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Microsporidial Stromal Keratitis

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Microsporidial Stromal Keratitis CLINICOPATHOLOGIC REPORTS, CASE REPORTS, AND SMALL CASE SERIES SECTION EDITOR: W. RICHARD GREEN, MD Microsporidial Stromal Keratitis Microsporida are spore-forming, ob- ligate eukaryotic protozoan para- sites that belong to the phylum Microspora. The ophthalmic mani- festations of ocular microsporidi- osis exhibit characteristic clinical fea- tures depending on the genus involved. With the genus Encepha- Figure 1. The clinical appearance of the right Figure 2. The clinical appearance of the right litozoon, infection is limited to the cornea at the time of the initial examination cornea 9 months after the initial examination epithelial cells of the cornea and con- shows a central area of stromal infiltration and displays a central epithelial defect associated junctiva, producing a diffuse punc- edema without suppuration. A 3% hypopyon is with a disciform opacity. Superficial peripheral tate epithelial keratoconjunctivitis. present inferiorly. corneal vascularization is observed superiorly. With the genera Nosema and Micro- sporidium, the infection typically in- and scrapings collected for bacte- wrinkled and folded. The endothe- volves the corneal stroma, includ- rial, chlamydial, fungal, and herpes- lium was attenuated with a retro- ing the keratocytes.1 virus cultures were all negative for corneal fibrovascular membrane, To date, only 5 case reports of microorganisms. containing few neutrophils. The cor- microsporidial stromal keratitis have Over the next 2 months, the vi- neal stroma showed round to oval been published.2-6 We report an ad- sual acuity improved to 20/25 OD, organisms measuring 2.0 to 4.0 µm. ditional case caused by Vittaforma with gradual resolution of the stro- These organisms were mostly lo- corneae (formerly known as No- mal edema. Four weeks later, while cated within the cytoplasm of kera- sema corneum), which was con- the patient was taking a tapering regi- tocytes and macrophages, as well as firmed by histological analysis and men of prednisolone acetate and tri- extracellularly. Gram stains showed electron microscopy. fluridine, stromal keratitis recurred gram-positive spores, some of which with a disciform appearance associ- exhibited a polar granule. These or- Report of a Case. A 65-year-old ated with central epithelial defect as ganisms stained positively with pe- white man was referred with a well as superficial corneal vascular- riodic acid–Schiff and Grocott- 4-month history of progressive red- ization superiorly (Figure 2). Vi- methenamine silver methods but ness, pain, and decreased vision in sual acuity was 20/200 OD. Re- were acid-fast negative. the right eye. The patient denied any peated cultures revealed only a few Transmission electron micros- history of herpes zoster, vesicular colonies of Staphylococcus epidermi- copy 1-µm sections revealed scat- eruptions, trauma, and contact lens dis. Despite appropriate antimicro- tered sporoblasts, displaying a dis- wear. Ophthalmic examination re- bial treatment, a persistent epithe- tinct cell wall with dikaryotic vealed a best-corrected visual acu- lial defect ensued with progressive arrangement of the nuclei, which is ity of 20/40 OD and 20/20 OS. Find- stromal thinning centrally. Ten characteristic of Vittaforma corneae7 ings from an examination of the left months after onset of symptoms, the (Figure 4). A diagnosis of micro- eye were normal. The right eye right cornea perforated. The patient sporidial stromal keratitis caused showed moderate diffuse conjunc- underwent a penetrating kerato- by Vittaforma corneae was made. tival hyperemia with a central area plasty of the right eye (8.25-mm do- Six months after the penetrat- of stromal infiltration and edema nor size to 7.75-mm recipient size). ing keratoplasty, the visual acuity without suppuration (Figure 1). The keratectomy specimen was sent improved to 20/25 OD. A blood The anterior chamber had 1+ cells for histopathological examination. sample tested with an enzyme- and flare with a 3% hypopyon infe- Microscopically, the corneal linked immunosorbent assay was riorly. Findings from the remain- epithelium showed intracellular negative for antibodies to human im- der of the ocular examination were edema with subepithelial bullae munodeficiency virus. The subse- unremarkable. The patient was (Figure 3). Bowman’s layer was quent postoperative course was com- treated with 1% prednisolone ac- mostly absent. The stroma re- plicated by severe microbial keratitis etate and 1% trifluridine, both 6 vealed marked areas of scarring and secondary to Pseudomonas aerugi- times a day in the right eye for pre- vascularization with a neutrophilic nosa infection, leading to perfora- sumed herpes simplex stromal kera- infiltrate, involving all layers of the tion. A second penetrating kerato- titis. Conjunctival and corneal swabs stroma. Descemet’s membrane was plasty was performed in the right eye (REPRINTED) ARCH OPHTHALMOL / VOL 121, JULY 2003 WWW.ARCHOPHTHALMOL.COM 1045 ©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Deep stromal infections of the cor- nea have been described in associa- tion with trauma leading to stromal scarring and vascularization,2 with atraumatic perforated corneal ulcer manifesting with keratouveitis and hyphema,3 and with foreign body and persistent corneal ulcer.4 In addi- tion, spontaneous stromal keratitis mimicking herpes simplex virus in- fection has also been described.5 Lastly, stromal microsporidiosis has also been reported in a patient with persistent stromal keratitis, which was initially managed as a case of herpes simplex stromal keratitis.6 Likewise, our patient was first seen with stro- mal keratitis resembling herpes sim- Figure 3. Thick sections (1 µm) depict swollen stromal keratocytes containing numerous intracellular plex virus infection, which ulti- round to oval organisms measuring 2.5 to 4.0 µm in maximal diameters (toluidine blue stain, original mately progressed to corneal thinning magnification ϫ252). and perforation, leading to a penetrat- ing graft. Thus, microsporidial ocu- lar infections should be considered in the differential diagnosis of culture- negative stromal keratitis refractory to conventional medical treatment. Full-thickness corneal trans- plantation appears to be the only pro- cedure that has proven to be success- ful for the treatment of deep stromal microsporidiosis. In one of the re- ported cases,6 a deep lamellar kera- toplasty was unable to prevent the re- currence of the disease. Furthermore, the use of both topical fumagillin and oral albendazole failed to control the infection, even after lamellar kerato- plasty. Of the 4 case reports of cor- neal microsporidiosis,4-6 including our own, no recurrences of micro- Figure 4. An electron micrograph depicts a sporoblast with 2 abutted nuclei (N), which is highly sporidial infection occurred at the last characteristic of Vittaforma corneae. follow-up examination following a full-thickness penetrating corneal graft. Therefore, one should con- Distinguishing Features of Corneal Microsporidiosis sider performing a full-thickness pen- etrating graft rather than a lamellar Feature Encephalitozoon hellem Vittaforma corneae* graft to avoid the possibility of re- Host status Immunocompromised Immunocompetent currences in the graft. Tissue Confined to corneal and conjunctival epithelium Corneal stroma Identification of microspo- No. of nuclei Monokaryotic Two abutted nuclei Autophagic vacuole Present Absent ridial ocular infections require cy- tologic and histopathological exami- *Vittaforma corneae was previously known as Nosema corneum. nation of corneal or conjunctival biopsy specimens combined with approximately 1 year after the first ter the second penetrating kerato- transmission electron microscopy, grafting. Histopathological exami- plasty, the graft remained clear, and which is essential for accurate spe- nation of the keratectomy speci- visual acuity was 20/40 OD. cies characterization. Distinguish- men showed acute necrotizing and ing features, including the clinical suppurative keratitis with stromal Comment. Well-documented cases findings and ultrastructural fea- thinning. No evidence of microspo- of microsporidiosis involving the cor- tures of Encephalitozoon hellem and ridial organisms was present. neal stroma are rare. Only 2 genera, Vittaforma corneae, are depicted in At the last follow-up examina- Nosema and Encephalitozoon, are the Table. In our patient, dikary- tion, approximately 15 months af- known to cause ocular infections.6 otic arrangement of the nuclei was (REPRINTED) ARCH OPHTHALMOL / VOL 121, JULY 2003 WWW.ARCHOPHTHALMOL.COM 1046 ©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 found, which is characteristic of Vit- ter EBV infection.1 Although the retina (Figure 1) with retinal hem- taforma corneae.6,7 virus has previously been impli- orrhages, and inflammatory sheath- cated in chorioretinitis and retinal ing of some retinal blood vessels. Ramon L. Font, MD vasculitis in patients with infec- Numerous round and oval-shaped Grant W. Su, MD tious mononucleosis,2 to our knowl- atrophic-appearing retinal pigment Alice Y. Matoba, MD edge there is only 1 report in the lit- epithelial lesions measuring approxi- Houston, Tex erature of retinal necrosis associated mately 300 µm in diameter were 3 The authors have no relevant finan- with XLPD. Herein we present the scattered throughout the entire pe- cial interest in this article. case of a 10-month-old
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