vere and specifically included the variation among villages in the analysis. Furthermore, our analy- Intraocular Invasion by Microsporidial sis assessed the prevalence of clinically active trachoma Spores in a Case of Stromal in a village as opposed to its presence in an individual. A village-level analysis is most useful for trachoma pro- icrobial keratitis is a visually disabling con- gram managers, who make treatment decisions based on dition caused by a variety of infectious organ- the prevalence of trachoma in a village. Our findings sug- isms. Although uncommon, microsporidial gest that in areas with hyperendemic trachoma treated M stromal keratitis has recently been reported as an emerg- through mass distribution of azithromycin, the signs of 1 active trachoma can be expected to resolve slowly, even ing cause of stromal keratitis. Intraocular microsporidi- if antibiotic distributions are quite successful in reduc- osis causing and sclerouveitis with clear 2,3 ing the prevalence of ocular chlamydia. has been reported, although there was no evi- dence of contiguous anterior chamber involvement. We Jeremy D. Keenan, MD, MPH report a rare case of microsporidial stromal keratitis in Takele Lakew, MD, MPH which microsporidial spores were detected from cor- Wondu Alemayehu, MD, MPH neal scraping, corneal tissue, and endothelial exudates. Muluken Melese, MD, MPH Jenafir I. House, MPH Report of a Case. A 40-year-old woman had intermit- Nisha R. Acharya, MD, MS tent pain, redness, , and decreased vision in Travis C. Porco, PhD, MPH her right eye for 1 year. She had trauma with a leaf 1 year Bruce D. Gaynor, MD before her initial visit to us. Since then, she had been Thomas M. Lietman, MD treated irregularly with topical antiviral medication (acy- clovir, 3%) by various health care providers. Author Affiliations: F. I. Proctor Foundation (Drs Keenan, On examination, her best-corrected visual acuity was Acharya, Porco, Gaynor, and Lietman and Ms House), Departments of (Drs Keenan, Acharya, 20/70 OD. Slitlamp biomicroscopic examination of the Porco, Gaynor, and Lietman) and Epidemiology and Bio- right eye revealed conjunctival congestion, central stro- statistics (Drs Porco and Lietman), and Institute for Global mal edema with Descemet folds, and keratic precipi- Health (Dr Lietman), University of California, San Fran- tates (Figure, A). Her intraocular pressure was normal. cisco; and ORBIS International, Addis Ababa, Ethiopia Based on results of the clinical evaluation, a diagnosis of (Drs Lakew, Alemayehu, and Melese). herpetic viral endotheliitis was made. She began treat- Correspondence: Dr Keenan, F. I. Proctor Foundation ment with systemic acyclovir, 400 mg 5 times daily, and and Department of Ophthalmology, University of Cali- topical corticosteroid (prednisolone acetate, 1%). Al- fornia, San Francisco, 95 Kirkham St, San Francisco, CA though her visual acuity and clinical picture improved, 94143 ([email protected]). she revisited us 4.5 months after the initial visit with a Financial Disclosure: None reported. decrease in vision, tearing, and pain that had lasted 15 Funding/Support: This work was supported by grants K23 days. She was using topical steroid once every other day. EY019071 and U10 EY016214 from the National Insti- Her visual acuity was light perception with projection OD. tutes of Health, the Heed Ophthalmic Foundation, the In- There was a 3.8ϫ2.7-mm central full-thickness stro- ternational Trachoma Initiative, the Bernard Osher Foun- mal infiltrate. The endothelium showed exudates ar- dation, That Man May See, the Peierls Foundation, the Bodri ranged as a sheet. The corneal scrapings examined in po- Foundation, the Harper Inglis Trust, the South Asia Re- tassium hydroxide and calcofluor white mount (Figure, search Fund, and Research to Prevent Blindness. B) showed multiple oval microsporidial spores. The spores Additional Contributions: The Ethiopian Ministry of were also seen in Gram staining of the corneal scraping Health and many health care professionals, including (Figure, C). She began intensive treatment with topical Tadesse Kebede, Berhanu Fikre, Mifta Shifa, MPH, and polyhexamethylene biguanide, 0.02%, eyedrops. Ow- Tadesse Birru, helped us organize and implement our fieldwork in Ethiopia. ing to progressive thinning and descemetocele forma- tion (Figure, D), she underwent tissue adhesive appli- 1. Solomon AW, Zondervan M, Kuper H, Buchan JC, Mabey DCW, Foster A. cation 4 days later. After a week with no response to Trachoma Control: A Guide for Programme Managers. Geneva, Switzerland: medical therapy, she underwent therapeutic penetrat- World Health Organization; 2006. 2. Melese M, Alemayehu W, Lakew T, et al. Comparison of annual and bian- ing keratoplasty. Histopathologic examination of the cor- nual mass antibiotic administration for elimination of infectious trachoma. neal tissue showed multiple microsporidial spores within JAMA. 2008;299(7):778-784. 3. Lakew T, House J, Hong KC, et al. Reduction and return of infectious tra- the stroma as well as in the subendothelial exudates with choma in severely affected communities in Ethiopia. PLoS Negl Trop Dis. 2009; intact Descemet membrane (Figure, E and F). The post- 3(2):e376. operative period was uneventful. At the last follow-up, 4. Keenan JD, Lakew T, Alemayehu W, et al. Clinical activity and polymerase chain reaction evidence of chlamydial infection after repeated mass antibi- 6 months postoperatively, the graft was clear with vi- otic treatments for trachoma. Am J Trop Med Hyg. 2010;82(3):482-487. sual acuity of 20/200 (Figure, G). 5. Bailey RL, Arullendran P, Whittle HC, Mabey DC. Randomised controlled trial of single-dose azithromycin in treatment of trachoma. Lancet. 1993;342(8869): 453-456. Comment. Stromal keratitis due to microsporidium is less 6. Fraser-Hurt N, Bailey RL, Cousens S, Mabey D, Faal H, Mabey DC. Efficacy of oral azithromycin vs topical tetracycline in mass treatment of endemic common than superficial . It is fre- trachoma. Bull World Health Organ. 2001;79(7):632-640. quently misdiagnosed as . Pre-

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 A B

C D

E F

G Figure. Clinical presentation and microbiological and histopathologic evidence of microsporidial stromal keratitis. A, Slitlamp picture showing corneal edema with Descemet folds during the initial visit. B, Clump of oval spores in the corneal scraping smear stained with calcofluor white and seen with a fluorescent microscope (original magnification ϫ400). C, Gram staining of corneal scraping showing intracellular and extracellular, oval, stippled, gram-positive, well-defined spores of microsporidia (original magnification ϫ1000). D, Slitlamp picture showing full-thickness stromal infiltrate with severe thinning. E, Section of the cornea showing subtle inflammation of the stroma with a focus of exudates posterior to Descemet membrane, suggestive of keratic precipitates (arrow) (hematoxylin-eosin, original magnification ϫ400). F, The exudates showing a single focus of microsporidia (arrow) (1% acid-fast stain, original magnification ϫ1000). G, Slitlamp picture showing clear corneal graft without any recurrence.

vious reports have described various clinical pictures of our knowledge, there are no reports documenting mi- stromal keratitis such as stromal edema with anterior to crosporidial spores in the endothelial exudates. The find- mid and/or deep stromal involvement with or without ing of intact Descemet membrane in histopathologic ex- endothelial exudates and .1 However, to amination suggests that microsporidial spores may indeed

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 pass through Descemet membrane into the anterior cham- Report of a Case. A 75-year-old woman underwent un- ber, similar to fungi. Recently, microsporidia have been complicated combined right PKP and lenticular phaco- phylogenetically shown to be fungi, and their tissue be- emulsification for Fuchs corneal dystrophy and cata- havior akin to that of fungi would be expected.4 ract. Three months postoperatively, she developed Our patient had clinical features of herpetic viral endo- peripheral stromal opacities associated with 2 loose su- theliitis at the initial visit, which improved initially with tures. These opacities grew despite topical treatment with antiviral treatment. There is a possibility that the patient tobramycin, and marked conjunctival injection and a mod- may have had viral keratitis initially and then became sec- erate anterior chamber inflammatory reaction devel- ondarily infected with microsporidium. Also, coinfection oped. She was referred to our service for treatment of cor- by microsporidia with herpes cannot be excluded. neal ulceration in the nasal and temporal portions of the Penetrating graft rather than lamellar keratoplasty is graft (Figure 1A). Corneal scrapings revealed no or- recommended for patients with deep stromal involve- ganisms on Gram or Giemsa staining, and no organisms ment to avoid any chance of recurrence in the lamellar grew on aerobic, anaerobic, fungal, or viral cultures. She bed.5 In our case, the presence of microsporidial spores was treated with fortified cefazolin and gentamicin sul- in the endothelial exudates highlights the possible pen- fate eyedrops but developed 2 new stromal infiltrates and etration of microsporidial spores through intact Desce- required repeat PKP (Figure 1B). Histopathologic analy- met membrane, thereby emphasizing the need for pen- etrating keratoplasty in cases of deep stromal involvement, sis of the removed tissue revealed full-thickness corneal especially with endothelial exudates. edema and stromal scarring, consistent with healed kera- We conclude that endothelial exudates may manifest titis. Gram staining at multiple levels failed to reveal the in microsporidial keratitis, and the spores may be pres- presence of organisms. ent in the endothelial exudates. Four months postoperatively, the patient noted a for- eign body sensation and was found to have an area of cor- Sujata Das, MS, FRCS(Glasg) neal thinning at the graft-host junction near the tempo- Savitri Sharma, MD ral site of previous ulceration. A loose suture in that area Srikant K. Sahu, MS was sent for culture and the patient was treated for pre- Geeta K. Vemuganti, MD sumed herpetic keratitis. No organisms grew from the suture, and the patient developed stromal opacities simi- Author Affiliations: Cornea and Anterior Segment Ser- vice (Dr Das and Mr Sahu) and Ocular Microbiology Ser- lar to her preoperative appearance. Repeat corneal ul- vice (Dr Sharma), LV Prasad Eye Institute, Bhu- ceration (Figure 1C and D) prompted another PKP with baneswar, and Ocular Pathology Service, LV Prasad Eye removal of a 1-mm-larger disc to encompass the previ- Institute, Hyderabad (Dr Vemuganti), India. ous graft and additional host cornea affected by ulcer- Correspondence: Dr Das, Cornea and Anterior Seg- ation and thinning. Histopathologic analysis of the re- ment Service, LV Prasad Eye Institute, Patia, Bhu- moved cornea revealed acute and chronic keratitis baneswar, Orissa 751024, India ([email protected]). associated with centrifugal intrastromal colonies of Financial Disclosure: None reported. strongly and uniformly gram-positive bacteria with Funding/Support: This work was supported by the short, stubby branches typical of Actinomyces species Hyderabad Eye Research Foundation. (Figure 2). Ziehl-Neelson acid-fast staining was nega- tive, suggesting Actinomyces rather than Nocardia spe- 1. Vemuganti GK, Garg P, Sharma S, Joseph J, Gopinathan U, Singh S. Is mi- crosporidial keratitis an emerging cause of stromal keratitis? a case series study. cies. Cultures of stromal tissue again were negative. BMC Ophthalmol. 2005;5:19. Postoperatively, graft and host corneal clarity were 2. Yoken J, Forbes B, Maguire AM, Prenner JL, Carpentieri D. Microsporidial maintained. After corneal suture removal, visual acuity endophthalmitis in a patient with acute myelogenous leukemia. . 2002; 22(1):123-125. of 20/20 was achieved with a rigid gas-permeable con- 3. Mietz H, Franzen C, Hoppe T, Bartz-Schmidt KU. Microsporidia-induced scler- tact . ouveitis with . Arch Ophthalmol. 2002;120(6):864-865. 4. Lee SC, Corradi N, Byrnes EJ III, et al. Microsporidia evolved from ancestral sexual fungi. Curr Biol. 2008;18(21):1675-1679. Comment. Actinomyces can be a rare cause of infectious 5. Font RL, Su GW, Matoba AY. Microsporidial stromal keratitis. Arch Ophthalmol. 2003;121(7):1045-1047. crystalline keratopathy, especially in an immune- suppressed condition such as a corneal graft. Infectious crystalline keratopathy is a unique corneal infection char- acterized by the slowly progressive development of needle- Actinomyces Infectious like opacities in the corneal stroma, most commonly Crystalline Keratopathy caused by streptococcal species.1,2 To our knowledge, this is the first case of infectious crystalline keratopathy due e report a difficult-to-treat, indolent infec- to an organism with morphologic characteristics consis- tion following penetrating keratoplasty (PKP) tent with Actinomyces. There have been other rare re- with the clinical appearance of infectious ports of Actinomyces corneal infections. Severe corneal W 3 crystalline keratopathy. The causative agent was not re- ulceration from Actinomyces has been reported, as has covered from multiple corneal scrapings but morpho- delayed-onset keratitis after laser in situ keratomileu- logically resembles Actinomyces species histopathologi- sis.4 In both of these cases, cure was achieved with de- cally in the deep stroma of corneal tissue removed at bridement of the infected cornea and intensive treat- repeat PKP. ment with topical antibiotics, as well as oral penicillin

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