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Case Reports and Small Case Series
October 1999

Infectious Ulcerative Keratitis After Laser In Situ Keratomileusis

Arch Ophthalmol. 1999;117(10):1423-1427. doi:

With any laser refractive surgical procedure in which the epithelial barrier is broken, there is an inherent risk of infectious complication. As laser in situ keratomileusis (LASIK) becomes more widely available, cases of LASIK-associated infectious keratitis have begun to be reported.16 We report 6 eyes of 5 patients that developed ulcerative keratitis after LASIK.

Report of Cases.
Case 1

A 33-year-old woman noted a foreign body sensation in the right eye 4 days after bilateral LASIK. She was found to have a corneal infiltrate. She was given subconjunctival injections of vancomycin hydrochloride, cefazolin sodium, and betamethasone sodium phosphate and started on therapy with ciprofloxacin hydrochloride eye drops every 20 minutes. After 3 weeks of minimal improvement with various combinations of topical ciprofloxacin and prednisolone acetate, the patient was referred to the Doheny Eye Institute, Los Angeles, Calif. On her initial visit to us, visual acuity was 20/200 OD and 20/20 OS. A 1.5×2-mm epithelial defect with surrounding infiltrate was present at the 7-o'clock position within the flap edge, extending to approximately 30% of the stromal thickness in the right eye. Both corneas showed moderate punctate staining. Corneal scrapings for culture and sensitivity were obtained. All eye drops were stopped, and the patient was prescribed topical fortified cefazolin sodium (50 mg/mL) and tobramycin sulfate (14 mg/mL), alternating every hour while awake. Within 2 days reepithelialization had begun, and medications were tapered to every 2 hours. One week later the patient had no epithelial defect, but there was still an organizing infiltrate. The next week the infiltrate was nearly resolved, and the eye drops were tapered off over the ensuing 3 weeks. After 3 weeks the infiltrate had resolved. The patient was left with a paraxial, 2-mm-round, anterior stromal scar within the flap edge (Figure 1). No organism was recovered. Final uncorrected visual acuity was 20/40 OD.

Figure 1.
Slitlamp photograph showing a paraxial 2-mm-round, anterior stromal scar within the flap edge, with striae extending radially. Visual acuity 20/40.

Slitlamp photograph showing a paraxial 2-mm-round, anterior stromal scar within the flap edge, with striae extending radially. Visual acuity 20/40.

Case 2.

One year after bilateral LASIK, a 31-year-old male physician complained of acute tearing and photophobia of the left eye, in which he had been using a soft contact lens. He was found to have an infiltrate at the flap edge. He was started on a regimen of topical ofloxacin every hour, diclofenac 4 times daily, and 1% atropine daily, and was referred to us the next day. On his initial visit, visual acuity was 20/20 OD and 20/40 OS. A curvilinear epithelial defect with surrounding stromal infiltrate was noted, extending from the 5- to 7-o'clock position at the LASIK flap edge. Cultures were obtained, and the patient was started on a regimen of topical fortified vancomycin hydrochloride (25 mg/mL), alternating hourly with ofloxacin. A cephalosporin was not used because of a history of penicillin allergy. Two days later the epithelial defect had widened to just beyond the flap margin and the stromal infiltrate had begun to organize (Figure 2). Cultures revealed the infectious organism to be Staphylococcus aureus. One week later the epithelial defect had healed and the infiltrate was organizing. The drops were tapered to every 3 hours. Over the next week the patient showed continued improvement of the infiltrate, with consolidation into a small stromal scar at the inferior flap margin. Antibiotics were slowly tapered over the next week. Uncorrected visual acuity returned to 20/30 OS.

Figure 2.
Slitlamp photograph showing an epithelial defect at the flap margin with organizing stromal infiltrate. Visual acuity 20/30.

Slitlamp photograph showing an epithelial defect at the flap margin with organizing stromal infiltrate. Visual acuity 20/30.

Case 3.

A 46-year-old woman complained of a foreign body sensation in her right eye 6 days after bilateral LASIK. She was found to have a small infiltrate at the flap edge. The patient had been wearing a soft contact lens in her right eye and was using topical prednisolone acetate in both eyes twice daily. She was prescribed ciprofloxacin eye drops every 30 minutes and referred to us the next day. On her initial visit, best-corrected visual acuity was 20/80 OD and 20/50 OS, with an 80% epithelial defect of the flap and a small infiltrate at the 7-o'clock position on the flap edge in the right eye, as well as marked punctate keratopathy in the left eye. The time at onset of the epithelial defect is unclear. Cultures were obtained, and the patient was prescribed topical ciprofloxacin every hour in the right eye and lubrication with artificial tears in both eyes. Drops were tapered over the next 2 weeks. At 2 weeks the epithelial defect had resolved in the right eye, and punctate keratopathy had improved in both eyes. A pinpoint scar remained at the 7-o'clock position at the LASIK flap edge. Final uncorrected visual acuity was 20/40 OD. No organism was recovered.

Case 4.

A 50-year-old man developed bilateral eye pain and photophobia 1 day after bilateral LASIK. The patient had also undergone radial keratotomy in the left eye 16 years previously. He had been seropositive for the human immunodeficiency virus (HIV) for 10 years but had no major sequelae of the viral infection. He was taking various antiretroviral medications, including protease inhibitors; his CD4 cell count was 0.3×109/L, and his viral load was undetectable. Because bilateral bacterial keratitis was suspected, both flaps were lifted, cultures were obtained, and the stromal beds were irrigated. The patient was hospitalized and given topical fortified cefazolin sodium (25 mg/mL), alternating with gentamycin sulfate (14 mg/mL), every 30 minutes. Two days after hospitalization, cultures returned positive for ciprofloxacin-resistant S aureus. Gentamycin was discontinued at this time. Four days later the patient's condition was improved and he was discharged with a regimen of hourly topical fortified cefazolin in both eyes. His condition slowly improved over the next 6 weeks as the drops were tapered. At 6 weeks, the right corneal flap was lifted to remove epithelial ingrowth. The patient's visual acuity stabilized to 20/40 OD and 20/200 OS. One month after discontinuation of all medications, he noted a sudden decrease in visual acuity and the onset of photophobia and was referred to us.

On his initial visit, visual acuity was 20/60 OD and 20/400 OS. Examination was remarkable for severe blepharitis. The right cornea had a hazy central anterior stromal scar, with corneal neovascularization extending across the flap from the 7- to 9-o'clock position. The left cornea had 8 radial keratotomy incisions with a dense, central, anterior stromal scar, extending to 30% depth, with neovascularization extending across the flap edge from the 8- to 9-o'clock position. The patient was treated for blepharitis with lid hygiene, topical erythromycin ointment, and oral tetracycline hydrochloride. Penetrating keratoplasty was eventually performed in the left eye. Final visual acuity was 20/40 OD and 20/100 OS.

Case 5.

Two days after hyperopic LASIK in the right eye, a 54-year-old man developed pain and acutely decreased vision in his right eye. The patient had undergone radial keratotomy, followed by 2 enhancement procedures in the right eye, 9 years previously. Eight years later he elected to undergo myopic photorefractive keratectomy, which left him overcorrected. One year later, the patient underwent hyperopic LASIK. On a visit to the referring ophthalmologist 2 days later, the flap appeared nonadherent and infected. With the presumptive diagnosis of "flap infection," the patient underwent flap revision and suturing. He also received various topical and subconjunctival antibiotics. After 2 weeks without improvement, the patient was referred to us.

On his initial visit to us, visual acuity was counting fingers OD and 20/40 OS. Diffuse corneal edema was noted in the right eye, with scattered focal infiltrates under the flap. The flap was thinned and poorly adherent in a wedge-shaped distribution at the 5- to 9-o'clock position. Three sutures at the 5-, 10-, and 11-o'clock positions held the flap in place (Figure 3). Cultures were obtained from the area under the peripheral flap thinning, and the patient was started on a regimen of topical fortified cefazolin sodium (50 mg/mL) and tobramycin sulfate (14 mg/mL), alternating every hour, along with ciprofloxacin ointment at bedtime. Cultures were positive the next day for Streptococcus viridans. Over the next several days, the thinned region of the flap became necrotic, but visual acuity improved to 20/400 OD. A topical antibiotic taper was then started. The inferotemporal peripheral region of the flap was noted to have been lost 10 days later. The decision was made to remove the remaining sutures, lift the flap, irrigate the stromal bed, and repair a radial keratotomy incision that had opened in the temporal bed. However, 2 days later, just prior to the planned surgery, the patient returned with markedly decreased symptoms and visual acuity improved to 20/150 OD. The amount of corneal edema had decreased, and the area of flap melt had reepithelialized. The patient refused further surgery. Final uncorrected visual acuity stabilized at 20/60 OD.

Figure 3.
Slitlamp photograph showing an edematous flap overlying a stromal bed, with scattered focal infiltrates dispersed between 8 radial keratotomy incisions. Visual acuity counting fingers.

Slitlamp photograph showing an edematous flap overlying a stromal bed, with scattered focal infiltrates dispersed between 8 radial keratotomy incisions. Visual acuity counting fingers.

Results.

All patients were treated with topical antibiotics for their presumed infectious ulcerative keratitis. Four of 5 eyes (3 patients) were culture positive for bacteria. In all cases, patients began to show improvement once a stable antibiotic regimen had been started and corticosteroids had been discontinued. Secondary interventions were only necessary in 3 eyes (2 patients): flap revision in 2 eyes and penetrating keratoplasty in 1 eye. All 5 patients reported foreign body sensation as their chief complaint, with 4 of 5 patients reporting severe photophobia as well.

All patients had residual stromal scarring after developing ulceration, but 4 of 6 eyes (4 patients) had uncorrected final visual acuities of 20/40 or better. The remaining 2 eyes had visual acuities of 20/100 or better but had undergone secondary interventions and had had radial keratotomy performed previously.

Comment.

We are beginning to see more cases of LASIK-associated ulcerative keratitis in our referral practice as LASIK becomes more widely available. Ulcerative keratitis may present at any time after LASIK; in fact, in 1 of our 5 patients it was noted to occur as late as 1 year after surgery. A review of our patients suggests a few possible risk factors for the development of ulcerative keratitis. Two patients were using soft contact lenses postoperatively, 1 in association with corticosteroid use. Contact lens wear and steroid use have long been associated with an increased risk of corneal ulceration.1 In both of our cases, the patients were not satisfied with the visual outcomes of their LASIK procedures and were given corrective contact lenses to augment their surgical correction. Neither patient was willing to undergo enhancement procedures.

Two patients had previously undiagnosed dry eye. Corneal ulceration can be one of the sequelae of keratoconjunctivitis sicca.2 In the setting of LASIK, dry eyes may significantly prolong epithelial healing time and therefore place the patient at a greater risk for ulcerative keratitis.

Our last patient had severe blepharitis and was HIV positive. In this particular case, the patient experienced no adverse sequelae of HIV, had a low viral load, and a normal CD4 cell count. It is unclear whether HIV is a risk factor for ulceration after LASIK. However, HIV-positive patients often experience severe ocular surface disease. The increased bacterial load associated with severe blepharitis, as well as the impaired ability to clear this load, may greatly increase the patient's risk for infection.3

A summary review of the literature reveals several reports of infectious complications associated with LASIK (Table 1). Aras et al4 reported a case of corneal interface abscess that occurred 6 days after LASIK and improved with topical antibiotics. Final best-corrected visual acuity was 20/20 with an inferotemporal, 1-mm-round, granular stromal opacity. Reviglio et al5 reported a case of Mycobacterium chelonae infection centrally on and under the flap 1 month after LASIK. This patient's condition did not improve with antibiotics, but had a good result with penetrating keratoplasty. Watanabe et al6 described a case of bilateral infectious keratitis, occurring 1 day after bilateral LASIK, from which S aureus was isolated as the causative agent. The patient's condition improved after a protracted course of topical and intravenous antibiotics, with a final best-corrected visual acuity of 20/40 OU. Scattered stromal opacities remained in both eyes. Mulhern et al9 described a case of corneal abscess with hypopyon and intense vitreous cellular reaction (ie, endophthalmitis) 3 days after LASIK. The infecting organism was Streptococcus pneumoniae. The patient's condition improved with intravenous and topical antibiotics. Final best-corrected visual acuity was 20/25 with a hazy stromal scar. Perez-Santonja et al7 reported a case of infectious keratitis involving the central cornea, secondary to Nocardia asteroides infection, 6 days after LASIK retreatment. The patient was treated with antibiotics, and final visual acuity returned to 20/40 with a small, round central scar. Nascimento et al8 also reported N asteroides infection centrally after a cap exchange was performed because of severe flap edema. The patient's condition improved with repeated cap exchange and topical antibiotics. Final visual acuity was 20/200 with a paracentral leukoma.

Review of Cases of LASIK-Associated Ulcerative Keratitis in Present Series and the Literature*
Review of Cases of LASIK-Associated Ulcerative Keratitis in Present Series and the Literature*

It should be emphasized that all of these described cases of infectious ulcerative keratitis differ from the entity of "diffuse lamellar keratitis" described by Smith and Maloney.10 They described a syndrome with infiltrates that were diffuse, multifocal, and confined to the flap interface, with no posterior or anterior extension, and with an intact overlying epithelium in each case. None of the infiltrates we observed were confined to the interface, and an epithelial defect was always present.

While not all of our cases had positive cultures for organisms, the clinical appearance and response to treatment were typical of infectious keratitis. Most also had antibiotic therapy prior to culture.

The increasing number of reported cases of infectious keratitis after LASIK, while still very small, provides additional support for a conservative approach when considering bilateral surgery and when discussing informed consent.

BackExtra

This work was supported in part by a grant from Research to Prevent Blindness, Inc, New York, NY (Dr McDonnell) and by a grant from the Heed Ophthalmic Foundation, Chicago, Ill (Dr Chuck).

Corresponding author: Peter J. McDonnell, MD, Department of Ophthalmology, University of California Irvine, Gottschaulk Medical Plaza, 2000 Medical Plaza Dr, 2004, Irvine, CA 92697 (e-mail: pjmcdonn@uci.edu).

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