Seminars in Ophthalmology
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
Clinical Features, Risk Factors, and Treatments of Microsporidial Epithelial Keratitis Onsiri Thanathanee, Raweewan Athikulwongse, Orapin Anutarapongpan, Porntip Laummaunwai, Wanchai Maleewong, Pewpan (Maleewong) Intapan & Olan Suwan-apichon To cite this article: Onsiri Thanathanee, Raweewan Athikulwongse, Orapin Anutarapongpan, Porntip Laummaunwai, Wanchai Maleewong, Pewpan (Maleewong) Intapan & Olan Suwanapichon (2014): Clinical Features, Risk Factors, and Treatments of Microsporidial Epithelial Keratitis, Seminars in Ophthalmology, DOI: 10.3109/08820538.2014.962161 To link to this article: http://dx.doi.org/10.3109/08820538.2014.962161
Published online: 12 Dec 2014.
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Date: 06 November 2015, At: 03:18
Seminars in Ophthalmology, Early Online, 1–5, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2014.962161
ORIGINAL ARTICLE
Clinical Features, Risk Factors, and Treatments of Microsporidial Epithelial Keratitis Onsiri Thanathanee1*, Raweewan Athikulwongse1, Orapin Anutarapongpan1, Porntip Laummaunwai2,3, Wanchai Maleewong2,3, Pewpan (Maleewong) Intapan2,3, and Olan Suwan-apichon1 Downloaded by [Central Michigan University] at 03:18 06 November 2015
1
Department of Ophthalmology, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 2Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, and 3 Research and Diagnostic Center for Emerging Infectious Diseases, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
ABSTRACT Objective: To report the clinical manifestations, risk factors, and treatments of microsporidial epithelial keratitis in Thailand. Methods: Twenty eyes of 19 patients were diagnosed and the clinical presentations, risk factors, and management were analyzed. Results: Of 19 patients, six patients (32%) had no apparent risk factors. Predisposing factors included soil exposure (6/19, 32%), water contamination (6/19, 32%), and eye liner (1/19, 4%). Twelve cases (63%) were detected in the rainy season. All cases presented with disseminated, punctated, elevated, epithelial keratitis. Corneal scrapings with Gram-chromotrope staining were positive in all patients. Moxifloxacin 0.5% eye drops were given and all 16 patients experienced complete resolution. Three recurrent cases were resolved with only topical moxifloxacin without corneal scraping or swabbing. Conclusions: Predisposing factors were not found in some patients; thus, corneal scraping with staining should be considered in cases having a high index of suspicion. The incidence is increased during the rainy season; therefore, clinicians should have more awareness during these times. Debridement with topical moxifloxacin eye drops, without any systemic medication, may be an effective treatment. Corneal scraping or swabbing may not be required in recurrences. Keywords: Epithelial keratitis, gram-chromotrope stain, microsporidia, risk factors, treatment
INTRODUCTION
This report is a case series of microsporidial epithelial keratitis in Thailand. Clinical features, risk factors, seasonal variation, treatments, and visual outcome have been evaluated and compared with previous studies.
In recent years, the incidence of microsporidial epithelial keratitis (keratoconjunctivitis) has significantly increased worldwide, especially in immunocompetent individuals.1 Sources and routes of human infection, however, are still unclear. Various risk factors (i.e., contamination from soil, mud, water, or history of contact lens use) were reported.2,3 In addition, treatment modalities varied among clinicians. Several options have been suggested; for example, corneal debridement with topical medications or a combination of topical and oral drugs.1,3
METHODS This retrospective, non-comparative case series of microsporidial epithelial keratitis was diagnosed between August 2012 and October 2013 at the Department of Ophthalmology, Srinagarind
Received 27 April 2014; accepted 31 August 2014; published online 11 December 2014 *This study was approved by the Ethics Committee (HE561154) at the Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. Correspondence: Olan Suwan-apichon, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. E-mail: [email protected]
1
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Hospital, Khon Kaen University. Twenty eyes from 19 patients were included. Medical and laboratory records of all cases with positive corneal smears for microsporidia were reviewed, after approval from the Khon Kaen University Ethics Committee for Human Research. Demographic data and the histories of contamination or trauma, including other possible risk factors, were carefully evaluated. Slit-lamp examinations were undertaken before scraping and confocal microscopy was performed in some patients. Corneal scrapings were performed by No.15 blades to remove whole lesions in 20 eyes of 19 cases, then scrapings were placed on microscopic glass slides and specimens were sent for Gram-chromotrope (modified-trichrome) staining. Contact lenses were placed and then removed when the corneal epithelium was completely healed. All cases were prescribed with topical 0.5% moxifloxacin eye drops, a fourth-generation fluoroquinolone, every two hours. The frequency of topical medications was decreased and then stopped when the lesions were completely resolved. No oral medications or keratoplasty were required in any patient. For recurrent cases, only topical moxifloxacin was given without repeated corneal debridement.
RESULTS Over a 12-month period, there were 19 cases involving 20 eyes of microsporidial epithelial keratitis diagnosed by the presence of 1–1.5 x 4 mm of red, rod-shaped organisms identified under microscopic examination. One case had bilateral involvement. The ages ranged from 19 to 67 years, the male:female ratio was 11:8, and the right eye was slightly predominant (OD:OS = 11:9). For risk factors, six patients (32%) had a history of eye exposure to dust/soil/mud, six patients (32%)
had water contamination, and one (5%) had a history of eyeliner exposure. Interestingly, six cases (32%) had no history of trauma or contamination. The onset of symptoms ranged from 2 to 14 days. The common symptoms were foreign body sensation (100%), slightly blurred vision (78%) with decreased best-corrected visual acuity of 1 to 2 Snellen lines, and tearing (63%) without discharge. All patients presented with tiny, disseminated, punctated, elevated, white epithelial lesions, whereas the epithelium remained intact in most cases. From observation, two characteristics of infiltration, which could be an oval to round shape (Figure 1A) or a peculiar blotchy infiltration (Figure 1B), were found. Mild conjunctival injection was found in all cases and only one case had anterior chamber cells (trace) without flare. Thailand is a tropical country in which the climate is controlled by tropical monsoons, and the weather in Thailand is generally hot and humid across most of the country throughout most of the year. Thailand’s seasons are generally divided into rainy from July to October, winter from November to February, and summer from March to June. Twelve cases (63%) were identified during the rainy season, four cases (21%) were reported in the cool season, and only three cases (16%) were found in the hot season. After corneal scraping and treating with topical moxifloxacin, 16 cases improved with complete resolution within 20 days. Three cases (two unilateral cases, right eye from the one bilateral case) were recurrent after cessation of topical medications. All recurrent epithelial keratitis cases were treated only with topical moxifloxacin without corneal debridement and the lesions completely disappeared. Five cases developed nummular keratitis (subepithelial infiltration or anterior stromal keratitis) after improvement of punctate epithelial keratitis (Figure 2). A mild foreign-body sensation without visual problems was reported. Topical
FIGURE 1. Slit-lamp photographs demonstrating character of corneal presentations: (A) Oval to round shape, raised, epithelial infiltration; (B) peculiar, blotchy, elevated, epithelial infiltration. Seminars in Ophthalmology
Microsporidial Epithelial Keratitis
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FIGURE 2. Nummular keratitis: (A) Subepithelial infiltration or anterior stromal keratitis (arrow); (B) nummular keratitis with increased magnification (32).
fluorometholone 0.1% eye drops were prescribed for four times a day until the corneas were clear. There was complete resolution of signs and symptoms in four cases. A few infiltrations remained in one patient without symptoms due to a compliance problem.
DISCUSSION Risk Factors Various predisposing factors (for example, contamination from soil, mud, contact lens, steroid, refractive surgery, and collagen crosslinking) have been proposed.1,3–13 From reviews of the literature, the source of microsporidia infection remains imprecise.1–3 It is a waterborne pathogen, spreading through water and food as the most likely routes of infection.1,2,6 Although microsporidia is a zoonotic disease which can be found in numerous animals, in our cases there were no reports of direct transmission from animals to humans. In our study, predisposing factors varied among patients with six patients having had no obvious risk, even with meticulous inquiry. The reason that it was not possible to identify risk factors in these patients may be due to the unawareness of contamination of water or soil.
Seasonal Variation The increased incidence during the rainy season was consistent with a previous report from India.2 In comparison to the current study, the proportions during this season were the same, which was approximately 60% (66% from India and 63% in this study from Thailand).2 A rainy environment may increase the chance of water exposure. This Thai study now reports a seasonal trend of microsporidial keratitis for which awareness should be raised for the rainy season. !
2014 Informa Healthcare USA, Inc.
FIGURE 3. Microsporidia spores stained by the Gram-chromotrope method. Oval, purple to pink spores with a belt-like strip in the middle band (dark band) (63).
Diagnosis Diagnostic methods vary according to laboratory availability. Special staining methods under light microscopy, such as modified trichrome (Figure 3), direct and indirect immunofluorescence assay (IFA), and polymerase chain reaction (PCR) are standard tests; however, these may not be available in some centers.1,14 Corneal findings and/or confocal microscopy may offer prompt and non-invasive tools for diagnosis.15,16 In the present authors’ observations, microsporidial epithelial keratitis has unique corneal findings. Generalized or focal punctate lesions with elevated epithelial infiltration were found in all cases. Characteristics of infiltration can be divided into oval to round shape and peculiarly blotchy infiltrations. Additionally, mild conjunctival injection without discharge is also one of the clues for diagnosis. In this study, all suspected cases by clinical findings had positive staining for microsporidia. Other laboratory investigations, such as staining or culture, may not be always be available. It is suggested that careful
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slit-lamp examination of corneal findings can guide the diagnosis.
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Treatment At present, there are no definite guidelines for the treatment of microsporidial epithelial keratitis. Corneal scraping plays a crucial role in both diagnosis and treatment. Nevertheless, discomfort and visual instability from the epithelial defect are problematic. Corneal swabbing has been reported to reduce pain after epithelial debridement. Needle or forceps were used to remove only infiltrations and thus we spared the normal epithelium around the lesions.17 Oral drugs, such as albendazole and itraconazole, have been prescribed, combined with topical antibiotics in some studies.1,9,11 Recent evidence, however, has shown that oral treatment may not be required for microsporidial epithelial keratitis.11 This observation is in accordance with the our study; all cases, including the recurrences, have been cured solely with topical fluoroquinolones. However, only moxifloxacin eye drops were used in this study and no other antibiotics were used. In addition, from this study, it is not possible to explain whether the use of no oral medications may have been responsible for recurrences. Topical moxifloxacin alone may be sufficient in selected cases. Various topical medications for treating this condition have been reported; these mainly are second- to fourth-eneration fluoroquinolones, polyhexamethylenebiguanide 0.02% (PHMB), fumagillin 0.3%, voriconazole 1%, and hexamidinediisethionate 0.1%.1,3,5,9,11,13,18,19 For PHMB, there was no significant difference in resolution time and final visual acuity in a clinical trial when compared with the placebo.18 Voriconazole monotherapy has been reported with successful treatment in two cases.19 There are two reported treatment options for frequency of antimicrobial eye drops, starting with four times a day or every two hours. The preference of the present authors is to start topical moxifloxacin every two hours for the first week, then taper off according to clinical responses. Although debridement or swabbing were recommended in most studies,1,3,5,12,17,20–22 an epithelial defect or corneal irregularity can interfere with driving or working abilities and cause painful reactions. Topical moxifloxacin, without repeated scraping or swabbing, resolved all recurrent cases; therefore, scrapping or swabbing may not be required in selected cases. One randomized clinical trial has found that microsporidia epithelial keratitis is a self-limiting disease and anti-microbial therapy is not required.18 Nevertheless, all self-limited patients from these studies received corneal scraping combined with
topical antibiotics; therefore, these may play a role in the improvement.1,18 In the final stages, some patients (5/20, 25%) developed nummular keratitis with subepithelial/ anterior stromal keratitis.6,11 These lesions are similar to subepithelial infiltration after viral conjunctivitis.23,24 Keys for distinguishing nummular keratitis usually occurred after resolving the punctate, raised epithelial infiltration. The treatment option is similar to the way in which topical corticosteroids work.25 Topical fluorometholone 0.1% was given for four times a day until the cornea was clear. The lesions of four patients disappeared without alteration of the best-corrected visual acuity. One patient did not receive corticosteroid eye drops, but the number of lesions decreased with few persistent infiltrations. This did not affect visual acuity. By observation, weak corticosteroid eye drops such as fluorometholone were adequate for the treatment. The limitations of this study are the small number of patients and not being a prospective clinical trial. In conclusion, some patients may not have had any apparent predisposing factors, awareness should be increased during a rainy season, typical clinical findings can be helpful for early diagnosis, and topical moxifloxacin without oral drugs may be sufficient in the treatment. Scraping or swabbing may not be required in selected cases, particularly in recurrences. The frequency of topical moxifloxacin was recommended to start every two hours, then tapered. Nummular keratitis can occur after resolution of epithelial keratitis and weak corticosteroid eye drops should be prescribed. Further studies with a larger sample size and a randomized trial are needed to verify all of these conclusions.
FUNDING This study was funded by a grant supported by Research Affairs, Faculty of Medicine, Srinagarind Hospital, Khon Kaen University.
ACKNOWLEDGMENTS We thank: (1) the patients for their participation; (2) the nursing and medical staff for their assistance; (3) the Department of Ophthalmology and the Faculty for financial support; and (4) Professor James A. Will for assistance with the English-language presentation.
DECLARATION OF INTEREST The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper. Seminars in Ophthalmology
Microsporidial Epithelial Keratitis
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REFERENCES 1. Sharma S, Das S, Joseph J, et al. Microsporidial keratitis: need for increased awareness. Surv Ophthalmol 2011;56: 1–22. 2. Reddy AK, Balne PK, Garg P, Krishnaiah S. Is microsporidial keratitis a seasonal infection in India? Clin Microbiol Infect 2011;17:1114–1116. 3. Tham AC, Sanjay S. Clinical spectrum of microsporidial keratoconjunctivitis. Clin Experiment Ophthalmol 2012;40: 512–518. 4. Bommala ML, Nalamada S, Sharma S, Garg P. Microsporidial keratoconjunctivitis in an immunocompetent patient with a past history of laser in situ keratomilieusis surgery. Indian J Med Microbiol 2011;29: 428–430. 5. Das S, Sharma S, Sahu SK. Diagnosis, clinical features and treatment outcome of microsporidial keratoconjunctivitis. Br J Ophthalmol 2012;96:793–795. 6. Fan NW, Wu CC, Chen TL, et al. Microsporidial keratitis in patients with hot springs exposure. J Clin Microbiol 2012;50: 414–418. 7. Fernandes M, Sharma S. Polymicrobial and microsporidial keratitis in a patient using Boston scleral contact lens for Sjogren’s syndrome and ocular cicatricial pemphigoid. Cont Lens Anterior Eye 2013;36:95–7. 8. Garg P. Microsporidia infection of the cornea: a unique and challenging disease. Cornea 2013;32 Suppl 1: S33–S38. 9. Gautam, Jhanji V, Satpathy G, et al. Microsporidial keratitis after collagen cross-linking. Ocul Immunol Inflamm 2013;21: 495–497. 10. Lam TS, Wong MH, Chuang SK. Microsporidial keratoconjunctivitis outbreak among athletes from Hong Kong who visited Singapore, 2012. Emerg Infect Dis 2013;19: 516–517. 11. Loh RS, Chan CM, Ti SE, et al. Emerging prevalence of microsporidial keratitis in Singapore: epidemiology, clinical features, and management. Ophthalmology 2009; 116:2348–2353. 12. Schwab IR. The changing spectrum of microbial keratitis: is microsporia increasing as a cause of microbial keratitis or
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is it a previously unrecognised cause? Br J Ophthalmol 2012; 96:774–775. Tung-Lien Quek D, Pan JC, Krishnan PU, et al. Microsporidial keratoconjunctivitis in the tropics: a case series. Open Ophthalmol J 2011;5:42–47. Bharathi MJ, Kumar GR, Ramakrishnan R, et al. Vittaforma corneae keratitis in southern India: role of a novel duplex PCR. J Med Microbiol 2013;62:553–559. Hau SC, Dart JK, Vesaluoma M, et al. Diagnostic accuracy of microbial keratitis with in vivo scanning laser confocal microscopy. Br J Ophthalmol 2010;94:982–987. Hsiao YC, Tsai IL, Kuo CT, Yang TL. Diagnosis of microsporidial keratitis with in vivo confocal microscopy. J Xray Sci Technol 2013;21:103–110. Fan NW, Lin PY, Chen TL, et al. Treatment of microsporidial keratoconjunctivitis with repeated corneal swabbing. Am J Ophthalmol 2012;154:927–933. Das S, Sahu SK, Sharma S, et al. Clinical trial of 0.02% polyhexamethylene biguanide versus placebo in the treatment of microsporidial keratoconjunctivitis. Am J Ophthalmol 2010;150:110–115. Khandelwal SS, Woodward MA, Hall T, et al. Treatment of microsporidia keratitis with topical voriconazole monotherapy. Arch Ophthalmol 2011;129:509–510. Sengupta J, Saha S, Khetan A, et al. Characteristics of microsporidial keratoconjunctivitis in an eastern Indian cohort: a case series. Indian J Pathol Microbiol 2011;54: 565–568. Das S, Sharma S, Sahu SK, Vemuganti GK. Intraocular invasion by microsporidial spores in a case of stromal keratitis. Arch Ophthalmol 2011;129:513–515. Didier ES, Weiss LM. Microsporidiosis: not just in AIDS patients. Curr Opin Infect Dis 2011;24:490–495. Aoki K, Kaneko H, Kitaichi N, et al. Clinical features of adenoviral conjunctivitis at the early stage of infection. Jpn J Ophthalmol 2011;55:11–15. Dosso AA, Rungger-Brandle E. Clinical course of epidemic keratoconjunctivitis: evaluation by in vivo confocal microscopy. Cornea 2008;27:263–268. Romanowski EG, Roba LA, Wiley L, et al. The effects of corticosteroids of adenoviral replication. Arch Ophthalmol 1996;114:581–585.
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
Clinical Features, Risk Factors, and Treatments of Microsporidial Epithelial Keratitis Onsiri Thanathanee, Raweewan Athikulwongse, Orapin Anutarapongpan, Porntip Laummaunwai, Wanchai Maleewong, Pewpan (Maleewong) Intapan & Olan Suwan-apichon To cite this article: Onsiri Thanathanee, Raweewan Athikulwongse, Orapin Anutarapongpan, Porntip Laummaunwai, Wanchai Maleewong, Pewpan (Maleewong) Intapan & Olan Suwanapichon (2014): Clinical Features, Risk Factors, and Treatments of Microsporidial Epithelial Keratitis, Seminars in Ophthalmology, DOI: 10.3109/08820538.2014.962161 To link to this article: http://dx.doi.org/10.3109/08820538.2014.962161
Published online: 12 Dec 2014.
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Article views: 50
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isio20 Download by: [Central Michigan University]
Date: 06 November 2015, At: 03:18
Seminars in Ophthalmology, Early Online, 1–5, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2014.962161
ORIGINAL ARTICLE
Clinical Features, Risk Factors, and Treatments of Microsporidial Epithelial Keratitis Onsiri Thanathanee1*, Raweewan Athikulwongse1, Orapin Anutarapongpan1, Porntip Laummaunwai2,3, Wanchai Maleewong2,3, Pewpan (Maleewong) Intapan2,3, and Olan Suwan-apichon1 Downloaded by [Central Michigan University] at 03:18 06 November 2015
1
Department of Ophthalmology, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 2Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, and 3 Research and Diagnostic Center for Emerging Infectious Diseases, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
ABSTRACT Objective: To report the clinical manifestations, risk factors, and treatments of microsporidial epithelial keratitis in Thailand. Methods: Twenty eyes of 19 patients were diagnosed and the clinical presentations, risk factors, and management were analyzed. Results: Of 19 patients, six patients (32%) had no apparent risk factors. Predisposing factors included soil exposure (6/19, 32%), water contamination (6/19, 32%), and eye liner (1/19, 4%). Twelve cases (63%) were detected in the rainy season. All cases presented with disseminated, punctated, elevated, epithelial keratitis. Corneal scrapings with Gram-chromotrope staining were positive in all patients. Moxifloxacin 0.5% eye drops were given and all 16 patients experienced complete resolution. Three recurrent cases were resolved with only topical moxifloxacin without corneal scraping or swabbing. Conclusions: Predisposing factors were not found in some patients; thus, corneal scraping with staining should be considered in cases having a high index of suspicion. The incidence is increased during the rainy season; therefore, clinicians should have more awareness during these times. Debridement with topical moxifloxacin eye drops, without any systemic medication, may be an effective treatment. Corneal scraping or swabbing may not be required in recurrences. Keywords: Epithelial keratitis, gram-chromotrope stain, microsporidia, risk factors, treatment
INTRODUCTION
This report is a case series of microsporidial epithelial keratitis in Thailand. Clinical features, risk factors, seasonal variation, treatments, and visual outcome have been evaluated and compared with previous studies.
In recent years, the incidence of microsporidial epithelial keratitis (keratoconjunctivitis) has significantly increased worldwide, especially in immunocompetent individuals.1 Sources and routes of human infection, however, are still unclear. Various risk factors (i.e., contamination from soil, mud, water, or history of contact lens use) were reported.2,3 In addition, treatment modalities varied among clinicians. Several options have been suggested; for example, corneal debridement with topical medications or a combination of topical and oral drugs.1,3
METHODS This retrospective, non-comparative case series of microsporidial epithelial keratitis was diagnosed between August 2012 and October 2013 at the Department of Ophthalmology, Srinagarind
Received 27 April 2014; accepted 31 August 2014; published online 11 December 2014 *This study was approved by the Ethics Committee (HE561154) at the Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. Correspondence: Olan Suwan-apichon, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. E-mail: [email protected]
1
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Hospital, Khon Kaen University. Twenty eyes from 19 patients were included. Medical and laboratory records of all cases with positive corneal smears for microsporidia were reviewed, after approval from the Khon Kaen University Ethics Committee for Human Research. Demographic data and the histories of contamination or trauma, including other possible risk factors, were carefully evaluated. Slit-lamp examinations were undertaken before scraping and confocal microscopy was performed in some patients. Corneal scrapings were performed by No.15 blades to remove whole lesions in 20 eyes of 19 cases, then scrapings were placed on microscopic glass slides and specimens were sent for Gram-chromotrope (modified-trichrome) staining. Contact lenses were placed and then removed when the corneal epithelium was completely healed. All cases were prescribed with topical 0.5% moxifloxacin eye drops, a fourth-generation fluoroquinolone, every two hours. The frequency of topical medications was decreased and then stopped when the lesions were completely resolved. No oral medications or keratoplasty were required in any patient. For recurrent cases, only topical moxifloxacin was given without repeated corneal debridement.
RESULTS Over a 12-month period, there were 19 cases involving 20 eyes of microsporidial epithelial keratitis diagnosed by the presence of 1–1.5 x 4 mm of red, rod-shaped organisms identified under microscopic examination. One case had bilateral involvement. The ages ranged from 19 to 67 years, the male:female ratio was 11:8, and the right eye was slightly predominant (OD:OS = 11:9). For risk factors, six patients (32%) had a history of eye exposure to dust/soil/mud, six patients (32%)
had water contamination, and one (5%) had a history of eyeliner exposure. Interestingly, six cases (32%) had no history of trauma or contamination. The onset of symptoms ranged from 2 to 14 days. The common symptoms were foreign body sensation (100%), slightly blurred vision (78%) with decreased best-corrected visual acuity of 1 to 2 Snellen lines, and tearing (63%) without discharge. All patients presented with tiny, disseminated, punctated, elevated, white epithelial lesions, whereas the epithelium remained intact in most cases. From observation, two characteristics of infiltration, which could be an oval to round shape (Figure 1A) or a peculiar blotchy infiltration (Figure 1B), were found. Mild conjunctival injection was found in all cases and only one case had anterior chamber cells (trace) without flare. Thailand is a tropical country in which the climate is controlled by tropical monsoons, and the weather in Thailand is generally hot and humid across most of the country throughout most of the year. Thailand’s seasons are generally divided into rainy from July to October, winter from November to February, and summer from March to June. Twelve cases (63%) were identified during the rainy season, four cases (21%) were reported in the cool season, and only three cases (16%) were found in the hot season. After corneal scraping and treating with topical moxifloxacin, 16 cases improved with complete resolution within 20 days. Three cases (two unilateral cases, right eye from the one bilateral case) were recurrent after cessation of topical medications. All recurrent epithelial keratitis cases were treated only with topical moxifloxacin without corneal debridement and the lesions completely disappeared. Five cases developed nummular keratitis (subepithelial infiltration or anterior stromal keratitis) after improvement of punctate epithelial keratitis (Figure 2). A mild foreign-body sensation without visual problems was reported. Topical
FIGURE 1. Slit-lamp photographs demonstrating character of corneal presentations: (A) Oval to round shape, raised, epithelial infiltration; (B) peculiar, blotchy, elevated, epithelial infiltration. Seminars in Ophthalmology
Microsporidial Epithelial Keratitis
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FIGURE 2. Nummular keratitis: (A) Subepithelial infiltration or anterior stromal keratitis (arrow); (B) nummular keratitis with increased magnification (32).
fluorometholone 0.1% eye drops were prescribed for four times a day until the corneas were clear. There was complete resolution of signs and symptoms in four cases. A few infiltrations remained in one patient without symptoms due to a compliance problem.
DISCUSSION Risk Factors Various predisposing factors (for example, contamination from soil, mud, contact lens, steroid, refractive surgery, and collagen crosslinking) have been proposed.1,3–13 From reviews of the literature, the source of microsporidia infection remains imprecise.1–3 It is a waterborne pathogen, spreading through water and food as the most likely routes of infection.1,2,6 Although microsporidia is a zoonotic disease which can be found in numerous animals, in our cases there were no reports of direct transmission from animals to humans. In our study, predisposing factors varied among patients with six patients having had no obvious risk, even with meticulous inquiry. The reason that it was not possible to identify risk factors in these patients may be due to the unawareness of contamination of water or soil.
Seasonal Variation The increased incidence during the rainy season was consistent with a previous report from India.2 In comparison to the current study, the proportions during this season were the same, which was approximately 60% (66% from India and 63% in this study from Thailand).2 A rainy environment may increase the chance of water exposure. This Thai study now reports a seasonal trend of microsporidial keratitis for which awareness should be raised for the rainy season. !
2014 Informa Healthcare USA, Inc.
FIGURE 3. Microsporidia spores stained by the Gram-chromotrope method. Oval, purple to pink spores with a belt-like strip in the middle band (dark band) (63).
Diagnosis Diagnostic methods vary according to laboratory availability. Special staining methods under light microscopy, such as modified trichrome (Figure 3), direct and indirect immunofluorescence assay (IFA), and polymerase chain reaction (PCR) are standard tests; however, these may not be available in some centers.1,14 Corneal findings and/or confocal microscopy may offer prompt and non-invasive tools for diagnosis.15,16 In the present authors’ observations, microsporidial epithelial keratitis has unique corneal findings. Generalized or focal punctate lesions with elevated epithelial infiltration were found in all cases. Characteristics of infiltration can be divided into oval to round shape and peculiarly blotchy infiltrations. Additionally, mild conjunctival injection without discharge is also one of the clues for diagnosis. In this study, all suspected cases by clinical findings had positive staining for microsporidia. Other laboratory investigations, such as staining or culture, may not be always be available. It is suggested that careful
4
O. Thanathanee et al.
slit-lamp examination of corneal findings can guide the diagnosis.
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Treatment At present, there are no definite guidelines for the treatment of microsporidial epithelial keratitis. Corneal scraping plays a crucial role in both diagnosis and treatment. Nevertheless, discomfort and visual instability from the epithelial defect are problematic. Corneal swabbing has been reported to reduce pain after epithelial debridement. Needle or forceps were used to remove only infiltrations and thus we spared the normal epithelium around the lesions.17 Oral drugs, such as albendazole and itraconazole, have been prescribed, combined with topical antibiotics in some studies.1,9,11 Recent evidence, however, has shown that oral treatment may not be required for microsporidial epithelial keratitis.11 This observation is in accordance with the our study; all cases, including the recurrences, have been cured solely with topical fluoroquinolones. However, only moxifloxacin eye drops were used in this study and no other antibiotics were used. In addition, from this study, it is not possible to explain whether the use of no oral medications may have been responsible for recurrences. Topical moxifloxacin alone may be sufficient in selected cases. Various topical medications for treating this condition have been reported; these mainly are second- to fourth-eneration fluoroquinolones, polyhexamethylenebiguanide 0.02% (PHMB), fumagillin 0.3%, voriconazole 1%, and hexamidinediisethionate 0.1%.1,3,5,9,11,13,18,19 For PHMB, there was no significant difference in resolution time and final visual acuity in a clinical trial when compared with the placebo.18 Voriconazole monotherapy has been reported with successful treatment in two cases.19 There are two reported treatment options for frequency of antimicrobial eye drops, starting with four times a day or every two hours. The preference of the present authors is to start topical moxifloxacin every two hours for the first week, then taper off according to clinical responses. Although debridement or swabbing were recommended in most studies,1,3,5,12,17,20–22 an epithelial defect or corneal irregularity can interfere with driving or working abilities and cause painful reactions. Topical moxifloxacin, without repeated scraping or swabbing, resolved all recurrent cases; therefore, scrapping or swabbing may not be required in selected cases. One randomized clinical trial has found that microsporidia epithelial keratitis is a self-limiting disease and anti-microbial therapy is not required.18 Nevertheless, all self-limited patients from these studies received corneal scraping combined with
topical antibiotics; therefore, these may play a role in the improvement.1,18 In the final stages, some patients (5/20, 25%) developed nummular keratitis with subepithelial/ anterior stromal keratitis.6,11 These lesions are similar to subepithelial infiltration after viral conjunctivitis.23,24 Keys for distinguishing nummular keratitis usually occurred after resolving the punctate, raised epithelial infiltration. The treatment option is similar to the way in which topical corticosteroids work.25 Topical fluorometholone 0.1% was given for four times a day until the cornea was clear. The lesions of four patients disappeared without alteration of the best-corrected visual acuity. One patient did not receive corticosteroid eye drops, but the number of lesions decreased with few persistent infiltrations. This did not affect visual acuity. By observation, weak corticosteroid eye drops such as fluorometholone were adequate for the treatment. The limitations of this study are the small number of patients and not being a prospective clinical trial. In conclusion, some patients may not have had any apparent predisposing factors, awareness should be increased during a rainy season, typical clinical findings can be helpful for early diagnosis, and topical moxifloxacin without oral drugs may be sufficient in the treatment. Scraping or swabbing may not be required in selected cases, particularly in recurrences. The frequency of topical moxifloxacin was recommended to start every two hours, then tapered. Nummular keratitis can occur after resolution of epithelial keratitis and weak corticosteroid eye drops should be prescribed. Further studies with a larger sample size and a randomized trial are needed to verify all of these conclusions.
FUNDING This study was funded by a grant supported by Research Affairs, Faculty of Medicine, Srinagarind Hospital, Khon Kaen University.
ACKNOWLEDGMENTS We thank: (1) the patients for their participation; (2) the nursing and medical staff for their assistance; (3) the Department of Ophthalmology and the Faculty for financial support; and (4) Professor James A. Will for assistance with the English-language presentation.
DECLARATION OF INTEREST The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper. Seminars in Ophthalmology
Microsporidial Epithelial Keratitis
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