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Timing of post-LASIK infections helps determine treatment
Source: Ophthalmology Times
By: Lynda Charters
Originally published: October 1, 2005

The incidence of microbial keratitis after LASIK has been reported to range from one in 1,000 cases to one in 10,000 cases. There are no prospective studies in the literature that accurately document the true occurrence rates.

The infections can be acute or subacute, and being mindful of the time of the infection in relation to the procedure will help determine the treatment approach, said David Ritterband, MD, assistant director, cornea and refractive surgery service, New York Eye & Ear Infirmary, New York, and clinical associate professor of ophthalmology, New York Medical College, Valhalla, NY.

"I define an acute infection as that occurring within 1 day to 1 week after LASIK and subacute infection as that developing 4 to 6 weeks after LASIK. Infections after LASIK are unusual in that the presentations vary considerably. They may present as multiple foci or a single abscess. They may be located peripherally or centrally. The infiltrates may be confined to the flap, present solely as an intralamellar abscess, or cause flap keratolysis," he said.

Confounding factors may be responsible for the diverse presentations: steroid use, interface locations of the infections with inoculation within the cornea, anaerobic growth conditions inside the flap preferred by some microorganisms, and delayed referrals for infection.

Included in the differential diagnosis of microbial keratitis are sterile marginal keratitis, post-viral subepithelial infiltrates that reactivate after LASIK, epithelial ingrowth, post-PRK haze, diffuse lamellar keratitis, recurrent flap erosion, and recurrent corneal erosion.

Acute infections are caused predominantly by gram-positive species—specifically the coagulase-negative Staphylococcus, Streptococcus viridans, and Streptococcus pneumoniae—plus some gram-negative species, such as Pseudomonas. Subacute infections are predominantly caused by non-tuberculous mycobacteria, Nocardia, and various fungi, explained Dr. Ritterband.

A recent review of the clinical experience from the University of Pittsburgh and the New York Eye & Ear Infirmary, plus a literature search, demonstrated that approximately 45% of all cases of microbial keratitis are caused by atypical mycobacteria, 23% are caused by gram-positive microorganisms, and the rest of infections are caused by various pathogens.

"If one of these cases is suspected, call the laboratory to inform them of what you suspect. For example, if the case occurred 3 or 4 weeks after LASIK, the laboratory should expect to find atypical mycobacteria. The flap should be lifted and a culture specimen taken from the interface. A Gram or Giemsa stain should be done; if the case is subacute, an acid-fast stain should be done," Dr. Ritterband advised.

He and his colleagues use traditional culture media, 5% sheep blood agar, chocolate agar, Sabouraud dextrose agar, and thioglycollate broth. They also add atypical mycobacteria-specific media, i.e., Lwenstein-Jensen agar and Middlebrook 7H-9 liquid media. Atypical mycobacteria may also grow slowly on chocolate agar.

After performing the cultures in cases with acute presentations, Dr. Ritterband debulks the lamellar flap interface and irrigates the interface with antibiotics, beginning with fortified vancomycin (25 mg/ml) (Vancocin, Eli Lilly) and either moxifloxacin (Vigamox, Alcon Laboratories) or gatifloxacin (Zymar, Allergan). If the flap is necrotic or has a buttonhole, the flap is excised, which, he explained, allows better antibiotic penetration.

In subacute presentations, debulking of the interface infiltrates is also done. He then irrigates with a combination of antibiotics, first, with clarithromycin 1% solution (Biaxin, Abbott Laboratories) and then with either moxifloxacin or gatifloxacin.

Importantly, clarithromycin should be irrigated out with either of the two fourth-generation fluoroquinolones.

If that is not done, particles of clarithromycin, which dissolves poorly in solution, can remain under the flap for up 18 months or indefinitely, he pointed out.

"Until the culture results are known, we use a fourth-generation fluoroquinolone (gatifloxacin or moxifloxacin) and vancomycin (25 to 50 mg/ml) in the event that methicillin-resistant Staphylococcus are present. When we suspect non-tuberculous mycobacteria, we use clarithromycin (10 to 20 mg/ml) and a fourth-generation fluoroquinolone hourly. We, personally, do not use amikacin (Amikin, Bristol-Myers Squibb), which has previously been reported as the antibiotic of choice, for non-tuberculous mycobacteria. In severe cases, we add oral doxycycline (Vibra-Tabs, Pfizer)," Dr. Ritterband said.

When treating non-tuberculous mycobacteria, he cautioned, patients should be treated with antibiotics for a long term (6 weeks or longer). Patients treated early for suspected non-tuberculous mycobacteria usually have a better prognosis. Steroids are absolutely contraindicated in these patients. Flap removal may be necessary to cure the infection.

Raising the flaps daily for irrigation may be a good approach to attain large doses of antibiotics in the bed, but patient resistance to a daily invasive procedure may be a problem.

Penetrating keratoplasty is the treatment of last resort to remove deep infections refractory to antibiotic therapy.

"In summary, acute post-LASIK infections that present 1 to 7 days after the procedure should call to mind gram-positive microorganisms," he concluded. "Subacute infections that present weeks after the procedure are likely caused by non-tuberculous mycobacteria or fungus. The choice of antibiotic therapy is driven by surgeon suspicions regarding the probable organism."



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