Antifungal Therapy in Eye Infections: New Drugs, New Trends

  • Joveeta Joseph
  • Savitri Sharma


Treatment of ocular fungal infections represents a challenge for the ophthalmic clinician. Although an increased number of fungal infections of the eye have been reported in the past few decades, in part, because of increased clinical awareness and improved laboratory techniques, it is not matched by availability of effective ocular antifungal drugs. In addition, the need for improved antifungal therapy is emphasized by the potentially poor clinical outcome in patients with severe ocular mycoses. For an adequate therapeutic response, besides correct drug choice, an effectively administration is necessary. Current treatment for systemic fungal infections is not always sufficiently effective for ocular mycoses. The slower research and development progress in antifungal therapy compared with antibacterial therapy stems from the fact that fungal cells, unlike bacteria, are eukaryotic, consequently any drug that is toxic to fungal cells could potentially exert similar effects on mammalian cells. There also has been less financial incentive for pharmaceutical companies to invest in the development of ocular antifungal agents. Despite certain therapeutic advances, the impact of the availability of new antifungal agents on ocular mycosis is unknown. This chapter presents information about the major antifungal drugs used in eye infections, their dosages, administration routes, side effects and overall effectiveness.


Minimum Inhibitory Concentration Antifungal Agent Ocular Tissue Fungal Keratitis Chlorhexidine Gluconate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abad JC, Foster CS (1996) Fungal keratitis. Int Ophthalmol Clin 36(3):1–15PubMedCrossRefGoogle Scholar
  2. Agarwal PK, Roy P, Das A, Banerjee A, Maity PK, Banerjee AR (2001) Efficacy of topical and systemic itraconazole as a broadspectrum antifungal agent in mycotic corneal ulcer. A preliminary study. Indian J Ophthalmol 49(3):173–176PubMedGoogle Scholar
  3. Al-Badriyeh D, Neoh CF, Stewart K, Kong DC (2010) Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis. Clin Ophthalmol 4:391–405PubMedPubMedCentralGoogle Scholar
  4. Alfonso ECGA, Miller D (2011) Fungal keratitis. In: Krachmer JH, Mannis MJ, Holland EJ (eds) Cornea: fundamentals, diagnosis and management, 3rd edn. Mosby Elsevier, New YorkGoogle Scholar
  5. Anderson KL, Mitra S, Salouti R, Pham TA, Taylor HR (2004) Fungal keratitis caused by Paecilomyces lilacinus associated with a retained intracorneal hair. Cornea 23(5):516–521PubMedCrossRefGoogle Scholar
  6. Arora R, Gupta D, Goyal J, Kaul R (2011) Voriconazole versus natamycin as primary treatment in fungal corneal ulcers. Clin Exp Ophthalmol 39:434–440PubMedCrossRefGoogle Scholar
  7. Avunduk AM, Beuerman RW, Warnel ED, Kaufman HE, Greer D (2003) Comparison of efficacy of topical and oral fluconazole treatment in experimental Aspergillus keratitis. Curr Eye Res 26(2):113–117PubMedCrossRefGoogle Scholar
  8. Axelrod AJ, Peyman GA, Apple DJ (1973) Toxicity of intravitreal injection of amphotericin B. Am J Ophthalmol 76(4):578–583PubMedCrossRefGoogle Scholar
  9. Bachmann SP, VandeWalle K, Ramage G, Patterson TF, Wickes BL, Graybill JR, López-Ribot JL (2002) In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother 46(11):3591–3596PubMedPubMedCentralCrossRefGoogle Scholar
  10. Barasch A, Griffin AV (2008) Miconazole revisited: new evidence of antifungal efficacy from laboratory and clinical trials. Future Microbiol 3(3):265–269PubMedCrossRefGoogle Scholar
  11. Behrens-Baumann W (ed) (1999) Mycosis of the eye and its Adnexa. Dev Ophthalmol. Basel, Karger. 32:I–X. doi: 10.1159/000060776
  12. Bernauer W, Allan BDS, Dart JKG (1998) Successful management of Aspergillus scleritis by medical and surgical treatment. Eye 12:311–316PubMedCrossRefGoogle Scholar
  13. Betts RF, Nucci M, Talwar D, Gareca M, Queiroz-Telles F, Bedimo RJ, Herbrecht R, Ruiz-Palacios G, Young JA, Baddley JW, Strohmaier KM, Tucker KA, Taylor AF, Kartsonis NA, Caspofungin High-Dose Study Group (2009) A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis 48:1676–1684PubMedCrossRefGoogle Scholar
  14. Bunya VY, Hammersmith KM, Rapuano CJ, Ayres BD, Cohen EJ (2007) Topical and oral voriconazole in the treatment of fungal keratitis. Am J Ophthalmol 143(1):151–153PubMedCrossRefGoogle Scholar
  15. Christmas NJ, Smiddy WE (1996) Vitrectomy and systemic fluconazole for treatment of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 27(12):1012–1018PubMedGoogle Scholar
  16. Clinical and Laboratory Standard Institute (2009) Method for antifungal disk diffusion susceptibility testing of yeasts; approved guideline, 2nd edn. M44-A2 Clinical and Laboratory Standards Institute, WayneGoogle Scholar
  17. Clinical Laboratory Standard Institute (2010) Reference method for antifungal disk diffusion susceptibility testing of non-dermatophyte filamentous fungi; approved guideline. CLSI document M51-A Clinical and Laboratory Standards Institute, VillanovaGoogle Scholar
  18. Clode AB, Davis JL, Salmon J, Michau TM, Gilger BC (2006) Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses. Am J Vet Res 67(2):296–301PubMedCrossRefGoogle Scholar
  19. Coley KC, Crain JL (1997) Miconazole-induced fatal dysrhythmia. Pharmacotherapy 17(2):379–382PubMedGoogle Scholar
  20. Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Buitrago MJ, Monzon A, Rodriguez-Tudela JL (2006) Head-to-head comparison of the activities of currently available antifungal agents against 3,378 Spanish clinical isolates of yeasts and filamentous fungi. Antimicrob Agents Chemother 50(3):917–921PubMedPubMedCentralCrossRefGoogle Scholar
  21. Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA (2003) Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol 41(8):3623–3626PubMedPubMedCentralCrossRefGoogle Scholar
  22. Dupuis A, Tournier N, Le Moal G, Venisse N (2009) Preparation and stability of voriconazole eye drop solution. Antimicrob Agents Chemother 53(2):798–799PubMedCrossRefGoogle Scholar
  23. Dursun D, Fernandez V, Miller D, Alfonso EC (2003) Advanced Fusarium keratitis progressing to endophthalmitis. Cornea 22(4):300–303PubMedCrossRefGoogle Scholar
  24. Fiscella RG, Moshifar M, Messick CR, Pendland PL, Chandler JW, Viana M (1997) Polyhexamethylene biguanide (PHMB) in the treatment of experimental Fusarium keratomycosis. Cornea 16:447–449PubMedCrossRefGoogle Scholar
  25. Fitzsimons R, Peters AL (1986) Miconazole and ketoconazole as a satisfactory first-line treatment for keratomycosis. Am J Ophthalmol 101(5):605–608PubMedCrossRefGoogle Scholar
  26. FlorCruz NV, Evans JR (2015) Medical interventions for fungal keratitis. Cochrane Database Syst Rev 4. doi: 10.1002/14651858.CD004241.pub4
  27. Foster CS (1981) Miconazole therapy for keratomycosis. Am J Ophthalmol 91(5):622–629PubMedCrossRefGoogle Scholar
  28. Foster CS, Stefanyszyn M (1979) Intraocular penetration of miconazole in rabbits. Arch Ophthalmol 97(9):1703–1706PubMedCrossRefGoogle Scholar
  29. Foster CS, Lass JH, Moran-Wallace K, Giovanoni R (1981) Ocular toxicity of topical antifungal agents. Arch Ophthalmol 99(6):1081–1084PubMedCrossRefGoogle Scholar
  30. Fothergill AW (2006) Miconazole: a historical perspective. Expert Rev Anti Infect Ther 4(2):171–175PubMedCrossRefGoogle Scholar
  31. Freda R (2006) Use of oral voriconazole as adjunctive treatment of severe cornea fungal infection: case report. Arq Bras Oftalmol 69(3):431–434PubMedCrossRefGoogle Scholar
  32. Friedberg ML, Pleyer U, Mondino BJ (1991) Device drug delivery to the eye. Collagen shields, iontophoresis and pumps. Ophthalmology 98:725–732PubMedCrossRefGoogle Scholar
  33. Gallis HA, Drew RH, Pickard WW (1990) Amphotericin B: 30 years of clinical experience. Rev Infect Dis 12(2):308–329PubMedCrossRefGoogle Scholar
  34. Gao H, Pennesi M, Shah K, Qiao X, Hariprasad SM, Mieler WF, Wu SM, Holz ER (2003) Safety of intravitreal voriconazole: electroretinographic and histopathologic studies. Trans Am Ophthalmol Soc 101:183–189PubMedGoogle Scholar
  35. Garcia- Valenzuela E, Song CD (2005) Intracorneal injection of amphothericin B for recurrent fungal keratitis and endophthalmitis. Arch Ophthalmol 123(12):1721–1723PubMedCrossRefGoogle Scholar
  36. Gauthier GM, Nork TM, Prince R, Andes D (2005) Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis. Clin Infect Dis 41(3):e27–e28PubMedCrossRefGoogle Scholar
  37. Giaconi JA, Marangon FB, Miller D, Alfonso EC (2006) Voriconazole and fungal keratitis: a report of two treatment failures. J Ocul Pharmacol Ther 22(6):437–439PubMedCrossRefGoogle Scholar
  38. Goldblum D, Frueh BE, Zimmerli S, Böhnke M (2000) Treatment of postkeratitis Fusarium endophthalmitis with amphotericin B lipid complex. Cornea 19(6):853–856PubMedCrossRefGoogle Scholar
  39. Goldblum D, Frueh BE, Sarra GM, Katsoulis K, Zimmerli S (2005) Topical caspofungin for treatment of keratitis caused by Candida albicans in a rabbit model. Antimicrob Agents Chemother 49(4):1359–1363PubMedPubMedCentralCrossRefGoogle Scholar
  40. Green WR, Bennett JE, Goos RD (1965) Ocular penetration of amphotericin B: a report of laboratory studies and a case report of postsurgical Cephalosporium endophthalmitis. Arch Ophthalmol 73:769–775PubMedCrossRefGoogle Scholar
  41. Groll AH, Mickiene D, Petraitiene R, Petraitis V, Lyman CA, Bacher JS, Piscitelli SC, Walsh TJ (2001a) Pharmacokinetic and pharmacodynamic modeling of anidulafungin (LY303366): reappraisal of its efficacy in neutropenic animal models of opportunistic mycoses using optimal plasma sampling. Antimicrob Agents Chemother 45:2845–2855PubMedPubMedCentralCrossRefGoogle Scholar
  42. Groll AH, Mickiene D, Petraitis V, Petraitiene R, Ibrahim KH, Piscitelli SC, Bekersky I, Walsh TJ (2001b) Compartmental pharmacokinetics and tissue distribution of the antifungal echinocandin lipopeptide micafungin (FK463) in rabbits. Antimicrob Agents Chemother 45:3322–3327PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hariprasad SM, Mieler WF, Lin TK, Sponsel WE, Graybill JR (2008) Voriconazole in the treatment of fungal eye infections: a review of current literature. Br J Ophthalmol 92(7):871–878PubMedCrossRefGoogle Scholar
  44. Heel RC, Brogden RN, Speight TM, Avery GS (1978) Econazole: a review of its antifungal activity and therapeutic efficacy. Drugs 16(3):177–201PubMedCrossRefGoogle Scholar
  45. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B, Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347(6):408–415Google Scholar
  46. Hirose H, Terasaki H, Awaya S, Yasuma T (1997) Treatment of fungal corneal ulcers with amphotericin B ointment. Am J Ophthalmol 124(6):836–838PubMedCrossRefGoogle Scholar
  47. Ishibashi Y (1983) Oral ketoconazole therapy for keratomycosis. Am J Ophthalmol 95(3):342–345PubMedCrossRefGoogle Scholar
  48. Ishibashi Y (1986) Miconazole and ketoconazole as a satisfactory first-line treatment for keratomycosis. Am J Ophthalmol 102(4):547–548PubMedCrossRefGoogle Scholar
  49. Ishibashi Y, Kaufman HE (1985) The effects of subconjunctival miconazole in the treatment of experimental Candida keratitis in rabbits. Arch Ophthalmol 103(10):1570–1573PubMedCrossRefGoogle Scholar
  50. Jang GJ, Kim KS, Shin WS, Lee WK (2005) Treatment of Candida chorioretinitis with voriconazole. Korean J Ophthalmol 19:73–76PubMedCrossRefGoogle Scholar
  51. Johns KJ, O’Day DM (1988) Pharmacologic management of keratomycoses. Surv Ophthalmol 33:178–188PubMedCrossRefGoogle Scholar
  52. Johnson LB, Kauffman CA (2003) Voriconazole: a new triazole antifungal agent. Clin Infect Dis 36(5):630–637PubMedCrossRefGoogle Scholar
  53. Jones D (2004) Diagnosis and management of fungal keratitis. In: Tasman W, Jaeger EA (eds) Duane’s clinical ophthalmology. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  54. Jones DB, Sexton R, Rebell G (1970) Mycotic keratitis in South Florida: a review of thirty-nine cases. Trans Ophthalmol Soc 89:781–797Google Scholar
  55. Jones DB, Forster FK, Rebell G (1972) Fusarium solani keratitis treated with natamycin (pimaricin): eighteen consecutive cases. Arch Ophthalmol 88(2):147–154PubMedCrossRefGoogle Scholar
  56. Kalavathy CM, Parmar P, Kaliamurthy J, Philip VR, Ramalingam MD, Jesudasan CA, Thomas PA (2005) Comparison of topical itraconazole 1% with topical natamycin 5% for the treatment of filamentous fungal keratitis. Cornea 24(4):449–452PubMedCrossRefGoogle Scholar
  57. Katz J, Khatry SK, Thapa MD, Schein OD, Kimbrough Pradhan E, LeClerq SC, West KP (2004) A randomised trial of povidone-iodine to reduce visual impairment from corneal ulcers in rural Nepal. Br J Ophthalmol 88(12):1487–1492PubMedPubMedCentralCrossRefGoogle Scholar
  58. Kaur IP, Rana C, Singh H (2008) Development of effective ocular preparations of antifungal agents. J Ocul Pharmacol Ther 24(5):481–493PubMedCrossRefGoogle Scholar
  59. Kaushik S, Ram J, Brar GS, Jain AK, Chakraborti A, Gupta A (2001) Intracameral amphotericin B: initial experience in severe keratomycosis. Cornea 20(7):715–719PubMedCrossRefGoogle Scholar
  60. Kermani NK, Aggarwal SP (2000) Isolated post-operative Aspergillus niger endophthalmitis. Eye (Lond). 14:114–116Google Scholar
  61. Khoo SH, Bond J, Denning DW (1994) Administering amphotericin B-a practical approach. J Antimicrob Chemother 33(2):203–213PubMedCrossRefGoogle Scholar
  62. Klotz SA, Zahid M, Bartholomew WR, Revera PM, Butrus S (1996) Candida albicans keratitis treated successfully with itraconazole. Cornea 15(1):102–104PubMedCrossRefGoogle Scholar
  63. Kobayashi D, Kondo K, Uehara N, Otokozawa S, Tsuji N, Yagihashi A, Watanabe N (2002) Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect. Antimicrob Agents Chemother 46(10):3113–3117PubMedPubMedCentralCrossRefGoogle Scholar
  64. Komadina TG, Wilkes TD, Shock JP, Ulmer WC, Jackson J, Bradsher RW (1985) Treatment of Aspergillus fumigatus keratitis in rabbits with oral and topical ketoconazole. Am J Ophthalmol 99(4):476–479PubMedCrossRefGoogle Scholar
  65. Kuriakose T, Kothari M, Paul P, Jacob P, Thomas R (2002) Intracameral amphotericin B injection in the management of deep keratomycosis. Cornea 21(7):653–656PubMedCrossRefGoogle Scholar
  66. Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, Sekhon JS, Freire A, Ramasubramanian V, Demeyer I, Nucci M, Leelarasamee A, Jacobs F, Decruyenaere J, Pittet D, Ullmann AJ, Ostrosky-Zeichner L, Lortholary O, Koblinger S, Diekmann-Berndt H, Cornely OA, Micafungin Invasive Candidiasis Working Group (2007) Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 369:1519–1527PubMedCrossRefGoogle Scholar
  67. Lalitha P, Shapiro BL, Srinivasan M, Prajna NV, Acharya NR, Fothergill AW, Ruiz J, Chidambaram JD, Maxey KJ, Hong KC, McLeod SD, Lietman TM (2007) Antimicrobial susceptibility of Fusarium, Aspergillus, and other filamentous fungi isolated from keratitis. Arch Ophthalmol 125(6):789–793PubMedCrossRefGoogle Scholar
  68. Lalitha P, Vijaykumar R, Prajna NV, Fothergill AW (2008) In vitro natamycin susceptibility of ocular isolates of Fusarium and Aspergillus species: comparison of commercially formulated natamycin eye drops to pharmaceutical-grade powder. J Clin Microbiol 46:3477–3478PubMedPubMedCentralCrossRefGoogle Scholar
  69. Lalitha P, Prajna NV, Oldenburg CE, Srinivasan M, Krishnan T, Mascarenhas J, Vaitilingam CM, McLeod SD, Zegans ME, Porco TC, Acharya NR, Lietman TM (2012) Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial. Cornea 31:662–667PubMedPubMedCentralCrossRefGoogle Scholar
  70. Lee SJ, Lee JJ, Kim SD (2009) Topical and oral voriconazole in the treatment of fungal keratitis. Korean J Ophthalmol 23(1):46–48PubMedPubMedCentralCrossRefGoogle Scholar
  71. Levin LA, Avery R, Shore JW, Woog JJ, Baker AS (1996) The spectrum of orbital aspergillosis: clinicopathological review. Surv Ophthalmol 41:142–154PubMedCrossRefGoogle Scholar
  72. Li L, Wang Z, Li R, Luo S, Sun X (2008) In vitro evaluation of combination antifungal activity against Fusarium species isolated from ocular tissues of keratomycosis patients. Am J Ophthalmol 146:724–728PubMedCrossRefGoogle Scholar
  73. Louie A, Liu W, Miller DA, Sucke AC, Liu QF, Drusano GL, Mayers M, Miller MH (1999) Efficacies of high-dose fluconazole plus amphotericin B and high-dose fluconazole plus 5-fluorocytosine versus amphotericin B, fluconazole, and 5-fluorocytosine monotherapies in treatment of experimental endocarditis, endophthalmitis, and pyelonephritis due to Candida albicans. Antimicrob Agents Chemother 43:2831–2840PubMedPubMedCentralGoogle Scholar
  74. Mahashabde S, Nahata MC, Shrivastava U (1987) A comparative study of anti-fungal drugs in mycotic corneal ulcer. Indian J Ophthalmol 35(5–6):149–152PubMedGoogle Scholar
  75. Mahdy RA, Nada WM, Wageh MM, Kader MA, Saleh MM, Alswad MM (2010a) Assessment safety and efficacy of a combination therapy of topical amphotericin B and subconjunctival fluconazole for the treatment of fungal keratitis. Cutan Ocul Toxicol 29(3):193–197PubMedCrossRefGoogle Scholar
  76. Mahdy RA, Nada WM, Wageh MM (2010b) Topical amphotericin B and subconjunctival injection of fluconazole (combination therapy) versus topical amphotericin B (monotherapy) in treatment of keratomycosis. J Ocul Pharmacol Ther 26(3):281–285PubMedCrossRefGoogle Scholar
  77. Manzouri B, Vafidis GC, Wyse RK (2001) Pharmacotherapy of fungal eye infections. Expert Opin Pharmacother 2:1849–1857PubMedCrossRefGoogle Scholar
  78. Marangon FB, Miller D, Giaconi JA, Alfonso EC (2004) In vitro investigation of voriconazole susceptibility for keratitis and endophthalmitis fungal pathogens. Am J Ophthalmol 137(5):820–825PubMedCrossRefGoogle Scholar
  79. Matsumoto Y, Dogru M, Goto E, Fujishima H, Tsubota K (2005) Successful topical application of a new antifungal agent, micafungin, in the treatment of refractory fungal corneal ulcers: report of three cases and literature review. Cornea 24(6):748–753PubMedCrossRefGoogle Scholar
  80. Matsumoto Y, Murat D, Kojima T, Shimazaki J, Tsubota K (2011) The comparison of solitary topical micafungin or fluconazole application in the treatment of Candida fungal keratitis. Br J Ophthalmol 95(10):1406–1409PubMedCrossRefGoogle Scholar
  81. Mithal K, Pathengay A, Bawdekar A, Jindal A, Vira D, Relhan N, Choudhury H, Gupta N, Gupta V, Koday NK, Flynn HW Jr (2015) Filamentous fungal endophthalmitis: results of combination therapy with intravitreal amphotericin B and voriconazole. Clin Ophthalmol 9:649–655PubMedPubMedCentralGoogle Scholar
  82. Mohan M, Gupta SK, Kalra VK, Vajpayee RB, Sachdev MS (1987) Silver sulphadiazine in the treatment of mycotic keratitis. Indian J Med Res 85:572–575PubMedGoogle Scholar
  83. Mohan M, Gupta SK, Kalra VK, Vajpayee RB, Sachdev MS (1988) Topical silver sulphadiazine: a new drug for ocular keratomycosis. Br J Ophthalmol 72:192–195PubMedPubMedCentralCrossRefGoogle Scholar
  84. Mohan M, Panda A, Gupta SK (1989) Management of human keratomycosis with miconazole. Aust N Z J Ophthalmol 17(3):295–297PubMedCrossRefGoogle Scholar
  85. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J, Caspofungin Invasive Candidiasis Study Group (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347(25):2020–2029PubMedCrossRefGoogle Scholar
  86. Morris MI, Villmann M (2006a) Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm 63(18):1693–1703PubMedCrossRefGoogle Scholar
  87. Morris MI, Villmann M (2006b) Echinocandins in the management of invasive fungal infections, part 2. Am J Health Syst Pharm 63(19):1813–1820PubMedCrossRefGoogle Scholar
  88. Motukupally SR, Nanapur VR, Chathoth KN, Murthy SI, Pappuru RR, Mallick A, Sharma S (2015) Ocular infections caused by Candida species: type of species, in vitro susceptibility and treatment outcome. Indian J Med Microbiol 33(4):538–546PubMedCrossRefGoogle Scholar
  89. Müller GG, Kara-José N, Castro RS (2013) Antifungals in eye infections: drugs and routes of administration. Revista Brasileira de Oftalmologia 72(2):132–141CrossRefGoogle Scholar
  90. Nulens E, Eggink C, Rijs AJ, Wesseling P, Verweij PE (2003) Keratitis caused by Scedosporium apiospermum successfully treated with a cornea transplant and voriconazole. J Clin Microbiol 41(5):2261–2264PubMedPubMedCentralCrossRefGoogle Scholar
  91. O’Brien TP (1999) Therapy of ocular fungal infections. Ophthalmol Clin North Am 12:33–50CrossRefGoogle Scholar
  92. O’Day DM (1987) Selection of appropriate antifungal therapy. Cornea 6(4):238–245PubMedCrossRefGoogle Scholar
  93. O’Day DM, Ray WA, Head WS, Robinson RD (1984) Influence of the corneal epithelium on the efficacy of topical antifungal agents. Invest Ophthalmol Vis Sci 25(7):855–859PubMedGoogle Scholar
  94. O’Day DM, Head WS, Robinson RD, Stern WH, Freeman JM (1985) Intraocular penetration of systemically administered antifungal agents. Curr Eye Res 4(2):131–134PubMedCrossRefGoogle Scholar
  95. O’Day DM, Head WS, Robinson RD, Clanton JA (1986) Corneal penetration of topical amphotericin B and natamycin. Curr Eye Res 5(11):877–882PubMedCrossRefGoogle Scholar
  96. O’Day DM, Foulds G, Williams TE, Robinson RD, Allen RH, Head WS (1990) Ocular uptake of fluconazole following oral administration. Arch Ophthalmol 108(7):1006–1008PubMedCrossRefGoogle Scholar
  97. O’Day DM, Ray WA, Robinson RD, Head WS, Williams TE (1991) Differences in response in vivo to amphotericin B among Candida albicans strains. Invest Ophthalmol Vis Sci 32(5):1569–1572PubMedGoogle Scholar
  98. Odds FC, van Gerven F, Espinel-Ingroff A, Bartlett MS, Ghannoum MA, Lancaster MV, Pfaller MA, Rex JH, Rinaldi MG, Walsh TJ (1998) Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob Agents Chemother 42:282–288PubMedPubMedCentralGoogle Scholar
  99. Oliveira PR, Resende SM, Oliveira FC, Oliveira AC (2001) Ceratite fúngica. Arq Bras Oftalmol 64(1):75–79CrossRefGoogle Scholar
  100. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of America (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535PubMedCrossRefGoogle Scholar
  101. Parchand S, Gupta A, Ram J, Gupta N, Chakrabarty A (2012) Voriconazole for fungal corneal ulcers. Ophthalmology 119(5):1083PubMedCrossRefGoogle Scholar
  102. Pearce JW, Giuliano EA, Moore CP (2009) In vitro susceptibility patterns of Aspergillus and Fusarium species isolated from equine ulcerative keratomycosis cases in the midwestern and southern United States with inclusion of the new antifungal agent voriconazole. Vet Ophthalmol 12(5):318–324PubMedCrossRefGoogle Scholar
  103. Polack FM, Kaufman HE, Newmark E (1971) Keratomycosis. Medical and surgical treatment. Arch Ophthalmol 85(4):410–416PubMedCrossRefGoogle Scholar
  104. Pradhan L, Sharma S, Nalamada S, Sahu SK, Das S, Garg P (2011) Natamycin in the treatment of keratomycosis: correlation of treatment outcome and in vitro susceptibility of fungal isolates. Indian J Ophthalmol 59:512–514PubMedPubMedCentralCrossRefGoogle Scholar
  105. Prajna NV, John RK, Nirmalan PK, Lalitha P, Srinivasan M (2003) A randomised clinical trial comparing 2% econazole and 5% natamycin for the treatment of fungal keratitis. Br J Ophthalmol 87(10):1235–1237PubMedPubMedCentralCrossRefGoogle Scholar
  106. Prajna NV, Nirmalan PK, Mahalakshmi R, Lalitha P, Srinivasan M (2004) Concurrent use of 5% natamycin and 2% econazole for the management of fungal keratitis. Cornea 23(8):793–796PubMedCrossRefGoogle Scholar
  107. Prajna NV, Mascarenhas J, Krishnan T, Reddy PR, Prajna L, Srinivasan M, Vaitilingam CM, Hong KC, Lee SM, McLeod SD, Zegans ME, Porco TC, Lietman TM, Acharya NR (2010) Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol 128(6):672–678PubMedPubMedCentralCrossRefGoogle Scholar
  108. Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Prajna L, Srinivasan M, Raghavan A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Porco TC, Acharya NR, Lietman TM, Mycotic Ulcer Treatment Trial Group. (2013) The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol 131(4):422–429PubMedPubMedCentralCrossRefGoogle Scholar
  109. Prakash G, Sharma N, Goel M, Titiyal JS, Vajpayee RB (2008) Evaluation of intrastromal injection of voriconazole as a therapeutic adjunctive for the management of deep recalcitrant fungal keratitis. Am J Ophthalmol 146(1):56–59PubMedCrossRefGoogle Scholar
  110. Qiu WY, Yao YF, Zhu YF (2005) Fungal spectrum identified by a new slide culture and in vitro drug susceptibility using E test in fungal keratitis. Curr Eye Res 30:1113–1120PubMedCrossRefGoogle Scholar
  111. Qu L, Li L, Xie H (2010) Corneal and aqueous humor concentrations of amphotericin B using three different routes of administration in a rabbit model. Ophthalmic Res 43(3):153–158PubMedCrossRefGoogle Scholar
  112. Rahman MR, Minassian DC, Srinivasan M, Martin MJ, Johnson GJ (1997) Trial of chlorhexidine gluconate for fungal corneal ulcers. Ophthal Epidemiol 4(3):141–149CrossRefGoogle Scholar
  113. Rahman MR, Johnson GJ, Husain R, Howlader SA, Minassian DC (1998) Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh. Br J Ophthalmol 82(8):919–925PubMedPubMedCentralCrossRefGoogle Scholar
  114. Rajasekaran J, Thomas PA, Kalavathy CM, Joseph PC, Abraham DJ (1987) Itraconazole therapy for fungal keratitis. Indian J Ophthalmol 35(5–6):157–160PubMedGoogle Scholar
  115. Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, Betts R, Wible M, Goldstein BP, Schranz J, Krause DS, Walsh TJ, Anidulafungin Study Group (2007) Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 356:2472–2482PubMedCrossRefGoogle Scholar
  116. Reddy PR, Reddy PS, Reddy AR, Saboo NK (1982) A comparative evaluation of Nystatin, Amphotericin-B and Miconazole in keratomycosis. Indian J Ophthalmol 30(4):249–250PubMedGoogle Scholar
  117. Rex J, Pfaller M (2002) Has antifungal susceptibility testing come of age? Clin Infect Dis 35:982–989PubMedCrossRefGoogle Scholar
  118. Riddell J IV, Comer GM, Kauffman CA (2011) Reviews of anti-infective agents: treatment of endogenous fungal endophthalmitis: focus on new antifungal agents. Clin Infect Dis 52(5):648–653PubMedCrossRefGoogle Scholar
  119. Rosa RH Jr, Miller D, Alfonso EC (1994) The changing spectrum of fungal keratitis in south Florida. Ophthalmology 101:1005–1013PubMedCrossRefGoogle Scholar
  120. Sawyer PR, Brogden RN, Pinder RM, Speight TM, Avery GS (1975) Miconazole: a review of its antifungal activity and therapeutic efficacy. Drugs 9(6):406–423PubMedCrossRefGoogle Scholar
  121. Seiff SR, Choo PH, Carter SR (1999) Role of local amphotericin B therapy for sino-orbital fungal infections. Ophthalmic Plast Reconstr Surg 15:28–31CrossRefGoogle Scholar
  122. Serracarbassa PD, Peyman GA, Liang C, Calixto N Jr, Nair MG (1998) Toxicity and efficacy of intravitreal injection of spartanamicin B in the treatment of Candida endophthalmitis. Int Ophthalmol 22(1):53–58PubMedCrossRefGoogle Scholar
  123. Sharma N, Agarwal P, Sinha R, Titiyal JS, Velpandian T, Vajpayee RB (2011) Evaluation of intrastromal voriconazole injection in recalcitrant deep fungal keratitis: case series. Br J Ophthalmol 95(12):1735–1737PubMedCrossRefGoogle Scholar
  124. Sharma N, Chacko J, Velpandian T, Titiyal JS, Sinha R, Satpathy G, Tandon R, Vajpayee RB (2013) Comparative evaluation of topical versus intrastromal voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis. Ophthalmology 120(4):677–681PubMedCrossRefGoogle Scholar
  125. Sharma N, Sankaran P, Agarwal T, Arora T, Chawla B, Titiyal JS, Tandon R, Satapathy G, Vajpayee RB (2015) Evaluation of intracameral amphotericin B in the management of fungal keratitis: randomized controlled trial. Ocul Immunol Inflamm 23:1–5CrossRefGoogle Scholar
  126. Sharma S, Das S, Virdi A, Fernandes M, Sahu SK, Kumar Koday N, Ali MH, Garg P, Motukupally SR (2015) Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial. Br J Ophthalmol 99(9):1190–1195PubMedCrossRefGoogle Scholar
  127. Shirley SF, Little JR (1979a) Immunopotentiating effects of amphotericin B. I. Enhanced contact sensitivity in mice. J Immunol 123(6):2878–2882PubMedGoogle Scholar
  128. Shirley SF, Little JR (1979b) Immunopotentiating effects of amphotericin B. II. Enhanced in vitro proliferative responses of murine lymphocytes. J Immunol 123(6):2883–2889PubMedGoogle Scholar
  129. Siatiri H, Daneshgar F, Siatiri N, Khodabande A (2011) The effects of intrastromal voriconazole injection and topical voriconazole in the treatment of recalcitrant Fusarium keratitis. Cornea 30(8):872–875PubMedCrossRefGoogle Scholar
  130. Singh SM, Khan R, Sharma S, Chatterjee PK (1989) Clinical and experimental mycotic corneal ulcer caused by Aspergillus fumigatus and the effect of oral ketoconazole in the treatment. Mycopathologia 106(3):133–141PubMedCrossRefGoogle Scholar
  131. Souri EN, Green WR (1974) Intravitreal amphotericin B toxicity. Am J Ophthalmol 78(1):77–81PubMedCrossRefGoogle Scholar
  132. Sponsel WE, Graybill JR, Nevarez HL, Dang D (2002) Ocular and systemic posaconazole(SCH-56592) treatment of invasive Fusarium solani keratitis and endophthalmitis. Br J Ophthalmol 86(7):829–830PubMedPubMedCentralCrossRefGoogle Scholar
  133. Srinivasan M, Gonzales CA, George C (1997) Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, South India. Br J Ophthalmol 81:965–971PubMedPubMedCentralCrossRefGoogle Scholar
  134. Sud IJ, Feingold DS (1981) Mechanisms of action of the antimycotic imidazoles. J Invest Dermatol 76(6):438–441PubMedCrossRefGoogle Scholar
  135. Sullivan LJ, Snibson G, Joseph C, Taylor HR (1994) Scedosporium prolificans sclerokeratitis. Aust N Z J Ophthalmol 22:207–209PubMedCrossRefGoogle Scholar
  136. Sun CQ, Prajna NV, Krishnan T, Mascarenhas J, Rajaraman R, Srinivasan M et al (2010) Expert prior elicitation and Bayesian analysis of the Mycotic Ulcer Treatment Trial I. Investig Ophthalmol Vis Sci 54(6):4167–4173CrossRefGoogle Scholar
  137. Sweetman S (2004) Martindale: the complete drug reference, 34th edn. Pharmaceutical Press, London, pp 550–554Google Scholar
  138. Thakar M (1994) Oral fluconazole therapy for keratomycosis. Acta Ophthalmol 72(6):765–767CrossRefGoogle Scholar
  139. Thevissen K, Ayscough KR, Aerts AM, Du W, De Brucker K, Meert EM, Ausma J, Borgers M, Cammue BP, François IE (2007) Miconazole induces changes in actin cytoskeleton prior to reactive oxygen species induction in yeast. J Biol Chem 282(30):21592–21597PubMedCrossRefGoogle Scholar
  140. Thomas PA, Kalavathy CM, Abraham DJ, Rajasekaran J (1987) Oral ketoconazole in Keratomycosis. Indian J Ophthalmol 35(4):197–203PubMedGoogle Scholar
  141. Torres MA, Mohamed J, Cavazos-Adame H, Martinez LA (1985) Topical ketoconazole for fungal keratitis. Am J Ophthalmol 100(2):293–298, trial. Cornea 2012; 31: 662–67PubMedCrossRefGoogle Scholar
  142. Torres HA, Hachem RY, Chemaly RF, Kontoyiannis DP, Raad II (2005) Posaconazole: a broad-spectrum triazole antifungal. Lancet Infect Dis 5(12):775–785PubMedCrossRefGoogle Scholar
  143. Tu EY, McCartney DL, Beatty RF, Springer KL, Levy J, Edward D (2007) Successful treatment of resistant ocular fusariosis with posaconazole (SCH-56592). Am J Ophthalmol 143(2):222–227PubMedCrossRefGoogle Scholar
  144. Uchida K, Abe S, Yamaguchi H (2006) The postantifungal effect (PAFE) of itraconazole, in comparison with those of miconazole and fluconazole, on Candida species. Microbiol Immunol 50(9):679–685PubMedCrossRefGoogle Scholar
  145. Ullmann AJ, Cornely OA, Burchardt A, Hachem R, Kontoyiannis DP, Töpelt K, Courtney R, Wexler D, Krishna G, Martinho M, Corcoran G, Raad I (2006) Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 50(2):658–666PubMedPubMedCentralCrossRefGoogle Scholar
  146. Urbak SF, Degn T (1994) Fluconazole in the management of fungal ocular infections. Ophthalmologica 208(3):147–156PubMedCrossRefGoogle Scholar
  147. Vermes A, Guchelaar HJ, Dankert J (2000) Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother 46(2):171–179PubMedCrossRefGoogle Scholar
  148. Wagner C, Graninger W, Presterl E, Joukhadar C (2006) The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology 78(4):161–177PubMedCrossRefGoogle Scholar
  149. Weinstein M, Reller L, Murphy J, Lichtenstein KA (1983) The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis 5(1):35–53PubMedCrossRefGoogle Scholar
  150. Wellington M, Gigliotti F (2001) Update on antifungal agents. Pediatr Infect Dis J 20(10):993–995PubMedCrossRefGoogle Scholar
  151. Wood TO, Williford W (1976) Treatment of keratomycosis with amphotericin B 0.15%. Am J Ophthalmol 81(6):847–849PubMedCrossRefGoogle Scholar
  152. Xuguang S, Zhixin W, Zhiqun W, Shiyun L, Ran L (2007) Ocular fungal isolates and antifungal susceptibility in northern China. Am J Ophthalmol 143(1):131–133PubMedCrossRefGoogle Scholar
  153. Yamaguchi H, Abe S, Tokuda Y (1993) Immunomodulating activity of antifungal drugs. Ann N Y Acad Sci 685:447–457PubMedCrossRefGoogle Scholar
  154. Yee RW, Cheng CJ, Meenakshi S, Ludden TM, Wallace JE, Rinaldi MG (1997) Ocular penetration and pharmacokinetics of topical fluconazole. Cornea 16(1):64–71PubMedCrossRefGoogle Scholar
  155. Yilmaz S, Maden A (2005) Severe fungal keratitis treated with subconjunctival fluconazole. Am J Ophthalmol 140(3):454–458PubMedCrossRefGoogle Scholar
  156. Yoon KC, Jeong IY, Im SK, Chae HJ, Yang SY (2007) Therapeutic effect of intracameral amphotericin B injection in the treatment of fungal keratitis. Cornea 26(7):814–818PubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2016

Authors and Affiliations

  1. 1.Jhaveri Microbiology CentreL V Prasad Eye InstituteMarg Banjara Hills, HyderabadIndia

Personalised recommendations