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Microsporidia Infection of the Cornea in a Man Seropositive for Human Immunodeficiency Virus
242
AMERICAN JOURNAL OF OPHTHALMOLOGY
and slow, fastidious growth in culture. Anaerobic cultures must be maintained beyond the usual five days to detect this organism. This growth also occurs in vivo, which explains why the patient suffered three recurrences, each time with a deeper involvement. The bacterium, because of its slow growth, requires prolonged therapy for its eradication. Photophobia, possibly related to bacterial spread along corneal nerves, is probably the best indicator of persistent infection. Dysgonic fermenter 2 has a wide spectrum of antibiotic sensitivity. It is particularly sensitive to penicillin, clindamycin, and rifampin.! Dysgonic fermenter 2 corneal involvement can mimic fungal, acanthamebal, or stromal keratitis. One should suspect this organism in cases where a dog's oral flora may have infected the cornea.
References 1. Parnel. G. J., Buckley, D. J., Frucht, J., Krausz, H., and Feldman, S. T.: Capnocytophaga keratitis. Am. J. Ophthalmol. 107:193, 1989. 2. Heidemann, D. G., Pflugfelder, S. c.. Kronish, J., Alfonso, E. c.. Dunn, S. P., and Ullman, S.: Necrotizing keratitis caused by Capnocytophaga ochracea. Am. J. Ophthalmol. 105:655, 1988. 3. Brenner, D. J., Hollis, D. G., Fanning, G. R., and Weaver, R. E.: Capnocqtophaga canimorsus sp. nov. (formerly CDC group DF-2), a cause of septicemia following dog bite, and C. cynodegmi sp. nov., a cause of localized wound infection following dog bite. J. Clin. Microbiol. 27:231, 1989. 4. Verghese, A., Hamati, F., Berk, S., Franzus, B., Berk, 5., and Smith, J. K.: Susceptibility of dysgonic fermenter 2 to antimicrobial agents in vitro. Antirnicrob. Agents Chemother. 32:78, 1988.
February, 1990
Inquiries to Careen Y. Lowder, M.D., Department of Ophthalmology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195-5024.
Microsporidia are obligate intracellular parasites that infect mammals, arthropods, fish, and birds. They rarely cause disease in humans.' Recently, however, microsporidia have been associated with hepatitis and enteritis in patients with the acquired immunodeficiency syndrome (AIDS).2 We encountered a case of microsporidia corneal infection in an individual who was seropositive for human immunodeficiency virus antibodies. A 30-year-old homosexual man with AIDSrelated complex and known to be HIVseropositive for three years, began having recurrent episodes of redness and crusting of both eyes in November 1988. Conjunctival cultures grew Streptococcus viridans and coagulase-negative staphylococcus. The patient was treated with the appropriate topical antibiotics without resolution of the condition. Ocular examination in February 1989 disclosed a bestcorrected visual acuity of 20/25 in each eye. Slit-lamp examination showed marked bilateral conjunctival hyperemia, mixed follicular-papillary tarsal conjunctival reaction, and diffuse punctate epithelial keratopathy. Conjunctival cultures for bacteria, fungi, chlamydia, herpes simplex virus, herpes zoster virus, and adenovirus were negative. The patient's epithelial keratopathy worsened over the next three months, and visual acuity deteriorated to 20/60 in each eye (Fig. 1). In May 1989 corneal epithelium was scraped from the right eye and healed rapidly, but the epithelial keratopathy recurred. Epithelial scrapings were submitted for cul-
Microsporidia Infection of the Cornea in a Man Seropositive for Human Immunodeficiency Virus Careen Y. Lowder, M.D., David M. Meisler, M.D., James T. McMahon, Ph.D., David L. Longworth, M.D., and Isobel Rutherford, M.D. Departments of Ophthalmology (C.Y.L., D.M.M.), Pathology (J.T.M.), Infectious Disease (D.L.L.), and Microbiology (l.R.), Cleveland Clinic Foundation.
Fig. 1 (Lowder and associates). Slit-lamp photograph of punctate epithelial keratopathy.
Vol. 109, No.2
Letters to the Journal
243
Fig. 2 (Lowder and associates). Transmission electron micrograph of intracellular microsporidial spores. Ultrastructural features of the organism include cell wall, coiled filament (arrows), polar vacuole (V), and single nucleus (N). Also present is a collapsed spore (CS) (X 24,000).
ture and microscopic studies. Cultures for bacteria, fungi, and retrovirus were negative. Light microscopy disclosed ribbons of corneal squamous epithelium. No inflammatory cells were observed. Gram-positive oval forms were seen within epithelial cells, and many of these inclusions had a vacuole and a densely staining nucleus. A single small periodic acid-Schiff stain-positive polar body was noted in many of the inclusions. Transmission electron microscopy demonstrated intracellular organisms, each measuring approximately 1 x 2 um (Fig. 2). Most were surrounded by an 80-nm thick cell wall composed of a thick, inner electron-lucent zone and a thin, outer dense layer. Some organisms were surrounded only by the outer, dense layer and were interpreted as immature spore forms. A homogeneously fine granular nucleus and variably fibrillar to granular vacuole were noted in many organisms. Adjacent to the cell membrane, a cytoplasmic tubular filament measuring 0.1 ~m in diameter formed six to eight coiled loops around the nucleus. This extended and attached to a dense plaquelike area on the cell membrane. The filament was often seen protruding from the organism, occasionally ex-
tending a considerable distance into the surrounding host cell cytoplasm. Numerous empty or collapsed cell walls, containing only remnants of cytoplasm and protruded filaments, were noted throughout the specimen. The histopathologic and ultrastructural findings confirmed the presence of the protozoan microsporidia. We found two reports of microsporidiosis of the human cornea.v' The infections resulted in severe keratitis in both cases. This led to perforation and enucleation of the eye in one case and penetrating keratoplasty in the other case. In our patient, the corneal infection appeared confined to the epithelium. The absence of an inflammatory response may be attributed to the patient's immunodeficient state. Microsporidia are fastidious and difficult to recover in culture. The specific diagnosis of microsporidiosis is made by light and electron microscopic identification of the unique structural features of the organisms. There is no known therapy for microsporidium infections, although sulfonamides have shown some efficacy in vitro. Some patients treated with sulfa drugs have survived.'
244
Microsporidia should be suspected in persistent epithelial keratopathy with negative cultures in HIV -seropositive individuals. Epi theIial scraping for light and electron microscopic evaluation is necessary for accurate diagnosis.
References 1. Shadduck, J. A., and Greeley, E.: Microsporidia and human infections. Clin. Microbiol. Rev. 2:158, 1989. 2. Shadduck, J. A.: Human microsporidiosis and AIDS. Rev. Infect. Dis. 11:203, 1989. 3. Ashton, N., and Wirasinha, P. A.: Encephalitozoonosis (Nosematosis) of the cornea. BT. J. Ophthalmol. 57:669,1973. 4. Pinnolis, M., Egbert, P. R., Font, R. L., and Winter, F. c.: Nosematosis of the cornea. Arch. Ophthalmol. 99:1044,1981.
Correspondence
Retinal Angiomalike and Macular Pucker
Lesion
EDITOR:
The article "Peripheral Retinal Angiemalike Lesion and Macular Pucker," by L. Laatikainen, I. Immonen, and P. 5ummanen (Am. J. Ophthalmol. 108:563, November 1989) described macular pucker formation in cases with peripheral vascular lesions. These cases are similar to series of cases in which Williams and I found traction retinal detachments in combination with various retinal vascular diseases such as von Hippel-Lindau disease, exudative vitreoretinopathy, and Coats' disease.' The cases reported by Laatikainen, Immonen, and 5ummanen probably represent a lesser degree of the same entity we reported.
a
We believed that the vascular tumors leak and cause reactive retinal glial proliferation resulting in preretinal membrane formation. These membranes can contract. They may cause puckers, depending on their location, or they may partially detach from the retina and cause traction retinal detachments. Therapy has to be aimed first at elimination of the vascular lesions. Vitreous surgery will be considered to remove preretinal or vitreous membranes depending on the amount and type of proliferation. ROBERT MACHEMER, M.D.
Durham, North Carolina
Reference 1. Machemer, R., and Williams, J. M., [r.: Pathogenesis and therapy of traction detachment in various retinal vascular diseases. Am. J. Ophthalmol. 105:170,1988.
_ _ _ _ _ _ _ Reply
Correspondence concerning recent articles or other material published in THE JOURNAL should be submitted within six weeks of publication. Correspondence must be typed double-spaced, on 8'12 xlI-inch bond paper with 1'12-inch margins on all four sides and should be no more than two typewritten pages in length. Every effort will be made to resolve controversies between the correspondents and the authors of the article before publication.
Peripheral
February, 1990
AMERICAN JOURNAL OF OPHTHALMOLOGY
_
EDITOR:
We did not discuss the pathogenesis of macular pucker in retinal vascular lesions in detail, but we agree with D~. Machemer that preretinal membrane formation at the posterior pole was most likely initiated by the leaking vascular process in the peripheral retina. Our cases were less advanced than those reported by Machemer and Williams. No retinal detachment was noted, and the vitreous was clear in all eyes. Our cases stress the importance of careful evaluation of the peripheral retina in all cases with macular pucker. Our aim in therapy was to treat the vascular lesion first, as was also proposed by Machemer. This seemed to stop membrane formation. Vitrectomy with membrane peeling was performed in two eyes after regression of the vascular changes because of significant visual disturbance. 50 far, no recurrent membranes or traction retinal detachments have been noted. LEILA LAATIKAINEN, M.D.
oui« Finland
ILKKA IMMONEN, M.D. PAULA SUMMANEN, M.D.
Helsinki, Finland
AMERICAN JOURNAL OF OPHTHALMOLOGY
and slow, fastidious growth in culture. Anaerobic cultures must be maintained beyond the usual five days to detect this organism. This growth also occurs in vivo, which explains why the patient suffered three recurrences, each time with a deeper involvement. The bacterium, because of its slow growth, requires prolonged therapy for its eradication. Photophobia, possibly related to bacterial spread along corneal nerves, is probably the best indicator of persistent infection. Dysgonic fermenter 2 has a wide spectrum of antibiotic sensitivity. It is particularly sensitive to penicillin, clindamycin, and rifampin.! Dysgonic fermenter 2 corneal involvement can mimic fungal, acanthamebal, or stromal keratitis. One should suspect this organism in cases where a dog's oral flora may have infected the cornea.
References 1. Parnel. G. J., Buckley, D. J., Frucht, J., Krausz, H., and Feldman, S. T.: Capnocytophaga keratitis. Am. J. Ophthalmol. 107:193, 1989. 2. Heidemann, D. G., Pflugfelder, S. c.. Kronish, J., Alfonso, E. c.. Dunn, S. P., and Ullman, S.: Necrotizing keratitis caused by Capnocytophaga ochracea. Am. J. Ophthalmol. 105:655, 1988. 3. Brenner, D. J., Hollis, D. G., Fanning, G. R., and Weaver, R. E.: Capnocqtophaga canimorsus sp. nov. (formerly CDC group DF-2), a cause of septicemia following dog bite, and C. cynodegmi sp. nov., a cause of localized wound infection following dog bite. J. Clin. Microbiol. 27:231, 1989. 4. Verghese, A., Hamati, F., Berk, S., Franzus, B., Berk, 5., and Smith, J. K.: Susceptibility of dysgonic fermenter 2 to antimicrobial agents in vitro. Antirnicrob. Agents Chemother. 32:78, 1988.
February, 1990
Inquiries to Careen Y. Lowder, M.D., Department of Ophthalmology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195-5024.
Microsporidia are obligate intracellular parasites that infect mammals, arthropods, fish, and birds. They rarely cause disease in humans.' Recently, however, microsporidia have been associated with hepatitis and enteritis in patients with the acquired immunodeficiency syndrome (AIDS).2 We encountered a case of microsporidia corneal infection in an individual who was seropositive for human immunodeficiency virus antibodies. A 30-year-old homosexual man with AIDSrelated complex and known to be HIVseropositive for three years, began having recurrent episodes of redness and crusting of both eyes in November 1988. Conjunctival cultures grew Streptococcus viridans and coagulase-negative staphylococcus. The patient was treated with the appropriate topical antibiotics without resolution of the condition. Ocular examination in February 1989 disclosed a bestcorrected visual acuity of 20/25 in each eye. Slit-lamp examination showed marked bilateral conjunctival hyperemia, mixed follicular-papillary tarsal conjunctival reaction, and diffuse punctate epithelial keratopathy. Conjunctival cultures for bacteria, fungi, chlamydia, herpes simplex virus, herpes zoster virus, and adenovirus were negative. The patient's epithelial keratopathy worsened over the next three months, and visual acuity deteriorated to 20/60 in each eye (Fig. 1). In May 1989 corneal epithelium was scraped from the right eye and healed rapidly, but the epithelial keratopathy recurred. Epithelial scrapings were submitted for cul-
Microsporidia Infection of the Cornea in a Man Seropositive for Human Immunodeficiency Virus Careen Y. Lowder, M.D., David M. Meisler, M.D., James T. McMahon, Ph.D., David L. Longworth, M.D., and Isobel Rutherford, M.D. Departments of Ophthalmology (C.Y.L., D.M.M.), Pathology (J.T.M.), Infectious Disease (D.L.L.), and Microbiology (l.R.), Cleveland Clinic Foundation.
Fig. 1 (Lowder and associates). Slit-lamp photograph of punctate epithelial keratopathy.
Vol. 109, No.2
Letters to the Journal
243
Fig. 2 (Lowder and associates). Transmission electron micrograph of intracellular microsporidial spores. Ultrastructural features of the organism include cell wall, coiled filament (arrows), polar vacuole (V), and single nucleus (N). Also present is a collapsed spore (CS) (X 24,000).
ture and microscopic studies. Cultures for bacteria, fungi, and retrovirus were negative. Light microscopy disclosed ribbons of corneal squamous epithelium. No inflammatory cells were observed. Gram-positive oval forms were seen within epithelial cells, and many of these inclusions had a vacuole and a densely staining nucleus. A single small periodic acid-Schiff stain-positive polar body was noted in many of the inclusions. Transmission electron microscopy demonstrated intracellular organisms, each measuring approximately 1 x 2 um (Fig. 2). Most were surrounded by an 80-nm thick cell wall composed of a thick, inner electron-lucent zone and a thin, outer dense layer. Some organisms were surrounded only by the outer, dense layer and were interpreted as immature spore forms. A homogeneously fine granular nucleus and variably fibrillar to granular vacuole were noted in many organisms. Adjacent to the cell membrane, a cytoplasmic tubular filament measuring 0.1 ~m in diameter formed six to eight coiled loops around the nucleus. This extended and attached to a dense plaquelike area on the cell membrane. The filament was often seen protruding from the organism, occasionally ex-
tending a considerable distance into the surrounding host cell cytoplasm. Numerous empty or collapsed cell walls, containing only remnants of cytoplasm and protruded filaments, were noted throughout the specimen. The histopathologic and ultrastructural findings confirmed the presence of the protozoan microsporidia. We found two reports of microsporidiosis of the human cornea.v' The infections resulted in severe keratitis in both cases. This led to perforation and enucleation of the eye in one case and penetrating keratoplasty in the other case. In our patient, the corneal infection appeared confined to the epithelium. The absence of an inflammatory response may be attributed to the patient's immunodeficient state. Microsporidia are fastidious and difficult to recover in culture. The specific diagnosis of microsporidiosis is made by light and electron microscopic identification of the unique structural features of the organisms. There is no known therapy for microsporidium infections, although sulfonamides have shown some efficacy in vitro. Some patients treated with sulfa drugs have survived.'
244
Microsporidia should be suspected in persistent epithelial keratopathy with negative cultures in HIV -seropositive individuals. Epi theIial scraping for light and electron microscopic evaluation is necessary for accurate diagnosis.
References 1. Shadduck, J. A., and Greeley, E.: Microsporidia and human infections. Clin. Microbiol. Rev. 2:158, 1989. 2. Shadduck, J. A.: Human microsporidiosis and AIDS. Rev. Infect. Dis. 11:203, 1989. 3. Ashton, N., and Wirasinha, P. A.: Encephalitozoonosis (Nosematosis) of the cornea. BT. J. Ophthalmol. 57:669,1973. 4. Pinnolis, M., Egbert, P. R., Font, R. L., and Winter, F. c.: Nosematosis of the cornea. Arch. Ophthalmol. 99:1044,1981.
Correspondence
Retinal Angiomalike and Macular Pucker
Lesion
EDITOR:
The article "Peripheral Retinal Angiemalike Lesion and Macular Pucker," by L. Laatikainen, I. Immonen, and P. 5ummanen (Am. J. Ophthalmol. 108:563, November 1989) described macular pucker formation in cases with peripheral vascular lesions. These cases are similar to series of cases in which Williams and I found traction retinal detachments in combination with various retinal vascular diseases such as von Hippel-Lindau disease, exudative vitreoretinopathy, and Coats' disease.' The cases reported by Laatikainen, Immonen, and 5ummanen probably represent a lesser degree of the same entity we reported.
a
We believed that the vascular tumors leak and cause reactive retinal glial proliferation resulting in preretinal membrane formation. These membranes can contract. They may cause puckers, depending on their location, or they may partially detach from the retina and cause traction retinal detachments. Therapy has to be aimed first at elimination of the vascular lesions. Vitreous surgery will be considered to remove preretinal or vitreous membranes depending on the amount and type of proliferation. ROBERT MACHEMER, M.D.
Durham, North Carolina
Reference 1. Machemer, R., and Williams, J. M., [r.: Pathogenesis and therapy of traction detachment in various retinal vascular diseases. Am. J. Ophthalmol. 105:170,1988.
_ _ _ _ _ _ _ Reply
Correspondence concerning recent articles or other material published in THE JOURNAL should be submitted within six weeks of publication. Correspondence must be typed double-spaced, on 8'12 xlI-inch bond paper with 1'12-inch margins on all four sides and should be no more than two typewritten pages in length. Every effort will be made to resolve controversies between the correspondents and the authors of the article before publication.
Peripheral
February, 1990
AMERICAN JOURNAL OF OPHTHALMOLOGY
_
EDITOR:
We did not discuss the pathogenesis of macular pucker in retinal vascular lesions in detail, but we agree with D~. Machemer that preretinal membrane formation at the posterior pole was most likely initiated by the leaking vascular process in the peripheral retina. Our cases were less advanced than those reported by Machemer and Williams. No retinal detachment was noted, and the vitreous was clear in all eyes. Our cases stress the importance of careful evaluation of the peripheral retina in all cases with macular pucker. Our aim in therapy was to treat the vascular lesion first, as was also proposed by Machemer. This seemed to stop membrane formation. Vitrectomy with membrane peeling was performed in two eyes after regression of the vascular changes because of significant visual disturbance. 50 far, no recurrent membranes or traction retinal detachments have been noted. LEILA LAATIKAINEN, M.D.
oui« Finland
ILKKA IMMONEN, M.D. PAULA SUMMANEN, M.D.
Helsinki, Finland