(See also Introduction to Corneal Disorders.)
Etiology
Corneal ulcers have many causes (see table Causes of Corneal Ulcers). Herpes simplex keratitis is discussed separately.
Bacterial ulcers are most commonly due to contact lens wear and are rarely due to secondary infection from traumatic abrasion or herpes simplex keratitis. The response to the treatment depends mostly on the bacterial species, and may be particularly refractory to treatment. The time course for ulcers varies. Ulcers caused by Acanthamoeba (also most commonly due to exposure to contaminated water while wearing contact lenses) and fungi (most commonly due to trauma with vegetable material) are indolent but progressive, whereas those caused by Pseudomonas aeruginosa (seen most frequently in contact lens wearers) develop rapidly, causing deep and extensive corneal necrosis. Wearing contact lenses while sleeping or wearing inadequately disinfected contact lenses can cause corneal ulcers (see Contact Lenses: Care and Complications).
Causes of Corneal Ulcers
Category |
Examples |
|
Nontraumatic corneal abnormalities |
Bullous keratopathy (ie, ruptured bullae) Mucous membrane pemphigoid (causes trichiasis and persistent corneal epithelial defects because of corneal epithelial stem cell failure) Herpes simplex keratitis, primary (viral) Herpes simplex keratitis, secondary (eg, bacterial or fungal superinfection) Dry eyes, primary Dry eyes, secondary (eg, neurotrophic keratitis) Trachoma (with secondary trichiasis) |
|
Corneal abrasion Penetrating corneal trauma Corneal foreign body (rare) Contact lenses (most commonly when worn during sleep and/or inadequately disinfected) |
|
|
Eyelid abnormalities |
Incomplete eye closure (eg, due to inadequate eye closure [lagophthalmos], peripheral facial nerve palsy, eyelid defects after trauma, or exophthalmos) |
|
Nutritional deficiencies |
Protein undernutrition |
Pathophysiology
Ulcers are characterized by corneal epithelial defects with underlying inflammation and necrosis of the corneal stroma. Corneal ulcers tend to heal with scar tissue, resulting in opacification of the cornea and decreased visual acuity. Uveitis, corneal perforation with iris prolapse, pus in the anterior chamber (hypopyon), panophthalmitis, and destruction of the eye may occur without treatment and, on occasion, even with the best available treatment, particularly if treatment is delayed. More severe symptoms and complications tend to occur with deeper ulcers.
Symptoms and Signs
Conjunctival redness, eye ache, foreign body sensation, photophobia, and lacrimation may be minimal initially.
A corneal ulcer begins as a corneal epithelial defect that stains with fluorescein and an underlying dull, grayish, circumscribed superficial opacity (representing an infiltrate). Subsequently, the ulcer suppurates and necroses to form an excavated ulcer. Considerable circumcorneal conjunctival hyperemia is usual. More severe ulcers may spread to involve the width of the cornea, may penetrate deeply, or both. Also, in these cases, a hypopyon (layered white blood cells [WBCs] in the anterior chamber) may occur. In long-standing cases, blood vessels may grow in from the limbus (corneal neovascularization).
Corneal ulcers due to Acanthamoeba are often intensely painful and may show transient corneal epithelial defects, multiple corneal stromal infiltrates, and, later, a large ring-shaped infiltrate. Fungal ulcers, which are more chronic than bacterial ulcers, are densely infiltrated and show occasional multiple discrete islands of infiltrate (satellite lesions) at the periphery. Dendritic ulcers are characteristic of herpes simplex keratitis.
Diagnosis
Diagnosis is made by slit-lamp examination; a corneal infiltrate with an overlying epithelial defect that stains with fluorescein is diagnostic. All but small ulcers should be cultured by scraping with a disposable #15 blade, sterile platinum spatula, or jeweler's forceps (typically by an ophthalmologist). Microscopic examination of scrapings can identify Acanthamoeba.
Treatment
Treatment for corneal ulcers, regardless of cause, begins with moxifloxacin 0.5% or gatifloxacin 0.3 to 0.5% for small ulcers and fortified (higher than stock concentration) antibiotic drops, such as tobramycin 15 mg/mL and cefazolin 50 mg/mL, for more significant ulcers, particularly those that are near the center of the cornea. Frequent dosing (eg, every 15 minutes for 4 doses, followed by every hour around the clock) is necessary initially. Patching is contraindicated because it creates a stagnant, warm environment that favors bacterial growth and prevents the administration of topical drugs.
Herpes simplex is treated with trifluridine 1% drops every 2 hours while the patient is awake to a total of 9 times/day, ganciclovir 0.15% gel 5 times/day, valacyclovir 1000 mg orally twice a day, or acyclovir 400 mg orally 3 to 5 times/day (or 3 times/day for recurrent herpes simplex keratitis) for about 14 days.
Fungal infections are treated with topical antifungal drops (eg, natamycin 5%, amphotericin B 0.15%, and sometimes voriconazole 1% [which is less effective]), initially every hour during the day and every 2 hours overnight. Deep infections may require addition of oral voriconazole 400 mg twice/day for 2 doses then 200 mg twice/day, ketoconazole 400 mg once/day, fluconazole 400 mg once then 200 mg once/day, or itraconazole 400 mg once then 200 mg once/day.
If Acanthamoeba is identified, therapy can include topical propamidine 0.1%, neomycin 0.175%, and polyhexamethylene biguanide 0.02% or chlorhexidine 0.02% supplemented with miconazole 1%, clotrimazole 1%, or oral ketoconazole 400 mg once/day or itraconazole 400 mg once then 200 mg once/day. The drops are used every 1 to 2 hours until clinical improvement is evident, then gradually reduced to 4 times/day and continued for a number of months until all inflammation has resolved. Polyhexamethylene biguanide and chlorhexidine are not commercially available as ocular agents but can be prepared by a compounding pharmacy. Oral miltefosine can be used for recalcitrant cases.
For all ulcers, treatment may also include a cycloplegic, such as atropine 1% or scopolamine 0.25% 1 drop 3 times/day, to decrease the ache of a corneal ulcer and to reduce the formation of posterior synechiae. In severe cases, debridement of the infected epithelium or even penetrating keratoplasty may be required. Patients who are poorly compliant or who have large, central, or refractory ulcers may need to be hospitalized. Very selective patients can be treated adjunctively with a corticosteroid drop (eg, prednisolone acetate 1% four times/day for 1 week then tapered over 2 to 3 weeks). The final appearance of the scar and final visual acuity are not improved with topical corticosteroids. Topical corticosteroids do decrease the pain and photophobia, and speed the increase in visual acuity, significantly. Because there is a very small risk of the ulcer worsening, adding topical corticosteroids is only indicated when a patient needs to get back to normal functioning (eg, work, driving) as soon as possible. Such treatment should only be prescribed by ophthalmologists and should be restricted to patients in whom clinical and microbiologic evidence indicates a favorable response to antimicrobial treatment and who can be closely followed.
Key Points
-
Causes of corneal ulcers include infection of the cornea (including overwearing of contact lenses), eye trauma, abnormalities of the eyelid, and nutritional deficiencies.
-
Ulcers may be accompanied by circumcorneal hyperemia and WBC layering in the anterior chamber (hypopyon).
-
All but the smallest ulcers are cultured, usually by an ophthalmologist.
-
Treatment usually involves frequent (eg, every 1 to 2 hours around the clock) application of topical antimicrobials.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
ketoconazole |
NIZORAL |
itraconazole |
SPORANOX |
clotrimazole |
MYCELEX |
gatifloxacin |
ZYMAR |
prednisolone |
ORAPRED, PRELONE |
trifluridine |
VIROPTIC |
valacyclovir |
VALTREX |
voriconazole |
VFEND |
moxifloxacin |
AVELOX |
fluconazole |
DIFLUCAN |
ganciclovir |
CYTOVENE |
scopolamine |
TRANSDERM SCOP |
tobramycin |
TOBI, TOBREX |
miconazole |
MONISTAT 3 |
cefazolin |
ANCEF, KEFZOL |
natamycin |
NATACYN |
acyclovir |
ZOVIRAX |
atropine |
ATROPEN |
neomycin |
NEO-FRADIN |
