Treating bacterial keratitis after corneal procedures

ByMarguerite B. McDonald, MD

Patients who have undergone penetrating keratoplasty or refractive surgery are permanently more susceptible to corneal infection and microbial invasion. In addition, if infection occurs, it progresses more rapidly than in a virgin eye. Ophthalmologists must instruct patients to have lifelong vigilance and seek immediate medical attention for suspicious symptoms, even years after surgery. Clinicians must assume that infectious etiology exists until proven otherwise and intensive therapy must begin immediately to protect the cornea and promote re-epithelialization and stromal repopulation.

Post-PK Infection

Bacterial keratitis infection rate after PK depends on the preoperative indication, and the differences are statistically significant. Patients with degenerative conditions, pediatric PK patients and patients with bullous keratopathy have the highest rate of infection after PK. Patients with a previous history of ulcerative keratitis, keratoconus and Fuchs dystrophy have the lowest rate of infection after PK. Gram-positive infections cause 83% of bacterial keratitis cases after PK.¹ The highest risk for post-PK infection occurs during the first postoperative year, but retained sutures can increase the risk for late-onset keratitis. Many 10-0 nylon sutures begin to dissolve between 2 years and 3 years postop. When these sutures break, they can migrate forward and cause complications.

“Treatment-related factors that have the potential to slow healing are direct cytotoxicity and impaired cell regeneration and migration.”
— Marguerite B. McDonald, MD, FACS

Bacterial keratitis as a complication of PK can impact graft survival as well. When a post-PK infection develops, there is an increased risk for graft failure and poor visual outcome. These patients have a less than 30% chance of achieving good or satisfactory visual acuity. Preop diagnosis also impacts graft survival. Patients who had keratoconus and preop scarring have an increased chance for graft survival, whereas patients with bullous keratopathy and previous failed graft who required PK or a repeat graft procedure have a decreased chance for graft survival.¹

When a patient presents with severe bacterial keratitis after PK, the predisposing factor must be identified, namely persistent corneal epithelium defects caused by compromised ocular defense mechanisms, ocular surface disease, and/or severely altered corneal topography caused by previous infectious keratitis. Unstable sutures can also be a predisposing factor. Integrity of the sutures must be examined for loose or broken parts, exposed knots, knots that have rotated under the epithelial surface and retained sutures that have slowly migrated to the corneal surface months or years after surgery.

If bacterial keratitis develops after a corneal procedure, then prompt, intensive topical antibiotic therapy is required to eradicate the pathogens, cure the infection, protect the cornea and promote re-epithelialization without provoking toxic side effects.¹ Treatment-related factors that have the potential to slow healing are direct cytotoxicity and impaired cell regeneration and migration. Cytotoxicity can be caused by antibiotics, particularly fortified aminoglycosides; preservatives; steroids; and nonsteroidal anti-inflammatory drugs. Fortified aminoglycosides have been responsible for some cases of unilateral severe blepharitis, scarring the orifices of the meibomian glands. Treatment can also cause pH alterations that slow healing. Fluoroquinolones, such as ciprofloxacin, can precipitate due to reduced solubility, and may cause a foreign body sensation and slower healing due to a “mass effect.”

Another treatment option is levofloxacin 1.5%. At a fortified concentration, levofloxacin 1.5% is safe.² The ocular events and nonocular adverse events were rare and not sight-threatening, which is typical of all fluoroquinolones. Levofloxacin 1.5% ophthalmic solution (Iquix, Vistakon Pharmaceuticals, LLC) is indicated for the treatment of corneal ulcers caused by the susceptible strains of the gram-positive bacteria including Corynebacterium species, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Viridans group streptococci and gram-negative bacteria, including Pseudomonas aeruginosa and Serratia marcescens.

Post-LASIK infection

“Infections that develop after LASIK have potentially devastating morbidity.”
— Marguerite B. McDonald, MD, FACS

Patients can develop bacterial keratitis after LASIK, but the true incidence is unknown. The incidence of bacterial keratitis is reduced with LASIK vs. surface ablation. During PRK, the epithelium in Bowman’s membrane is removed centrally; it regenerates in 3 to 5 days, during which time the cornea is susceptible to infection. A large series study by Steven C. Schallhorn, MD, and Optical Express (S.C. Schallhorn, MD, personal communication, December 2008) has shown that post-PRK infections, although rare, most likely occur at approximately five times the rate of post-LASIK infections. Lamellar flaps can create a permanent portal for microbial penetration into the eye. Infection progresses more rapidly in eyes that underwent LASIK than in virgin eyes. Any small break allows microbial penetration into the flap and along the interface where natural ocular surface defenses cannot attack the pathogen.^3,4

Infectious keratitis that develops after LASIK can be separated into two categories. The first is early onset, which occurs in the first 14 days and is caused by a gram-positive pathogen such as S aureus or S pneumoniae. The second category is delayed onset, an insidious infection that develops weeks, months or years after LASIK and is often caused by opportunistic pathogens such as atypical bacteria, fungus or P aeruginosa. Bacterial Keratitis

Infections that develop after LASIK have potentially devastating morbidity. Moderate and severe visual reductions occur in as many as 50% of patients, and therapeutic or corrective keratoplasty is necessary for 15% of patients. In addition, these patients have a predisposition to rapid perforation because the infection occurs near the corneal endothelium. Often, infective corneal infiltrate occurs in the absence of an epithelial defect. White blood cells appear at the interface, prompting the diagnosis of diffuse lamellar keratitis and treatment with steroids, which can worsen the infection and result in increased ocular morbidity.^4,5

If a patient has symptoms after LASIK, I suggest that any infiltrate be considered infectious until proven otherwise. Treatment begins immediately, but is modified when culture results become available approximately 24 to 48 hours later. Physicians must elevate the flap, culture it, and stain at least 10 slides to look for unusual pathogens. Patients must be treated with intensive dosing of topical antibiotics, a fluoroquinolone or fortified antibiotic that penetrates the interface, such as vancomycin 50 mg/mL. Fluoroquinolones have optimal subepithelial penetration. Flap removal may be necessary if the infection progresses despite intensive antibiotic therapy.^3,4

Physicians must educate patients on the dangers of bacterial keratitis and encourage them to seek medical attention for even the most minor symptom. After PK or refractive surgery, the cornea will forever be more susceptible to aggressive infections. Physicians must begin treatment promptly, using a broad-spectrum antibiotic that penetrates and persists at the infection site, particularly for sequestered infections at the lamellar interface. Treatment should eradicate microbes and cure the infection, protect the cornea, and minimize the delay in re-epithelialization and in stromal keratocyte repopulation.

Editor’s Note: Iquix solution is indicated for the treatment of corneal ulcer.

Marguerite B. McDonald, MD, FACS, is a clinical professor of ophthalmology at New York University in New York, an adjunct clinical professor of ophthalmology at Tulane University Health Sciences Center in New Orleans, Louisiana, and a surgeon at the Ophthalmic Consultants of Long Island in Lynbrook, New York. Dr. McDonald is also a Refractive Surgery Section member of the Ocular Surgery News Editorial Board. Dr. McDonald can be reached at 516-593-7709; e-mail: mmcdonald@ocli.net.

References:

Wagoner MD, Al-Swailem SA, Sutphin JE, Zimmerman MB. Bacterial keratitis after penetrating keratoplasty: incidence, microbiological profile, graft survival, and visual outcome. Ophthalmology. 2007;114:1073-1079.
McDonald MB. Research review and update: IQUIX (levofloxacin 1.5%). Int Ophthalmol Clin. 2006;46:47-60.
Karp CL, Tuli SS, Yoo SH, et al. Infectious keratitis after LASIK. Ophthalmology. 2003;110:503-510.
Vieira AC, Pereira T, de Freitas D. Late-onset infections after LASIK. J Refract Surg. 2008;24:411-413.
Chang MA, Jain S, Azar DT. Infections following laser in situ keratomileusis: an integration of the published literature. Surv Ophthalmol. 2004;49:269-280.