Anterior segment exam of the right eye revealed central, deep corneal stromal haze with edema.
A 32-year-old man with a history of soft contact lens wear presented to the New England Eye Center with complaints of decreased vision in the right eye associated with severe pain, photophobia and tearing for 1 month. He was being treated with prednisolone acetate 1% and sodium chloride 5% ointment every 4 hours after completing a 3-day course of ciprofloxacin ophthalmic drops four times a day in the right eye. He had worn soft contact lenses for 10 years and admitted to more than 16 hours of daily wear but denied overnight wear. He reported using tap water to rinse the case and contact lenses, and he occasionally wore the lenses in the hot tub.
The patient had no other significant medical or ocular history. Social history was remarkable for an interest in exotic pets; he owned pet snakes, turtles and frogs.
On examination, the patient’s best corrected visual acuity was counting fingers measured at 4 feet in the right eye and 20/15 in the left eye. Manifest refraction yielded no improvement. The pupils measured 4 mm, and no afferent pupillary defect was found. Extraocular motility was full. Anterior segment examination of the right eye revealed central, deep corneal stromal haze with edema. No corneal epithelial defect or anterior chamber reaction was detected (Figures 1 and 2). Anterior segment examination of the left eye was unremarkable. Posterior segment examination revealed healthy optic nerve heads and retinas in both eyes.
Figure 1. Anterior segment photo of the right eye depicting minimal conjunctival injection and central corneal haze.
Images: Bhavsar K, Wu HK
Figure 2. Slit beam photo of the right eye illustrating stromal edema and haze.
What is your diagnosis?
Deep stromal keratitis
The differential diagnosis of unilateral deep stromal keratitis in a soft contact lens wearer includes infectious etiologies such as Acanthamoeba or microsporidial keratitis, bacterial keratitis and fungal keratitis. Inflammatory etiologies related to herpes simplex, acquired syphilis and tuberculosis, as well as collagen vascular diseases, should be considered, especially if the infectious work-up is negative.
Infectious etiologies were highly suspected in this patient due to his history of soft contact lens wear associated with high-risk habits. The insidious onset, pain out of proportion to findings on physical examination, and lack of significant ulceration were concerning for Acanthamoeba or microsporidial keratitis. Bacterial keratitis and fungal keratitis could not be ruled out; however, bacterial infection was considered less likely given the insidious course of presentation. Absence of classic feathery infiltrate made fungal infection also less likely.
Interstitial keratitis or inflammatory response could be responsible. Herpes simplex stromal keratitis accounts for the most cases of immune-mediated stromal inflammation with an intact epithelium. Less commonly, acquired syphilis and tuberculosis can manifest as unilateral interstitial keratitis. Collagen vascular diseases (eg, systemic lupus erythematosus, rheumatoid arthritis) can rarely incite a stromal keratitis and should be considered in patients with corresponding systemic symptoms or signs.
Diagnosis and management
The patient was asked to discontinue topical steroid drops and sodium chloride ointment. Corneal cultures were taken, which were negative on Gram stain and on final growth. Antibiotic therapy with gatifloxacin ophthalmic drops was initiated every 2 hours while the patient was awake. Results of a confocal scan revealed increased inflammatory cells in the epithelium and anterior stroma. Additionally, hyper-reflective dot-like structures were surrounding keratocyte nuclei, a pattern consistent with microsporidial infection. No double-walled cysts or fungal elements were seen.
Given the results of the confocal microscopy, the patient’s treatment was altered to cover microsporidial keratitis. The patient was started on fumagillin ophthalmic drops (0.113 mg/mL) and continued on the gatifloxacin ophthalmic drops every 2 hours while awake; oral itraconazole 200 mg was added twice a day. One week later, his vision was stable at count fingers and the clinical exam was unchanged; however, he noted significant improvement in pain and photophobia. Two weeks later, examination revealed stable visual acuity and improved corneal edema. A repeat confocal microscopic examination showed a stable pattern of hyper-reflective dot-like structures. Albendazole 400 mg orally twice a day was added to his regimen to replace the topical fumagillin, which was causing considerable local irritation.
The patient was maintained on oral medications until 6-month follow-up, at which point his visual acuity had improved to 20/400, the corneal edema had resolved, and stromal scarring was present (Figure 3). A repeat confocal microscopy was ordered at that time, but because of insurance issues, the patient did not receive it.
Figure 3. Anterior segment photo at 6-month follow-up revealing resolved corneal edema and stromal scarring.
Microsporidia are a spore-forming group of obligate intracellular parasites, and this opportunistic pathogen can cause significant gastrointestinal, sinus, pulmonary, muscular, renal, neurological and ocular disease in the human host. The first case of microsporidial keratitis was described in 1973, and there was a subsequent rise in the number of cases seen by ophthalmologists during the AIDS epidemic. Risk factors for infection include exposure to animals, infected water sources and systemic immunodeficiency. Significant local risk factors for ocular infection include contact lens wear and topical steroid therapy.
Ophthalmic manifestations of microsporidial disease include keratoconjunctivitis described in immunocompromised patients as a bilateral diffuse punctate epithelial keratopathy associated with conjunctivitis. Immunocompetent patients typically develop either deep intrastromal keratitis or unilateral punctate keratopathy. Patients may also less commonly develop scleritis and anterior uveitis.
Diagnosis requires high clinical suspicion, as serologic testing and culture are not routinely available. Light microscopy may be useful to identify the organism by specific spore characteristics using trichrome and Ziehl-Neelsen staining methods.
Confocal microscopy was particularly critical for the diagnosis and management of this patient, and it typically reveals a characteristic pattern of hyper-reflective spots suggestive of microsporidial spores. Definitive diagnosis is via corneal biopsy, which may be considered in challenging cases to ascertain a diagnosis.
Medical therapy includes topical fluoroquinolones, topical fumagillin/Fumidil B, oral itraconazole, oral albendazole and polyhexamethylene biguanide. Surgical therapy is rarely described but includes epithelial debridement to debulk spore load and penetrating keratoplasty for severe cases of stromal scarring.
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For more information:
- Kavita Bhavsar, MD, and Helen K. Wu, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.
- Edited by Catherine A. Cox, MD, and Jordana F. Goren MD, MS. Drs. Cox and Goren can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.