Diagnosis and treatment of fungal keratitis. Part I

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Abstract

Fungal keratitis (FK) is a difficult diagnostic challenge for ophthalmologists.

The aim is to familiarize practicing physicians with the diagnostic algorithm worked out in the Ophthalmological Center of SPB City hospital No. 2 using modern research methods, and to assess the epidemiology of fungal keratitis in the North-West Region.

Materials and methods. Patients underwent laboratory diagnostics (fluorescence microscopy of corneal scrapings from the cornea, сulture on Sabouraud agar and broth), confocal in vivo microscopy, optical coherence tomography.

Results. During the period from 2007 to 2017, 41 cases of FK were identified in the City hospital No. 2, of which filamentous fungi were the causative agent in 32 cases (78%), yeast fungi — in 9 cases (22%). Our analysis included patients with fungal keratitis over the past three years, all of them underwent a full diagnostic cycle. Filamentous fungi were found among 12 of them (63%), yeast — in 7 (37%). Our data, considering the statistics of fungal keratitis in the North-West of Russia — a region with a high level of urbanization and industrialization, and located in the temperate zone — showed a predominance of filamentous fungi as pathogens (prevalence 1.3 times higher). Our scheme of keratitis diagnostics — confocal in vivo microscopy, OCT, fungal culture — is a reliable way to identify fungal pathogens in the cornea, and can be recommended for use in practical ophthalmology.

About the authors

Yelena V. Skryabina

City Multi-Field Hospital No 2

Author for correspondence.
Email: scryabelena@mail.ru

MD, ophthalmologist, Microsurgery Department No 4

Russian Federation, Saint Petersburg

Yuriy S. Astakhov

I.P. Pavlov State Medical University of St. Petersburg

Email: astakhov73@mail.ru

MD, Doctor of Medical Science, Professor. Department of Ophthalmology

Russian Federation, Saint Petersburg

Yanina S. Konenkova

City Multi-Field Hospital No 2

Email: Krocon@mail.ru

MD, Head of Department, Microsurgery Department No 4

Russian Federation, Saint Petersburg

Farkhod O. Kasymov

City Multi-Field Hospital No 2

Email: farkkas@yahoo.com

MD, PhD, Assistant Professor, Ophthalmology Department

Russian Federation, Saint Petersburg

Nataliya G. Zumbulidze

North-Western State Medical University n.a. I.I. Mechnikov

Email: zumbulenok@mail.ru

MD, PhD, Assistant Professor, Ophthalmology Department

Russian Federation, Saint Petersburg

Tatiana S. Varganova

City Multi-Field Hospital No 2

Email: Varganova.ts@yandex.ru

MD, Candidate of Medical Sciences, ophthalmologist, Consultative-Diagnostic Department of Ophthalmology

Russian Federation, Saint Petersburg

Vladimir P. Petukhov

City Multi-Field Hospital No 2

Email: v.p.petukhov@gmail.com

MD, Ophthalmologist, Department of Laser Microsurgery

Russian Federation, Saint Petersburg

Alyona A. Pirgunova

North-Western State Medical University n.a. I.I. Mechnikov

Email: cvcv4698@yandex.ru

Second Year Ophthalmology Resident. Department of Ophthalmology

Russian Federation, Saint Petersburg

Janek Masian

North-Western State Medical University n.a. I.I. Mechnikov

Email: phaser.j@gmail.com

Second Year Ophthalmology Resident. Department of Ophthalmology

Russian Federation, Saint Petersburg

Nikolai N. Klimko

North-Western State Medical University n.a. I.I. Mechnikov

Email: n_klimko@mail.ru

MD, Doctor of Medical Science, Professor, Head of the Department of Clinical Mycology, Allergology and Immunology

Russian Federation, Saint Petersburg

Tatyana S. Bogomolova

North-Western State Medical University n.a. I.I. Mechnikov

Email: tatiyna.bogomolova@szgmu.ru

Head of the Research Laboratory of Mycological Monitoring and Fungal Biology of the P.N. Kashkin

Russian Federation, Saint Petersburg, Russia

Ekaterina A. Desyatik

North-Western State Medical University n.a. I.I. Mechnikov

Email: e_desyatik@mail.ru

allergologist-immunologist of the Mycological Department of the P.N. Kashkin Research Institute of Medical Mycology

Russian Federation, Saint Petersburg

References

  1. Huang W, Ling S, Jia X, et al. Tacrolimus (FK506) suppresses TREM-1 expression at an early but not at a late stage in a murine model of fungal keratitis. PLoS One. 2014;9(12):e114386. doi: 10.1371/journal.pone.0114386.
  2. Hu J, Hu Y, Chen S, et al. Role of activated macrophages in experimental Fusarium solani keratitis. Exp Eye Res. 2014;129:57-65. doi: 10.1016/j.exer.2014.10.014.
  3. Karthikeyan RS, Leal SM, Jr, Prajna NV, et al. Expression of innate and adaptive immune mediators in human corneal tissue infected with Aspergillus or Fusarium. J Infect Dis. 2011;204(6):942-950. doi: 10.1093/infdis/jir426.
  4. Qu X, Che C, Gao A, et al. Association of Dectin-1 and DC-SIGN gene single nucleotide polymorphisms with fungal keratitis in the northern Han Chinese population. Mol Vis. 2015;21:391-402.
  5. Xu Q, Zhao G, Lin J, et al. Role of Dectin-1 in the innate immune response of rat corneal epithelial cells to Aspergillus fumigatus. BMC Ophthalmol. 2015;15:126. doi: 10.1186/s12886-015-0112-1.
  6. Zhu CC, Zhao GQ, Lin J, et al. Dectin-1 agonist curdlan modulates innate immunity to Aspergillus fumigatus in human corneal epithelial cells. International Journal of Ophthalmology. 2015;8(4):690-696. doi: 10.3980/j.issn.2222-3959.2015.04.09
  7. Kredics L, Narendran V, Shobana C, Grou I-H. Filamentous fungal infections of the cornea: a global overview of epidemiology and drug sensitivity. Mycoses. 2015;58:243-260. doi: 10.1111/myc.12306.
  8. Астахов Ю.С., Скрябина Е.В., Коненкова Я.С., и др. Диагностика и лечение грибковых кератитов // Офтальмологические ведомости. - 2013. - T. 6. - № 2. - С. 75-80. [Astakhov YS, Skryabina EV, Konenkova YS, et al. Diagnosis and treatment of fungal keratitis. Ophtalmology Journal. 2013;7(2):75-80. (In Russ.)]
  9. Gopinathan U, Sharma S, Garg P, Rao GN. Review of epidemiological features, microbiological diagnosis and treatment outcome of microbial keratitis: experience of over a decade. Indian Journal of Ophthalmology. 2009;57:273-279. doi: 10.4103/0301-4738.53051.
  10. Xie L, Zhong W, Shi W, Sun S. Spectrum of fungal keratitis in north China. Ophthalmology. 2006;113:1943-1948.
  11. Bhartiya P, Daniell M, Constantinou M, et al. Fungal keratitis in Melbourne. Clinical and Experimental Ophthalmology. 2007;35:124-130. doi: 10.1111/j.1442-9071.2006.01405.x.
  12. Ritterband DC, Seedor JA, Shah MK, et al. Fungal keratitis at the New York Eye and Ear Infirmary. Cornea. 2006;25:264-267. doi: 10.1097/01.ico.0000177423.77648.8d.
  13. Tuft SJ, Tullo AB. Prospective study of fungal keratitis in the United Kingdom 2003-2005. Eye (London). 2009;23:308-313. doi: 10.1038/eye.2008.298.
  14. Bourcier T, Sauer А, Dory А, et al. Fungal keratitis. Journal Français d’Ophtalmologie. 2017;40:307-313. doi: 10.1016/j.jfo.2017.08.001.
  15. Mukherjee PK, Chandra J, Yu C, et al. Characterization of Fusarium keratitis outbreak isolates: contribution of biofilms to antimicrobial resistance and pathogenesis. Investigative Ophthalmology and Visual Science. 2012;53:4450-7. doi: 10.1167/iovs.12-9848.
  16. Keay LJ, Gower EW, Iovieno A, et al. Clinical and microbiological characteristics of fungal keratitis in the United States, 2001-2007: a multicenter study. Ophthalmology. 2011;118(5):920-6. doi: 10.1016/j.ophtha.2010.09.011.
  17. Камилов Х.М., Абдуллаев Ш.Р., Касымова М.С. Особенности клинического течения посттравматического грибкового бактериального язвенного кератита // Вестник проблем биологии и медицины. - 2012. - № 3. - Т. 1 (94). - С. 59. [Kamilov XM, Abdulaev SR, Kasymova MS. Features of the clinical course of posttraumatic fungal bacterial ulcerative keratitis. Vestnik problem biologii i mediciny. 2012;(3):59. (In Russ.)]
  18. Lan L, Wang FY, Zeng G. Staining with methylthioninium chloride for the diagnosis of fungal keratitis. Experimental and Therapeutic Medicine. 2013;6(5):1229-1232. doi: 10.3892/etm.2013.1288.
  19. Thomas PA, Kaliamurthy J. Mycotic keratitis: epidemiology, diagnosis and management. Clinical microbiology and Infection. 2013;19(3):210-220. doi: 10.1111/1469-0691.12126.
  20. Ansari Z, Miller D, Galor A. Current thoughts in fungal keratitis: diagnosis and treatment. Curr Fungal Infect Rep. 2013;7(3):209-218. doi: 10.1007/s12281-013-0150-110.1007/s12281-013-0150-1.
  21. van Diepeningen AD, Brankovics B, Iltes J, et al. Diagnosis of fusarium infections: approaches to identification by the clinical mycology laboratory. Current Fungal Infection Reports. 2015;9(3):135-143. doi: 10.1007/s12281-015-0225-2.
  22. Zhao G, Zhai H, Yuan Q, et al. Rapid and sensitive diagnosis of fungal keratitis with direct PCR without template DNA extraction. Clinical Microbiology and Infection. 2014;20(10):O776-O782. doi: 10.1111/1469-0691.12571.
  23. Labbe A, Khammari C, Dupas B, et al. Contribution of in vivo confocal microscopy to the diagnosis and management of infectious keratitis. Ocular Surface. 2009;7:41-52.
  24. Ledbetter EC, Norman ML, Starr JK. In vivo confocal microscopy for the detection of canine fungal keratitis and monitoring of therapeutic response. Veterinary Ophthalmology. 2015;19(3):220-229. doi: 10.1111/vop.12287.
  25. Азнабаев Б.М., Алимбекова З.Ф., Мухамадеев Т.Р., Габбасов А.Р. Лазерная сканирующая томография глаза: передний и задний отрезок. - М., 2008. - C. 90-92. [Aznabaev BM, Alimbekova ZF, Muhamadeev TR, Gabbasov AR. Lazer skaniruryushaya tomographya glaza: perednii i zadnii otrezok. Moscow; 2008. P. 90-92. (In Russ.)]
  26. Villani E, Baudouin C, Efron N, et al. In vivo confocal microscopy of the ocular surface: from bench to bedside. Current Eye Research. 2014;39(3):213-231. doi: 10.3109/02713683.2013.842592.
  27. Wang LY, Xu ZZ, Zhang JJ, et al. [Topical voriconazole as an effective treatment for fungal keratitis]. Zhonghua Yan Ke Za Zhi. 2016;52(9):657-62. doi: 10.3760/cma.j.issn.0412-4081.2016.09.005.
  28. Soliman W, Fathalla AM, El-Sebaity DM, Al-Hussaini AK. Spectral domain anterior segment optical coherence tomography in microbial keratitis. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2013;251(2):549-553. doi: 10.1007/s00417-012-2086-5.
  29. Bongomin F, Gago S, Oladele RO, Denning DW. Global and Multi-National Prevalence of Fungal Diseases - Estimate Precision. J Fungi (Basel). 2017;3(4):57-86. doi: 10.3390/jof3040057.

Supplementary files

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2. Fig. 1. Distribution of patients by age categories

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3. Fig. 2. Geography of pathogens of fungal keratitis and their distribution by genus [20, 29]

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4. Fig. 3. Hyphae of fungi in cornea sections at different depths in different patients: a — patient K., 68 years old; b — patient L., 67 years old; c — patient I., 52 years old

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5. Fig. 4. Pseudo-mycelium of yeast fungi (arrows)

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6. Fig. 5. Microscopy of culture (mag. ×400). Culture grew Fusarium spp.

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7. Fig. 6. Direct light microscopy of corneal scrapings. Culture grew Aspergillus fumigatus

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8. Fig. 7. Optical coherence tomography of the anterior segment of the eye

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Copyright (c) 2018 Skryabina Y.V., Astakhov Y.S., Konenkova Y.S., Kasymov F.O., Zumbulidze N.G., Varganova T.S., Petukhov V.P., Pirgunova A.A., Masian J., Klimko N.N., Bogomolova T.S., Desyatik E.A.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
 


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