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Doi:10.1016/j.jcrs.2005.10.030J CATARACT REFRACT SURG - VOL 31, OCTOBER 2005 Management of infectious keratitis following laser Eric D. Donnenfeld, MD, Terry Kim, MD, Edward J. Holland, MD, Dimitri T. Azar, MD, F. Rick Palmon, MD, Jonathan B. Rubenstein, MD, Sheraz Daya, MD, Sonia H. Yoo, MD Laser in situ keratomileusis (LASIK) is the most commonly not diagnosed on initial presentation. Nine patients re- performed refractive surgical procedure for the correction quired flap excision, and 1 flap sloughed spontaneously.
of ametropia. The advantages of LASIK include rapid visual One case required enucleation, and 10 required penetrating rehabilitation, decreased stromal scarring, less irregular keratoplasty for visual rehabilitation.
astigmatism, minimal regression, less postoperative pain, In most cases, it is difficult to determine the origin of and the ability to treat a greater range of refractive disor- the infection. A recent ASCRS survey of infectious keratitis ders.Unlike surface-ablation procedures, LASIK pre- following photorefractive keratectomy (PRK) and LASIK serves the integrity of Bowman’s membrane and the for the year 2004 (Donnenfeld, ASCRS 2005) revealed a overlying epithelium, thus decreasing the risk for microbial significant decrease in atypical mycobacteria, with only keratitis. However, microbial keratitis following LASIK has 2 cases reported. Prophylaxis with a fourth-generation become an increasingly recognized, sight-threatening com- fluoroquinolone was not done in either case. Sixty-one per- cent of cases reported in this survey were due to Staphylo- The incidence of infectious keratitis following LASIK is coccus bacteria. Forty-eight infections were reported by difficult to estimate and can vary widely depending on the 46 surgeons who had performed an estimated 102 300 pro- source of the information. One large retrospective study in- cedures; an incidence of 1 infection for every 2131 proce- vestigating the complications associated with LASIK found dures performed during the year 2004.
an incidence of 2 infections in 1062 ; a similar study A review of the published reports of LASIK-associated found an incidence of 1 infection in 1019 eyes.A more re- microbial keratitis in the peer-reviewed literature reveals cent case series of LASIK-associated infections encountered over 100 cases with a striking preponderance of atypical at a single institution reports an estimated incidence be- mycobacterial (47%) and staphylococcal (19%) species.
tween 1:1000 and Based on a comprehensive re- Another interesting yet concerning observation regarding view and analysis of the literature on infections following these atypical mycobacterial LASIK infections involves LASIK, Chang et state that the incidence of infection their ability to occur in clusters or epidemics. Separate clus- after LASIK can vary widely (0% to 1.5%). In a survey by ters of atypical mycobacterial infections following LASIK the American Society of Cataract and Refractive Surgery have been published in the peer-reviewed literature. Chan- (ASCRthe incidence reported by LASIK surgeons dra et al.report a series of 7 eyes in 4 patients, all of whom who had experienced an infectious keratitis was 1 in had hyperopic LASIK at the same surgery center by the 2919 cases performed during the year 2001. In this study same surgeon on the same day. The causative organism, My- of 116 cases, 76 presented the first week after surgery, 7 cobacterium chelonae, presumably originated from a contact during the second week, 17 between the second week lens that was used intraoperatively to mask a portion of the and the fourth week, and 16 after 1 month. The most com- laser’s ablation. Another cluster is reported by Fulcher and mon organisms cultured were atypical mycobacteria (33 of coauthin 7 eyes of 7 patients; Mycobacterium szulgai 116 cases, 28%) and staphylococci (23 of 116 cases, 20%) was traced back to the ice that was used to chill BSS on species. In 47 of the 116 cases, infectious keratitis was the surgical field. Freitas et al.report a cluster of infectionsin 11 eyes of 10 patients; M chelonae was found in the por-table steaming unit used to clean the microkeratome. An-other large cluster that has not been published but has Accepted for publication August 5, 2005.
been investigated by the Centers for Disease Control and Authors are members of the American Society of Cataract and Prevention (CDCP) occurred in a surgery center in Georgia Refractive Surgery Cornea Clinical Committee.
and involved 24 patients presumed to be infected with No author has a proprietary or financial interest in any material or Mycobacterium gordonaeKarp et al.report a series of sporadic cases of atypical mycobacteria. Based on their SPECIAL REPORTS: MANAGEMENT OF POST-LASIK INFECTIOUS KERATITIS findings, the CDCP concluded that LASIK-associated kera-titis from atypical mycobacteria may be more common thanpreviously thought and also suggested that LASIK could bea risk factor for the development of atypical mycobacterialkeratitis.
Infectious keratitis is a potentially devastating compli- cation of LASIK. In addition to the ASCRS survey findingsregarding the morbidity of these infections,the series ofclustered atypical mycobacterial infections (25 eyes of 21patients) shows that 4 patients experienced bilateral infec-tions, almost 50% of the affected eyes required flap ampu-tation, and all patients required aggressive topical and oralantimicrobial therapy for a 2- to 3-month period.
The organisms encountered in infectious keratitis fol- lowing LASIK can be unusual, difficult to predict, andwill often not respond to empiric therapy with older-gener-ation topical fluoroquinolone antibiotic agents. For this Figure 1. Clinical photograph of DLK showing diffuse intralamellar reason, we highly recommend lifting the flap and taking corneal scrapings for appropriate stains and cultures ifany suspicious infiltrate appears following LASIK. The re- PREVENTION OF INFECTIOUS KERATITIS FOLLOWING LASIK sults of these stains and cultures can be helpful in guidingantimicrobial therapy. A high degree of suspicion coupled Several steps may help prevent infectious keratitis fol- with a rapid diagnosis and appropriate therapy can result lowing LASIK. Preoperatively, the lids and lacrimal appara- in eradication of the infection and visual recovery. We rec- tus of all patients considering refractive surgery should be ommend that any focal infiltrate following LASIK should be thoroughly examined. Treatment of infectious lid disease considered infectious, and we discourage the practice of with hot compresses and an antibiotic ointment applied 3 empirical antibiotic treatment without culturing.
times a day to the lid margin may help reduce the risk for Diffuse lamellar keratitis (DLK) is a sterile inflamma- bacterial keratitis. Proper sterilization techniques can pre- tion of the lamellar interface following LASIK and is associ- vent the use of contaminated instruments. A minority of ated with epithelial abrasions and trauma. It traditionally clinicians recommend performing monocular surgery or occurs within the first few days after LASIK unless there using separate instruments when performing bilateral sur- is postoperative ocular trauma.Therapy is high-dose gery,although this is not the practice of the members of topical corticosteroids; in severe cases, oral corticosteroids the ASCRS Cornea Clinical Committee. Some clinicians and interface irrigation may be necessary recommend the use of sterile drapes, gowns, gloves, and Infectious keratitis following LASIK often presents with inflammation in the corneal interface, which can mimicDLK. Because of this, many cases are typically treatedwith frequent topical corticosteroid therapy that can cloudthe clinical picture with transient improvement in the in-flammation. However, unlike DLK, the inflammation asso-ciated with LASIK-associated infections usually persistsdespite topical corticosteroids, and the underlying infec-tions can potentially worsen with corticosteroid tapering.
The appearance of an interface inflammation more than 1week after LASIK should be presumed to be of an infectiousetiology until proven otherwise. Diffuse lamellar keratitischaracteristically has a diffuse appearance (asthe name suggests, while infectious keratitis has a focalarea of infiltration surrounded by diffuse inflammation(or even focal inflammation limited to the areaof the infiltrate. Any focal infiltrate surrounded by inflam-mation should be presumed infectious until proven Figure 2. Clinical photograph of infectious keratitis following LASIK with a focal infiltrate surrounded by diffuse inflammation.
J CATARACT REFRACT SURG - VOL 31, OCTOBER 2005 SPECIAL REPORTS: MANAGEMENT OF POST-LASIK INFECTIOUS KERATITIS masks by the treating physician and assisting technician. A 0.5% given in a loading dose every 5 minutes for 3 doses povidone–iodine solution (Betadine 10%) lid prep before and then every 30 minutes, alternating with an antimicro- cataract surgery has been shown to reduce the incidence bial that is rapidly bacteriocidal and has increased activity of endophthalmitis postoperatively and is recommended against gram-positive organisms, such as fortified cefazolin by many clinicians when performing LASIK.Finally, sev- 50 mg/mL every 30 minutes. In patients who work in a hos- eral epidemics of atypical mycobacteria have been associ- pital environment, there is an added risk for methicillin-re- ated with the use of nonsterile water to clean instruments sistant Staphylococcus aureus (MRSA). In these patients, or the use of ice during LASIK.All fluids applied to we recommend the substitution of fortified vancomycin the eye before, during, and after LASIK should be sterile.
50 mg/mL for cefazolin every 30 minutes to provide moreeffective therapy against MRSA In addition,we advocate the use of oral doxycycline 100 mg twicea day to inhibit collagenase production and also discontin- TREATMENT OF INFECTIOUS KERATITIS FOLLOWING LASIK We divide infectious keratitis following LASIK into For delayed-onset keratitis, which is commonly due to early onset (occurring within the first 2 weeks of surgery) atypical mycobacteria, nocardia, and fungi, we recommend and late onset (occurring 2 weeks to 3 months after sur- beginning therapy with amikacin 35 mg/mL every 30 min- gery). The organisms seen in early-onset infectious keratitis utes, alternating with a fourth-generation fluoroquinolone are common bacterial pathogens such as staphylococcal (gatifloxacin 0.3% or moxifloxacin 0.5%) every 30 min- and streptococcal species. Gram-negative organisms are utes, starting oral doxycycline 100 mg twice a day, and dis- rare. The organisms seen in late-onset infectious keratitis continuing corticosteroids (This treatment will are usually opportunistic such as fungi, nocardia, and atyp- not affect fungal infections; therefore, treatment in all cases ical mycobacteria. The literature review of LASIK-associated of infectious keratitis should be modified based on culture infections by Chang and coauthorssupports this classifi- and scraping results and clinical response to therapy.
cation of infection. Based on their study, gram-positive In conclusion, infectious keratitis is a potentially dev- organisms were more likely to present within 7 days of sur- astating complication following LASIK. Culture results re- gery (P Z.001) while mycobacterial infections were more veal opportunistic infections and gram-positive bacteria as likely to present 10 or more days after surgery (P!.001).
the most common organisms. Infectious keratitis may pres- Since the organisms responsible for infectious keratitis ent as late as months after LASIK, and its frequent misdiag- following LASIK will often not respond to empiric therapy, nosis at initial presentation may result in significant vision we recommend lifting the flap, scraping and culturing sus- loss. We do not recommend empiric therapy as most organ- picious cases, and selecting appropriate culture media in- isms are opportunistic and do not respond to conventional cluding blood agar, chocolate agar, Sabouraud’s agar, and therapy. A high degree of suspicion with flap elevation and thioglycolate broth. For infectious keratitis after 2 weeks, culturing should be performed in all eyes suspected of we recommend a growth media for atypical mycobacteria having an infectious infiltrate(s) following LASIK.
such as Lowenstein-Jensen or Middlebrook 7H-9 agar in We hope the information contained in this report will addition to the other culture media. If these special media help LASIK surgeons assess their respective approaches to are unavailable, we recommend using blood agar as atypi- the management of post-LASIK infectious keratitis. The cal mycobacteria grow quite well on these plates. At thetime of culture, we also recommend scraping the infiltrate Elevate flap
and performing a Gram stain, Gomori-methenamine silverstain, and Ziehl-Neelsen stain to rule out unusual patho- Culture and scrape
gens such as nocardia, atypical mycobacteria, and fungi.
Onset 2 Weeks or Less
In cases in which cultures are negative and the infectioncontinues to worsen, a corneal biopsy or polymerase chain gatifloxacin 0.3
or moxifloxacin 0.5
cefazolin 50 mg/mL every 30 minutes
For the treatment of rapid-onset and delayed-onset in- If patient is exposed to hospital environment, substitute vancomycin 50 mg/mL
fectious keratitis, the recommendation is to elevate the flap for cefazolin
and culture. Irrigation of the flap interface with an appro- Onset 2 Weeks or More
priate antibiotic solution (fortified vancomycin 50 mg/mLfor rapid-onset keratitis and fortified amikacin 35 mg/mL gatifloxacin 0.3
or moxifloxacin 0.5
for delayed-onset keratitis) may be helpful. For rapid-onset amikacin 35 mg/mL every 30 minutes
keratitis, we recommend a fourth-generation topical fluo-roquinolone such as gatifloxacin 0.3% or moxifloxacin Figure 3. Treatment of infectious keratitis following LASIK.
J CATARACT REFRACT SURG - VOL 31, OCTOBER 2005 SPECIAL REPORTS: MANAGEMENT OF POST-LASIK INFECTIOUS KERATITIS goal is to standardize treatment, minimize visual loss, and 10. Chang MA, Jain S, Azar DT. Infections following laser in situ keratomi- leusis: an integration of the published literature. Surv Ophthalmol2004; 49:269–280 11. Solomon R, Donnenfeld ED, Azar DT, et al. Infectious keratitis after la- ser in situ keratomileusis: results of an ASCRS survey. J Cataract RefractSurg 2003; 29:2001–2006 1. Hersh PS, Brint SF, Maloney RK, et al. Photorefractive keratectomy ver- 12. Chandra NS, Torres MF, Winthrop KL, et al. Cluster of Mycobacterium sus laser in situ keratomileusis for moderate to high myopia; a ran- chelonae keratitis cases following laser in-situ keratomileusis. Am J domized prospective study. Ophthalmology 1998; 105:1512–1522; 13. Fulcher SFA, Fader RC, Rosa RH, Holmes GP. Delayed-onset mycobac- 2. Pallikaris IG, Papatzanaki ME, Stathi EZ, et al. Laser in situ keratomileu- terial keratitis after LASIK. Cornea 2002; 21:546–554 14. Freitas D, Alvarenga L, Sampaio J, et al. An outbreak of Mycobacterium 3. Pe´rez-Santonja JJ, Bellot J, Claramonte P, et al. Laser in situ keratomi- chelonae infection after LASIK. Ophthalmology 2003; 110:276–285 leusis to correct high myopia. J Cataract Refract Surg 1997; 23:372– 15. Winthrop KL, Steinberg EB, Holmes G, et al. Epidemic and sporadic cases of nontuberculous mycobacterial keratitis associated with laser 4. Helmy SA, Salah A, Badawy TT, Sidky AN. Photorefractive keratectomy in situ keratomileusis. Am J Ophthalmol 2003; 135:223–224 and laser in situ keratomileusis for myopia between 6.00 and 10.00 di- 16. Bu¨hren J, Kohnen T. Corneal wound healing after laser in situ kerato- opters. J Refract Surg 1996; 12:417–421 mileusis flap lift and epithelial abrasion. J Cataract Refract Surg 2003; 5. Salah T, Waring GO III, El-Maghraby A, et al. Excimer laser in-situ ker- atomileusis (LASIK) under a corneal flap for myopia of 2 to 20 D. Trans 17. Stulting RD, Randleman JB, Couser JM, Thompson KP. The epidemiol- Am Ophthalmol Soc 1995; 93:163–183; discussion 184–190 ogy of diffuse lamellar keratitis. Cornea 2004; 23:680–688 6. Azar DT, Farah SG. Laser in situ keratomileusis versus photorefractive 18. Hoffman RS, Fine IH, Packer M. Incidence and outcomes of LASIK with keratectomy; an update on indications and safety [guest editorial].
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