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Infectious keratitis after photorefractive keratectomy
Infectious Keratitis after Photorefractive Keratectomy Eric D. Donnenfeld, MD,1,2 Terrence P. O’Brien, MD,3 Rene´e Solomon, MD,2 Henry D. Perry, MD,1,2 Mark G. Speaker, MD,4 John Wittpenn, MD1,2 Purpose: To elucidate risk factors, microbial culture results, and visual outcomes for infectious keratitis after photorefractive keratectomy (PRK). Design: Multicenter, retrospective chart review, case report, and literature review. Methods: The records of 12 patients with infectious keratitis after PRK were reviewed. Main Outcome Measures: Causative organism, response to medical treatment, and visual outcome. Results: Infectious keratitis developed in 13 eyes of 12 patients after PRK. Organisms cultured were Staphylococcus aureus (n ⫽ 5), including a bilateral case of methicillin-resistant Staphylococcus aureus; Staphylococcus epidermidis (n ⫽ 4); Streptococcus pneumoniae (n ⫽ 3); and Streptococcus viridans (n ⫽ 1). Four patients manipulated their contact lenses, and 2 patients were exposed to nosocomial organisms while working in a hospital environment. Prophylactic antibiotics used were tobramycin (nine cases), polymyxin B-trimethoprim (three cases), and ciprofloxacin (one case). Final best spectacle-corrected visual acuity ranged from 20/20 to 20/100. Conclusions: Infectious corneal ulceration is a serious potential complication of PRK. Gram-positive organisms are the most common pathogens. Antibiotic prophylaxis should be broad spectrum and should include gram-positive coverage. Ophthalmology 2003;110:743–747 © 2003 by the American Academy of Ophthalmology.
The use of the excimer laser to correct refractive errors has increased markedly since Food and Drug Administration approval in 1995. Multiple studies have documented the efficacy and safety of the procedure.1,2 Unfortunately, infectious keratitis after photorefractive keratectomy (PRK) remains a rare, but potentially devastating, complication. Previous case reports have documented the occurrence of this rare complication of PRK.3–13 The purpose of this study was to review the characteristics of a series of infectious corneal ulcers after PRK in 3 referral cornea and refractive practices and to elucidate risk factors, patient histories, microbial culture results, and visual outcomes. In addition to the largest series of infectious keratitis after PRK, we present the first case, to our knowledge, of bilateral bacterial keratitis after PRK and the first case of methicillin-resistant Staphylococcus aureus corneal ulceration after PRK.
Originally received: February 15, 2002. Accepted: December 7, 2002. Manuscript no. 220109. 1 Department of Ophthalmology, Nassau University Medical Center, East Meadow, New York. 2 Ophthalmic Consultants of Long Island, Rockville Centre, New York. 3 Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins Hospital, Baltimore, Maryland. 4 Department of Ophthalmology, New York Eye and Ear Infirmary, New York, New York. Supported in part by the Lions Eye Bank of Long Island, New York. Correspondence and reprint requests to Eric D. Donnenfeld, MD, Ophthalmic Consultants of Long Island, Ryan Medical Arts Building, Suite 402, 2000 North Village Avenue, Rockville Centre, NY 11570. © 2003 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
Materials and Methods A retrospective chart review took place of 3 referral cornea and refractive disease practices. All charts were reviewed, surgeons were questioned, and patients were interviewed for risk factors related to infectious keratitis. All patients underwent microbial culturing and sensitivity testing, were treated with fluoroquinolones, fortified antibiotics, or both, and were followed up for a minimum of 4 months.
Results Bacterial keratitis developed in 13 eyes of 12 patients, with a mean age of 28.4 years, after PRK, and these patients were followed up for a minimum of 4 months (Table 1). Eight patients sought treatment on the first postoperative day, 3 patients sought treatment on the second postoperative day, and one patient sought treatment on the third postoperative day. Six ulcers developed in the right eye, 5 ulcers developed in the left eye, and bilateral corneal ulcerations developed in a single patient. All 13 eyes had been given a therapeutic bandage contact lens. In 4 patients, the contact lens was manipulated by the patient, and in 2 of these patients, the lens fell out and was replaced by the patient without being disinfected. In two eyes, the contact lens was believed to be irritating the patient and was manipulated manually without being removed. Two patients were health-care workers; one was an intensive care unit nurse in whom a Staphylococcus epidermidis ulcer developed and the second patient was an internal medicine resident in whom bilateral methicillin-resistant S. aureus ulcerations developed. During surgery, all 13 eyes received prophylactic antibiotics, and the patients were sent home and prescribed antibiotic drops 4 times daily. The prophylactic antibiotics used were tobramycin 0.3% in ISSN 0161-6420/03/$–see front matter doi:10.1016/S0161-6420(02)01936-X
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Ophthalmology Volume 110, Number 4, April 2003 Table 1. Summary of Cases—Infectious Keratitis after Photorefractive Keratectomy Patient No.
Eye
1 2 3 4 5 6 7 8 9 10 11 12
Right Right Left Right Right Both Right Right Left Left Left Right
Risk Factors Manipulated CL Manipulated CL Manipulated CL Medical resident ICU nurse Manipulated CL
Prophylactic Antibiotic
Organism
Tobramycin Tobramycin Polymyxin B–trimethoprim Tobramycin Polymyxin B–trimethoprim Tobramycin Polymyxin B–trimethoprim Tobramycin Tobramycin Tobramycin Ciprofloxacin Tobramycin
Staphylococcus aureus Staphylococcus viridans Staphylococcus aureus Staphylococcus epidermidis Staphylococcus epidermidis MRSA Streptococcus pneumoniae Staphylococcus epidermidis Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus pneumoniae
CL ⫽ contact lens; ICU ⫽ intensive care unit; MRSA ⫽ methicillin-resistant Staphylococcus aureus.
9 eyes, polymyxin B-trimethoprim (Polytrim威; Allergan, Irvine, Ca.) in 3 eyes, and ciprofloxacin 0.3% (Ciloxan威 0.3%; Alcon, Fort Worth, Tx.) in one eye. The patients were treated for their infectious corneal ulcerations with a variety of medications, including commercially available ofloxacin and ciprofloxacin, as well as fortified vancomycin and cefazolin. All 13 eyes were culture positive. The most common organisms cultured were 5 cases of S. aureus, including a bilateral case of methicillin-resistant S. aureus, 4 cases of S. epidermidis, 3 cases of Streptococcus pneumoniae, and 1 case of Streptococcus viridans. No gram-negative organisms, opportunistic bacteria, fungi, or amoeba were cultured in these patients. All patients responded to medical therapy. No patient had a history of corneal ulceration before this event, diabetes mellitus, corneal anesthesia, atopy, or was in any way immunocompromised. Final visual acuity ranged from 20/20 to 20/100, with a minimal healing time of 4 months. Best spectacle-corrected visual acuity was 20/20 (5 cases), 20/25 (3 cases), 20/40 (3 cases), 20/70 (1 case), and 20/100 (1 case). No patient required additional surgery, although one patient is awaiting a penetrating keratoplasty.
Case Report A 26-year-old female medical resident with a refraction of ⫺7.00 in the right eye and ⫺6.75 in the left eye underwent bilateral PRK. After surgery, the patient received one drop of tobramycin 0.3% solution in both eyes and proparacaine 0.5% topical anesthetic. In both eyes, the PRK was uneventful, and after the PRK, the patient was fit with a bandage soft contact lens and was given tobramycin 0.3%, fluorometholone 0.1%, and diclofenac sodium 0.1% 4 times daily. The patient was sent home with oral acetaminophen and codeine. On the first postoperative day, the patient was seen for a routine visit by the treating ophthalmologist. The patient reported significant pain. On examination, it was noted that the contact lenses were in place. The patient had a 5-mm epithelial defect in both eyes and no infiltrate was visualized. The patient continued to have pain on the second postoperative day and was seen again by her ophthalmologist. Bilateral corneal ulcerations were noted, and the patient was referred for corneal consultation. In consultation, the visual acuity was counting fingers at 2 feet in both eyes. The contact lenses were in place in both eyes. The patient had a 4-mm paracentral corneal infiltrate in the right eye
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and a 2-mm infiltrate in the left eye, with a 5-mm epithelial defect in both eyes. On the surface of the infiltrate was tenacious mucous, and the anterior chamber had a 5% hypopyon in the right eye and a 2% hypopyon in the left eye. The patient was diagnosed with infectious keratitis. The contact lenses were removed and the patient underwent corneal scrapings of each eye on blood agar, chocolate agar, Sabouraud’s, and thioglycolate. Gram stain revealed gram-positive cocci. Blood agar lid cultures were also performed. Because of the patient’s occupation as a chief medical resident, the prophylactic antibiotic tobramycin, and the gram stain results, the presumed diagnosis was methicillin-resistant S. aureus, and the patient was immediately started on vancomycin, 35 mg/ml every half hour, and ofloxacin 0.3% every hour around the clock. The patient was seen 24 hours later, at which time the pain had diminished, the corneal infiltrate was slightly smaller, and the hypopyons had resolved. At 48 hours after the corneal culture, the diagnosis of methicillin-resistant S. aureus in both eyes was confirmed. Cultures of her lids also revealed methicillin-resistant S. aureus. At this point, the ofloxacin was decreased to four times daily, and the vancomycin was continued on an hourly basis. The patient showed gradual resolution of her infectious corneal ulcers in both eyes, and the antibiotics were tapered off over a 2-week period. On the third day of treatment, topical prednisolone acetate 1% was started in both eyes four times daily and tapered off over a 2-month period. The best-corrected visual acuity improved over a 4-month period to 20/100 in the right eye and 20/25 in the left eye with a refraction of ⫹3.25–2.50 at 170° in the right eye and ⫹0.50 –1.00 at 150° in the left eye. Three months after the infection, the right eye revealed approximately 40% corneal thinning, and the left eye approximately 10% thinning in the area of the corneal ulceration. The patient is awaiting corneal transplantation in the right eye.
Discussion Infectious keratitis is a potentially devastating complication of PRK. The predisposing risk factors for infectious keratitis are breakdown of the barrier function of the corneal epithelium and the use of a bandage contact lens on an extendedwear basis.14 In addition, the use of topical steroids to control wound healing may suppress the ability of the immune system to fight infection.
Donnenfeld et al 䡠 Infectious Keratitis after PRK Table 2. Summary of Cases of Literature Search: Infections after Photorefractive Keratectomy Investigators
Unilateral or Bilateral
Prophylactic Antibiotic
Organism Mycobacterium chelonae Pseudomonas aeruginosa Streptococcus pneumoniae Culture negative Staphylococcus epidermidis Nonhemolytic Streptococcus Aspergillosis Staphylococcus aureus Acremonium Penicilium Aurobasidium pullulans Staphylococcus aureus
Brancato et al Wee et al Sampath et al Amayem et al
Unilateral Unilateral Unilateral Unilateral
Tobramycin None Clobetasone butyrate Chloramphenicol, tobramycin
Malling et al
Unilateral
Garamycin, chloramphenicol
Faschinger et al Hill et al Dunphy et al
Unilateral ⫻ 3 Unilateral Unilateral
None Bactrim Tobramycin dexamethasone
Heidemann et al
Bilateral
Ciprofloxacin
Kouyoumdijan et al Waked and Ojeimi
Unilateral Unilateral
Unknown Polymyxin B neomycin bacitracin
Scopulariopsis Culture negative
Postoperative BestCorrected Visual Acuity 20/20 20/20 CF 20/150 20/30 CF 20/100 20/100 (⫹PSC) 20/80 right eye 20/400 left eye 20/20 20/20
CF ⫽ counting fingers; PSC ⫽ posterior subcapsular cataract.
Although laser in situ keratomileusis (LASIK) has surpassed PRK as the most prevalent form of refractive surgery, PRK remains an extremely common procedure. In addition, as larger ablation zone treatments become more common and the depth of the ablation exceeds the Food and Drug Administration recommended residual stromal bed precluding LASIK, PRK becomes the treatment of choice. New excimer delivery systems, including the Gaussian flying spot and more gradual transition zones, have resulted in better PRK results with less risk of stromal haze.15 Although haze is a rare problem after PRK, mitomycin C has been shown to be safe and effective in treating this complication.16 In addition, there is recent evidence that the LASIK flap creates topographic changes that affect the accuracy of wavefront ablations. Finally, laser subepithelial keratomileusis is gaining increased popularity.17 We suggest that although no infections with this procedure have been published to date, the infections should be similar to PRK. All of these factors suggest a resurgence of the PRK procedure. In our review of the literature (Table 2), we found 14 cases of infectious keratitis occurring after PRK.3–13 Four cases were associated with opportunistic organisms including the bacterial infection Mycobacterium chelonae. One case of fungal keratitis was associated with 3 different fungi: Acremonium, Penicillium, and Aureobasidium pullulans, and the other 2 cases of fungal keratitis were the result of Scopulariopsis and Aspergillosis. Of the 10 remaining cases, 4 were Staphylococcus species (either S. aureus or S. epidermidis) and 2 were Streptococcus species (S. pneumoniae and S. viridans). There was a single case of Pseudomonas aeruginosa reported, in which the patient did not receive prophylactic antibiotics. Three were culture-negative cases. Combining these cases with the 13 cases we report, there have been 11 Staphylococcus species, 6 Streptococcus species, and 1 Pseudomonas species responsible for nonopportunistic infectious keratitis after PRK. In addition, there have been 2 cases of infectious keratitis after
phototherapeutic keratectomy, one case was culture negative and the other was the result of S. aureus. The latter case did not use prophylactic antibiotics.18,19 In a further review of the literature, we looked at cases of infectious keratitis after LASIK.20 – 43 Again, other than the opportunistic infections of M. chelonae, Nocardia, and fungus, all of the cases of infectious keratitis occurring after LASIK have been the result of gram-positive organisms. Previous studies of contact lens-related bacterial keratitis have documented a high incidence of P. aeruginosa.44 – 46 In our series, no patient cultured this organism, and in the review of the literature, there has been only a single documented case. The aminoglycosides (tobramycin and gentamicin) and Polymyxin-B–trimethoprim provide excellent prophylaxis against gram-negative organisms. Unfortunately, tobramycin and gentamicin have little efficacy against S. epidermidis and Streptococcus species, which are responsible for the great majority of infections occurring after PRK.47 Polymyxin-B–trimethoprim is a bacteriostatic drug, again with poor activity against Streptococcus species. For this reason, we do not recommend these antibiotics be used after refractive surgery. We suggest that after PRK, gram-positive organisms pose the greatest risk of infectious keratitis, and, because of significant risk factors and ocular morbidity associated with infectious keratitis, we strongly recommend the use of prophylactic antibiotics after PRK. The fluoroquinolones offer broad-spectrum coverage against gram-positive and gramnegative organisms with excellent tissue penetration and solubility.48 Only one patient in our series and one report in the literature documented bacterial keratitis in a patient treated prophylactically with ciprofloxacin. There were no cases reported in our series or to our knowledge in the literature of bacterial keratitis after LASIK or PRK in patients treated prophylactically with ofloxacin or levofloxacin. In addition, the fluoroquinolones also demonstrate efficacy against atypical mycobacteria that has been reported
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Ophthalmology Volume 110, Number 4, April 2003 after PRK, but is a common pathogen in LASIK microbial infections.49 Because of their high potency, efficacy, and broad-spectrum coverage, as well as minimal wound healing complications, we strongly recommend that fluoroquinolones be used after PRK. The next generation of fluoroquinolones, including gatifloxacin and moxifloxacin, will provide significantly improved gram-positive coverage and likely will replace the current fluoroquinolones as the prophylaxis of choice for PRK. Two patients in our series were health care workers: one patient was a physician and another was an intensive care unit nurse in whom infectious keratitis developed after PRK. The most significant case of infectious keratitis was a case of bilateral methicillin-resistant S. aureus in the physician. To our knowledge, this is the first reported case of bilateral infectious keratitis after PRK, although there have been 2 reports of bilateral infectious keratitis in patients after LASIK.40,41 We suggest that patients who live or work in a medical environment should be treated prophylactically more aggressively after PRK and LASIK, or should consider monocular treatment because of their increased risk of experiencing resistant infections. Finally, as with all contact lens wearers, bandage contact lens wearers after PRK should be cautioned of the risk of contact lens manipulation and the increased risk of infectious keratitis with poor contact lens hygiene.50 In conclusion, infectious corneal ulceration is an uncommon but serious PRK complication. Antibiotic prophylaxis should be broad spectrum and should include gram-positive coverage. We recommend the use of the fluoroquinolones prophylactically after PRK and LASIK. Health-care workers may experience keratitis from microbes associated with nosocomial infections and should be treated prophylactically more aggressively than the general population. Patients should be informed of the risk factors and warning signs of infectious keratitis and should be informed to seek medical attention immediately should they experience signs or symptoms of infectious keratitis.
References 1. Salz JJ, Maguen E, Nesburn AB, et al. A two-year experience with excimer laser photorefractive keratectomy for myopia. Ophthalmology 1993;100:873– 82. 2. Seiler T, Wollensak J. Myopic photorefractive keratectomy with the excimer laser. One-year follow-up. Ophthalmology 1991;98:1156 – 63. 3. Brancato R, Carones F, Venturi E, et al. Mycobacterium chelonae keratitis after excimer laser photorefractive keratectomy. Arch Ophthalmol 1997;115:1316 – 8. 4. Wee WR, Kim JY, Choi YS, Lee JM. Bacterial keratitis after photorefractive keratectomy in a young, healthy man. J Cataract Refract Surg 1997;23:954 – 6. 5. Sampath R, Ridgway AE, Leatherbarrow B. Bacterial keratitis following excimer laser photorefractive keratectomy: a case report. Eye 1994;8:481–2. 6. Amayem A, Ali AT, Waring GO 3rd, Ibrahim O. Bacterial keratitis after photorefractive keratectomy. J Refract Surg 1996;12:642– 4. 7. Malling S. Keratitis with loss of useful vision after photorefractive keratectomy. J Cataract Refract Surg 1999;25:137–9.
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8. Faschinger C, Faulborn J, Ganser K. Infectious corneal ulcers — once with endophthalmitis—after photorefractive keratotomy with disposable contact lens. Klin Monatsb Augenheilkd 1995;206:96 –102. 9. Hill VE, Brownstein S, Jackson WB, Mintsioulis G. Infectious keratopathy complicating photorefractive keratectomy [letter]. Arch Ophthalmol 1998;116:1382– 4. 10. Dunphy D, Andrews D, Seamone C, Ramsey M. Fungal keratitis following excimer laser photorefractive keratectomy. Can J Ophthalmol 1999;34:286 –9. 11. Kouyoumdjian GA, Forstot SL, Durairaj VD, Damiano RE. Infectious keratitis after laser refractive surgery. Ophthalmology 2001;108:1266 – 8. 12. Waked NE, Ojeimi GK. Excimer laser photorefractive keratectomy in Lebanon. J Refract Surg 1995;11:S270 –3. 13. Heidemann DG, Clune M, Dunn SP, Chow CYC. Infectious keratitis after photorefractive keratectomy in a comanaged setting. J Cataract Refract Surg 2000;26:140 –1. 14. Schein OD, Buehler PO, Stamler JF, et al. The impact of overnight wear on the risk of contact lens-associated ulcerative keratitis. Arch Ophthalmol 1994;112:186 –90. 15. Hersh PS, Brint SF, Maloney RK, et al. Photorefractive keratectomy versus laser in situ keratomileusis for moderate to high myopia. A randomized prospective study. Ophthalmology 1998;105:1512–22; discussion 1522–3. 16. Majmudar PA, Forstot SL, Dennis RF, et al. Topical mitomycin-C for subepithelial fibrosis after refractive corneal surgery. Ophthalmology 2000;107:89 –94. 17. Lee JB, Seong GJ, Lee JH, et al. Comparison of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia. J Cataract Refract Surg 2001;27:565–70. 18. Faschinger CW. Phototherapeutic keratectomy of a corneal scar due to presumed infection after photorefractive keratectomy. J Cataract Refract Surg 2000;26:296 –300. 19. Fulton JC, Cohen EJ, Rapuano CJ. Bacterial ulcer 3 days after excimer laser phototherapeutic keratectomy. Arch Ophthalmol 1996;114:626 –7. 20. Stulting RD, Carr JD, Thompson KP, et al. Complications of laser in situ keratomileusis for the correction of myopia. Ophthalmology 1999;106:13–20. 21. Pe´ rez-Santonja JJ, Sakla HF, Abad JL, et al. Nocardial keratitis after laser in situ keratomileusis. J Refract Surg 1997;13: 314 –7. 22. Solomon A, Karp CL, Miller D, et al. Mycobacterium interface keratitis after laser in situ keratomileusis. Ophthalmology 2001;108:2201– 8. 23. Chandra NS, Torres MF, Winthrop KL, et al. Cluster of Mycobacterium chelonae keratitis cases following laser in-situ keratomileusis. Am J Ophthalmol 2001;132:819 –30. 24. Rubinfeld RS, Negvesky GJ. Methicillin-resistant Staphylococcus aureus ulcerative keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2001;27:1523–5. 25. Gupta V, Dada T, Vajpayee RB, et al. Polymicrobial keratitis after laser in situ keratomileusis. J Refract Surg 2001;17: 147– 8. 26. Rudd JC, Moshirfar M. Methicillin-resistant Staphylococcus aureus keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2001;27:471–3. 27. Levartovsky S, Rosenwasser GOD, Goodman DF. Bacterial keratitis after laser in situ keratomileusis [published erratum appears in Ophthalmology 2001;108:1012]. Ophthalmology 2001;108:321–5. 28. Garg P, Bansal AK, Sharma S, Vemuganti GK. Bilateral infectious keratitis after laser in situ keratomileusis: A case report and review of the literature. Ophthalmology 2001;108: 121–5.
Donnenfeld et al 䡠 Infectious Keratitis after PRK 29. Alio´ JL, Pe´ rez-Santoja JJ, Tervo T, et al. Postoperative inflammation, microbial complications, and wound healing following laser in situ keratomileusis. J Refract Surg 2000;16: 523–38. 30. Karp KO, Hersh PS, Epstein RJ. Delayed keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000;26:925– 8. 31. Sridhar MS, Garg P, Bansal AK, Sharma S. Fungal keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000;26:613–5. 32. Gelender H, Carter HL, Bowman B, et al. Mycobacterium keratitis after laser in situ keratomileusis. J Refract Surg 2000;16:191–5. 33. Dada T, Sharma N, Dada VK, Vajpayee RB. Pneumococcal keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000;26:460 –1. 34. Chung MS, Goldstein MH, Driebe WT Jr, Schwartz BH. Mycobacterium chelonae keratitis after laser in situ keratomileusis successfully treated with medical therapy and flap removal. Am J Ophthalmol 2000;129:382– 4. 35. Chung MS, Goldstein MH, Driebe WT Jr, Schwartz B. Fungal keratitis after laser in situ keratomileusis: a case report. Cornea 2000;19:236 –7. 36. Quiros PA, Chuck RS, Smith RE, et al. Infectious ulcerative keratitis after laser in situ keratomileusis. Arch Ophthalmol 1999;117:1423–7. 37. Reviglio V, Rodriguez ML, Picotti GS, et al. Mycobacterium chelonae keratitis following laser in situ keratomileusis. J Refract Surg 1998;14:357– 60. ¨ zdamar A, Bahc¸ ecioglu M, Sener B. Corneal inter38. Aras C, O face abscess after excimer laser in situ keratomileusis. J Refract Surg 1998;14:156 –7. 39. Mulhem MG, Condon PI, O’Keefe M. Endophthalmitis after astigmatic myopic laser in situ keratomileusis. J Cataract Refract Surg 1997;23:948 –50.
40. Watanabe H, Sato S, Maeda N, et al. Bilateral corneal infection as a complication of laser in situ keratomileusis [letter]. Arch Ophthalmol 1997;115:1593– 4. 41. Hovanesian JA, Faktorovich EG, Hoffbauer JD, et al. Bilateral bacterial keratitis after laser in situ keratomileusis in a patient with human immunodeficiency virus infection. Arch Ophthalmol 1999;117:968 –70. 42. Al-Reefy M. Bacterial keratitis following laser in situ keratomileusis for hyperopia. J Refract Surg 1999;15:S216 –7. 43. Webber SK, Lawless MA, Sutton GL, Rogers CM. Staphylococcal infection under a LASIK flap. Cornea 1999;18: 361–5. 44. Cohen EJ, Laibson PR, Arentsen JJ, Clemons CS. Corneal ulcers associated with cosmetic extended wear soft contact lenses. Ophthalmology 1987;94:109 –14. 45. Donnenfeld ED, Cohen EJ, Arentsen JJ, et al. Changing trends in contact lens associated corneal ulcers: an overview of 116 cases. CLAO J 1986;12:145–9. 46. Alfonso E, Mandelbaum S, Fox MJ, Forster RK. Ulcerative keratitis associated with contact lens wear. Am J Ophthalmol 1986;101:429 –33. 47. Jensen HG, Felix C. In vitro antibiotic susceptibilities of ocular isolates in North and South America. In Vitro Antibiotic Testing Group. Cornea 1998;17:79 – 87. 48. Donnenfeld ED, Schrier A, Perry HD, et al. Penetration of topically applied ciprofloxacin, norfloxacin, and ofloxacin into the aqueous humor. Ophthalmology 1994;101:902–5. 49. Helm CJ, Holland GN, Lin R. Comparison of topical antibiotics for treating Mycobacterium fortuitum keratitis in an animal model. Am J Ophthalmol 1993;116:700 –7. 50. Matthews TD, Frazer DG, Minassian DC, et al. Risks of keratitis and patterns of use with disposable contact lenses. Arch Ophthalmol 1992;110:1559 – 6.
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The use of the excimer laser to correct refractive errors has increased markedly since Food and Drug Administration approval in 1995. Multiple studies have documented the efficacy and safety of the procedure.1,2 Unfortunately, infectious keratitis after photorefractive keratectomy (PRK) remains a rare, but potentially devastating, complication. Previous case reports have documented the occurrence of this rare complication of PRK.3–13 The purpose of this study was to review the characteristics of a series of infectious corneal ulcers after PRK in 3 referral cornea and refractive practices and to elucidate risk factors, patient histories, microbial culture results, and visual outcomes. In addition to the largest series of infectious keratitis after PRK, we present the first case, to our knowledge, of bilateral bacterial keratitis after PRK and the first case of methicillin-resistant Staphylococcus aureus corneal ulceration after PRK.
Originally received: February 15, 2002. Accepted: December 7, 2002. Manuscript no. 220109. 1 Department of Ophthalmology, Nassau University Medical Center, East Meadow, New York. 2 Ophthalmic Consultants of Long Island, Rockville Centre, New York. 3 Department of Ophthalmology, The Wilmer Eye Institute, The Johns Hopkins Hospital, Baltimore, Maryland. 4 Department of Ophthalmology, New York Eye and Ear Infirmary, New York, New York. Supported in part by the Lions Eye Bank of Long Island, New York. Correspondence and reprint requests to Eric D. Donnenfeld, MD, Ophthalmic Consultants of Long Island, Ryan Medical Arts Building, Suite 402, 2000 North Village Avenue, Rockville Centre, NY 11570. © 2003 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
Materials and Methods A retrospective chart review took place of 3 referral cornea and refractive disease practices. All charts were reviewed, surgeons were questioned, and patients were interviewed for risk factors related to infectious keratitis. All patients underwent microbial culturing and sensitivity testing, were treated with fluoroquinolones, fortified antibiotics, or both, and were followed up for a minimum of 4 months.
Results Bacterial keratitis developed in 13 eyes of 12 patients, with a mean age of 28.4 years, after PRK, and these patients were followed up for a minimum of 4 months (Table 1). Eight patients sought treatment on the first postoperative day, 3 patients sought treatment on the second postoperative day, and one patient sought treatment on the third postoperative day. Six ulcers developed in the right eye, 5 ulcers developed in the left eye, and bilateral corneal ulcerations developed in a single patient. All 13 eyes had been given a therapeutic bandage contact lens. In 4 patients, the contact lens was manipulated by the patient, and in 2 of these patients, the lens fell out and was replaced by the patient without being disinfected. In two eyes, the contact lens was believed to be irritating the patient and was manipulated manually without being removed. Two patients were health-care workers; one was an intensive care unit nurse in whom a Staphylococcus epidermidis ulcer developed and the second patient was an internal medicine resident in whom bilateral methicillin-resistant S. aureus ulcerations developed. During surgery, all 13 eyes received prophylactic antibiotics, and the patients were sent home and prescribed antibiotic drops 4 times daily. The prophylactic antibiotics used were tobramycin 0.3% in ISSN 0161-6420/03/$–see front matter doi:10.1016/S0161-6420(02)01936-X
743
Ophthalmology Volume 110, Number 4, April 2003 Table 1. Summary of Cases—Infectious Keratitis after Photorefractive Keratectomy Patient No.
Eye
1 2 3 4 5 6 7 8 9 10 11 12
Right Right Left Right Right Both Right Right Left Left Left Right
Risk Factors Manipulated CL Manipulated CL Manipulated CL Medical resident ICU nurse Manipulated CL
Prophylactic Antibiotic
Organism
Tobramycin Tobramycin Polymyxin B–trimethoprim Tobramycin Polymyxin B–trimethoprim Tobramycin Polymyxin B–trimethoprim Tobramycin Tobramycin Tobramycin Ciprofloxacin Tobramycin
Staphylococcus aureus Staphylococcus viridans Staphylococcus aureus Staphylococcus epidermidis Staphylococcus epidermidis MRSA Streptococcus pneumoniae Staphylococcus epidermidis Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus pneumoniae
CL ⫽ contact lens; ICU ⫽ intensive care unit; MRSA ⫽ methicillin-resistant Staphylococcus aureus.
9 eyes, polymyxin B-trimethoprim (Polytrim威; Allergan, Irvine, Ca.) in 3 eyes, and ciprofloxacin 0.3% (Ciloxan威 0.3%; Alcon, Fort Worth, Tx.) in one eye. The patients were treated for their infectious corneal ulcerations with a variety of medications, including commercially available ofloxacin and ciprofloxacin, as well as fortified vancomycin and cefazolin. All 13 eyes were culture positive. The most common organisms cultured were 5 cases of S. aureus, including a bilateral case of methicillin-resistant S. aureus, 4 cases of S. epidermidis, 3 cases of Streptococcus pneumoniae, and 1 case of Streptococcus viridans. No gram-negative organisms, opportunistic bacteria, fungi, or amoeba were cultured in these patients. All patients responded to medical therapy. No patient had a history of corneal ulceration before this event, diabetes mellitus, corneal anesthesia, atopy, or was in any way immunocompromised. Final visual acuity ranged from 20/20 to 20/100, with a minimal healing time of 4 months. Best spectacle-corrected visual acuity was 20/20 (5 cases), 20/25 (3 cases), 20/40 (3 cases), 20/70 (1 case), and 20/100 (1 case). No patient required additional surgery, although one patient is awaiting a penetrating keratoplasty.
Case Report A 26-year-old female medical resident with a refraction of ⫺7.00 in the right eye and ⫺6.75 in the left eye underwent bilateral PRK. After surgery, the patient received one drop of tobramycin 0.3% solution in both eyes and proparacaine 0.5% topical anesthetic. In both eyes, the PRK was uneventful, and after the PRK, the patient was fit with a bandage soft contact lens and was given tobramycin 0.3%, fluorometholone 0.1%, and diclofenac sodium 0.1% 4 times daily. The patient was sent home with oral acetaminophen and codeine. On the first postoperative day, the patient was seen for a routine visit by the treating ophthalmologist. The patient reported significant pain. On examination, it was noted that the contact lenses were in place. The patient had a 5-mm epithelial defect in both eyes and no infiltrate was visualized. The patient continued to have pain on the second postoperative day and was seen again by her ophthalmologist. Bilateral corneal ulcerations were noted, and the patient was referred for corneal consultation. In consultation, the visual acuity was counting fingers at 2 feet in both eyes. The contact lenses were in place in both eyes. The patient had a 4-mm paracentral corneal infiltrate in the right eye
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and a 2-mm infiltrate in the left eye, with a 5-mm epithelial defect in both eyes. On the surface of the infiltrate was tenacious mucous, and the anterior chamber had a 5% hypopyon in the right eye and a 2% hypopyon in the left eye. The patient was diagnosed with infectious keratitis. The contact lenses were removed and the patient underwent corneal scrapings of each eye on blood agar, chocolate agar, Sabouraud’s, and thioglycolate. Gram stain revealed gram-positive cocci. Blood agar lid cultures were also performed. Because of the patient’s occupation as a chief medical resident, the prophylactic antibiotic tobramycin, and the gram stain results, the presumed diagnosis was methicillin-resistant S. aureus, and the patient was immediately started on vancomycin, 35 mg/ml every half hour, and ofloxacin 0.3% every hour around the clock. The patient was seen 24 hours later, at which time the pain had diminished, the corneal infiltrate was slightly smaller, and the hypopyons had resolved. At 48 hours after the corneal culture, the diagnosis of methicillin-resistant S. aureus in both eyes was confirmed. Cultures of her lids also revealed methicillin-resistant S. aureus. At this point, the ofloxacin was decreased to four times daily, and the vancomycin was continued on an hourly basis. The patient showed gradual resolution of her infectious corneal ulcers in both eyes, and the antibiotics were tapered off over a 2-week period. On the third day of treatment, topical prednisolone acetate 1% was started in both eyes four times daily and tapered off over a 2-month period. The best-corrected visual acuity improved over a 4-month period to 20/100 in the right eye and 20/25 in the left eye with a refraction of ⫹3.25–2.50 at 170° in the right eye and ⫹0.50 –1.00 at 150° in the left eye. Three months after the infection, the right eye revealed approximately 40% corneal thinning, and the left eye approximately 10% thinning in the area of the corneal ulceration. The patient is awaiting corneal transplantation in the right eye.
Discussion Infectious keratitis is a potentially devastating complication of PRK. The predisposing risk factors for infectious keratitis are breakdown of the barrier function of the corneal epithelium and the use of a bandage contact lens on an extendedwear basis.14 In addition, the use of topical steroids to control wound healing may suppress the ability of the immune system to fight infection.
Donnenfeld et al 䡠 Infectious Keratitis after PRK Table 2. Summary of Cases of Literature Search: Infections after Photorefractive Keratectomy Investigators
Unilateral or Bilateral
Prophylactic Antibiotic
Organism Mycobacterium chelonae Pseudomonas aeruginosa Streptococcus pneumoniae Culture negative Staphylococcus epidermidis Nonhemolytic Streptococcus Aspergillosis Staphylococcus aureus Acremonium Penicilium Aurobasidium pullulans Staphylococcus aureus
Brancato et al Wee et al Sampath et al Amayem et al
Unilateral Unilateral Unilateral Unilateral
Tobramycin None Clobetasone butyrate Chloramphenicol, tobramycin
Malling et al
Unilateral
Garamycin, chloramphenicol
Faschinger et al Hill et al Dunphy et al
Unilateral ⫻ 3 Unilateral Unilateral
None Bactrim Tobramycin dexamethasone
Heidemann et al
Bilateral
Ciprofloxacin
Kouyoumdijan et al Waked and Ojeimi
Unilateral Unilateral
Unknown Polymyxin B neomycin bacitracin
Scopulariopsis Culture negative
Postoperative BestCorrected Visual Acuity 20/20 20/20 CF 20/150 20/30 CF 20/100 20/100 (⫹PSC) 20/80 right eye 20/400 left eye 20/20 20/20
CF ⫽ counting fingers; PSC ⫽ posterior subcapsular cataract.
Although laser in situ keratomileusis (LASIK) has surpassed PRK as the most prevalent form of refractive surgery, PRK remains an extremely common procedure. In addition, as larger ablation zone treatments become more common and the depth of the ablation exceeds the Food and Drug Administration recommended residual stromal bed precluding LASIK, PRK becomes the treatment of choice. New excimer delivery systems, including the Gaussian flying spot and more gradual transition zones, have resulted in better PRK results with less risk of stromal haze.15 Although haze is a rare problem after PRK, mitomycin C has been shown to be safe and effective in treating this complication.16 In addition, there is recent evidence that the LASIK flap creates topographic changes that affect the accuracy of wavefront ablations. Finally, laser subepithelial keratomileusis is gaining increased popularity.17 We suggest that although no infections with this procedure have been published to date, the infections should be similar to PRK. All of these factors suggest a resurgence of the PRK procedure. In our review of the literature (Table 2), we found 14 cases of infectious keratitis occurring after PRK.3–13 Four cases were associated with opportunistic organisms including the bacterial infection Mycobacterium chelonae. One case of fungal keratitis was associated with 3 different fungi: Acremonium, Penicillium, and Aureobasidium pullulans, and the other 2 cases of fungal keratitis were the result of Scopulariopsis and Aspergillosis. Of the 10 remaining cases, 4 were Staphylococcus species (either S. aureus or S. epidermidis) and 2 were Streptococcus species (S. pneumoniae and S. viridans). There was a single case of Pseudomonas aeruginosa reported, in which the patient did not receive prophylactic antibiotics. Three were culture-negative cases. Combining these cases with the 13 cases we report, there have been 11 Staphylococcus species, 6 Streptococcus species, and 1 Pseudomonas species responsible for nonopportunistic infectious keratitis after PRK. In addition, there have been 2 cases of infectious keratitis after
phototherapeutic keratectomy, one case was culture negative and the other was the result of S. aureus. The latter case did not use prophylactic antibiotics.18,19 In a further review of the literature, we looked at cases of infectious keratitis after LASIK.20 – 43 Again, other than the opportunistic infections of M. chelonae, Nocardia, and fungus, all of the cases of infectious keratitis occurring after LASIK have been the result of gram-positive organisms. Previous studies of contact lens-related bacterial keratitis have documented a high incidence of P. aeruginosa.44 – 46 In our series, no patient cultured this organism, and in the review of the literature, there has been only a single documented case. The aminoglycosides (tobramycin and gentamicin) and Polymyxin-B–trimethoprim provide excellent prophylaxis against gram-negative organisms. Unfortunately, tobramycin and gentamicin have little efficacy against S. epidermidis and Streptococcus species, which are responsible for the great majority of infections occurring after PRK.47 Polymyxin-B–trimethoprim is a bacteriostatic drug, again with poor activity against Streptococcus species. For this reason, we do not recommend these antibiotics be used after refractive surgery. We suggest that after PRK, gram-positive organisms pose the greatest risk of infectious keratitis, and, because of significant risk factors and ocular morbidity associated with infectious keratitis, we strongly recommend the use of prophylactic antibiotics after PRK. The fluoroquinolones offer broad-spectrum coverage against gram-positive and gramnegative organisms with excellent tissue penetration and solubility.48 Only one patient in our series and one report in the literature documented bacterial keratitis in a patient treated prophylactically with ciprofloxacin. There were no cases reported in our series or to our knowledge in the literature of bacterial keratitis after LASIK or PRK in patients treated prophylactically with ofloxacin or levofloxacin. In addition, the fluoroquinolones also demonstrate efficacy against atypical mycobacteria that has been reported
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Ophthalmology Volume 110, Number 4, April 2003 after PRK, but is a common pathogen in LASIK microbial infections.49 Because of their high potency, efficacy, and broad-spectrum coverage, as well as minimal wound healing complications, we strongly recommend that fluoroquinolones be used after PRK. The next generation of fluoroquinolones, including gatifloxacin and moxifloxacin, will provide significantly improved gram-positive coverage and likely will replace the current fluoroquinolones as the prophylaxis of choice for PRK. Two patients in our series were health care workers: one patient was a physician and another was an intensive care unit nurse in whom infectious keratitis developed after PRK. The most significant case of infectious keratitis was a case of bilateral methicillin-resistant S. aureus in the physician. To our knowledge, this is the first reported case of bilateral infectious keratitis after PRK, although there have been 2 reports of bilateral infectious keratitis in patients after LASIK.40,41 We suggest that patients who live or work in a medical environment should be treated prophylactically more aggressively after PRK and LASIK, or should consider monocular treatment because of their increased risk of experiencing resistant infections. Finally, as with all contact lens wearers, bandage contact lens wearers after PRK should be cautioned of the risk of contact lens manipulation and the increased risk of infectious keratitis with poor contact lens hygiene.50 In conclusion, infectious corneal ulceration is an uncommon but serious PRK complication. Antibiotic prophylaxis should be broad spectrum and should include gram-positive coverage. We recommend the use of the fluoroquinolones prophylactically after PRK and LASIK. Health-care workers may experience keratitis from microbes associated with nosocomial infections and should be treated prophylactically more aggressively than the general population. Patients should be informed of the risk factors and warning signs of infectious keratitis and should be informed to seek medical attention immediately should they experience signs or symptoms of infectious keratitis.
References 1. Salz JJ, Maguen E, Nesburn AB, et al. A two-year experience with excimer laser photorefractive keratectomy for myopia. Ophthalmology 1993;100:873– 82. 2. Seiler T, Wollensak J. Myopic photorefractive keratectomy with the excimer laser. One-year follow-up. Ophthalmology 1991;98:1156 – 63. 3. Brancato R, Carones F, Venturi E, et al. Mycobacterium chelonae keratitis after excimer laser photorefractive keratectomy. Arch Ophthalmol 1997;115:1316 – 8. 4. Wee WR, Kim JY, Choi YS, Lee JM. Bacterial keratitis after photorefractive keratectomy in a young, healthy man. J Cataract Refract Surg 1997;23:954 – 6. 5. Sampath R, Ridgway AE, Leatherbarrow B. Bacterial keratitis following excimer laser photorefractive keratectomy: a case report. Eye 1994;8:481–2. 6. Amayem A, Ali AT, Waring GO 3rd, Ibrahim O. Bacterial keratitis after photorefractive keratectomy. J Refract Surg 1996;12:642– 4. 7. Malling S. Keratitis with loss of useful vision after photorefractive keratectomy. J Cataract Refract Surg 1999;25:137–9.
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8. Faschinger C, Faulborn J, Ganser K. Infectious corneal ulcers — once with endophthalmitis—after photorefractive keratotomy with disposable contact lens. Klin Monatsb Augenheilkd 1995;206:96 –102. 9. Hill VE, Brownstein S, Jackson WB, Mintsioulis G. Infectious keratopathy complicating photorefractive keratectomy [letter]. Arch Ophthalmol 1998;116:1382– 4. 10. Dunphy D, Andrews D, Seamone C, Ramsey M. Fungal keratitis following excimer laser photorefractive keratectomy. Can J Ophthalmol 1999;34:286 –9. 11. Kouyoumdjian GA, Forstot SL, Durairaj VD, Damiano RE. Infectious keratitis after laser refractive surgery. Ophthalmology 2001;108:1266 – 8. 12. Waked NE, Ojeimi GK. Excimer laser photorefractive keratectomy in Lebanon. J Refract Surg 1995;11:S270 –3. 13. Heidemann DG, Clune M, Dunn SP, Chow CYC. Infectious keratitis after photorefractive keratectomy in a comanaged setting. J Cataract Refract Surg 2000;26:140 –1. 14. Schein OD, Buehler PO, Stamler JF, et al. The impact of overnight wear on the risk of contact lens-associated ulcerative keratitis. Arch Ophthalmol 1994;112:186 –90. 15. Hersh PS, Brint SF, Maloney RK, et al. Photorefractive keratectomy versus laser in situ keratomileusis for moderate to high myopia. A randomized prospective study. Ophthalmology 1998;105:1512–22; discussion 1522–3. 16. Majmudar PA, Forstot SL, Dennis RF, et al. Topical mitomycin-C for subepithelial fibrosis after refractive corneal surgery. Ophthalmology 2000;107:89 –94. 17. Lee JB, Seong GJ, Lee JH, et al. Comparison of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia. J Cataract Refract Surg 2001;27:565–70. 18. Faschinger CW. Phototherapeutic keratectomy of a corneal scar due to presumed infection after photorefractive keratectomy. J Cataract Refract Surg 2000;26:296 –300. 19. Fulton JC, Cohen EJ, Rapuano CJ. Bacterial ulcer 3 days after excimer laser phototherapeutic keratectomy. Arch Ophthalmol 1996;114:626 –7. 20. Stulting RD, Carr JD, Thompson KP, et al. Complications of laser in situ keratomileusis for the correction of myopia. Ophthalmology 1999;106:13–20. 21. Pe´ rez-Santonja JJ, Sakla HF, Abad JL, et al. Nocardial keratitis after laser in situ keratomileusis. J Refract Surg 1997;13: 314 –7. 22. Solomon A, Karp CL, Miller D, et al. Mycobacterium interface keratitis after laser in situ keratomileusis. Ophthalmology 2001;108:2201– 8. 23. Chandra NS, Torres MF, Winthrop KL, et al. Cluster of Mycobacterium chelonae keratitis cases following laser in-situ keratomileusis. Am J Ophthalmol 2001;132:819 –30. 24. Rubinfeld RS, Negvesky GJ. Methicillin-resistant Staphylococcus aureus ulcerative keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2001;27:1523–5. 25. Gupta V, Dada T, Vajpayee RB, et al. Polymicrobial keratitis after laser in situ keratomileusis. J Refract Surg 2001;17: 147– 8. 26. Rudd JC, Moshirfar M. Methicillin-resistant Staphylococcus aureus keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2001;27:471–3. 27. Levartovsky S, Rosenwasser GOD, Goodman DF. Bacterial keratitis after laser in situ keratomileusis [published erratum appears in Ophthalmology 2001;108:1012]. Ophthalmology 2001;108:321–5. 28. Garg P, Bansal AK, Sharma S, Vemuganti GK. Bilateral infectious keratitis after laser in situ keratomileusis: A case report and review of the literature. Ophthalmology 2001;108: 121–5.
Donnenfeld et al 䡠 Infectious Keratitis after PRK 29. Alio´ JL, Pe´ rez-Santoja JJ, Tervo T, et al. Postoperative inflammation, microbial complications, and wound healing following laser in situ keratomileusis. J Refract Surg 2000;16: 523–38. 30. Karp KO, Hersh PS, Epstein RJ. Delayed keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000;26:925– 8. 31. Sridhar MS, Garg P, Bansal AK, Sharma S. Fungal keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000;26:613–5. 32. Gelender H, Carter HL, Bowman B, et al. Mycobacterium keratitis after laser in situ keratomileusis. J Refract Surg 2000;16:191–5. 33. Dada T, Sharma N, Dada VK, Vajpayee RB. Pneumococcal keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000;26:460 –1. 34. Chung MS, Goldstein MH, Driebe WT Jr, Schwartz BH. Mycobacterium chelonae keratitis after laser in situ keratomileusis successfully treated with medical therapy and flap removal. Am J Ophthalmol 2000;129:382– 4. 35. Chung MS, Goldstein MH, Driebe WT Jr, Schwartz B. Fungal keratitis after laser in situ keratomileusis: a case report. Cornea 2000;19:236 –7. 36. Quiros PA, Chuck RS, Smith RE, et al. Infectious ulcerative keratitis after laser in situ keratomileusis. Arch Ophthalmol 1999;117:1423–7. 37. Reviglio V, Rodriguez ML, Picotti GS, et al. Mycobacterium chelonae keratitis following laser in situ keratomileusis. J Refract Surg 1998;14:357– 60. ¨ zdamar A, Bahc¸ ecioglu M, Sener B. Corneal inter38. Aras C, O face abscess after excimer laser in situ keratomileusis. J Refract Surg 1998;14:156 –7. 39. Mulhem MG, Condon PI, O’Keefe M. Endophthalmitis after astigmatic myopic laser in situ keratomileusis. J Cataract Refract Surg 1997;23:948 –50.
40. Watanabe H, Sato S, Maeda N, et al. Bilateral corneal infection as a complication of laser in situ keratomileusis [letter]. Arch Ophthalmol 1997;115:1593– 4. 41. Hovanesian JA, Faktorovich EG, Hoffbauer JD, et al. Bilateral bacterial keratitis after laser in situ keratomileusis in a patient with human immunodeficiency virus infection. Arch Ophthalmol 1999;117:968 –70. 42. Al-Reefy M. Bacterial keratitis following laser in situ keratomileusis for hyperopia. J Refract Surg 1999;15:S216 –7. 43. Webber SK, Lawless MA, Sutton GL, Rogers CM. Staphylococcal infection under a LASIK flap. Cornea 1999;18: 361–5. 44. Cohen EJ, Laibson PR, Arentsen JJ, Clemons CS. Corneal ulcers associated with cosmetic extended wear soft contact lenses. Ophthalmology 1987;94:109 –14. 45. Donnenfeld ED, Cohen EJ, Arentsen JJ, et al. Changing trends in contact lens associated corneal ulcers: an overview of 116 cases. CLAO J 1986;12:145–9. 46. Alfonso E, Mandelbaum S, Fox MJ, Forster RK. Ulcerative keratitis associated with contact lens wear. Am J Ophthalmol 1986;101:429 –33. 47. Jensen HG, Felix C. In vitro antibiotic susceptibilities of ocular isolates in North and South America. In Vitro Antibiotic Testing Group. Cornea 1998;17:79 – 87. 48. Donnenfeld ED, Schrier A, Perry HD, et al. Penetration of topically applied ciprofloxacin, norfloxacin, and ofloxacin into the aqueous humor. Ophthalmology 1994;101:902–5. 49. Helm CJ, Holland GN, Lin R. Comparison of topical antibiotics for treating Mycobacterium fortuitum keratitis in an animal model. Am J Ophthalmol 1993;116:700 –7. 50. Matthews TD, Frazer DG, Minassian DC, et al. Risks of keratitis and patterns of use with disposable contact lenses. Arch Ophthalmol 1992;110:1559 – 6.
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