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Acremonium fungal infection in 4 patients after laser in situ keratomileusis
Acremonium fungal infection in 4 patients after laser in situ keratomileusis Jose´ F. Alfonso, MD, PhD, M. Begon˜a Baamonde, MD, PhD, M. Jesu´s Santos, MD, PhD, Aurora Astudillo, MD, PhD, Luis Ferna´ndez-Vega, MD, PhD We present 4 patients who had laser in situ keratomileusis and were referred to our clinic with a diagnosis of infectious keratitis. Laser in situ keratomileusis was performed in all cases in the same operating room by different surgeons between April and May 2002. A partial penetrating keratoplasty was performed in all patients to control the process. A study of the corneas demonstrated the presence of the fungus Acremonium in all cases. Rigid asepsis during the surgical procedure is important to prevent this serious complication. J Cataract Refract Surg 2004; 30:262–267 2004 ASCRS and ESCRS
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nfectious keratitis is an uncommon complication of corneal refractive surgery but can have serious visionrelated consequences. Cases of infectious keratitis or endophthalmitis after radial keratotomy,1,2 refractive photokeratectomy,3,4 and laser in situ keratomileusis5–22 (LASIK) are found in the literature. In most cases, these infections are of bacterial origin, especially Staphylococcus aureus6–8 and Mycobacterium,9–13 but infections caused by fungi have also been observed.14–18 We present 4 cases of fungal infection in which LASIK was performed by different surgeons in the same time period and the same operating room.
Case Reports Case 1 A 35-year-old woman had LASIK for myopia on April 22, 2002. Three weeks after surgery, the patient presented with interstitial keratitis in the right eye that became worse
Accepted for publication May 13, 2003. From the Instituto Oftalmolo´gico Dres Ferna´ndez-Vega, Oviedo, Asturias, Spain. None of the authors has a financial or proprietary interest in any material or method mentioned. David H. Wallace, European Association of Science Editors, assisted with the English translation and correction. Reprint requests to Dr. Jose´ F. Alfonso, Instituto Oftalmolo´gico Ferna´ndezVega, Oviedo, Asturias, Spain. E-mail: [email protected]. 2004 ASCRS and ESCRS Published by Elsevier Inc.
despite treatment with topical and systemic corticosteroids. Two days later, the surgeon lifted the flap, washed the interface, and added topical ofloxacin 0.3% hourly to the previous treatment. Forty-eight hours later, the clinical situation had ostensibly worsened with hyperemia, corneal infiltration, hypopyon of 2.5 mm, and the presence of a membrane in the pupillary area. Samples taken for culture demonstrated the existence of a Staphylococcus species. Treatment was started with oral deflazacort (30 mg/day) and ciprofloxacin (1 g/12 hours); topical betamethasone every 3 hours; ofloxacin 0.3%, tobramycin, and vancomycin hourly; and cyclopentolate 1% every 12 hours. The patient’s condition continued to worsen, and 1 week later she visited our clinic with a totally infiltrated cornea and hypopyon that occupied the anterior chamber and did not permit evaluation of the iris or lens (Figure 1, A). Echography did not show changes in the vitreous or retina. With a diagnosis of endophthalmitis, treatment was begun with systemic vancomycin (1 g/12 hours), ciprofloxacin (500 mg/12 hours), and methylprednisolone (40 mg/24 hours) as well as subconjunctival injections of vancomycin and ceftazidime and topical rifamycin, tobramycin, and amphotericin B 0.15% hourly. The next day, the patient was taken to the operating room to clear the anterior chamber of exudates and for a partial penetrating keratoplasty (PKP). Surgery was difficult due to a thick membrane adhered to the iris and the anterior capsule of the lens (Figure 1, B). The capsule ruptured during the peeling of the membrane, producing expulsion of the lens content. However, it was possible to complete the keratoplasty and leave the anterior chamber without fibrin, with a rigid medium-sized pupil and an intact posterior capsule (Figure 1, C). After surgery, the systemic and topical treatment was maintained. Histopathologic examination of the cornea dem0886-3350/03/$–see front matter doi:10.1016/S0886-3350(03)00646-1
CASE REPORTS: ALFONSO
Figure 1. (Alfonso) A: Preoperative view shows corneal infiltrate and hypopyon. B: Keratoplasty with extraction of fibrinous membrane from the anterior chamber. Total expulsion of the lens nucleus and cortex occurred during surgery. C: Postoperative view 4 months after corneal graft. D: Histopathologic section with Grocott staining shows the presence of fungi on the stroma and the endothelium (original magnification ⫻20).
onstrated a fungal infection (Figure 1, D); on culture, it was confirmed to belong to the Acremonium species. During the next few days, the infection appeared to be under control, although an increase in intraocular pressure (IOP) due to the formation of anterior synechias was observed. Antiglaucoma treatment was given, and a neodymium:YAG laser iridotomy was performed. Four months after surgery, the graft remained transparent without signs of infection and the IOP was controlled with medical treatment. The patient had a second surgical intervention to release the anterior and posterior synechias from the iris, and a bifocal diffractive intraocular lens was implanted. No complications were observed postoperatively, and 1 month after the last procedure, the eye remained stable with a transparent graft.
Case 2 A 28-year-old man had LASIK for myopia on April 20, 2002, in the same operating room as the patient in Case 1 but performed by a different surgeon. One month after surgery, the patient began to experience discomfort, epiphora, and loss of vision in the left eye. On exploration, the surgeon observed interstitial keratitis that did not resolve with antibiotic and topical corticosteroid treatment. The patient was referred to our clinic approximately 2 months after surgery, presenting with a corneal infiltrate and moderate anterior chamber reaction (Figure 2, A). In light of the diagnosis in Case 1, the patient was taken to the operating room to obtain samples for culture. Treatment was started with topical rifamycin, tobramycin, and amphotericin B 0.15% hourly; oral ciprofloxacin (750 mg/12 hours); and itraconazole (200 mg/12 hours). The culture was sterile.
Despite these measures, the condition worsened 4 days later (Figure 2, B). Thus, partial PKP was performed and the antifungal agent voriconazole (200 mg/12 hours) was administered. The surgery and the postoperative period were uneventful. The same treatment was maintained for 1 month. Four months after intervention, the corneal graft was transparent without signs of inflammation (Figure 2, C). Histopathology and culture of the cornea demonstrated that the etiological agent was Acremonium (Figure 2, D).
Case 3 A 49-year-old woman had LASIK for hyperopia at the same clinic on May 22, 2002, performed by a different surgeon than in Cases 1 and 2. In the initial postoperative period, the patient had slight inflammation in the left eye that resolved with washing of the interface and antibiotic therapy. After 3 weeks, the infection returned. The surgeon performed another scraping of the interface and obtained samples for culture. No growth was observed, and treatment was restarted with topical antibiotics and amphotericin B 0.15%. The patient’s condition worsened, and she was referred to our clinic 1 week later. The eye presented with a round and central corneal infiltrate that protruded into the anterior chamber (Figure 3, A). Corneal transplantation was scheduled and voriconazole treatment started as in Case 2. Three days before surgery, the eye worsened considerably, with the anterior chamber and the sclerocorneal limbus the most affected (Figure 3, B). During PKP and washing of the anterior chamber, expulsion of the lens content occurred, similar to Case 1.
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Figure 2. (Alfonso) A: Corneal view upon the patient’s referral to our clinic. B: Four days later, the condition was worse. C: Four months after keratoplasty, the graft was transparent with no infection. D: Histopathologic PAS staining shows fungi with septate and branches (orignal magnification ⫻20).
Postoperative progress was good; 4 months after surgery, the eye remained quiet and without infection. However, the graft was not transparent (Figure 3, C). Culture and histopathology of the receptor cornea demonstrated the presence of Acremonium (Figure 3, D).
Case 4 A 42-year-old woman had LASIK for astigmatism on May 8, 2002, in the same clinic as Cases 1, 2, and 3 but
performed by a different surgeon. Approximately 3 weeks after surgery, the patient experienced 5 episodes of discomfort (ocular hyperemia and loss of vision). The discomfort improved slightly with topical antibiotics and corticosteroids. At the end of 4 months, the patient was diagnosed with a fungal infection and topical amphotericin B was added to the previous treatment. The patient presented at our clinic 5 months after refractive surgery with a clinical situation similar to that in Case
Figure 3. (Alfonso) A: Condition of the cornea on referral to our clinic. B: Cornea 4 days later. C: The keratoplasty was made excentrically to cover the infected area. After 4 months, the eye was stable without infection but the graft was not transparent. D: Hematoxylin-eosin staining shows damage from acute inflammation in all the corneal layers (original magnification ⫻10).
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Figure 4. (Alfonso) A: Clinical aspect of the eye before surgery. B: Keratoplasty was performed uneventfully. Considerable inflammation of the eye is evident. C: Corneal status 1 month after the graft. D: Hematoxylin–eosin staining shows the presence of inflammatory cells infiltrating the inner corneal layers. Surgical flap dehiscence is also visible (original magnification ⫻10).
2. Corneal infiltrate and moderate reaction in the anterior chamber were present (Figure 4, A). Five days later, PKP was performed (Figure 4, B). At 1 month, the graft was transparent and without infection (Figure 4, C). It was demonstrated that the infection was caused by Acremonium (Figure 4, D).
Histopathology Hematoxylin–eosin periodic acid-Schiff (PAS), Grocott, and Masson trichrome stainings were performed for the histopathologic study. The corneas showed the same characteristics in all patients: total or partial dehiscence of the surgical flap, the presence of fungi, and signs of acute inflammation affecting all corneal layers, including the endothelium.
Discussion Ocular infection after LASIK is a rare condition and is less frequent than with other refractive surgery techniques, possibly because the integrity of Bowman’s membrane and the corneal epithelium are maintained. However, with an increase in the number of surgeries, the frequency of such infections and other postoperative complications may increase. Preventing or recognizing these infections as soon as they appear is important to treating them adequately. The first infection described after LASIK was caused by Nocardia asteroides.19 Later, other cases of bacterial keratitis caused by Staphylococcus,6–8 Streptococcus,20,21 and
Mycobacterium9–13 were reported, along with fungal keratitis due to Aspergillus,14–16 Curvularia,17 and Scedosporium,18 among others. As cases in the literature demonstrate, LASIK does not completely avoid this type of complication, which generally affects healthy and immunocompetent persons. Even though it is only for a short period of time, the corneal stroma is exposed during surgery to infectious agents that may come from the patient, the instrumentation, the surgeon, and the operating room. Furthermore, as reported by Sridhar and coauthors,18 other factors can favor a possible infection such as the administration of topical corticosteroids, a decrease in corneal sensitivity, and the use of therapeutic contact lenses. All factors must be controlled to guarantee strict asepsis throughout the procedure. Of the possible factors mentioned, we emphasize the possibility of contamination arising from the operating room as this was the source of the infection in our cases. When refractive surgery is performed at commercial centers, the requirements for the operating room, material, and personnel should be the same as those for other ophthalmology settings. The asepsis protocol of the operating room where the surgery was performed was not obtained. It was not a conventional operating room and was situated in the cellar of the clinic. The microbiological analysis per-
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formed after discovering the infections demonstrated the presence of Acremonium on the operating room’s walls and furniture and in the air vents. It seems that the origin of the fungus was decomposing organic material (plant leaves) in the garden outside the clinic. In general, fungal infections have a late onset (2 weeks after surgery) and do not respond to the usual antimicrobial therapy. In these circumstances, it must be suspected that the origin of the infection is fungi (although there are also cases of late-onset infection by S epidermidis22 and Mycobacterium10–12). An etiological diagnosis must be reached as soon as possible by lifting the flap and taking samples for culture. Only with an early diagnosis and treatment can the infection be medically controlled. Even so, PKP is necessary in most cases given the low efficacy of the antifungal agents which do not penetrate the cornea well, especially if the epithelium is intact. In the patients described here, the infection began 3 to 4 weeks after surgery as a stromal infiltrate similar to sterile interstitial keratitis but worsened with conventional treatment of topical and systemic corticosteroids. Upon the patients’ arrival at our clinic, the infections in Cases 1 and 3 were highly advanced and it was necessary to perform the corneal graft immediately. Cases 2 and 4 were not as badly affected, but they became worse in the following days despite antifungal treatment. Therefore, PKP was performed. Following our experience with these patients, the natural history of this process would be as follows: The infection begins as a slight stromal corneal infiltrate that increases in density. Later, the infiltrate grows toward the anterior chamber and is accompanied by a moderate inflammatory reaction. Next, hypopyon appears and can occupy the entire anterior chamber; parallel to this, a dense fibrinous membrane forms that strongly adheres to the iris and the anterior capsule of the lens. Acremonium is a saprophytic soil fungi and a common environmental contaminant that infrequently is the cause of ophthalmological infections. Although cases of endophthalmitis caused by this fungi after cataract surgery have been described,23 most were corneal infections after nonsurgical trauma. The only report of infection by Acremonium after LASIK that we found in the literature is a patient who had bilateral hyperopic LASIK 266
and in whom the infection developed 8 months later, after perforating trauma by a piece of wood.24 In regard to treatment, in vitro studies show that this organism is highly sensitive to amphotericin B. However, in vivo, the persistence of positive cultures after the intravitreous administration of amphotericin B have been described, even when associated with systemic fluconazole.23 For this reason, in Cases 2 and 3, we tried a new antifungal agent, voriconazole, which acts by interfering with the biosynthesis of ergosterol and whose antifungal activity has been proved in experimental and clinical studies.25 The treatment was well tolerated in both patients, although we cannot guarantee its efficacy in cases of infection by Acremonium PKP since these patients began the treatment after PKP and the surgery was probably a greater determining factor in the healing process than the antifungal agent. Infection, both bacterial and fungal, is a possible complication of LASIK. Strict asepsis during the procedure, both of the instrumentation and the operating room, is important.
References 1. Duffey RJ. Bilateral Serratia marcescens keratitis after simultaneous bilateral radial keratotomy. Am J Ophthalmol 1995; 119:233–236 2. Beldavs RA, Al-Ghamdi S, Wilson LA, Waring GO III. Bilateral microbial keratitis after radial keratotomy. Arch Ophthalmol 1993; 111:440 3. Fo¨rster W, Becker K, Hungermann D, Busse H. Methicillin-resistant Staphylococcus aureus keratitis after excimer laser photorefractive keratectomy. J Cataract Refract Surg 2002; 28:722–724 4. Kouyoumdjian GA, Forstot SL, Durairaj VD, Damiano RE. Infectious keratitis after laser refractive surgery. Ophthalmology 2001; 108:1266–1268 5. Levartovsky S, Rosenwasser GOD, Goodman DF. Bacterial keratitis after laser in situ keratomileusis. Ophthalmology 2001; 108:321–325; errata, 1012 6. Suresh PS, Rootman DS. Bilateral infectious keratitis after a laser in situ keratomileusis enhancement procedure. J Cataract Refract Surg 2002; 28:720–721 7. Rudd JC, Moshirfar M. Methicillin-resistant Staphylococcus aureus keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2001; 27:471–473 8. Rubinfeld RS, Negvesky GJ. Methicillin-resistant Staphylococcus aureus ulcerative keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2001; 27:1523– 1525
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9. Giaconi J, Pham R, Ta CN. Bilateral Mycobacterium abscessus keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2002; 28:887–890 10. Solomon A, Karp CL, Miller D, et al. Mycobacterium interface keratitis after laser in situ keratomileusis. Ophthalmology 2001; 108:2201–2208 11. 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; 108:121–125 12. 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; 129:382–384 13. Chandra NS, Torres MF, Winthrop KL, et al. Cluster of Mycobacterium chelonae keratitis cases following laser in-situ keratomileusis. Am J Ophthalmol 2001; 132: 819–830 14. Sridhar MS, Garg P, Bansal AK, Gopinathan U. Aspergillus flavus keratitis after laser in situ keratomileusis. Am J Ophthalmol 2000; 129:802–804 15. Ritterband D, Kelly J, McNamara T, et al. Delayedonset multifocal polymicrobial keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2002; 28:898– 899 16. Kuo IC, Margolis TP, Cevallos V, Hwang DG. Aspergillus fumigatus keratitis after laser in situ keratomileusis. Cornea 2001; 20:342–344
17. Chung MS, Goldstein MH, Driebe WT Jr, Schwartz B. Fungal keratitis after laser in situ keratomileusis: A case report. Cornea 2000; 19:236–237 18. Sridhar MS, Garg P, Bansal AK, Sharma S. Fungal keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:613–615 19. Pe´rez-Santonja JJ, Sakla HF, Abad JL, et al. Nocardial keratitis after laser in situ keratomileusis. J Refract Surg 1997; 13:314–317 20. Dada T, Sharma N, Dada VK, Vajpayee RB. Pneumococcal keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:460–461 21. Ramı´rez M, Herna´ndez-Quintela E, Beltra´n F, NaranjoTackman R. Pneumococcal keratitis at the flap interface after laser in situ keratomileusis. J Cataract Refract Surg 2002; 28:550–552 22. Karp KO, Hersh PS, Epstein RJ. Delayed keratitis after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:925–928 23. Weissgold DJ, Maguire AM, Brucker AJ. Management of postoperative Acremonium endophthalmitis. Ophthalmology 1996; 103:749–756 24. Read RW, Chuck RSH, Rao NA, Smith RE. Traumatic Acremonium atrogriseum keratitis following laserassisted in situ keratomileusis. Arch Ophthalmol 2000; 118: 418–421 25. Reis A, Sundmacher R, Tintelnot K, et al. Successful treatment of ocular invasive mould infection (fusariosis) with the new antifungal agent voriconazole [letter]. Br J Ophthalmol 2000; 84:932–933
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nfectious keratitis is an uncommon complication of corneal refractive surgery but can have serious visionrelated consequences. Cases of infectious keratitis or endophthalmitis after radial keratotomy,1,2 refractive photokeratectomy,3,4 and laser in situ keratomileusis5–22 (LASIK) are found in the literature. In most cases, these infections are of bacterial origin, especially Staphylococcus aureus6–8 and Mycobacterium,9–13 but infections caused by fungi have also been observed.14–18 We present 4 cases of fungal infection in which LASIK was performed by different surgeons in the same time period and the same operating room.
Case Reports Case 1 A 35-year-old woman had LASIK for myopia on April 22, 2002. Three weeks after surgery, the patient presented with interstitial keratitis in the right eye that became worse
Accepted for publication May 13, 2003. From the Instituto Oftalmolo´gico Dres Ferna´ndez-Vega, Oviedo, Asturias, Spain. None of the authors has a financial or proprietary interest in any material or method mentioned. David H. Wallace, European Association of Science Editors, assisted with the English translation and correction. Reprint requests to Dr. Jose´ F. Alfonso, Instituto Oftalmolo´gico Ferna´ndezVega, Oviedo, Asturias, Spain. E-mail: [email protected]. 2004 ASCRS and ESCRS Published by Elsevier Inc.
despite treatment with topical and systemic corticosteroids. Two days later, the surgeon lifted the flap, washed the interface, and added topical ofloxacin 0.3% hourly to the previous treatment. Forty-eight hours later, the clinical situation had ostensibly worsened with hyperemia, corneal infiltration, hypopyon of 2.5 mm, and the presence of a membrane in the pupillary area. Samples taken for culture demonstrated the existence of a Staphylococcus species. Treatment was started with oral deflazacort (30 mg/day) and ciprofloxacin (1 g/12 hours); topical betamethasone every 3 hours; ofloxacin 0.3%, tobramycin, and vancomycin hourly; and cyclopentolate 1% every 12 hours. The patient’s condition continued to worsen, and 1 week later she visited our clinic with a totally infiltrated cornea and hypopyon that occupied the anterior chamber and did not permit evaluation of the iris or lens (Figure 1, A). Echography did not show changes in the vitreous or retina. With a diagnosis of endophthalmitis, treatment was begun with systemic vancomycin (1 g/12 hours), ciprofloxacin (500 mg/12 hours), and methylprednisolone (40 mg/24 hours) as well as subconjunctival injections of vancomycin and ceftazidime and topical rifamycin, tobramycin, and amphotericin B 0.15% hourly. The next day, the patient was taken to the operating room to clear the anterior chamber of exudates and for a partial penetrating keratoplasty (PKP). Surgery was difficult due to a thick membrane adhered to the iris and the anterior capsule of the lens (Figure 1, B). The capsule ruptured during the peeling of the membrane, producing expulsion of the lens content. However, it was possible to complete the keratoplasty and leave the anterior chamber without fibrin, with a rigid medium-sized pupil and an intact posterior capsule (Figure 1, C). After surgery, the systemic and topical treatment was maintained. Histopathologic examination of the cornea dem0886-3350/03/$–see front matter doi:10.1016/S0886-3350(03)00646-1
CASE REPORTS: ALFONSO
Figure 1. (Alfonso) A: Preoperative view shows corneal infiltrate and hypopyon. B: Keratoplasty with extraction of fibrinous membrane from the anterior chamber. Total expulsion of the lens nucleus and cortex occurred during surgery. C: Postoperative view 4 months after corneal graft. D: Histopathologic section with Grocott staining shows the presence of fungi on the stroma and the endothelium (original magnification ⫻20).
onstrated a fungal infection (Figure 1, D); on culture, it was confirmed to belong to the Acremonium species. During the next few days, the infection appeared to be under control, although an increase in intraocular pressure (IOP) due to the formation of anterior synechias was observed. Antiglaucoma treatment was given, and a neodymium:YAG laser iridotomy was performed. Four months after surgery, the graft remained transparent without signs of infection and the IOP was controlled with medical treatment. The patient had a second surgical intervention to release the anterior and posterior synechias from the iris, and a bifocal diffractive intraocular lens was implanted. No complications were observed postoperatively, and 1 month after the last procedure, the eye remained stable with a transparent graft.
Case 2 A 28-year-old man had LASIK for myopia on April 20, 2002, in the same operating room as the patient in Case 1 but performed by a different surgeon. One month after surgery, the patient began to experience discomfort, epiphora, and loss of vision in the left eye. On exploration, the surgeon observed interstitial keratitis that did not resolve with antibiotic and topical corticosteroid treatment. The patient was referred to our clinic approximately 2 months after surgery, presenting with a corneal infiltrate and moderate anterior chamber reaction (Figure 2, A). In light of the diagnosis in Case 1, the patient was taken to the operating room to obtain samples for culture. Treatment was started with topical rifamycin, tobramycin, and amphotericin B 0.15% hourly; oral ciprofloxacin (750 mg/12 hours); and itraconazole (200 mg/12 hours). The culture was sterile.
Despite these measures, the condition worsened 4 days later (Figure 2, B). Thus, partial PKP was performed and the antifungal agent voriconazole (200 mg/12 hours) was administered. The surgery and the postoperative period were uneventful. The same treatment was maintained for 1 month. Four months after intervention, the corneal graft was transparent without signs of inflammation (Figure 2, C). Histopathology and culture of the cornea demonstrated that the etiological agent was Acremonium (Figure 2, D).
Case 3 A 49-year-old woman had LASIK for hyperopia at the same clinic on May 22, 2002, performed by a different surgeon than in Cases 1 and 2. In the initial postoperative period, the patient had slight inflammation in the left eye that resolved with washing of the interface and antibiotic therapy. After 3 weeks, the infection returned. The surgeon performed another scraping of the interface and obtained samples for culture. No growth was observed, and treatment was restarted with topical antibiotics and amphotericin B 0.15%. The patient’s condition worsened, and she was referred to our clinic 1 week later. The eye presented with a round and central corneal infiltrate that protruded into the anterior chamber (Figure 3, A). Corneal transplantation was scheduled and voriconazole treatment started as in Case 2. Three days before surgery, the eye worsened considerably, with the anterior chamber and the sclerocorneal limbus the most affected (Figure 3, B). During PKP and washing of the anterior chamber, expulsion of the lens content occurred, similar to Case 1.
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Figure 2. (Alfonso) A: Corneal view upon the patient’s referral to our clinic. B: Four days later, the condition was worse. C: Four months after keratoplasty, the graft was transparent with no infection. D: Histopathologic PAS staining shows fungi with septate and branches (orignal magnification ⫻20).
Postoperative progress was good; 4 months after surgery, the eye remained quiet and without infection. However, the graft was not transparent (Figure 3, C). Culture and histopathology of the receptor cornea demonstrated the presence of Acremonium (Figure 3, D).
Case 4 A 42-year-old woman had LASIK for astigmatism on May 8, 2002, in the same clinic as Cases 1, 2, and 3 but
performed by a different surgeon. Approximately 3 weeks after surgery, the patient experienced 5 episodes of discomfort (ocular hyperemia and loss of vision). The discomfort improved slightly with topical antibiotics and corticosteroids. At the end of 4 months, the patient was diagnosed with a fungal infection and topical amphotericin B was added to the previous treatment. The patient presented at our clinic 5 months after refractive surgery with a clinical situation similar to that in Case
Figure 3. (Alfonso) A: Condition of the cornea on referral to our clinic. B: Cornea 4 days later. C: The keratoplasty was made excentrically to cover the infected area. After 4 months, the eye was stable without infection but the graft was not transparent. D: Hematoxylin-eosin staining shows damage from acute inflammation in all the corneal layers (original magnification ⫻10).
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Figure 4. (Alfonso) A: Clinical aspect of the eye before surgery. B: Keratoplasty was performed uneventfully. Considerable inflammation of the eye is evident. C: Corneal status 1 month after the graft. D: Hematoxylin–eosin staining shows the presence of inflammatory cells infiltrating the inner corneal layers. Surgical flap dehiscence is also visible (original magnification ⫻10).
2. Corneal infiltrate and moderate reaction in the anterior chamber were present (Figure 4, A). Five days later, PKP was performed (Figure 4, B). At 1 month, the graft was transparent and without infection (Figure 4, C). It was demonstrated that the infection was caused by Acremonium (Figure 4, D).
Histopathology Hematoxylin–eosin periodic acid-Schiff (PAS), Grocott, and Masson trichrome stainings were performed for the histopathologic study. The corneas showed the same characteristics in all patients: total or partial dehiscence of the surgical flap, the presence of fungi, and signs of acute inflammation affecting all corneal layers, including the endothelium.
Discussion Ocular infection after LASIK is a rare condition and is less frequent than with other refractive surgery techniques, possibly because the integrity of Bowman’s membrane and the corneal epithelium are maintained. However, with an increase in the number of surgeries, the frequency of such infections and other postoperative complications may increase. Preventing or recognizing these infections as soon as they appear is important to treating them adequately. The first infection described after LASIK was caused by Nocardia asteroides.19 Later, other cases of bacterial keratitis caused by Staphylococcus,6–8 Streptococcus,20,21 and
Mycobacterium9–13 were reported, along with fungal keratitis due to Aspergillus,14–16 Curvularia,17 and Scedosporium,18 among others. As cases in the literature demonstrate, LASIK does not completely avoid this type of complication, which generally affects healthy and immunocompetent persons. Even though it is only for a short period of time, the corneal stroma is exposed during surgery to infectious agents that may come from the patient, the instrumentation, the surgeon, and the operating room. Furthermore, as reported by Sridhar and coauthors,18 other factors can favor a possible infection such as the administration of topical corticosteroids, a decrease in corneal sensitivity, and the use of therapeutic contact lenses. All factors must be controlled to guarantee strict asepsis throughout the procedure. Of the possible factors mentioned, we emphasize the possibility of contamination arising from the operating room as this was the source of the infection in our cases. When refractive surgery is performed at commercial centers, the requirements for the operating room, material, and personnel should be the same as those for other ophthalmology settings. The asepsis protocol of the operating room where the surgery was performed was not obtained. It was not a conventional operating room and was situated in the cellar of the clinic. The microbiological analysis per-
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formed after discovering the infections demonstrated the presence of Acremonium on the operating room’s walls and furniture and in the air vents. It seems that the origin of the fungus was decomposing organic material (plant leaves) in the garden outside the clinic. In general, fungal infections have a late onset (2 weeks after surgery) and do not respond to the usual antimicrobial therapy. In these circumstances, it must be suspected that the origin of the infection is fungi (although there are also cases of late-onset infection by S epidermidis22 and Mycobacterium10–12). An etiological diagnosis must be reached as soon as possible by lifting the flap and taking samples for culture. Only with an early diagnosis and treatment can the infection be medically controlled. Even so, PKP is necessary in most cases given the low efficacy of the antifungal agents which do not penetrate the cornea well, especially if the epithelium is intact. In the patients described here, the infection began 3 to 4 weeks after surgery as a stromal infiltrate similar to sterile interstitial keratitis but worsened with conventional treatment of topical and systemic corticosteroids. Upon the patients’ arrival at our clinic, the infections in Cases 1 and 3 were highly advanced and it was necessary to perform the corneal graft immediately. Cases 2 and 4 were not as badly affected, but they became worse in the following days despite antifungal treatment. Therefore, PKP was performed. Following our experience with these patients, the natural history of this process would be as follows: The infection begins as a slight stromal corneal infiltrate that increases in density. Later, the infiltrate grows toward the anterior chamber and is accompanied by a moderate inflammatory reaction. Next, hypopyon appears and can occupy the entire anterior chamber; parallel to this, a dense fibrinous membrane forms that strongly adheres to the iris and the anterior capsule of the lens. Acremonium is a saprophytic soil fungi and a common environmental contaminant that infrequently is the cause of ophthalmological infections. Although cases of endophthalmitis caused by this fungi after cataract surgery have been described,23 most were corneal infections after nonsurgical trauma. The only report of infection by Acremonium after LASIK that we found in the literature is a patient who had bilateral hyperopic LASIK 266
and in whom the infection developed 8 months later, after perforating trauma by a piece of wood.24 In regard to treatment, in vitro studies show that this organism is highly sensitive to amphotericin B. However, in vivo, the persistence of positive cultures after the intravitreous administration of amphotericin B have been described, even when associated with systemic fluconazole.23 For this reason, in Cases 2 and 3, we tried a new antifungal agent, voriconazole, which acts by interfering with the biosynthesis of ergosterol and whose antifungal activity has been proved in experimental and clinical studies.25 The treatment was well tolerated in both patients, although we cannot guarantee its efficacy in cases of infection by Acremonium PKP since these patients began the treatment after PKP and the surgery was probably a greater determining factor in the healing process than the antifungal agent. Infection, both bacterial and fungal, is a possible complication of LASIK. Strict asepsis during the procedure, both of the instrumentation and the operating room, is important.
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