Bilateral Fusarium oxysporum keratitis after laser in situ keratomileusis

Bilateral Fusarium oxysporum keratitis after laser in situ keratomileusis

CASE REPORT Bilateral Fusarium oxysporum keratitis after laser in situ keratomileusis Georgios Labiris, MD, PhD, Leonie Troeber, MD, Zisis Gatzioufas...

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CASE REPORT

Bilateral Fusarium oxysporum keratitis after laser in situ keratomileusis Georgios Labiris, MD, PhD, Leonie Troeber, MD, Zisis Gatzioufas, MD, PhD, Evangelos Stavridis, MD, Berthold Seitz, MD, ML, FEBO

We report the successful management of a rare case of bilateral post-laser in situ keratomileusis (LASIK) Fusarium oxysporum keratitis and propose a therapeutic strategy. A 19-year-old white man with no systemic diseases was referred to our emergency service 3 days after microkeratome-assisted myopic bilateral LASIK correction. He complained of blurred-vision, photophobia, and ocular pain. Clinical findings (satellite lesions, hypopyon) suggested fungal keratitis. Flaps were immediately lifted and rinsed with povidone–iodine 10%, and intensive topical and systemic and combined antifungal and antibacterial treatment was introduced. Topical cortisone drops were administered after 3 days. Despite initial deterioration of the clinical picture, all symptoms resolved quickly. Polymerase chain reaction indicated F oxysporum. Relapse occurred in the left eye, which was successfully managed. The final uncorrected distance visual acuity was 20/20 in both eyes. Fusarium oxysporum post-LASIK keratitis may occur in the early phase. Prompt diagnosis, interface irrigation with povidone-iodine solution, and intensive long-term treatment contribute to a favorable outcome. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2012; 38:2040–2044 Q 2012 ASCRS and ESCRS

Laser in situ keratomileusis (LASIK) is a wellestablished, safe refractive procedure that is commonly used for the treatment of refractive errors. Post-LASIK infection, although rare, cannot always be prevented1; therefore, early diagnosis and treatment are important for a satisfactory clinical outcome, especially in cases of fungal keratitis, which often results in devastating ocular complications.2 We present a case of post-LASIK bilateral Fusarium oxysporum keratitis with a satisfactory outcome and propose a therapeutic strategy.

Submitted: January 24, 2012. Final revision submitted: May 3, 2012. Accepted: May 4, 2012. From the Department of Ophthalmology (Labiris, Troeber, Gatzioufas, Stavridis, Seitz), University of Saarland Medical Center UKS, Homburg/Saar, Germany and the Department of Ophthalmology (Labiris), Democritus University, Alexandroupolis, Greece. Corresponding author: Berthold Seitz, MD, ML, FEBO, Department of Ophthalmology, University of Saarland Medical Center UKS, Homburg/Saar, Germany. E-mail: [email protected].

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Q 2012 ASCRS and ESCRS Published by Elsevier Inc.

CASE REPORT A 19-year-old white man was referred to the emergency service of the Department of Ophthalmology at the University Medical Center of Saarland, Germany, 3 days after bilateral, myopic, uneventful, microkeratome-assisted LASIK correction in a private ophthalmology center. The patient complained of bilateral blurred vision, ocular discomfort, and pain. The symptoms started about 24 hours postoperatively and gradually became worse despite the patient’s report of careful administration of the prescribed postoperative regimen. On admission, the patient complained of intense photophobia and tearing; the uncorrected distance visual acuity (UDVA) was 20/30 in the right eye and 20/60 in the left eye. Slitlamp biomicroscopy indicated bilateral conjunctival injection with multiple corneal infiltrates in the right eye and satellite corneal infiltrates in a ring-like configuration with hypopyon in the left eye (Figure 1). Clinical examination suggested the possibility of fungal infection, and the following therapeutic plan was selected to address the sight-threatening situation: Flaps were lifted, corneal smears were obtained (Gram and Giemsa stains), and interfaces were thoroughly rinsed with vancomycin 2.0% and amphotericin B 0.5% solutions followed by povidone–iodine 10% solution for 1 minute. Topical therapy was modified to amphotericin B 0.5% drops hourly; cefuroxime fortified 5.0% drops hourly; tobramycin fortified 4.2% drops hourly; and combined bacitracin, neomycin, polymyxin B, gramicidin ointment (Polyspectran) every night. Adjuvant systemic therapy was initiated, including 0886-3350/$ - see front matter http://dx.doi.org/10.1016/j.jcrs.2012.08.037

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Figure 1. A: Left eye. Corneal infiltrates in a satellite configuration in the interface (dashed arrows) and hypopyon (continuous arrow). B. Right eye. Minor paracentral infiltrates in the interface.

intravenous (IV) administration of voriconazole (Vfend) 400 mg twice a day, ceftriaxone (Rocephin) 2 gr daily, and oral administration of doxycycline 100 mg twice a day to minimize the risk for corneal melting. Despite intense local and systemic treatment, slitlamp biomicroscopy on the day after the flap lifting indicated deterioration of the clinical picture in the left eye with more pronounced corneal infiltration and higher levels of hypopyon (Figure 2). The treatment plan was not modified and after 3 days, prednisolone acetate 1% eyedrops (Inflanefran forte) 5 times daily were additionally administered. Within 1 week, subjective ocular discomfort disappeared and the UDVA improved to 20/20 in the right eye and 20/25 in the left eye. The fourth day after admission, polymerase chain reaction analysis of the corneal specimens indicated F oxysporum/Galactomyces geotrichum in both eyes, confirming the clinical diagnosis. Despite the improvement in the symptoms, the patient was treated for a total of 2 months with amphotericin B eyedrops, cefuroxime fortified 5.0% eyedrops, tobramycin fortified 4.2% eyedrops, gramicidin ointment, prednisolone

acetate 1.0% eyedrops, and sodium hyaluronate 0.1% eyedrops. Five months after the initial LASIK procedure, only minor corneal scarring could be visualized, primarily in the left eye (Figure 3). However, at 6 months, the patient experienced nonspecific ocular discomfort in the left eye. Corneal infiltrates were seen in the interface. Because of the possibility of fungal relapse (Figure 4), the patient was readmitted. An intensive combination of topical (amphotericin B eyedrops, cefuroxime fortified 5.0% eyedrops, tobramycin fortified 4.2% eyedrops, gramicidin ointment, prednisolone acetate eyedrops) and systemic (voriconazole 200 mg and doxycycline 100 mg) therapy was applied for 3 months, which resulted in a rapid alleviation of symptoms and improvement of the UDVA to 20/20 in both eyes (Figure 5). No other relapses occurred during a 3-year follow-up.

Figure 2. Left eye 24 hours after flap lifting and interface rinsing (day 4). Clinical picture deteriorated with more intense conjunctival injection and higher levels of hypopyon (arrow).

Figure 3. Left eye. Evidence of corneal scarring 5 months after surgery.

DISCUSSION Post-LASIK fungal infection is a rare but sightthreatening complication. Since the first reports in

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Figure 4. Left eye. Suspicion of relapse 6 months after surgery. Interface infiltrates.

2000,3,4 both unilateral5–9 and bilateral cases have been reported.2,10–12 Visual outcomes following post-LASIK fungal infection range from no light perception due to evisceration and counting fingers2 to varying degrees of suboptimal visual acuity.5–8,10–13 Only Chen et al.9 report a UDVA of 20/20 in their unilateral case with Candida parapsilosis. Our case is the first to report optimal uncorrected visual recovery following bilateral postLASIK fungal infection with the F oxysporum species. The impressive visual outcome in our report could be associated with the following factors: 1. Prompt introduction of treatment based on slitlamp biomicroscopy findings. Differential diagnosis of interface keratitis includes bacterial, viral, mycobacterial, fungal, Nocardia, and polymicrobial causes.14 Diffuse lamellar keratitis10 was excluded immediately because of the pattern of corneal infiltrations (satellite

lesions rather than diffuse infiltrates), the intense conjunctival injection, and the presence of hypopyon. The intense redness, in association with the watery discharge and the presence of hypopyon, introduced the possibility of fungus in the differential diagnosis.14 Moreover, the intensity of symptoms in the immediate postoperative period distinguished the diagnosis from mycobacterial infection, which is known to manifest primarily as a late-onset infection.14 Microbial coinfection could not be excluded; therefore, intensive topical and systemic antibiotic treatment was also administered. Note that at the time of the patient’s admission, moxifloxacin and gatifloxacin eyedrop preparations were not readily available at our department. However, the clinical picture did not raise suspicion of atypical mycobacterial infection; therefore, amikacin was not applied. 2. Prompt lifting of the flap and irrigation of the interface. The American Society of Cataract and Refractive Surgery recommends flap lifting for culturing and irrigating with the proper antimicrobial solution.15 A brief review of a series of post-LASIK fungal keratitis reports suggested that early flap lifting and interface rinsing are usually associated with better visual outcomes9,10 while delayed or no flap lifts are usually associated with poor ones.2,6,10,11 In our case, both interfaces were thoroughly rinsed within 24 hours of referral and also rinsed with povidone–iodine solution and antifungal agents after 4 postoperative days. Because of the severity of the symptoms and the potential sight-threatening complications, we used povidone– iodine 10% solution for interface rinsing. However, we do not know of specific published data on the potential efficacy and safety of povidone–iodine 10% solution on corneal stroma. In our case, direct rinsing of the interface for 1 minute proved to be efficient with no

Figure 5. A: Left eye 1 year after surgery. Minor corneal scars are visualized. The UDVA was 20/20. B: Right eye 1 year after surgery. Minor corneal scars are visualized. The UDVA was 20/20. J CATARACT REFRACT SURG - VOL 38, NOVEMBER 2012

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evident damage to the exposed stroma. Other concentrations (2.5% or 5.0%) might have induced similar outcomes; however, this can only be confirmed in a research setting rather than a clinical setting. 3. Prompt introduction of cortisone drops. The controversial role of topical steroid use as a predisposing factor for fungal keratitis has been documented.16,17 It is known that a significant percentage of ophthalmologists are reluctant to administer cortisone drops on suspicion of fungal keratitis. Moreover, the surgical trauma following a LASIK procedure is an additional predisposing factor.16 Only one post-LASIK fungal infection report definitely states that topical cortisone treatment was administered to control severe anterior chamber inflammation.7 The other reports tapered, stopped,5,10,11 or omitted specific information on cortisone use. In our case, we administered topical prednisolone after 3 days of amphotericin B since earlier experimental data suggest that its efficacy remains unaffected.18 We are confident that this had a beneficial impact on local inflammation and minimized the incidence of corneal scarring. Although natamycin and voriconazole are also efficient in Fusarium ulcers, we are not aware of published data that prove unaffected efficacy during cortisone coadministration. 4. Length of treatment. Fungal keratitis requires long-term administration of treatment. In our case, we experienced a mild relapse in the left eye for 2 possible reasons: The initial 2-month treatment duration was insufficient, and/or the use of topical cortisone in the first week of treatment requires even longer periods of topical antifungal chemoprophylaxis. Because Fusarium species are well known for their resistance capacity,19 a 6-month period of chemoprophylaxis should perhaps be recommended. However, in retrospect, the prompt introduction of combined antibacterial and antifungal treatment on fungal relapse might have been avoided and only antifungal agents might have been administered since the possibility of microbial coinfection was minimal. It is beyond the objective of this report to comment on the possible causes of a post-LASIK fungal infection; rather, we would like to propose a therapeutic strategy that in our case resulted in a fortunate outcome in visual acuity. However, thorough povidone–iodine rinsing prior to LASIK and use of a new blade in each eye are among the fundamental safety precautions against bilateral infections. Moreover, femtosecond-assisted flap creation with a new interface in each eye might also provide sufficient safety. Nevertheless, in case of post-LASIK fungal infection, our experience suggests prompt initiation of combined antibacterial and antifungal treatment in a case with a suspicious clinical picture without waiting for laboratory confirmation; prompt lifting of the flap and

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irrigation of the interface with antifungal agents and povidone–iodine solution; use of topical cortisone drops for inflammation control and minimization of postinflammatory corneal scarring; and on laboratory confirmation of fungal infection, long-term chemoprophylaxis, possibly for 6 months, to prevent a relapse. Further reports on post-LASIK fungal keratitis are needed to confirm our therapeutic proposal and contribute to the knowledge about this sight-threatening complication. REFERENCES 1. Solomon R, Donnenfeld ED, Azar DT, Holland EJ, Palmon FR, Pflugfelder SC, Rubenstein JB. Infectious keratitis after laser in situ keratomileusis: results of an ASCRS survey. J Cataract Refract Surg 2003; 29:2001–2006  mur M, Ersoz TR, 2. Taylan Sekeroglu H, Erdem E, Yar K, Yag Uguz A. A rare devastating complication of LASIK: bilateral fungal keratitis. J Ophthalmol 2010; 2010:450230. Available at: http://downloads.hindawi.com/journals/jop/2010/450230. pdf. Accessed July 5, 2012 3. Chung MS, Goldstein MH, Driebe WT Jr, Schwartz B. Fungal keratitis after laser in situ keratomileusis: a case report. Cornea 2000; 19:236–237 4. Sridhar MS, Garp P, Bansal AK, Gopinathan U. Aspergillus flavus keratitis after laser in situ keratomileusis. Am J Ophthalmol 2000; 129:802–804 5. Solomon R, Biser SA, Donnenfeld ED, Perry HD, Doshi SJ, Lee CC. Candida parapsilosis keratitis following treatment of epithelial ingrowth after laser in situ keratomileusis. Eye Contact Lens 2004; 30:85–86 6. Pache M, Schipper I, Flammer J, Meyer P. Unilateral fungal and mycobacterial keratitis after simultaneous laser in situ keratomileusis. Cornea 2003; 22:72–75 7. Verma S, Tuft SJ. Fusarium solani keratitis following LASIK for myopia [letter]. Br J Ophthalmol 2002; 86:1190–1191. Available at: http://bjo.bmj.com/content/86/10/1190.full.pdf. Accessed July 5, 2012 8. Leung EH, Moskalewicz R, Parada JP, Kovach KJ, Bouchard C. Exophiala jeanselmei keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2008; 34:1809–1811 9. Chen W-L, Tsai Y-Y, Lin J-M, Chiang C-C. Unilateral Candida parapsilosis interface keratitis after laser in situ keratomileusisdcase report and review of the literature. Cornea 2009; 28:105–107 10. Peng Q, Holzer MP, Kaufer PH, Apple DJ, Solomon KD. Interface fungal infection after laser in situ keratomileusis presenting as diffuse lamellar keratitis; a clinicopathological report. J Cataract Refract Surg 2002; 28:1400–1408 11. Muallem MS, Alfonso EC, Romano AC, Miller D, Kurstin J, Marangon FB, Culbertson WW, Yoo SH. Bilateral Candida parapsilosis interface keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2003; 29:2022–2025 12. Sun Y, Jain A, Ta CN. Aspergillus fumigatus keratitis following laser in situ keratomileusis. J Cataract Refract Surg 2007; 33:1806–1807 13. Karimian F, Feizi S, Nazari R, Zarin-Bakhsh P. Delayed-onset Actinomyces keratitis after laser in situ keratomileusis. Cornea 2008; 27:843–846 14. Chang MA, Jain S, Azar DT. Infections following laser in situ keratomileusis: an integration of the published literature. Surv Ophthalmol 2004; 49:269–280 15. Donnenfeld ED, Kim T, Holland EJ, Azar DT, Palmon FR, Rubenstein JB, Daya S, Yoo SH. ASCRS white paper;

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asp?issnZ0301-4738;yearZ2003;volumeZ51;issueZ4;spage Z315;epageZ321;aulastZBharathi. Accessed July 5, 2012 18. O’Day DM, Ray WA, Robinson R, Head WS. Efficacy of antifungal agents in the cornea. II. Influence of corticosteroids. Invest Ophthalmol Vis Sci 1984; 25:331–335. Available at: http:// www.iovs.org/content/25/3/331.full.pdf. Accessed July 5, 2012 19. Edelstein SL, Akduman L, Durham BH, Fothergill AW, Hsu HY. Resistant fusarium keratitis progressing to endophthalmitis. Eye Contact Lens 2011 Oct 8 [Epub ahead of print]

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