Microsporidiosis should be considered in culture-negative stromal keratitis refractory

Diagnosis can be easily made based on morphological features of protozoa in the keratectomy specimens.

ByMichelle Stephenson

HOUSTON — Microsporidial ocular infections should be considered in the differential diagnosis of culture-negative stromal keratitis or keratoconjunctivitis that does not respond to conventional medical treatment.

“Because these organisms are morphologically distinctive by light and electron microscopy, [I] suggest corneal biopsy for histopathologic diagnosis of stromal infections. So far, no successful medical treatment is available for microsporidial corneal stromal infections,” said Ramon L. Font, MD, of the Cullen Eye Institute at Baylor College of Medicine here.

Persistent stromal keratitis

In 1997, Dr. Font and his colleagues examined a 67-year-old Hispanic man who was referred from Monterey, Mexico, because of an 8-month history of persistent stromal keratitis and progressively decreased visual acuity in his right eye. The patient was initially treated with topical antibiotics. Later, he was diagnosed with herpes simplex viral stromal keratitis and was treated with topical steroids and antivirals without resolution of the condition.

In September 1997, ophthalmologic examination revealed uncorrected visual acuity of 20/80 in the right eye and 20/20 in the left eye. “The right cornea showed dense grayish white stromal infiltrates involving its temporal aspect and extending across the visual axis, sparing only the nasal perilimbal area. The infiltrates centrally had a crystalline-like pattern. Superficial corneal vascularization was present temporally to approximately 3 mm from the limbus. The overlying epithelium was spared. The conjunctiva was not injected, and no follicular or papillary reactions were noted. The anterior chamber was quiet in the right eye. The left eye was entirely normal,” Dr. Font explained.

After the topical steroids were discontinued, the ophthalmologic examination revealed significant conjunctival injection and increased corneal vascularization peripherally. The corneal infiltrates’ appearance was essentially unchanged. The deep stroma up to the level of Descemet’s membrane was involved with the infiltrative process, and scattered infiltrates were noted on the endothelial surface.

Culture results

Conjunctival and corneal swabs and scrapings were cultured for bacterial, chlamydial, fungal and herpes virus. Culture results were all negative. In mid-September, a corneal punch biopsy was performed. At this point, a histopathologic diagnosis of microsporidial stromal keratitis was made, and the patient was started on oral albendazole 400 mg three times daily and fluorometholone four times daily.

In mid-October, the patient was started on topical fumagillin bicyclohexylammonium salt (Fumadil B).

“After 6 and 4 weeks of treatment with albendazole and fumagillin bicyclohexylammonium salt, respectively, the right cornea showed no clinical improvement, and the visual acuity remained unchanged. Fumagillin bicyclohexylammonium salt was well tolerated during the course of treatment with no adverse side effects. Stool, urine and sputum specimens tested negative for Microsporidia on two occasions. The patient was seronegative for the human immunodeficiency virus,” he said.

In early November, an eccentric lamellar keratoplasty 9.5 mm in diameter was performed. The lamellar stromal dissection was carried deep, just anterior to Descemet’s membrane. Postoperatively, treatment with albendazole and fumagillin bicyclohexylammonium salt six times a day was resumed. Additionally, the patient was started on ofloxacin in the right eye. On the fifth postoperative day, complete epithelialization of the lamellar graft was achieved.

Infiltrates recurred

One week postoperatively, infiltrates recurred at different locations in the interface. “One month later, the interface infiltrates and opacities had spread anteriorly and started to involve the graft. On December 17, 1997, a penetrating keratoplasty was performed. The patient was last examined on May 22, 1998. At that time, the graft remained clear without evidence of recurrence,” Dr. Font said.

The patient currently uses topical prednisolone acetate 1% once daily. The corneal graft is still clear, and his uncorrected visual acuity is 20/70.

“In our case, both topical fumagillin bicyclohexylammonium salt and oral albendazole failed to improve or control the progression of the infection after lamellar keratoplasty. This can be explained, in part, by the presumed inadequate drug penetration into the deep corneal stroma. The deep opacities (infiltrates) first noted at the level of Descemet’s membrane and endothelial cells proved to be viable infective organisms rather than only an inflammatory reaction, as we had initially presumed clinically. This ultimately necessitated a full-thickness corneal transplant for complete control of the infection,” he added.

While not effective in this case with stromal involvement, topical fumagillin has been shown to be effective in epithelial disease.

“We noted fumagillin to be well tolerated by the ocular surface with no adverse side effects; in our patient, complete epithelialization of the graft occurred while he was using fumagillin drops. Further studies regarding the drug delivery and dosage of fumagillin are necessary to establish its efficacy and toxicity,” he said.

For Your Information:

Ramon L. Font, MD, can be reached at the Ophthalmic Pathology Laboratory, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030 U.S.A.; +(1) 713-798-4644; e-mail: rfont@bcm.tmc.edu. Ocular Surgery News could not confirm whether or not Dr. Font has a direct financial interest in any of the products mentioned in this article or if he is a paid consultant for any companies mentioned.

Reference:

Font RL, Samaha AN, Keener MJ, Chevez-Barrios P, Goosey JD. Corneal microsporidiosis: Report of case, including electron microscopic observations. Ophthalmology. 2000; 107:1769-1775.