Fungal Keratitis Treatment & Management

  • Author: Daljit Singh, MBBS, MS, DSc; Chief Editor: Hampton Roy Sr, MD   more...
 
Updated: Oct 27, 2011
 

Medical Care

Antifungal agents are classified into the following groups:

Polyenes include natamycin, nystatin, and amphotericin B. Polyenes disrupt the cell by binding to fungal cell wall ergosterol and are effective against both filamentous and yeast forms.

Amphotericin B is the drug of choice to treat patients with fungal keratitis caused by yeasts.

Although polyenes penetrate ocular tissue poorly, amphotericin B is the drug of choice for treatment of fungal keratitis caused by Candida. In addition, it has efficacy against many filamentous fungi. Administration is every 30 minutes for the first 24 hours, every hour for the second 24 hours, and then is slowly tapered according to the clinical response.

Natamycin has a broad-spectrum of activity against filamentous organisms. The penetration of topically applied amphotericin B is found to be less than that of topically applied natamycin through the intact corneal epithelium.

Natamycin is the only commercially available topical ophthalmic antifungal preparation. It is effective against filamentous fungi, particularly for infections caused by Fusarium. However, because of poor ocular penetration, it has primarily been useful in cases with superficial corneal infection.

Azoles (imidazoles and triazoles) include ketoconazole, miconazole, fluconazole, itraconazole, econazole, and clotrimazole. Azoles inhibit ergosterol synthesis at low concentrations, and, at higher concentrations, they appear to cause direct damage to cell walls.

Oral fluconazole and ketoconazole are absorbed systemically with good levels in the anterior chamber and the cornea; therefore, they should be considered in the management of deep fungal keratitis.

Imidazoles and triazoles are synthetic chemical antifungal agents. High cornea levels of ketoconazole and fluconazole have been demonstrated in animal studies. Because of excellent penetration in ocular tissue, these medications, given systemically, are the preferred treatment of keratitis caused by filamentous fungi and yeast.

The adult dose of ketoconazole is 200-400 mg/d, which can be increased to 800 mg/d. However, because of the secondary effects, increasing the dose should be done carefully. Gynecomastia, oligospermia, and decreased libido have been reported in 5-15% of patients who have been taking 400 mg/d for a long period.

The potential role of itraconazole in treatment of fungal keratitis is still unclear. However, it may be a helpful adjunctive agent in fungal keratitis.

Fluorinated pyrimidines, such as flucytosine, are other antifungal agents. Flucytosine is converted into a thymidine analog that blocks fungal thymidine synthesis. It usually is administered in combination with an azole or amphotericin B; it is synergistic with these medications. Otherwise, if flucytosine is the only drug used in therapy for candidal infections, emergence of resistance rapidly develops. Therefore, flucytosine should never be used alone.

Treatment should be instituted promptly with topical fortified antifungal drops, initially every hour during the day and every 2 hours over night.

Subconjunctival injections may be used in patients with severe keratitis or keratoscleritis. They also can be used when poor patient compliance exists.

An oral antifungal (eg, ketoconazole, fluconazole) should be considered for patients with deep stromal infection. Antifungal therapy usually is maintained for 12 weeks, and patients are monitored closely.

Fluconazole has been shown to penetrate better into the cornea after systemic administration compared to other azoles and may be associated with fewer adverse effects.

A study by Matsumoto et al has shown that topical 0.1% micafungin eye drops are comparable to 0.2% fluconazole in the treatment of fungal keratitis no matter patient’s age, gender, or ulcer size.[3]

In vitro antifungal sensitivities often are performed to assess resistance patterns of the fungal isolate. However, in vitro susceptibility testing may not correspond with in vivo clinical response because of host factors, corneal penetration of the antifungal, and difficulty in standardization of antifungal sensitivities. Therefore, they should be performed in a standardized method at a reference laboratory.

The promotion of fungal growth by corticosteroid treatment is well recognized; therefore, corticosteroid drops should not be used in the treatment of fungal keratitis until after 2 weeks of antifungal treatment and clear clinical evidence of infection control. Steroids should only be used when the active inflammation is believed to be causing significant damage to the structure of the cornea and/or vision. The steroid is always used in conjunction with the topical antifungal.

Therapy may be modified.

Decisions about alternate therapy must be based on the biomicroscopic signs and on the tolerance of the topical medications. Improvement in clinical signs may be difficult to detect during the initial days of antifungal therapy. However, some of the biomicroscopic signs that may be helpful to evaluate efficacy are as follows:

  • Blunting of the perimeters of the infiltrate
  • Reduction of the density of the suppuration
  • Reduction in cellular infiltrate and edema in the surrounding stroma
  • Reduction in anterior chamber inflammation
  • Progressive reepithelization
  • Loss of the feathery perimeter of the stromal inflammation

Successful antifungal therapy for fungal keratitis requires frequent drug administration for prolonged periods (ie, at least 12 wk). Some corneal manifestations of toxicity are as follows:

  • Protracted epithelial ulceration
  • Punctuate corneal epithelial erosion
  • Diffuse stromal haze
Next

Surgical Care

Patients who do not respond to medical treatment of topical and oral antifungal medications usually require surgical intervention, including corneal transplantation. Approximately 15-27% of patients require surgical intervention. In some cases, though, even corneal surgery will not restore vision, and patients will be blind or otherwise visually impaired. Therefore, early diagnosis coupled with appropriate treatment is critical to recovery from fungal keratitis.

Frequent corneal debridement with a spatula is helpful; it debulks fungal organisms and epithelium and enhances penetration of the topical antifungal agent.

Approximately one third of fungal infections fail to respond to medical treatment and may result in corneal perforation. In these cases, a therapeutic penetrating keratoplasty is necessary. Penetrating keratoplasty generally should be performed within 4 weeks of presentation. A small number of patients have been treated successfully with a conjunctival flap. The main goals of surgery are to control the infection and to maintain the integrity of the globe. Topical antifungal therapy, in addition to systemic fluconazole or ketoconazole, should be continued following penetrating keratoplasty. The use of topical corticosteroids in the postoperative period remains controversial.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Daljit Singh, MBBS, MS, DSc  Professor Emeritis, Department of Ophthalmology, Guru Nanak Dev University, Amritsar, India; Director, Daljit Singh Eye Hospital

Daljit Singh, MBBS, MS, DSc is a member of the following medical societies: All India Ophthalmological Society, American Society of Cataract and Refractive Surgery, Indian Medical Association, International Intraocular Implant Club, and Intraocular Implant and Refractive Society, India

Disclosure: Nothing to disclose.

Coauthor(s)

Arun Verma, MD  Senior Consultant, Department of Ophthalmology, Dr Daljit Singh Eye Hospital, India

Disclosure: Nothing to disclose.

Specialty Editor Board

Anastasios J Kanellopoulos, MD  Assistant Program Director, Clinical Associate Professor, Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York University

Anastasios J Kanellopoulos, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Eye Bank Association of America, and International Society of Refractive Surgery

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Christopher J Rapuano, MD  Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other; Vistakon Honoraria Speaking and teaching; EyeGate Pharma Consulting; Inspire Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting fee Consulting

Lance L Brown, OD, MD  Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, George Alexandrakis, MD, to the development and writing of this article.

References

  1. Haynes KA, Westerneng TJ, Fell JW, Moens W. Rapid detection and identification of pathogenic fungi by polymerase chain reaction amplification of large subunit ribosomal DNA. J Med Vet Mycol. Sep-Oct 1995;33(5):319-25. [Medline].

  2. Vaddavalli PK, Garg P, Sharma S, et al. Role of confocal microscopy in the diagnosis of fungal and acanthamoeba keratitis. Ophthalmology. Jan 2011;118(1):29-35. [Medline].

  3. Matsumoto Y, Murat D, Kojima T, Shimazaki J, Tsubota K. The comparison of solitary topical micafungin or fluconazole application in the treatment of Candida fungal keratitis. Br J Ophthalmol. Oct 2011;95(10):1406-9. [Medline].

  4. Accensi F J, Cano L, Figuera, ML Abarca and FJ. Cabañes. New PCR methods to differentiate species in the Aspergillus niger aggregate. FEMS Microbiol. Lett. 1999;180:191-196.

  5. Alexandrakis G, Jalali S, Gloor P. Diagnosis of Fusarium keratitis in an animal model using the polymerase chain reaction. Br J Ophthalmol. Mar 1998;82(3):306-11. [Medline].

  6. Avunduk AM, Beuerman RW, Varnell ED, Kaufman HE. Confocal microscopy of Aspergillus fumigatus keratitis. Br J Ophthalmol. Apr 2003;87(4):409-10. [Medline].

  7. Borne MJ, Elliott JH, O'Day DM. Ocular fluconazole treatment of Candida parapsilosis endophthalmitis after failed intravitreal amphotericin B. Arch Ophthalmol. Oct 1993;111(10):1326-7. [Medline].

  8. Chen YC, Eisner JD, Kattar MM, Rassoulian-Barrett SL, LaFe K, Yarfitz SL, et al. Identification of medically important yeasts using PCR-based detection of DNA sequence polymorphisms in the internal transcribed spacer 2 region of the rRNA genes. J Clin Microbiol. Jun 2000;38(6):2302-10. [Medline].

  9. Chowdhary A, Singh K. Spectrum of fungal keratitis in North India. Cornea. Jan 2005;24(1):8-15. [Medline].

  10. Donnenfeld ED, Perry HD, Snyder RW, Moadel R, Elsky M, Jones H. Intracorneal, aqueous humor, and vitreous humor penetration of topical and oral ofloxacin. Arch Ophthalmol. Feb 1997;115(2):173-6. [Medline].

  11. Driebe WT Jr, Mandelbaum S, Forster RK, Schwartz LK, Culbertson WW. Pseudophakic endophthalmitis. Diagnosis and management. Ophthalmology. Apr 1986;93(4):442-8. [Medline].

  12. Dunlop AA, Wright ED, Howlader SA, Nazrul I, Husain R, McClellan K. Suppurative corneal ulceration in Bangladesh. A study of 142 cases examining the microbiological diagnosis, clinical and epidemiological features of bacterial and fungal keratitis. Aust N Z J Ophthalmol. May 1994;22(2):105-10. [Medline].

  13. Einsele H, Hebart H, Roller G, Löffler J, Rothenhofer I, Muller CA. Detection and identification of fungal pathogens in blood by using molecular probes. J Clin Microbiol. Jun 1997;35(6):1353-60. [Medline].

  14. Esteve-Zarzoso B, Belloch C, Uruburu F, Querol A. Identification of yeasts by RFLP analysis of the 5.8S rRNA gene and the two ribosomal internal transcribed spacers. Int J Syst Bacteriol. Jan 1999;49 Pt 1:329-37. [Medline].

  15. Ferrer C S, Frases F, Colom, J L Alio, J L Abad, and M E. Mulet. Molecular diagnosis of fungal ocular infections in an animal model. Rev. Iberoam. Micol. 2000;17:S134.

  16. Florakis GJ, Moazami G, Schubert H, Koester CJ, Auran JD. Scanning slit confocal microscopy of fungal keratitis. Arch Ophthalmol. Nov 1997;115(11):1461-3. [Medline].

  17. Forster RK, Abbott RL, Gelender H. Management of infectious endophthalmitis. Ophthalmology. Apr 1980;87(4):313-9. [Medline].

  18. Garg P, Mahesh S, Bansal AK, Gopinathan U, Rao GN. Fungal infection of sutureless self-sealing incision for cataract surgery. Ophthalmology. Nov 2003;110(11):2173-7. [Medline].

  19. Guzek JP, Roosenberg JM, Gano DL, Wessels IF. The effect of vehicle on corneal penetration of triturated ketoconazole and itraconazole. Ophthalmic Surg Lasers. Nov 1998;29(11):926-9. [Medline].

  20. Hidalgo JA, Alangaden GJ, Eliott D, Akins RA, Puklin J, Abrams G. Fungal endophthalmitis diagnosis by detection of Candida albicans DNA in intraocular fluid by use of a species-specific polymerase chain reaction assay. J Infect Dis. Mar 2000;181(3):1198-201. [Medline].

  21. Jaeger EE, Carroll NM, Choudhury S, Dunlop AA, Towler HM, Matheson MM, et al. Rapid detection and identification of Candida, Aspergillus, and Fusarium species in ocular samples using nested PCR. J Clin Microbiol. Aug 2000;38(8):2902-8. [Medline].

  22. Jordan JA. PCR identification of four medically important Candida species by using a single primer pair. J Clin Microbiol. Dec 1994;32(12):2962-7. [Medline].

  23. Kauffman CA, Bradley SF, Vine AK. Candida endophthalmitis associated with intraocular lens implantation: efficacy of fluconazole therapy. Mycoses. Jan-Feb 1993;36(1-2):13-7. [Medline].

  24. Keyhani K, Seedor JA, Shah MK, Terraciano AJ, Ritterband DC. The incidence of fungal keratitis and endophthalmitis following penetrating keratoplasty. Cornea. Apr 2005;24(3):288-91. [Medline].

  25. Knox CM, Cevellos V, Dean D. 16S ribosomal DNA typing for identification of pathogens in patients with bacterial keratitis. J Clin Microbiol. Dec 1998;36(12):3492-6. [Medline].

  26. Kumar M, Shukla PK. Use of PCR targeting of internal transcribed spacer regions and single-stranded conformation polymorphism analysis of sequence variation in different regions of rrna genes in fungi for rapid diagnosis of mycotic keratitis. J Clin Microbiol. Feb 2005;43(2):662-8. [Medline].

  27. Lott TJ, Kuykendall RJ, Reiss E. Nucleotide sequence analysis of the 5.8S rDNA and adjacent ITS2 region of Candida albicans and related species. Yeast. Nov 1993;9(11):1199-206. [Medline].

  28. Mabon M. Fungal keratitis. Int Ophthalmol Clin. 1998;38(4):115-23. [Medline].

  29. Makimura K, Murayama SY, Yamaguchi H. Detection of a wide range of medically important fungi by the polymerase chain reaction. J Med Microbiol. May 1994;40(5):358-64. [Medline].

  30. Miyakawa Y, Mabuchi T, Kagaya K, Fukazawa Y. Isolation and characterization of a species-specific DNA fragment for detection of Candida albicans by polymerase chain reaction. J Clin Microbiol. Apr 1992;30(4):894-900. [Medline].

  31. Okhravi N, Adamson P, Mant R, Matheson MM, Midgley G, Towler HM. Polymerase chain reaction and restriction fragment length polymorphism mediated detection and speciation of Candida spp causing intraocular infection. Invest Ophthalmol Vis Sci. May 1998;39(6):859-66. [Medline].

  32. Panda A, Sharma N, Das G, Kumar N, Satpathy G. Mycotic keratitis in children: epidemiologic and microbiologic evaluation. Cornea. May 1997;16(3):295-9. [Medline].

  33. Prajna NV, John RK, Nirmalan PK, Lalitha P, Srinivasan M. A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis. Br J Ophthalmol. Oct 2003;87(10):1235-7. [Medline].

  34. Prajna NV, Nirmalan PK, Mahalakshmi R, Lalitha P, Srinivasan M. Concurrent use of 5% natamycin and 2% econazole for the management of fungal keratitis. Cornea. Nov 2004;23(8):793-6. [Medline].

  35. Reiss E, Tanaka K, Bruker G, Chazalet V, Coleman D, Debeaupuis JP. Molecular diagnosis and epidemiology of fungal infections. Med Mycol. 1998;36 Suppl 1:249-57. [Medline].

  36. Riggsby WS, Torres-Bauza LJ, Wills JW, Townes TM. DNA content, kinetic complexity, and the ploidy question in Candida albicans. Mol Cell Biol. Jul 1982;2(7):853-62. [Medline].

  37. Rosa RH Jr, Miller D, Alfonso EC. The changing spectrum of fungal keratitis in south Florida. Ophthalmology. Jun 1994;101(6):1005-13. [Medline].

  38. Srinivasan M. Fungal keratitis. Curr Opin Ophthalmol. Aug 2004;15(4):321-7. [Medline].

  39. Tang CM, Holden DW, Aufauvre-Brown A, Cohen J. The detection of Aspergillus spp. by the polymerase chain reaction and its evaluation in bronchoalveolar lavage fluid. Am Rev Respir Dis. Nov 1993;148(5):1313-7. [Medline].

  40. Thomas PA. Fungal infections of the cornea. Eye. Nov 2003;17(8):852-62. [Medline].

  41. Upadhyay MP, Karmacharya PC, Koirala S, Tuladhar NR, Bryan LE, Smolin G. Epidemiologic characteristics, predisposing factors, and etiologic diagnosis of corneal ulceration in Nepal. Am J Ophthalmol. Jan 15 1991;111(1):92-9. [Medline].

  42. Weissgold DJ, Orlin SE, Sulewski ME, Frayer WC, Eagle RC Jr. Delayed-onset fungal keratitis after endophthalmitis. Ophthalmology. Feb 1998;105(2):258-62. [Medline].

  43. White TJ, Bruns T, Lee S, Tailor S. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. In: Innins MA, Gelfand DH, Sninsky JJ, White TJ, eds. PCR Protocols. A Guide to Methods and Applications. San Diego, CA: Academic Press, Inc; 1990:315-22.

 
Previous
Next
 
Fungal corneal ulcer.
Perforated fungal ulcer.
Fungal infection under treatment.
Perforated fungal corneal ulcer.
Fungal ulcer in an elderly woman.
Fungal ulcer.
Fungal corneal ulcer, with excessive vascularization.
Marginal ulcer, fungus positive.
Healed fungal ulcer.
Fungal keratitis.
Corneal perforation, blocked by a crystalline lens and being covered by epithelium.
Fungal keratitis, being controlled.
Fungal infection.
Fungal infection.
Fungal abscess.
Fungal corneal abscess/ulcer. A proven case of fungal infection, 5 days' duration. Intense infiltration around the abscess.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.