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Chronic Microsporidial Stromal Keratitis in an Immunocompetent, Non-Contact Lens Wearer

Fogla, Rajesh DNB, FRCS; Padmanabhan, Prema MS; Therese, K Lily PhD; Biswas, Jyotirmay MS; Madhavan, H N MD, PhD

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Indian Journal of Ophthalmology: Apr–Jun 2005 - Volume 53 - Issue 2 - p 123-125
doi: 10.4103/0301-4738.16177
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Microsporidia are small oval, obligate, intracellular protozoan parasites that have been associated with human disease primarily in immunocompromised individuals with human immunodeficiency virus (HIV) infection.12 Corneal involvement in humans was first reported by Ashton et al in 1973.3 Two distinct clinical manifestations have been described, a superficial punctate keratoconjunctivitis occurring in patients with acquired immune deficiency syndrome (AIDS) and a stromal keratitis which occurs in immunocompetent patients.2 However, stromal involvement is rare and has been reported infrequently,456 compared to superficial punctate keratoconjunctivitis.78

Case Report

A 82-year-old man, presented to the cornea clinic with complaints of pain, watering and photophobia associated with mild decrease in vision in the left eye of 3 weeks′ duration. He did not give any history of trauma, contact lens wear or occurrence of similar episodes in the past. He was otherwise healthy, not using medications for any systemic illness. On examination his visual acuity was 6/9 in the right eye and 6/12 in the left eye. Slitlamp biomicroscopy showed the right eye to be essentially normal apart from age-related lenticular changes. The left cornea showed grayish white stromal infiltrates measuring 1.5-2.0 mm diameter, in the mid-periphery at the 3 o′ clock and 8 o′ clock positions. The stromal infiltrates were located at midstromal depth, and fluorescein staining did not show any epithelial defect. Corneal sensation was considerably reduced. The anterior chamber had 1+ flare and cells. A few keratic precipitates were also noted inferiorly. Intraocular pressure was considered raised on digital tonometry. A presumptive clinical diagnosis of viral stromal keratitis was made and the patient was started on topical therapy with acyclovir 3% five times daily, atropine 1% twice daily, ciprofloxacin 0.3% six times daily, and timolol 0.5% twice daily. Corneal scrapings, when performed a week later, did not reveal any organisms. Fluorometholone 0.1% four times daily was now added to the regimen, and resulted in clinical improvement. However, recurrence of stromal keratitis was noted a month later, once the topical corticosteroids were tapered and discontinued. Topical prednisolone acetate 1% four times daily was now substituted for fluorometholone 0.1% (besides acyclovir, ciprofloxacin and timolol) following which an initial resolution of the stromal infiltrates was noted. A month later, the stromal lesions recurred on tapering and discontinuation of topical corticosteroids. The infiltrates now increased in size, involved full thickness of the corneal stroma along with peripheral corneal vascularisation, and linear endothelial exudates [Figure 1]. On microbiological examination of the corneal biopsy specimen, several oval cells measuring 4-5 m in length were noted in KOH, Giemsa, Calcofluor and Gram′s stains [Figure 2]. These organisms were also acid-fast positive [Figure 3]. Based on these features and the clinical presentation a presumed diagnosis of microsporidial keratitis was made.

Figure 1:
Slit lamp photograph of the left eye showing dense grayish white stromal infiltrate involving the mid-peripheral cornea
Figure 2:
KOH – Calcofluor stained smear of the corneal biopsy showing numerous bluish white fluorescing oval spores of microsporidia measuring 4-5 μ x 2-3 μ, (original magnification, x40)
Figure 3:
Modified acid fast stain (1% sulphuric acid as the decoloriser), showing acid fast oval microsporidial spores (original magnification, x100)

Systemic evaluation by an internist did not show any evidence of immunosuppression or any other illness. The patient was seronegative for HIV. Due to the extensive corneal involvement a therapeutic penetrating keratoplasty was performed in the left eye. Light microscopy of the keratoplasty specimen revealed an atrophic corneal epithelium with intact Bowman′s layer. Numerous tiny, refractile, oval organisms were seen within the stromal lamellae and the cytoplasm of histiocytes (Figure 4). These microorganisms, measuring 4-5 μ in length were Gram positive and also stained positive with periodic acid-Schiff and acid-fast stains. Numerous epithelioid histiocytes were noted along with a few acute inflammatory cells. We were unable to culture any organism from the corneal specimen. Transmission electron microscopy of the corneal specimen revealed multiple spores measuring 3-5 μ in length and 2-3 μ in width, among most of the corneal lamellae. Under high magnification the sporoblast disclosed diplokaryotic arrangement of the nuclei, besides multiple coils of the polar filament [Figure 5]. These features were consistent with microsporidial aetiology and confirmed our earlier diagnosis of microsporidial keratitis.

Figure 4:
Histopathology of the corneal button, showing numerous tiny refractile ovoid spores of Microsporidia within the corneal stroma. (H/E, original magnification x40)
Figure 5:
Transmission electron microscopy showing a spore of Nosema Corneum, loose multiple coils of the Polar Filament (arrows) and the two nuclei (arrow heads). (Original magnification x30,000). Inset shows multiple spaces in the corneal stroma

He was then started on topical propamidine isethionate 0.1% six times daily, Neosporin (neomycin, bacitracin and polymyxin B) twice daily, atropine sulphate 1% twice daily, timolol 0.5% twice daily and oral albendazole 400 mg three times daily. No recurrence of infection was noted in the post-operative period. Oral albendazole was reduced to 400 mg daily after a week and was continued for a duration of six weeks. When last examined 10 months later, he was asymptomatic (besides decreased vision due to a failed graft) and there was no evidence of any recurrence of infection.


Microsporidia are now well recognised as opportunistic infectious pathogens in patients with AIDS.12345678 Diffuse superficial keratopathy and conjunctivitis are the usual clinical presentations of ocular microsporidiosis in these AIDS patients. But the clinical presentation of ocular microsporidiosis is different in immunocompetent patients. It usually presents as unilateral stromal keratitis, caused by the Nosema species.3456 In the two initial cases reported by Ashton et al,3 and Pinnolis et al,4 microsporidial stromal keratitis occurred in younger individuals, and presented as an advanced corneal disease. In contrast, the two cases subsequently reported by Davis et al5 and Font et al6 occurred in older individuals, presenting as indolent stromal keratitis. Both these patients were diagnosed initially as viral stromal keratitis based on the clinical findings and were treated with antivirals and corticosteroids. The indolent clinical presentation could be attributed to the local immunosuppression secondary to use of corticosteroids, apart from old age. Our case also had a similar presentation and course of management.

Electron microscopy is essential for a definitive genus identification of microsporidial organisms.56Nosema species measure 3-5 m in length and are larger than the Encephalitozoon species which measure 2-3 m in length. Numerous coils of the polar filament are noted, which are greater in number in Nosema species.56 Based on these features on EM, our patient also had microsporidial infection, possibly by Nosema corneum.

Effective medical treatment does not exist for the treat-ment of microsporidial stromal keratitis. Agents that have been used to manage such infections include topical propamidine isethionate 0.1%, neosporin, and fumagil-lin.789 Oral therapy with itraconazole and albendazole has also been recommended to ensure complete resolution.9 Lamellar procedures have been suggested if the infection is limited to the anterior or mid stroma.6 Due to the advanced nature of the stromal disease, a full thickness penetrating keratoplasty was performed in our patient. Our patient was also treated with topical propamidine isethionate 0.1%, and Neosporin, along with systemic albendazole following therapeutic penetrating keratoplasty. No recurrence of infection was noted.

In conclusion, microsporidial stromal keratitis can have a clinical presentation that mimics viral stromal keratitis. Therefore it should be considered in the differential diagnosis of culture-negative stromal keratitis not responding to standard medical therapy in immunocompetent individuals. Corneal biopsy is essential for diagnosis. In the absence of effective medical therapy for stromal lesions, surgical intervention is necessary in addition to topical and systemic medications, to successfully eradicate the infection.

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2. Weber R, Bryan RT, Schwartz DA, Owen RL. Human microsporidian infections Clin Microbiol Rev. 1994;7:426–61
3. Ashton N, Wirasinha PA. Encephalitozoonosis (nosematosis) of the cornea Br J Ophthalmol. 1973;57:669–74
4. Pinnolis M, Egbert PR, Font RL, Winter FC. Nosematosis of the cornea. Case report, including electron microscopic studies Arch Ophthalmol. 1981;99:1044–7
5. Davis RM, Font RL, Kiesler MS, Shadduck JA. Corneal microsporidiosis. A case report including ultrastructural observations Ophthalmology. 1990;97:953–7
6. Font RL, Samaha AN, Keener MJ, Chevez-Barrios C, Goosey JD. Corneal microsporidiosis. Report of a case, including electron microscopic observations Ophthalmology. 2000;107:1769–75
7. Cali A, Miesler DM, Rutherford I, Lowder CY, McMohan JT, Longworth DL, et al Corneal microsporidiosis in a patient with AIDS Am J Trop Med Hyg. 1991;44:463–8
8. Metcalfe TW, Doran RM, Rowlands PL, Curry A, Lacey CJ. Microsporidial keratoconjunctivitis in a patient with AIDS Br J Ophthalmol. 1992;76:177–8
9. Rossi P, Urbani C, Donelli G, Pozio E. Resolution of microsporidial sinusitis and keratoconjunctivitis by itraconazole treatment Am J Ophthalmol. 1999;127:210–2

Financial Support: Nil,

Proprietary Interest: None


Microsporidiosis; stromal keratitis; immunocompetent individual; penetrating keratoplasty

© 2005 Indian Journal of Ophthalmology | Published by Wolters Kluwer – Medknow