Author Affiliations: Emory Eye Center and Emory Vision, Atlanta, Georgia (Drs Khandelwal, Hall, Grossniklaus, and Stulting); and W. K. Kellogg Eye Center, Ann Arbor, Michigan (Dr Woodward).
Microsporidia are obligate intracellular eukaryotic pathogens known to cause superficial punctate keratitis and stromal keratitis in both immunocompromised and immunocompetent individuals. Traditionally, microsporidia were classified as primitive eukaryotes; however, recent genomic evidence supports their reclassification as fungi.1
Definitive treatment for microsporidial keratitis has not been established. Based on the classification of microsporidia as fungi, use of topical antifungal agents may be beneficial as monotherapy. Voriconazole is available through compounding pharmacies in topical form and is effective against several fungal pathogens.2 Herein, we report 2 cases of microsporidial superficial punctate keratitis that were responsive to treatment with topical voriconazole. To our knowledge, this is the first case series of the successful treatment of microsporidial superficial punctate keratitis with topical voriconazole.
A 49-year-old white man was seen in August 2009 with foreign-body sensation, blurred vision, and redness of his right eye for 2 weeks. Medical history was significant for metastatic thyroid cancer. His chemotherapy was discontinued because of neutropenia 1 month earlier and his white blood cell count had subsequently normalized. His best-corrected visual acuity (BCVA) was 20/25 OD and 20/15 OS. Right eye slitlamp examination demonstrated 20 to 25 raised epithelial opacities diffusely throughout the cornea with subepithelial infiltrates (Figure 1A). Follicles were present on the palpebral conjunctiva. Examination was otherwise normal in the right eye. Slitlamp examination of the left eye was normal. The clinical diagnosis was viral conjunctivitis, and treatment was started with topical prednisolone acetate, 1%, 3 times daily. At 1 week, the epithelial opacities and subepithelial infiltrates were improved, so corticosteroid use was tapered and discontinued. Three weeks later, the symptoms and signs returned, and BCVA worsened to 20/30 OD. Microsporidial keratitis was suspected based on clinical appearance and time course. Microscopic examination of a diagnostic epithelial scraping revealed aggregates of intracellular organisms in the cytoplasm of epithelial cells consistent with microsporidia (Figure 2A). Steroid use was discontinued, and treatment was begun with topical voriconazole, 1%, every 2 hours. After 8 days, BCVA was 20/25 OD with improved symptoms and signs. Voriconazole use was tapered over 4 weeks. The patient had resolution of symptoms and signs at his visit after the taper. Final BCVA was 20/15 OD.
Slitlamp photographs. A, Case 1 slitlamp photograph shows multiple raised epithelial opacities diffusely throughout the cornea with subepithelial infiltrates. B, Case 2 slitlamp photograph shows diffuse punctate epithelial keratopathy.
Microscopic examination of a diagnostic epithelial scraping. A, Case 1. There are numerous 2.0 × 1.0–μm organisms in the cytoplasm of an epithelial cell (arrow) (Giemsa, original magnification ×250). B, Case 2. An epithelial cell is distended with 2.0 × 1.0–μm organisms in its cytoplasm (arrow) compared with a normal cell (arrowhead) (Gram, original magnification ×250).
A 63-year-old white man with no medical history was referred for left eye redness and irritation. Treatment elsewhere had included topical prednisolone acetate, 1%. A diffuse punctate epitheliopathy with a “dendritiform pattern” subsequently developed. Treatment with topical trifluorothymidine was started; however, the signs did not improve, and the patient was referred for further evaluation. At presentation in our clinic, BCVA measured 20/20 OD and 20/30 OS. Slitlamp examination of the right eye was normal. The left eye showed a diffuse punctate epithelial keratopathy (Figure 1B). We suspected microsporidial infection and performed an initial epithelial scraping, results of which were inconclusive. At 2 weeks, his visual acuity remained at 20/30 OD with worsening punctate epithelial keratopathy. Another scraping was performed. Microscopic examination of this specimen revealed aggregates of intraepithelial organisms consistent with microsporidia (Figure 2B). Trifluorothymidine use was discontinued, and treatment was begun with topical voriconazole, 1%, every 2 hours. Visual acuity improved to 20/20 OD, and clinical signs improved over 1 to 2 weeks. Use of voriconazole drops was tapered over the course of 4 weeks, and there was no recurrence of signs or symptoms.
An optimal monotherapy for microsporidia keratitis does not currently exist despite trials of oral and topical agents. Treatment with numerous topical medications has been attempted without success. Oral medications, such as albendazole and itraconazole, have shown efficacy, but the risk of systemic adverse effects and drug-drug interactions exists.3 Combinations of medications, both topical and oral, have been attempted with varying success.
Given the efficacy of azoles systemically, we treated our patients with a topical azole (voriconazole, 1%) to target the superficial cornea locally. Voriconazole has proven efficacy in treating ocular fungal infections secondary to its broad spectrum of activity and excellent ocular penetration.4 In human eyes, Hariprasad et al5 demonstrated aqueous concentrations exceeding the minimum inhibitory concentration required to inhibit the growth of 90% of organisms of most fungal pathogens, often by 5-fold, after use of topical voriconazole, 1%, every 2 hours for 24 hours.
It is possible microsporidia is a self-limited disease in immunocompetent patients.6 We know that our first patient was immunosuppressed. Our second patient was healthy, but the human immunodeficiency virus status was unknown. This patient did not respond to topical steroids. Once treated with topical voriconazole, the patient improved quickly.
Both of our patients had epithelial debridement to establish the diagnosis. Debridement alone may be therapeutic; however, our second patient only improved after the second debridement was accompanied by treatment with voriconazole.
We conclude that topical voriconazole, 1%, is an effective treatment for keratitis due to microsporidia. Both patients were treated for approximately 6 weeks with complete resolution of signs and symptoms. Neither patient had complaints of adverse effects during treatment. As such, we believe topical voriconazole, 1%, should be further investigated as a potential treatment of choice for patients with microsporidial superficial punctate keratitis.
Correspondence: Dr Woodward, W. K. Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105 (email@example.com).
Financial Disclosure: None reported.
Funding/Support: Supported in part by Research to Prevent Blindness.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Ophthalmology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 4
Customize your page view by dragging & repositioning the boxes below.
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.