Kelly D. Schweitzer
Stephanie Baxter

BASICS

DESCRIPTION

• The cornea absorbs the majority of ultraviolet (UV) (10–8 m) and X-ray (10–10 m) energy in the radiation spectrum.

• Acute or chronic damage may occur to all corneal layers (epithelium, stroma, endothelium) in a cumulative fashion secondary to photochemical reactions, heat, structural changes, or metabolic disturbance.

• It is often the earliest cause of vision loss post-periocular radiation therapy.

EPIDEMIOLOGY

Incidence

• Photokeratitis secondary to UV radiation is uncommon.

• Radiation keratopathy secondary to X-ray radiation is rare.

Prevalence

Unknown

RISK FACTORS

• Sun exposure, especially at high altitudes, without protective eyewear

• Occupational exposure (e.g., welder)

• Ocular, CNS, head and neck neoplasm treated with radiation therapy >60 Gy

• Preexisting ocular surface disease or a denervated cornea

Genetics

No specific genetic association

GENERAL PREVENTION

• Protective eyewear and limited UV exposure time

• Ocular considerations in the radiation treatment plan including ocular and lacrimal gland shielding are critical in the prevention of radiation keratopathy.

PATHOPHYSIOLOGY

• Radiation generates highly reactive free radicals which inhibit mitosis, damage cellular DNA, and render the cell incapable of repair and replication leading to cell death.

• Free radicals are produced directly by electrons from the radiation source or indirectly by electrons from the irradiated tissues.

ETIOLOGY

• Photokeratitis secondary to UV radiation (e.g., solar exposure or reflection, welder’s or carbon arcs, tanning beds, lightning sparks)

• Brachytherapy: Direct irradiation secondary to radiation therapy of intraocular tumors

• Indirect irradiation within the field of external beam radiation (X-ray teletherapy) for paranasal sinus tumors, eyelid lesions, or CNS neoplasms

• The above may result in direct injury to the cornea or indirect injury due to tear film abnormalities secondary to lacrimal and meibomian gland dysfunction, or conjunctival goblet cell loss.

COMMONLY ASSOCIATED CONDITIONS

• Pinguecula, pterygium

• Spheroidal degeneration

• Hyperkeratosis

• Endothelial dystrophy

• Squamous metaplasia, carcinoma

• Epidermoid carcinoma of the bulbar conjunctiva associated with UV radiation

DIAGNOSIS

HISTORY

• Eliciting an accurate history on timing, type, and duration of radiation exposure and on ocular protection is key.

• Ocular pain and irritation, redness, foreign-body sensation, photophobia, and tearing

• May be associated with decreased visual acuity

• Symptoms develop ∼6–12 h after UV exposure or hours-to-years after radiation therapy exposure.

PHYSICAL EXAM

• Diffuse epithelial erosions

• Frank epithelial defects

• Filamentary keratitis secondary to epithelial toxicity

• Stromal edema from loss of epithelium or from endothelial dysfunction

• Stromal ulceration from direct toxicity to keratocytes (more frequent at high radiation does >60 Gy over 6 weeks)

• Endothelial granules and keratic precipitates

• Anterior chamber flare and cell

• Corneal opacification, neovascularization, keratinization, thinning or perforation in advanced cases

DIAGNOSTIC TESTS & INTERPRETATION

Imaging

Accurate clinical drawings combined with anterior segment photographs to assess for progression of disease and response to treatment

Diagnostic Procedures/Other

• Pachymetry could be considered to monitor corneal thickness in both edematous and thinned corneas.

• If infectious corneal ulceration is suspected, corneal scraping for culture and sensitivity may be required.

Pathological Findings

• Involutional atrophy of meibomian and lacrimal glands post periocular radiation treatment

• Conjunctival goblet cell loss and squamous metaplasia

DIFFERENTIAL DIAGNOSIS

• Trauma

• Exposure keratopathy

• Dry eye syndrome

• Topical drug toxicity

TREATMENT

MEDICATION

First Line

• Aggressive lubrication (q1–2h) with preservative-free tears and ointment recognizing that the irradiated cornea has a poor capacity to heal

• Topical antibiotic drops (t.i.d.–q.i.d.) combined with ointment at bedtime

• Cycloplegia

• Bandage contact lens or pressure patch in patients with significant loss of epithelium

• Prompt diagnostic and therapeutic measures for infected corneal ulcers

• Eye protection for the affected and unaffected eye

Second Line

Oral analgesics

ADDITIONAL TREATMENT

Issues for Referral

• Nonhealing epithelial defects

• Infected corneal ulcers

• Advanced corneal scarring

• Corneal thinning or perforation

SURGERY/OTHER PROCEDURES

• If risk of perforation or severe corneal changes occur due to tear film abnormalities, conjunctival flaps or amniotic membrane grafting may be considered.

• Limbal stem cell transplantation may be considered with persistent evidence of limbal stem cell deficiency.

IN-PATIENT CONSIDERATIONS

Admission Criteria

• If the patient is unable to meet the significant demands of ocular lubrication due to physical or cognitive deficits, admission is required.

• Severe corneal ulceration may require admission.

Nursing

Hospital care staff must be informed of the importance regarding intensive ocular lubrication treatment regimens.

Discharge Criteria

An established care system that is capable of meeting the treatment plan demands

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

After acute stabilization, regularly scheduled follow-ups post-treatment are necessary to diagnose late ocular surface changes if history of large doses of radiation.

PATIENT EDUCATION

• Emphasis on preventative strategies to avoid re-injury

• Commitment to lifetime maintenance treatment for radiation therapy-induced keratopathy

• Emphasis on eye protection with unilateral loss of vision to protect a well-seeing eye

PROGNOSIS

• It depends on the type and extent of radiation injury and use of ocular and lacrimal gland shielding.

• UV injury prognosis is generally excellent.

COMPLICATIONS

• Limbal ischemia and limbal stem cell deficiency

• Nonhealing epithelial defect or ulceration

• Secondary infectious keratitis

• Panophthalmitis

• Corneal vascularization, opacification, perforation, lipid infiltration

• Neurotrophic and exposure keratopathy from cranial nerve 5 and 7 dysfunction

ADDITIONAL READING

• Barabino S, et al. Radiotherapy-induced ocular surface disease. Cornea 2005;24(8):909–914.

• Cullen A. Photokeratitis and other phototoxic effects on the cornea and conjunctiva. Int J Toxicol 2001;21:455–464.

• Kwok SK, et al. An analysis of the incidence and risk factors of developing severe keratopathy in eyes after megavoltage external beam irradiation. Ophthalmology 1998;105:2051–2055.

CODES

ICD9

• 940.4 Other burn of cornea and conjunctival sac

• 990 Effects of radiation, unspecified

CLINICAL PEARLS

• Proper documentation of whether the protective eyewear was worn at the time of injury is necessary for legal and workmen’s compensation cases.

• Progression of corneal injury can be extensive so close follow-up (24–48 h) is warranted early until full extent of injury is ascertained.

• Commitment to ophthalmologic follow-up and maintenance treatment can prevent or minimize many long-term radiation problems.

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