produce a clinical response.14 Acute UV-induced changes to the conjunctiva includes photoconjunctivitis, which presents as injected conjunctival blood vessels, edema, and epithelial cell damage.29 Injection occurs approximately 4 hours after exposure and peaks within 6 to 8 hours with the clinical signs of photoconjunctivitis resolving within 48 hours.14 Photoconjunctivitis is not painful and generally resolves in a similar timeframe as the cornea in photokeratitis.14,29 Direct solar exposure may cause a minimal conjunctival response in approximately 86 seconds for a Zenith angle of 60 degrees.14 Due to the geometry of solar radiation on the eye, most people who do not need to look into the sun do not develop acute ocular damage on a sunny day with the sun directly overhead.14,33 Within the NB-UVB phototherapy unit, damage to the conjunctiva may begin after a 22.63 mJ/cm2 dose of the 290 to 320 nm waveband.10 With solar UVR exposure, containing both UVA and UVB radiation, there is direct damage to the conjunctival cells as well as an immune response consistent with changes in pterygia (wedge-shaped growth of the scleral conjunctiva that involves the cornea) and possibly pingueculae (yellowish thickening of the conjunctiva on the sclera).5,13,14,34,35 Chronic solar UVR exposure to the conjunctiva is also associated with squamous cell carcinoma, particularly in the interpalpebral fissures, spheroidal degeneration (characteristic oil deposits at the limbus), and hyperkeratosis.14,29

J. DePry et al. absorbed by more anterior structures such as the cornea.13,37 NB-UVB damage to the unprotected crystalline lens during phototherapy can be induced after 9.71 J/cm2 exposure for the wavelengths between 295 nm and 320 nm.10 One of the most detrimental effects associated with lens exposure to UVR is cataract formation. The wavelength range for UV-induced cataractogenesis occurs between 295 nm and 320 nm with the 300 nm wavelength being the most effective at inducing cortical cataracts.13,37 As the radiant exposure approaches threshold, anterior subcapsular opacities begin to form and, as they become larger, they begin to create a network.13 Suprathreshold UV exposures can cause permanent lenticular opacities.13 Cataract formation is a multifactorial disease, with malnutrition, age, and light exposure being factors. Studies suggest that UV-induced damage is cumulative.36,38 UVB is known to be strongly associated with cortical cataract formation, but the association between UVR and nuclear sclerotic or posterior subcapsular cataracts is inconclusive.5 The photo-oxidation of the of the lens crystallins, lens membrane lipids, and damage to lens epithelial DNA are three major biochemical mechanisms that have been proposed to cause such cataracts.23

Retina Less than 1% of UVR is transmitted to the retina, but even small doses of radiation may cause retinal damage.37,39 At approximately 300 nm and beyond, UV radiation is no longer completely absorbed by the crystalline lens and cornea; therefore, the radiation can induce photochemical lesions in the retina.13,40 Children and young adults are more susceptible to UVB-induced retinal phototoxicity because crystalline lens protection is deficient.41 UVR transmission to the retina peaks at 320 nm.42 At 325 nm, the aphakic (absence of a crystalline lens) retinal threshold is only 5 J/cm2 (more sensitive than the cornea by a factor of 5) and the phakic (crystalline lens present) retinal threshold is 12 J/cm2 (more sensitive than the cornea by a factor of 2).13 For aphakic patients undergoing UV phototherapy treatment, UV ocular protection is of the upmost importance to protect the retina and screening the patients for their aphakic status should be considered standard procedure before initiating such treatment.

Pharmaceutical agents

Crystalline lens Unlike the cornea and conjunctiva, the crystalline lens has little ability to repair itself and therefore damage accumulates.36 The crystalline lens absorbs UVR from approximately 290 nm to 375 nm, although only 5% of the 300 nm waveband, the most effective wavelength at producing UV-induced cataracts, reaches the crystalline lens because most of this radiation is

A large number of pharmaceutical agents can increase ocular and cutaneous sensitivity to UV and visible radiation. Although photosensitivity may create a therapeutic benefit such as in the use of psoralen during UVA phototherapy, many other medications can cause unintended side effects. Medicationinduced photosensitivity can be classified as a phototoxic or photoallergic reaction, though it can be difficult to distinguish the type of reaction in some cases.43 Photosensitivity occurs when an agent decreases the capacity of the eye to react to sunlight

Phototherapy-related ophthalmologic disorders through the agent’s absorption of radiation, photochemical reaction, and production of reactive intermediates that affect ocular structures.13 Phototoxic reactions are defined by biologic reactions to agents with UVR exposure that occur in a very short time.13 Photoallergic reactions are delayed reactions and are produced by the formation of photoantigenic compounds.13 Many commonly used pharmaceutical agents may induce ocular photosensitivity, including antiarrhythmics, antibiotics, and diuretics.13,44 The list of pharmaceutical agents that may induce ocular photosensitivity is extensive and continues to grow; therefore, it is important to review a patient’s medications before treatment initiation, check for medication changes throughout the treatment course, monitor for photosensitivity, and provide sufficient ocular protection.

PUVA phototherapy PUVA photochemotherapy is the combination of psoralen (a phototoxic agent) and ultraviolet A radiation (UVA) (340-400 nm) that is used to treat a variety of dermatologic diseases. Psoralens are plant-derived or synthetic compounds that can be given topically or orally to produce a photochemical reaction that alters the function of cells and DNA. 8-Methoxypsoralen is the psoralen that is used in the United States. PUVA may have its effect through inhibiting cell proliferation, immunosuppression, and stimulating melanogenesis.45 Short-term adverse effects of PUVA include nausea, vomiting, headache, generalized photosensitization, erythema, pruritus, pain or burning sensation, pigmentation, and reactivation of herpes simplex. Long-term adverse effects include photoaging, a dose-related increase in skin cancer (especially nonmelanoma skin cancers), and possibly cataracts. These adverse effects dictate the need for photoprotection of the skin when going outdoors on days of psoralen ingestion as well as monitoring with annual skin examinations. UVA toxicity is particularly a concern for people who work outdoors or use sunscreens and stay in the sun for a long duration. Additionally, given the risk of adverse effects, age younger than 12 years is considered a relative contraindication for oral PUVA.46

Ocular effects of PUVA phototherapy There are multiple reported adverse effects of PUVA on the eye, especially when eye protection is not used. These include conjunctival hyperemia, decreased lacrimation, and possibly lens opacification.47 It has long been believed that PUVA increases the rate of developing cataracts by entering the lens and leading to formation of protein-psoralen photoproducts. Experimental studies with rodents have found that exposure of unprotected eyes to PUVA in rodents can accelerate the development of lens opacity.48 In contrast to these findings, a 2007 cohort study of 1237 individuals receiving PUVA for psoriasis, followed up for 25 years, found that increasing exposure to PUVA was not associated with a higher risk of cataracts.49 Another 10-year follow-up

251 study of 198 patients receiving PUVA for psoriasis showed there was no development of cataracts, lens opacities, or impairment of visual acuity in yearly ophthalmologic examinations.50 This may be a result of the strict eye protection recommendations in place, and, to be prudent, eye protection should be used during PUVA therapy.51

Photodynamic therapy Photodynamic therapy (PDT), which is used in many medical specialties, is used in dermatology to treat actinic keratosis, skin cancer, acne vulgaris, and photoaging. A topical photosensitizer such as ALA or methylaminolevulinate (MAL) is applied to a specific treatment area that is subsequently irradiated with a light source such as blue or red light–emitting diodes, visible light lasers, or intense pulsed lasers. The process results in cellular injury and death with clinical manifestations of phototoxicity including erythema, edema, vesiculation, and erosions. Most of the PDT sensitizers are planar porphyrin derivatives with centers and side chains that vary for solubility. The photosensitizer is preferentially absorbed by hyperproliferative tissue and therefore minimal damage to adjacent normal tissues occurs. Other common side effects of PDT include a burning sensation, pruritus, hyper- or hypopigmentation, allergic contact dermatitis to the photosensitizer, and elevated liver enzymes with systemic PDT. Photodynamic therapy is also used in ophthalmology with different photosensitizers to treat a variety of ocular diseases due to its selective vascular targeting.52 Verteporfin is a secondgeneration photosensitizing medication that can be used in ocular photodynamic therapy to treat age-related macular degeneration, presumed ocular histoplasmosis, pathologic myopia, and occult subfoveal choroidal neovascularization. It is a benzoporphyrin derivative of monoacid ring A that leads to apoptosis of HepG2 cells, which produces its photodynamic effect.53 The medication is given intravenously and light activated 15 minutes after the start of the infusion with a nonthermal diode laser (690 nm). Recent in vitro studies have shown that verteporfin PDT can destroy not only the vascular endothelial cells but also other targeted ocular cells.54 Common adverse effects of verteporfin that occur in more than 10% of patients include injection site reactions, blurred vision, flashes of light, decreased visual acuity, and visual defects. Less common adverse reactions include systemic reactions of most organ systems, including cardiovascular, central nervous system, gastrointestinal, and hematologic.

Intense pulsed light therapy Intense pulsed light therapy (IPL) used a filtered xenon flash lamp that emits brief pulses of polychromatic and broadspectrum radiation from 480 nm to 1200 nm. IPL is used for nonablative skin rejuvenation, treatment of vascular and pigmented lesions, and hair removal. There are many reports of ocular damage from inadvertent exposure of eyes to IPL, including chronic and severe eye pain, severe photophobia,

252 vision disturbances, anterior uveitis, and pupillary defects.55,56 In addition, multiple at-home IPL handheld devices are available, which, if not used properly, may pose a potential risk to users of ocular and cutaneous adverse effects.57

Tanning beds Indoor tanning devices are a common source of exposure to UV radiation, especially in older adolescent and young adult women and non-Hispanic whites.58,59 Access by minors to tanning beds is determined primarily at the state level, with certain states requiring parental permission, exposure time limitation, and eye protection.60 Several studies have reported incomplete compliance of recommendations and regulations by indoor tanning facility operators or consumers.61 Indoor tanning lamps before 1980 produced large amounts of UVC and UVB, but after 1985 they primarily emitted UVA radiation, with high-pressure lamps producing up to 10 times more UVA than sunlight.61 In the 1990s, lamps began to emit a larger proportion of UVB to better resemble sun exposure.62 Indoor tanning causes many adverse effects, including burns, photoaging (including sunbed lentigines), pruritus, xerosis, and nausea. Other less common side effects include pseudoporphyria, polymorphous light eruption, disseminated superficial actinic porokeratosis, and actinic granulomas. Phototoxic and photoallergic reactions are common, especially secondary to medications. Most importantly, indoor tanning has been proven to increase the risk of squamous cell carcinoma, basal cell carcinoma, and melanoma.59,63–66

Ocular effects of indoor tanning Although the eyes are normally somewhat protected from direct sun exposure by the eyebrows, tanning booths and beds provide a particularly direct and damaging source of UVA radiation to the eyes.67 Ocular injuries from indoor tanning including uveitis, photokeratitis, and cataracts, and corneal burns are very common. In addition, a review by the International Agency for Research on Cancer (IARC) and World Health Organization (WHO) suggests an association between UV-emitting tanning devices and ocular melanoma.61 One study in Australia reported that the use of sunlamps increases risk of choroidal and ciliary body melanoma, which was independent of sun exposure.68 Certain states require operators to provide eyewear, whereas others only require that users wear approved eye protection. Federal regulations state that it is the tanning operator’s responsibility to make sure that customers use compliant eyewear; however, this is difficult to enforce and therefore goggles may not always be used or may be used incorrectly.

Photoprotection of the eyes: Goggles Many types of goggles can be used to provide adequate ocular protection during UV phototherapy. Ideally, wrap-

J. DePry et al. around goggles should be used to prevent lateral incident radiation on ocular structures. A variety of materials can be incorporated into the lens as well as coat the lens of protective goggles to filter ultraviolet radiation. UV protective lenses are typically made of a polycarbonate polymer that can have excellent UV-blocking properties.39 Polycarbonate lenses are ideal because they can be easily coated with materials that make them scratch resistant and offer great UV protection.17 CR-39, a commonly used ophthalmic material, begins to have transmittance around 350 nm and shows maximum transmittance at 400 nm.17 UV transmission can be decreased in the UVA waveband, and the lens can provide great UVC, UVB, and UVA protection as more UV-absorbing monomer is added to the CR-39 polymer.37 Metallic oxides can be incorporated into lenses to filter optical radiation.17 Iron oxides can absorb approximately 95% of UV and infrared radiation.37 A metallic, vacuum-deposited coating such as silver, gold, and aluminum can be added to the lens to provide protection against infrared radiation.17 Aluminum coatings protect against UV, visible spectrum (VIS), and infrared (IR) radiation, whereas silver, gold, and copper transmit approximately 60% of UV radiation.17 It is important to note that the color of the lens does not determine its UV-protective abilities; however, color filters can be used to block harmful wavebands while allowing maintenance of VIS radiation transmittance.17,37 Whereas gray, brown, and green lenses limit color distortion, brown lenses absorb blue visible light, which is associated with macular degeneration.5,69

Photoprotection of the eyes: Contact lenses The use of UV-blocking goggles, the most common form of eye protection within phototherapy units, precludes periorbital UV treatment. The eyelid blocks the majority of radiation to the eye, as reported by Prystowsky’s study on seven patients, each receiving more than than 100 PUVA or broadband UVB phototherapy treatments.11 The PUVA group included one patient with lymphomatoid papulosis who received 106 treatments, one patient with cutaneous Tcell lymphoma who received 148 treatments, and three patients with vitiligo who received 160, 196, and 246 treatments. The broadband UVB group included two patients with psoriasis who received approximately 150 and more than 300 treatments. The patients experienced no UVinduced ocular changes after these treatments.11 This study found that only negligible quantities of UV radiation between 280 nm and 400 nm were transmitted through the eyelid after testing five excised eyelids.11 Prystowsky concluded that eyelid phototherapy is a safe and effective treatment in patients with eyelid photoresponsive dermatoses and recommends UV-blocking contact lenses for UVA and

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UVB phototherapy if patients are poorly compliant or eyelid closure is incomplete.11 Several studies have suggested that UV-blocking hydrophilic (soft) contact lenses could potentially be used during phototherapy because they could provide sufficient protection against UV-induced ocular damage.10,11,39 There are many commercially available hydrophilic and rigid gaspermeable contact lenses that offer UV protection. Hydrophilic lenses are typically 14 mm in diameter. They drape over the approximately 11 mm cornea and land on the conjunctiva, providing complete coverage of the cornea, entrance to the pupil, and perilimbal conjunctiva. Rigid gaspermeable lenses are also available with UV protection, but these lenses do not typically provide complete corneal coverage unless extremely large scleral lenses are used; therefore, hydrophilic contact lenses that completely cover the cornea offer better protection to the ocular structures than the smaller rigid gas-permeable contact lenses. Food and Drug Administration (FDA) class I contact lenses are those that block more than 90% of UVA and 99% of UVB and offer better UV protection than FDA class II contact lenses that block more than 70% of UVA and 95% of UVB (Table 1). UV-blocking lenses contain chromatophores that absorb UV radiation. The chromatophores, such as benzophenone monomers incorporated into some class II blockers or benzotriazole monomer used in class I blockers, are typically vinyl groups that are covalently attached to the lens polymer matrix.39 These materials absorb UV radiation and convert it to heat that is released from the anterior surface of the lens.19 There are several options of lens materials that confer variable UV-blocking properties, oxygen permeability, and frequency of disposal, depending on the patient needs. Class I silicone hydrogel lenses are made of a variety of materials, including senofilcon A, narafilcon A, and galyfilcon A. Some class II materials include etafilcon A, enfilcon A, and ocufilcon D. The radiation transmittance of contact lenses depends on the material of the lens as well as its thickness, with lower power lenses being more uniform in thickness than higher minus power lenses that have greater UVblocking properties in the periphery due to the increased lens thickness in the periphery.70 Several animal studies have found that UV-blocking contact lenses provide protection against UVB-induced ocular damage. The eyes of 12 rabbits were exposed to 1.667 J/cm2 (0.98 mW/cm2) broadband UVB daily for 5 days and showed that class I UV-absorbing silicone hydrogel polymer contact lenses, made of senofilcon A, significantly

Table 1

FDA classification of contact lenses

UVA blocked UVB blocked

Class 1

Class II

N 90% N 99%

N 70% N 95%

decreased corneal cell apoptosis and provided adequate protection of the cornea, aqueous humor, and crystalline lens against UV ocular damage in rabbits.12 Giblin’s study, which also used senofilcon A class I UV-blocking contact lenses in rabbits, supports these findings. In this study, rabbit eyes were either covered with UV blocking or non–UV-blocking lenses or the eyes were not covered with a contact lens.71 The corneas were exposed to 30 minutes of 1.7 mW/cm2 (3.06 J/cm2) UVB radiation at wavelengths between 270 nm and 360 nm with a peak irradiance of 310 nm.71 The eyes without protection showed corneal epithelial cell loss, epithelial cell swelling and haziness, vacuole formation, DNA damage, and anterior subcapsular opacification.71 The class I blocking contact lens provided nearly complete protection against UVB-induced cataract and damage to the corneal and crystalline lens epithelium.71 In a recent study, two class I and four class II UVblocking contact lenses were evaluated to determine if they could provide adequate ocular protection during NB-UVB phototherapy.10 Contact lens UVB transmittance within the NB-UVB phototherapy unit was measured and the theoretical safe exposure durations for the crystalline lens, cornea, and conjunctiva were determined using data from animal studies and the American Conference of Government Industrial Hygienists. The authors found that the UVblocking contact lenses had less than 1 × 10- 7 Watts/cm2 of radiation transmittance within the narrowband phototherapy unit, whereas an open aperture had an irradiance of 2.39 W/cm2.10 The safe exposure durations for the cornea and crystalline lens during NB-UVB phototherapy were greater than 1.46 J/cm2 with the UV-blocking lenses tested for the 250- to 320nm and 295- to 320-nm wavebands, respectively.10 The conjunctiva, which is not covered completely by the contact lens, had a safe exposure duration during NB-UVB phototherapy of approximately 22.63 mJ/cm2 for the 290- to 320-nm waveband with or without the lens present.10 The study indicated that some UV-blocking contact lenses could potentially provide sufficient ocular protection during NB-UVB phototherapy because the crystalline lens and cornea are adequately protected if patients were to open their eyes for a short time. The safe exposure duration for the retina is not known, and although UV blocking contact lenses could potentially provide sufficient protection of the crystalline lens and cornea, the conjunctiva is not fully covered by the contact lens. Few studies have examined the effects of UV radiation on the conjunctiva, and the radiation dose needed for chronic effects such as pterygium formation is not known. Fortunately, the conjunctiva can repair itself and patients are likely at low risk for chronic damage if they do not open their eyes for a long time. Routine ophthalmologic examinations are recommended given the lack of research in this area. Additionally, more data are needed to determine the safe exposure duration for the retina. According to Pitts, damage from UVB and UVA radiation in aphakes can be prevented with the use of UV-absorptive lenses.13 Many UV-protective contact lenses provide good protection for wavelengths between 280 nm and 320 nm and

254 therefore could potentially adequately protect the cornea and crystalline lens in broadband UVB phototherapy in addition to narrowband UVB phototherapy. UV-blocking contact lenses primarily protect against UVB and not UVA radiation because the contact lenses lose their protective capabilities with the UVA range. A study of several contact lenses showed that one contact lens made of phemfilcon A provided good protection against the full UVA spectrum, potentially conferring the ability to treat with PUVA therapy.39 The transmission spectra of the contact lenses were tested at 5-nm intervals between 290 nm and 400 nm.39 At 390 nm, one phemfilcon A lens had a protection factor of 22.7 at 390 nm and an overall UVA protection factor of 99.6.39 Protection factor is equal to 100 divided by the average percentage transmittance. These contact lenses could also possibly protect against posttreatment delayed ocular photosensitivity if worn after treatment, but further studies are needed in this area.

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