Bilateral Candida parapsilosis interface keratitis after laser in situ keratomileusis Marcus S. Muallem, MD, Eduardo C. Alfonso, MD, Andre C. Romano, MD, Darlene Miller, MPH, Joseph Kurstin, MD, Fabiana B. Marangon, MD, William W. Culbertson, MD, Sonia H. Yoo, MD We report a case of Candida infection after laser in situ keratomileusis (LASIK) and review the literature for reports of post-LASIK fungal infections. Risk factors may include postoperative surgical intervention and extended use of topical steroids. J Cataract Refract Surg 2003; 29:2022–2025 © 2003 ASCRS and ESCRS
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hile the risk for infection may be higher after photorefractive keratectomy because of the presence of a large epithelial defect,1 laser in situ keratomileusis (LASIK) can also be associated with severe, vision-threatening infectious keratitis. The literature contains reports of infectious keratitis after LASIK.2 Most, however, describe keratitis of bacterial or mycobacterial etiology, with only a few cases of fungal keratitis.2 We describe a case of Candida parapsilosis keratitis after LASIK.
Case Report A 64-year-old man was referred on February 14, 2002, for the evaluation of dense, white, interface opacities in both eyes. The patient had had uneventful LASIK on August 24, 2001, to correct a ⫹3.25 diopter (D) refractive error in both eyes. The preoperative uncorrected visual acuity (UCVA) was 20/200 in both eyes, correctable to 20/20 with spectacles. The
Accepted for publication February 14, 2003. From the Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida, USA. Presented at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, Philadelphia, Pennsylvania, USA, June 2002. None of the authors has a financial or proprietary interest in any material or method mentioned. Correspondence to Eduardo C. Alfonso, MD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, Florida 33149, USA. E-mail:
[email protected]. © 2003 ASCRS and ESCRS Published by Elsevier Inc.
targeted correction was ⫹3.85 D in the right eye and ⫹6.00 D in the left eye (monovision). On the first postoperative day, the UCVA was 20/50 in the right eye and J1 in the left eye. One week later, the UCVA was 20/40 and J1, respectively, and trace diffuse lamellar keratitis was noticed. Fluorometholone 0.1% (FML威) eyedrops were prescribed 6 times a day. Two weeks later, some interface opacities were seen in the temporal interface in the right eye. On October 3, 2001, the right flap was lifted and the opacities were scraped with the application of alcohol 20%. A bandage soft contact lens was applied. The next day, some residual interface opacities were noticed. The contact lens was removed, and FML drops 8 times a day and ofloxacin 0.3% drops (Ocuflox威) 4 times a day were prescribed. About 1 month later, on November 6, 2001, some opacities in the temporal interface, several smaller ones inferiorly, and diffuse haze were seen in the right eye. Prednisolone acetate 1% (Pred Forte威) every 30 minutes and Ocuflox 4 times a day were prescribed, with no subsequent change in the opacities. On November 16, 2001, interface sheath opacity was seen in the left eye, which progressed in the following 2 weeks and was believed to be epithelial ingrowth. Pred Forte was given 4 times a day in both eyes, and on January 10, the dosage was increased to every 15 minutes. On January 16, 2002, the lower nasal border of the left flap was noted to be melting. The 2 flaps were lifted, and the opacities, believed to be epithelial ingrowth, were scraped using alcohol 20%. Five days later, new interface opacities developed in the eyes. Pred Forte every 2 hours was restarted, and 1 week later, the dosage increased to every 30 minutes. During the next 2 weeks, the opacities worsened and the Pred Forte was discontinued. When first seen on February 14, 2002, the patient complained of a decrease in visual acuity, pain, burning, itching, 0886-3350/03/$–see front matter doi:10.1016/S0886-3350(03)00217-7
CASE REPORTS: MUALLEM
Figure 1. (Muallem) The interface infiltrates as seen at presentation in the right (A) and left (B) eye. Melting can be seen at the inferonasal edge of the left flap. C and D: The right and left eye, respectively, 4 days after a 100-day course of topical antifungal therapy.
and foreign-body sensation in the eyes that had been present for 2 weeks. The UCVA was 20/30⫹2 in the right eye and 20/50 in the left eye. Refraction could not be measured because of patient discomfort. Intraocular pressure (IOP) was 32 mm Hg in the right eye and 17 mm Hg in the left eye. Both conjunctivas had moderate injection. Interface infiltrates were seen in both eyes, with melting of the inferonasal border of the left flap (Figure 1, A and B). The rest of the examination was unremarkable. Confocal microscopy (ConfoScan 3, Nidek) was performed (Figure 2). Deposits suggestive of yeast were seen in the interface. The next day, the left flap was lifted and the infiltrate scraped from the stromal bed and the inner surface of the flap. The infiltrate was easily scraped off, but a faint residual opacity remained. Samples were sent for direct microscopic examination and cultures (chocolate, blood, Sabouraud, and Lo¨ wenstein-Jensen agars and thioglycolate broth). The flap was refloated in place, and a bandage soft contact lens was applied. The smears showed the presence of yeast (Figure 3, B). The patient was started on topical drops of amphotericin B 0.15% every hour in both eyes. Three days later, the UCVA was 20/50 in the right eye and 20/60 in the left eye and the IOP was 22 mm Hg and 10 mm Hg, respectively. A significant improvement was noted in the right eye. There was a heavy growth of C parapsilosis in the cultures (Figure 3, A). The contact lens was removed. The patient was followed closely, and the inferotemporal border of the right flap started to melt. The amphotericin B drops were tapered to every 2 hours. Four days later, topical flucytosine 1% drops were added every 2 hours to both eyes because of the reported toxicity of
frequent administration of amphotericin B drops. Meanwhile, the amphotericin dosage was continued every 2 hours for 3 days to prevent recurrence, but both topical antifungals were tapered slowly thereafter. On March 14, the flucytosine drops were discontinued after a 3-week course. On April 25, the amphotericin B drops were stopped, concluding a 100-day course. The UCVA was 20/40 and the IOP was 12 mm Hg in both eyes. Photographs taken 4 days later are shown in Figure 1, C and D. There was no recurrence of infection on June 8, 6 weeks after the antifungal drops were discontinued.
Figure 2. (Muallem) Confocal microscopy shows highly reflective, round organisms, 3.0 to 4.5 m in diameter, suggestive of a yeast infection.
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Figure 3. (Muallem) A: Heavy growth of C parapsilosis on blood agar. B: Smears revealed the presence of yeast with some epithelial cells. There is beading of some yeast cells.
Discussion The incidence of post-LASIK infections is believed to be approximately 1 in 5000 cases.3 Nascimento and coauthors4 were the first to report a case of post-LASIK infectious keratitis caused by Nocardia asteroides. At the end of 1999, there were only 10 published reports of culture-proven infectious keratitis occurring after LASIK,4 –13 and none was of fungal etiology. It was not until 2000 that the first 3 reports of fungal keratitis after LASIK were published,14 –16 followed by 2 more cases in 2001.3,17 The fungi implicated were Scedosporium apiospermum, Aspergillus flavus, Curvularia, Aspergillus fumigatus, and Fusarium solani. Excluding the case of polymicrobial keratitis (Staphylococcus epidermidis, F solani, and herpes simplex virus) after LASIK reported by Gupta et al.,17 the risk factors for fungal infection in the 4 remaining cases were that all were treated with topical/systemic steroids and 3 had an additional surgical procedure after LASIK. These factors were also encountered in our patient. The onset of symptoms after the last procedure ranged from 2 days to 2 weeks (5 days in our patient). Referral to a cornea specialist was 15 to 44 days from the last procedure (1 month in our patient). The visual acuity at presentation was light perception in 2 patients, counting fingers in 1, and 20/30 in the last. The infiltrate was 2.5 to 7.5 mm in diameter. It was full corneal thickness in 2 cases and superficial in 1, and there was 60% corneal thinning in the fourth case. Three patients had hypopyon at presentation, and 1 had epithelial ingrowth. Specimens for cultures were obtained from corneal scrapings in all 4, and 1 needed a corneal biopsy. All 4 were treated with topical natamycin 5%, and 2 received topical amphotericin B 0.15% in combination. In addition, 3 patients received systemic antifungals (2 received ketoconazole and 1, itraconazole). 2024
The outcomes varied significantly. Two patients had therapeutic penetrating keratoplasty, with the eye quiet and the graft edematous 4 months postoperatively in 1 patient and the other with no follow-up recorded. Visual acuity was 20/30 with superficial scarring in the third patient 1 month after diagnosis. The fourth patient had corneal perforation after biopsy. Glue and a bandage soft contact lens were applied. With treatment, the infiltrate resolved over weeks with neovascularization of the interface. The UCVA was 20/200, correctable to 20/40 with a rigid contact lens. In our case, the patient had interface opacities, most likely epithelial ingrowth, that had been scraped twice in the right eye and once in the left eye before referral. During an extended period after LASIK, the patient was treated with topical steroids that may have affected the ocular surface defense mechanisms. Candida parapsilosis had the highest incidence among tested fungi in the normal outer eye,18 and extended topical steroid treatment might have facilitated its inoculation and survival in the patient’s interface. Inoculation might have been the result of trauma caused by the bottle tip or epithelial toxicity from the steroid or the preservative. The solution could have also been contaminated. None of the topical steroid bottles was available for culture in our case. The opacities in both eyes had a similar clinical appearance, and it was reasonable to assume a similar etiology for both. Confocal microscopy helped confirm the similar appearance of the deposits. Since the visual acuity was worse in the left eye at presentation, we chose to lift only the left flap for scrapings and await the results. When the smears revealed yeast cells, we decided to treat the right eye medically and observe for worsening before lifting the flap and scraping the opacity in this eye. Indeed, 3 days after initiating the topical treatment, significant improvement occurred in the right eye.
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Unlike bacterial keratitis, which can be controlled by potent antibiotics, fungal keratitis is difficult to manage because of the lack of effective antifungal agents, low bioavailability, ocular toxicity, decreased solubility, and late presentation with large infiltrates. The favorable outcome in our patient might have been the result of a less virulent species, peripheral corneal location of infiltrates, a specimen collected directly from the site of infection, and a thorough microbiological study that yielded an early diagnosis, appropriate therapy, and flap melt at the area of infection in both eyes that may have augmented the antifungal agents’ penetration. To our knowledge, Candida keratitis after LASIK has not been reported. Fungal keratitis is a potential sight-threatening complication of LASIK. Risk factors may include steroid treatment and additional surgical procedures. Topical steroids should not be used for the treatment of epithelial ingrowth for extended periods. Such therapy has no support in the literature or in community standards. Confocal microscopy can be of diagnostic value. Flap “lift and scrape” with a thorough microbiological workup should be encouraged to rule out infection in cases of suspicious post-LASIK interface opacities. Sampling at the site of infection is the only way to obtain a relevant positive culture.
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