Skip to main content

Advertisement

SpringerLink
Log in

Multicenter prospective observational study of fungal keratitis in Japan: analyses of culture-positive cases

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the clinical characteristics and causative fungi in patients with fungal keratitis in Japan, and to determine factors related to the prognosis.

Study design

Multicenter prospective observational study.

Methods

Eligible patients were enrolled from November 2011 to October 2013 at the 1st stage and from April 2015 to March 2016 at the 2nd stage. The corneal foci were scraped, and the scrapings were cultured in potato dextrose agar. The isolated fungi were identified by gene analyses. Data were collected from the clinical records and statistically analyzed by Cox and logistic regression analyses.

Results

Ninety-four fungal strains were isolated from 93 cases, including 42 yeast-like fungi and 52 filamentous fungi. The fungi affected the deep layers of the cornea in 23 cases (24.7%) and the peripheral cornea in 29 cases (31.2%). The incidences of lid swelling/redness, ciliary injection, anterior chamber cells/flare, anterior chamber fibrin, and hyphate ulcer in cases of filamentous fungi were significantly higher than in yeast-like fungi. No history of topical steroids, absence of a main lesion in the peripheral cornea, and best-corrected visual acuity (BCVA) of more than 0.04 at the first visit were related to a shorter healing time. No history of ocular surgery, absence of lesion at one-third deep stromal layer and BCVA of more than 0.04 at the first visit were correlated with BCVA at 3 months after the initial examination.

Conclusion

Fungal keratitis is caused by various species of fungi and can become refractory due to poor prognosis factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Gopinathan U, Garg P, Fernandes M, Sharma S, Athmanathan S, Rao GN. The epidemiological feature and laboratory results of fungal keratitis. A 10-year review at a referral eye care center in south India. Cornea. 2002;21:555–9.

    Article  Google Scholar 

  2. Xie L, Zhong W, Shi W, Sun S. Spectrum of fungal keratitis in north China. Ophthalmology. 2006;113:1943–8.

    Article  Google Scholar 

  3. Gowr EW, Keay LJ, Oechsler RA, Iovieno A, Alfonso EC, Jones DB, et al. Trends in fungal keratitis in the United States, 2001 to 2007. Ophthalmology. 2010;117:2263–7.

    Article  Google Scholar 

  4. Chowdhary A, Singh K. Spectrum of fungal keratitis in north India. Cornea. 2005;24:8–15.

    Article  Google Scholar 

  5. Rosa RH, Miller D, Alfonso EC. The changing spectrum of fungal keratitis in south Florida. Ophthalmology. 1994;101:1005–13.

    Article  Google Scholar 

  6. Bharathi MJ, Ramakrishnan R, Vasu S, Meenakshi R, Palaniappan R. Epidemiological characteristics and laboratory diagnosis of fungal keratitis A three-year study. Indian J Ophthalmol. 2003;51:315–21.

    PubMed  Google Scholar 

  7. Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Prajna L, Srinivasan M, et al. The mycotic ulcer treatment trial A randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol. 2013;131:422–9.

    Article  Google Scholar 

  8. Taenaka N, Hibino T, Fukuda M, Mishima H, Otori T. A retrospective study of 11 cases of keratomycosis managed since 1995 at Kinki University Hospital. Folia Opphthalnmol Jpn. 1997;48:883 (in Japanese).

    Google Scholar 

  9. Takebayashi H, Shiota H, Naito T, Kinouchi Y, Mimura Y. Review of keratomycosis. Jpn J Clin Ophthalmol. 1997;51:33–6 (in Japanese).

    Google Scholar 

  10. Okuda T, Matsumoto K, Miyajima S, Muto A, Negi A. Evaluation of nine cases of keratomycosis. J Eye. 1999;16:959–62 (in Japanese).

    Google Scholar 

  11. Suzuki T, Uno T, Uda T, Miyamoto H, Sunada A, Asari S, et al. Typing and prognosis of keratomycosis caused by filamentous fungi. Jpn J Clin Ophthalmol. 2004;58:2153–7 (in Japanese).

    Google Scholar 

  12. Yamamoto S, Ishii H, Monden Y, Kumagai N, Yamakawa R. Review of keratomycosis at Krume University Hosipital. Jpn J Clin Ophthalmol. 2013;67:1879–83 (in Japanese).

    Google Scholar 

  13. Mitsui Y, Kitano S, Uchida Y, Tanaka N, Kobayasi S, Tokuda H, et al. Clinical evaluation of pimaricin in the treatment of mycotic infections of the cornea. Nippon Ganka Gakkai Zasshi. 1982;86:2213–23 (in Japanese).

    CAS  PubMed  Google Scholar 

  14. Ishibashi Y. Keratomycosis in Japan reported from 1976 to 1980. Nippon Ganka Gakkai Zasshi. 1982;86:651–6 (in Japanese).

    CAS  PubMed  Google Scholar 

  15. Ishibashi Y, Matsumoto Y, Hommura S. Keratomycosis in Japan reported from 1981 to 1985. Nippon Ganka Gakkai Zasshi. 1987;91:712–6 (in Japanese).

    CAS  PubMed  Google Scholar 

  16. Inoue Y, Ohashi Y, Asari S, Ishibashi Y, Uno T, Kinoshita S, et al. Guidelines for the clinical management of infectious keratitis (2nd edition). Nippon Ganka Gakkai Zasshi. 2013;117:467–509 (in Japanese).

    Google Scholar 

  17. Study group of national surveillance of infectious keratitis in Japan. National surveillance of infectious keratitis in Japan–Current status of isolates, patient background, and treatment. Nippon Ganka Gakkai Zasshi. 2006;110:961–72 (in Japanese).

    Google Scholar 

  18. Uno T, Fukuda M, Ohashi Y, Shimomura Y, Ishibashi Y, Inaba M, et al. Survey of severe contact lens-associated microbial keratitis in Japan. Nippon Ganka Gakkai Zasshi. 2011;115:107–15 (in Japanese).

    PubMed  Google Scholar 

  19. Inoue Y, Ohashi Y, Suzuki T, Shimomura Y, Fukuda M, Sotozono C, et al. Multicenter prospective observational study of fungal keratitis –current status of patients’ background, clinical findings, treatment and prognosis-. Nippon Ganka Gakkai Zasshi. 2016;120:5–16 (in Japanese).

    CAS  PubMed  Google Scholar 

  20. Sunada A, Asari S, Inoue Y, Ohashi Y, Suzuki T, Shimomura Y, et al. Multicenter prospective observational study of fungal keratitis –identification and susceptibility test of fungi-. Nippon Ganka Gakkai Zasshi. 2016;120:17–27 (in Japanese).

    CAS  PubMed  Google Scholar 

  21. Kimura K, Inoue Y, Asari S, Sunada A, Ohashi Y, Shimomura Y, et al. Multicenter prospective observational study of fungal keratitis in Japan: Analyses of in vitro susceptibility tests for combination of drugs. Jpn J Ophthalmol, 2022. https://doi.org/10.1007/s10384-022-00907-2.

    Article  PubMed  Google Scholar 

  22. Garg P, Gopinathan U, Choudhary K, Rao GN. keratomycosis: clinical and microbiologic experience with dematiaceous fungi. Ophthalmology. 2000;107:574–80.

    Article  CAS  Google Scholar 

  23. Sun CQ, Lalitha P, Prajna V, Karpagam R, Geetha M, O’Brien KS, et al. Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis. Ophthalmology. 2014;121:1495–500.

    Article  Google Scholar 

  24. Zhao X, Tong Y, Wang X, Zhang X, Chen S, Lu H. Comparison of the ocular penetration and pharmacokinetics between natamycin and voriconazole after topical instillation in rabbits. J Ocul Pharmacol Ther. 2018;34:460–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Japan National Society for the Prevent of Blindness. The members of the Multicenter Study Group of Fungal Keratitis in Japan―Yoshitsugu Tagawa (Hokkaido University), Hidetaka Masahara (Eguchi Eye Clinic), Shunji Yokokura, Megumi Uematsu (Tohoku University), Hiroyuki Namba (Yamagata University), Daisuke Todokoro (Gunma University), Tetsuro Oshika, Yuichi Kaji (University of Tsukuba), Hiroto Obata (Jichi Medical University), Shiro Amano, Takashi Miyai (University of Tokyo), Masahiko Usui, Hiroshi Goto, Shigeto Kumakura (Tokyo Medical University), Etsuko Takamura, Kazumi Shinozaki (Tokyo Women's Medical University), Masakazu Yamada, Chika Shigeyasu (National Institute of Sensory Organs, National Tokyo Medical Center), Noriko Inada, Mitsuru Sawa (Nihon University), Manabu Mochizuki, Kei Morohoshi (Tokyo Medical and Dental University), Tairo Kimura (Ueno Eye Clinic), Hisashi Nakagawa (Tokushima Eye Clinic), Norio Usui (Shinkawabashi Hospital), Hiroshi Hatano (Hatano Eye Clinic), Saichi Hoshi (Fujieda Municipal General Hospital), Kazuko Kitagawa (Kanazawa Medical University), Kiyofumi Mochizuki (Gifu University), Shigeru Kinoshita, Chie Sotozono (Kyoto Prefectural University),　Naoyuki Maeda, Takeshi Soma, Hisataka Fujimoto (Osaka University), Yoshikazu Shimomura, Masahiko Fukuda (Kindai University), Yoshitsugu Inoue, Dai Miyazaki (Tottori University), Tai-ichiro Chikama (Hiroshima University), Koh-Hei Sonoda, Naoyuki Morishige (Yamaguchi University), Hiroshi Eguchi, Tatsuro Miyamoto (University of Tokushima), Hiroshi Shiota (Kaisei General Hospital), Yuichi Ohashi, Toshihiko Uno, Atsushi Shiraishi, Takashi Suzuki (Ehime University), Shigeki Okamoto (Okamoto Eye Clinic), Tamaki Sumi (Kochi Medical School), Eiichi Uchio, Masahiko Ozawa (Fukuoka University), Kaoru Araki-Sasaki, Naoki Kumagai (Ideta Eye Hospital), Koki Matsumoto (Kumamoto Shinto General Hospital), Yu Monden (Kurume University), Masafumi Uematsu (Nagasaki University), Kazunori Miyata, Ryohei Nejima (Miyata Eye Hospital), Seishi Asari, Atsuko Sunada, Keigo Kimura (Osaka University Hospital), Takashi Yaguchi (Chiba University), Koichi Makimura (Teikyo University).

Author information

Authors and Affiliations

  1. Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, Tottori, 683-8504, Japan

    Yoshitsugu Inoue

  2. Department of Ophthalmology, Minami-Matsuyama Hospital, Matsuyama, Ehime, Japan

    Yuichi Ohashi

  3. Department of Ophthalmology, Fuchu Eye Center, Izumi, Osaka, Japan

    Yoshikazu Shimomura

  4. Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Chie Sotozono

  5. Hatano Eye Clinic, Fujisawa, Kanagawa, Japan

    Hiroshi Hatano

  6. Department of Ophthalmology, Kindai University Nara Hospital, Ikoma, Nara, Japan

    Masahiko Fukuda

  7. Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan

    Hiroshi Eguchi

  8. Department of Ophthalmology, Kansai Medical University, Hirakata, Osaka, Japan

    Kaoru Araki-Sasaki

  9. Department of Ophthalmology, Faculty of Medicine, Toho University, Tokyo, Japan

    Takashi Suzuki

  10. Horikiri Eye Clinic, Tokyo, Japan

    Saichi Hoshi

  11. Laboratory for Clinical Investigation, Osaka University Hospital, Osaka, Japan

    Seishi Asari, Atsuko Sunada & Keigo Kimura

  12. Medical Mycology Research Center, Chiba University, Chiba, Japan

    Takashi Yaguchi

  13. Institute of Medical Mycology, Teikyo University, Tokyo, Japan

    Koichi Makimura

Authors
  1. Yoshitsugu Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuichi Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshikazu Shimomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chie Sotozono
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Hatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masahiko Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroshi Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kaoru Araki-Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takashi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Saichi Hoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Seishi Asari
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Atsuko Sunada
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Keigo Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takashi Yaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Koichi Makimura
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Multicenter Study Group of Fungal Keratitis in Japan

Corresponding author

Correspondence to Yoshitsugu Inoue.

Ethics declarations

Conflicts of interest

Y. Inoue, Grant, Consulting fee (Senju); Y. Ohashi, Grant, Consulting fee (Senju); Y. Shimomura, None; C. Sotozono, None; H. Hatano, None; M. Fukuda, None; H. Eguchi, None; K. A-Sasaki, None; T. Suzuki, Endowed course (Senju); S. Hoshi, None; S. Asari, None; A. Sunada, None; K. Kimura, None; T. Yaguchi, None; K. Makimura, None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Corresponding author: Yoshitsugu Inoue

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inoue, Y., Ohashi, Y., Shimomura, Y. et al. Multicenter prospective observational study of fungal keratitis in Japan: analyses of culture-positive cases. Jpn J Ophthalmol 66, 227–239 (2022). https://doi.org/10.1007/s10384-022-00904-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-022-00904-5

Keywords

Search

Navigation