Keratitis

Table I.

Type of Infection	Organism	Specific Comments
Bacterial	Neisseria gonorrhoeae, Neisseria meningitidis, Corynebacterium diphtheriae, Listeria monocytogenes, Shigella species, Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis, viridans streptococci, Streptococcus pyogenes, Enterococcus species, Peptostreptococcus, Corynebacterium diphtheriae, Bacillus cereus, Clostridium species, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Aeromonas hydrophila Pasteurella multocida, Acinetobacter species, Moraxella species	Neisseria sp. elaborate toxins and enzymes that permit penetration of the corneaStaphylococcus aureus is the most common cause of keratitisS. pneumoniae produces ulcers with sharp margins and an early hypopyonPseudomonas is the most destructive and produces a large hypopyon and green exudateMoraxella sp cause chronic ulcers in debilitated patients, including alcoholics
Viral	Herpes simplexVaricella zosterEpstein-Barr virusMeasles	Herpes simplex frequently leads to a recurrent red eye; dendritic lesions are seenVaricella zoster involves the ophthalmic branch of the 5th cranial nerve
Fungal	Aspergillus and other molds, Candida species	Mold infections usually result from eye injury by organic matter; risk is increased by chronic use of steroid eye drops; ulcers are elevated and an immune ring can be seenCandida is more indolent, and produces a marked hypopyon
Protozoal	Acanthamoeba species	Seen in patients who clean their contact lenses with tap water; lesion is painful and progresses slowly

1. Bacterial -Account for 65-90% of cases. Some bacteria elaborate toxins that penetrate the corneal epithelium; other bacteria require a break in the epithelium to invade the cornea. The most common pathogens are Gram-positive, and the one most frequently isolated is Staphylococcus aureus. Pseudomonas aeruginosa can be especially destructive; infection with this Gram-negative rod is commonly associated with the wearing of hard contact lenses. Pain is particularly severe and a large hypopyon can be seen. Perforation occurs quickly. There is often a greenish exudate, and the infiltrate appears soupy. Other Gram-negative organisms can also cause keratitis, including Neisseria.

2. Viral – Recurrent keratitis is most often caused by herpes simplex virus; latent virus in the 5th cranial nerve reactivates and migrates down the nerve to the corneal surface. Reactivation can be caused by UV light exposure, menstruation, fever and other acute stresses. In the hospitalized patient with a unilateral red eye, always suspect herpes simplex keratitis. Corneal anesthesia may be present initially, minimizing pain; however, a foreign body sensation and erythema with tearing are frequently present. Slit-lamp exam reveals a classic dendritic lesion that stains with fluorescein dye. Other forms of viral keratitis are less common

3. Fungal – Corneal ulcers caused by molds, such as Aspergillus usually follow an eye injury from organic material (e.g. a tree branch). Use of chronic glucocorticoid eye drops increases the risk of fungal keratitis. Ulcers tend to be superficial and often are elevated above the corneal surface. The infiltrate is usually irregular and an immune ring is often apparent. The main infiltrate may be surrounded by smaller satellite lesions. A severe anterior chamber reaction is often associated with a hypopyon. Yeast-like fungi (e.g. Candida) can also cause corneal ulcers. These infections tend to be more indolent, but otherwise can fully mimic the ulcers formed by molds.

4. Protozoal – These infections are rare but serious. Acanthamoeba sp. develop most commonly in contact lens wearers, particularly if they use unsterilized tap water in their cleaning solutions. These ulcers are painful, progress slowly, and of course fail to respond to local antibiotics.

Beware: there are other diseases that can mimic keratitis

Because a corneal ulcer can present with a unilateral, painful red eye, other considerations include conjunctivitis, episcleritis, scleritis, subconjunctival hemorrhage, uveitis, blepharitis and acute angle closure glaucoma.

What laboratory studies should you order and what should you expect to find?

If a bacterial or fungal cause is suspected, send corneal scrapings for culture, Gram stain, Giemsa stain and methenamine silver stain. These are obtained by gently scraping a surgical blade across the surface of the ulcer and inoculating the resulting samples onto solid media. Anerobic bacteria grow readily on standard media within 48 hours. Special processing is required if Acanthamoeba, a fungus, Mycobacteria or Chlamydia are suspected. Viral keratitis can usually be diagnosed by appearance and generally does not require culturing.

What imaging studies will be helpful in making or excluding the diagnosis of keratitis?

No imaging studies are required.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has keratitis, what therapies should you initiate immediately?

When keratitis is suspected, urgent ophthalmalogic consultation is indicated, because treatment must be instituted emergently. A careful slit exam should be done immediately. Because of the potential risk of perforation and visual loss, patients with bacterial keratitis and significant ulceration are often hospitalized for close observation.

Initial therapy can be based on the Gram stain in approximately 75% of patients. If the initial stain is not definitive, broad antibiotic coverage is warranted. Antibiotics are commonly given topically and, in some instances, subconjunctivally. Patients with imminent perforation should also receive systemic antibiotics.

Topical regimens:

1. Streptococcus pneumoniae: bacitracin 5000U/mL and gentamicin (13mg/mL)

2. Staphylococcus aureus and other gram positive cocci: cephalothin (50mg/mL) plus bacitracin

3. Pseudomonas sp: tobramycin (13.6 to 15mg/mL) or gentamicin

4. Other gram negative species: gentamicin

5. Yeasts: amphotericin B (1.5 to 3mg/mL) plus flucytosine (1%)

6. Molds: natamycin (5%)

7. Acanthamoeba sp: neomycin (5-8mg/mL) plus pentamidine isethionate (0.15%)

Note: For bacterial keratitis, topical fluoroquinolones are also effective and have been used as empiric therapy for non-sight-threatening disease. Moxifloxacin 0.5% is effective and the least toxic; it is often combined with topical cephalothin.

Eye drops are administered every half hour during the day and hourly during sleep for 7-10 days. Subconjunctival injections should be repeated every 12-24 hours for a total of 3-6 doses.

Herpes simplex: topical ganciclovir (Zirgan) 0.15% gel is the treatment of choice; it is given 5 times daily until the corneal epithelium heals and then 3 times a day for 1 week. The previous preferred therapy, trifluorothymidine 1% (Viroptic) causes significant epithelial cell toxicity and requires administration 8-9 times per day. Oral acyclovir 400mg orally 5 x per day is nearly as effective as topical therapy. Because of the high risk of recurrence, many clinicians maintain their patients on oral acyclovir 400mg twice daily for several months or even years after the acute event.

What's the evidence

Clarke, B, Sinha, A, Parmar, DN, Sykakis, E. “Advances in the diagnosis and treatment of acanthamoeba keratitis”. J Ophthalmol. 2012. pp. 484892

Hanet, MS, Jamart, J, Chaves, AP. “Fluoroquinolones or fortified antibiotics for treating bacterial keratitis: systematic review and meta-analysis of comparative studies”. Can J Ophthalmol. vol. 47. Dec 2012. pp. 493-499.

Leibowitz, HM. “The red eye”. The New England journal of medicine. vol. 343. Aug 3 2000. pp. 345-351.

Lichtinger, A, Yeung, SN, Kim, P. “Shifting trends in bacterial keratitis in Toronto: an 11-year review”. Ophthalmology. vol. 119. Sep 2012. pp. 1785-1790.

Wong, RL, Gangwani, RA, Yu, LW, Lai, JS. “New treatments for bacterial keratitis”. J Ophthalmol. 2012. pp. 831502

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