Laser in situ keratomileusis (LASIK) is the most common refractive surgery procedure performed for the correction of myopia and astigmatism in the United States. Infection after LASIK surgery is uncommon, with a reported incidence of 1 in 2919 cases.1 Atypical mycobacteria are the leading cause of infection after LASIK, followed by Gram-positive organisms, including methicillin resistant Staphylococcus aureus, and other uncommon pathogens such as Nocardia, fungal, and acanthamoeba species. We describe what appears to be the first case of microbial lamellar keratitis caused by Bacillus megaterium following LASIK.
A previously healthy 23-year-old man underwent evaluation and treatment of myopia at the Yale Eye Center, New Haven, Connecticut. The patient had no medical or ophthalmic history of note, except for myopia corrected by spectacles and contact lenses. He had not worn his daily- wear soft disposable contact lenses for 2 weeks prior to preoperative examination and subsequent procedure. A complete examination was performed. Manifest refraction revealed -3.50 -0.50 × 050 in the right eye and -4.00 -0.50 × 160 in the left eye. After reviewing surgical and non-surgical options for the correction of myopia, the patient provided informed consent for myopic LASIK.
Per our routine for all LASIK surgery, the patient was prescribed lid hygiene using lid scrubs (Ocusoft, Richmond, Tex) at bedtime for 3 days before surgery, and ciprofloxacin 0.3% ophthalmic eye drops (Ciloxan; Alcon, Ft Worth, Tex) to be used four times per day, for 3 days prior to the LASIK surgery. At surgery, 5% povidone iodine was used to cleanse the lid margin and periorbital region. The lid margin was isolated from the surgical field by Tegaderm drape (3M, St Paul, Minn) after an operculated drape was used to cover the patient's face. An aspirating wire speculum was used to expose the operative field. The patient then underwent uneventful simultaneous sequential myopic LASIK using the SKBM microkeratome (Alcon) as well as the LADARVision4000 (Alcon) excimer laser. A new blade and sterile microkeratome head were used for each eye. The patient was instructed to continue topical antibiotic four times daily and to begin prednisolone acetate 1% (Econopred R, Alcon) every 6 hours.
On postoperative day 1, uncorrected visual acuity (UCVA) was 20/15 in both eyes. The patient complained of mild dryness and preservative free artificial tears (Bion Tears, Alcon) were added. On day 7, UCVA was 20/15 in the right eye and 20/15-2 in the left eye. Both eyes appeared quiet and comfortable. The corneas revealed no folds, striae, or interface debris. Topical ciprofloxacin, prednisolone acetate, and artificial tears were discontinued for both eyes. Follow-up was scheduled for 1 month. However, 2 weeks later the patient complained of blurred vision in the right eye with a foreign-body and burning sensation. Uncorrected visual acuity was 20/40+1 in the right eye and 20/15 + 2 in the left eye. Clinical examination was unremarkable, without evidence of infection, inflammation, or corneal staining defect. The patient was restarted on preservative-free artificial tears every hour. The next day the patient returned with photophobia, tearing, and blurred vision, without relief from artificial tears in the right eye. Slit-lamp examination of the right eye showed ciliary injection and an area of paracentral interface haze measuring approximately 0.2 mm in diameter with indistinct borders. Delayed onset microbial lamellar keratitis was suspected.
The patient underwent a flap lift with culture of the right eye. Both Gram stain and acid-fast staining revealed no cells or bacterial organisms. The patient was started on topical ciprofloxacin 0.3%, amikacin 50 mg/mL, and azithromycin 2 mg/mL every hour for the right eye and oral clarithromycin 500 mg every 12 hours. Two days later a Bacillus species was isolated from bacterial cultures and was sensitive to all antibiotics tested, including ciprofloxacin, aminoglycosides, and vancomycin. Further chromatographic analysis and characterization of the organism's cellular fatty acid profile at the State of Connecticut Public Health Laboratory Services identified the organism as Bacillus megaterium.
Within 24 hours symptomatic relief occurred and in 2 weeks, with daily follow-up, the patient's UCVA recovered to 20/15 in the right eye. One year after surgery, UCVA was stable at 20/15 in the right eye; a faint peripheral non-visually significant scar remained in the stromal bed in the affected eye.
Microbial keratitis is an uncommon complication following LASIK. The incidence of infection after LASIK is estimated to be 1 in 2919 cases,1 as reported by the Cornea Clinical Committee of the American Society of Cataract and Refractive Surgery. The nature of the LASIK flap, which preserves Bowman's layer and the integrity of the corneal epithelium, maybe, in part, responsible for the lower incidence of infection compared to photorefractive keratectomy for which the incidence is 1 in 1000 procedures.2 Keratitis caused by Bacillus species accounts for 1.4% to 2% of all bacterial keratitis.3,4 Possible risk factors associated with keratitis caused by these organisms include trauma, lagophthalmos, topical corticosteroid therapy, bullous keratopathy, previous corneal scars, and diabetes.3 Bacillus cereus is the most common cause of keratitis caused by this group of organisms, which is usually associated with post-traumatic endophthalmitis5 especially in the presence of intraocular metallic foreign bodies. Other clinical ocular infections caused by Bacillus species include conjunctivitis, keratitis, corneal ulcers, iridocyclitis, dacryocystitis, and orbital abscess.6
An extensive literature review revealed a single reported infection by Bacillus megaterium following cataract surgery7 and an isolated conjunctival culture obtained from a patient 40 years ago.0
Bacillus is a large genus containing over 70 species of organisms. The defining feature of this genus is the production of endospores in the presence of oxygen. The survivability of Bacillus species lies on their ability to produce endospores, which are protected by thick cell walls. Most are saprophytic organisms that are widely distributed in the environment. B cereus and B anthracis are the most familiar human pathogens to most physicians. Spores can remain viable after long periods of time; they are 100,000 times more resistant to heat and 7 to 50 times more resistant to ultraviolet irradiation than vegetatively growing cells. Active sporicidal agents, including chlorine, iodine, and hydrogen peroxide, are required in greater concentrations with longer contact times to kill spores as opposed to vegetative cells.9 Although eye infections can occur in healthy persons, they are most often seen in immunocompromised patients such as those with hematologic malignancies, parenteral drug users, patients with severe trauma, or those with human immunodeficiency virus infection.10 The time for presentation of Bacillus keratitis symptoms ranges from 1 day to 3 months following inoculation. In our case, the infection presented on postoperative day 13 and the organism isolated was sensitive to all antibiotics tested, including ciprofloxacin. Bacillus species are usually sensitive to aminoglycosides and fluoroquinolones.3
Despite the use of a strict aseptic surgical technique with topical fluoroquinolone antibiotic prophylaxis, the patient developed delayed onset microbial keratitis in his right eye. Endospore formation was unlikely to be the source of the patient's clinical infection as this patient was a healthy immunocompetent male with no history of ocular trauma. In addition, he had not worn his soft contact lenses for over 2 weeks before surgery.
The use of topical postoperative corticosteroids may have contributed to the development of a localized immunosuppressive state, causing inhibition of neutrophil migration in response to chemotactic factors released during microbial infection.
In this case, the use of topical ciprofloxacin, amikacin, and azithromycin and systemic oral clarithromycin was justified as initial therapy to provide additional coverage against atypical mycobacteria and organisms such as Nocardia species. Due to the patient's fast symptomatic relief and complete visual recovery within 2 weeks, we advocate the use of systemic antibiotics in cases of delayed onset microbial keratitis to maximize microbiologic coverage.
Laser in situ keratomileusis must be considered an ophthalmic surgical procedure, which should follow strict principles of sterile operative technique. When choosing prophylactic antibiotics, penetration into the lamellar bed through an intact corneal epithelium and adequate coverage of both atypical mycobacteria and Gram-positive organisms must be considered. Written instructions must be given to patients about avoiding eye make-up before LASIK and suspending contact lens wear for at least 48 to 72 hours before surgery.
Furthermore, it is important to differentiate postoperative lamellar infections from cases of diffuse lamellar keratitis as well as epithelial ingrowth, both of which are well-described complications that may occur after routine LASIK. The lamellar bed must be broadly cultured in all cases in which the diagnosis of microbial keratitis is entertained after LASIK, and aggressive empiric antibiotic therapy must be immediately initiated with consideration of the potentially infecting agents.
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