12/3/2016 Update on management of Disclosure fungal keratitis Voriconazole donated by Pfizer Natamycin and Moxifloxacin donated by Alcon Tom Lietman, MD NIH-NEI U10 EY018573 F I Proctor Foundation NIH-NEI U10 EY022880 Department of Ophthalmology Research to Prevent Blindness That Man May See University of California San Francisco World Blindness 1993 Acknowledgments N. V. Prajna Nisha Acharya • Cataract Lalitha Prajna Jennifer Rose-Nussbaumer M. Srinivasan Stephen McLeod • Trachoma Jeena Mascarenhas John P. Whitcher R. Vijayakumar Jeremy Keenan • Glaucoma Sumithra Vicky Cevallos R.D. Ravindran Chuck Leiter • Corneal Ulcers Tiruvengada Krishnan Travis Porco Rabindranath Reddy Kathryn Ray • Vaitilingam Vitamin A Deficiency Kevin Hong Jayanthi Catie Oldenburg • Kavita Dhakhwa Kieran O’Brien Onchocerciasis Kamal Bahadur Khadka Michael E. Zegans • R.P. Kandel Christine Toutain Leprosy Ivan Schwab Anthony Aldave Thylefors et al, Bull WHO 1995 Whitcher et al, BJO 1997 1
12/3/2016 World Blindness 2002 World Blindness 2010 • • Cataract Cataract • • Glaucoma Glaucoma • • AMD AMD • • Corneal Ulcers Corneal Ulcers • • Diabetic Retinopathy Refractive error • • Childhood blindness Childhood blindness • • Trachoma Trachoma • • Diabetic Retinopathy Onchocerciasis Resnikoff et al, Bull WHO 2004 Mariotti et al, BJO 2012 2
12/3/2016 Bacterial vs Fungal Experts correct 66% (63 to 68%) Good news: p <0.001 Bad news: need to do better Google trends: “Fusarium” Metagenomic Deep Sequencing presumed infectious failed diagnostics clinical progression Thuy Doan, MD PhD 3
12/3/2016 Corneal Ulcer RCTs with >50 Ulcers Comparison N Inclusion Criteria Results Ofloxacin versus cefazolin No significant difference 248 Bacterial and tobramycin 52 Ofloxacin monotherapy No significant difference versus fortified gentamicin 122 All microbial and cefuroxime 54 Chlorhexidine versus No significant difference 71 Fungal natamycin 60 Econazole versus No significant difference 116 Fungal natamycin 53 Moxifloxacin versus ofloxacin No significant difference or fortified 229 Bacterial tobramycin/cephazolin 51 Povidone-iodine as adjunctive No significant difference therapy versus standard 358 All microbial therapy 61 PHMB versus chlorhexidine No significant difference 56 Acanthamoeba as monotherapy 55 Natamycin versus No significant difference 120 Fungal voriconazole 6 Corticosteroid versus placebo No significant difference as adjunctive therapy with 500 Bacterial moxifloxacin 50 Survey of Cornea Specialists Mycotic Ulcer Treatment Trial I Most preferred antifungal in an ideal world? Natamycin voriconazole 79% versus Voriconazole Loh et al, Cornea 2009 4
12/3/2016 MUTT I ( N =323) MUTT I Which topical agent, voriconazole or natamycin, is more effective in the treatment of filamentous fungal keratitis? Prajna et al., Archives of Ophthalmology 2013 NEI U10 EY018573 3-month Acuity 3-month Acuity Fusarium species 2-lines better with Natamycin 4-lines better with Natamycin ( P =0.006) ( P <0.001) 5
12/3/2016 Corneal Ulcer RCTs with >50 Ulcers Comparison Authors N Etiology Results Ofloxacin versus cefazolin and O’Brien et al No significant difference 248 Bacterial Archives 1995 tobramycin Do NOT use voriconazole Ofloxacin versus gentamicin and Ofloxacin Study Group No significant difference 122 All microbial Ophthalmology 1997 cefuroxime Rahman et al No significant difference Chlorhexidine versus natamycin 71 Fungal BJO 1998 Prajna et al monotherapy for No significant difference Econazole versus natamycin 116 Fungal BJO 2003 Povidone-iodine as adjunctive Katz et al No significant difference 358 All microbial BJO 2004 therapy versus standard Moxifloxacin versus ofloxacin or Constantinou et al No significant difference 229 Bacterial Ophthalmology 2007 Fusarium species tobramycin and cephazolin Lim et al No significant difference PHMB versus chlorhexidine 56 Acanthamoeba AJO 2008 Prajna et al No significant difference Natamycin versus voriconazole 120 Fungal Archives 2010 Steroid versus placebo Srinivasan et al No significant difference 500 Bacterial Archives 2011 with moxifloxacin Prajna et al ? Natamycin versus voriconazole 323 Fungal Archives 2013 Corneal Ulcer RCTs with >50 Ulcers Comparison Authors N Etiology Results Ofloxacin versus cefazolin and O’Brien et al No significant difference 248 Bacterial Archives 1995 tobramycin Ofloxacin versus gentamicin and Ofloxacin Study Group No significant difference 122 All microbial Ophthalmology 1997 cefuroxime Rahman et al No significant difference Chlorhexidine versus natamycin 71 Fungal BJO 1998 Prajna et al No significant difference Econazole versus natamycin 116 Fungal BJO 2003 Povidone-iodine as adjunctive Katz et al No significant difference 358 All microbial BJO 2004 therapy versus standard Moxifloxacin versus ofloxacin or Constantinou et al No significant difference 229 Bacterial Ophthalmology 2007 tobramycin and cephazolin Lim et al No significant difference PHMB versus chlorhexidine 56 Acanthamoeba AJO 2008 Prajna et al No significant difference Natamycin versus voriconazole 120 Fungal Archives 2010 Steroid versus placebo Srinivasan et al No significant difference 500 Bacterial Archives 2011 with moxifloxacin Prajna et al Natamycin better Natamycin versus voriconazole 323 Fungal Archives 2013 6
12/3/2016 MUTT II Does adjunctive oral voriconazole help in severe fungal ulcers? NEI U10 EY018573 MUTT II ( N =240) MUTT II ( N =240) 7
12/3/2016 MUTT II ( N =240) Corneal cross-linking? New with fungal ulcers? experts are moderately expert natamycin better than voriconazole oral voriconazole not necessary metagenomic deep sequencing corneal cross-linking 8
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