Disclosure fungal keratitis Voriconazole donated by Pfizer - - PowerPoint PPT Presentation

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Update on management of fungal keratitis

Tom Lietman, MD F I Proctor Foundation Department of Ophthalmology University of California San Francisco

Disclosure

Voriconazole donated by Pfizer Natamycin and Moxifloxacin donated by Alcon NIH-NEI U10 EY018573 NIH-NEI U10 EY022880 Research to Prevent Blindness That Man May See

Acknowledgments

• N. V. Prajna

Lalitha Prajna

• M. Srinivasan

Jeena Mascarenhas

• R. Vijayakumar

Sumithra R.D. Ravindran Tiruvengada Krishnan Rabindranath Reddy Vaitilingam Jayanthi Kavita Dhakhwa Kamal Bahadur Khadka R.P. Kandel Nisha Acharya Jennifer Rose-Nussbaumer Stephen McLeod John P. Whitcher Jeremy Keenan Vicky Cevallos Chuck Leiter Travis Porco Kathryn Ray Kevin Hong Catie Oldenburg Kieran O’Brien Michael E. Zegans Christine Toutain Ivan Schwab Anthony Aldave

• Cataract
• Trachoma
• Glaucoma
• Corneal Ulcers
• Vitamin A Deficiency
• Onchocerciasis
• Leprosy

World Blindness 1993

Thylefors et al, Bull WHO 1995 Whitcher et al, BJO 1997

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• Cataract
• Glaucoma
• AMD
• Corneal Ulcers
• Diabetic Retinopathy
• Childhood blindness
• Trachoma
• Onchocerciasis

World Blindness 2002

Resnikoff et al, Bull WHO 2004

• Cataract
• Glaucoma
• AMD
• Corneal Ulcers
• Refractive error
• Childhood blindness
• Trachoma
• Diabetic Retinopathy

World Blindness 2010

Mariotti et al, BJO 2012

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Bacterial vs Fungal

Experts correct 66% (63 to 68%) Good news: p<0.001 Bad news: need to do better

Metagenomic Deep Sequencing

presumed infectious failed diagnostics clinical progression

Thuy Doan, MD PhD

Google trends: “Fusarium”

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Comparison N Inclusion Criteria Results Ofloxacin versus cefazolin and tobramycin52 248 Bacterial No significant difference Ofloxacin monotherapy versus fortified gentamicin and cefuroxime54 122 All microbial No significant difference Chlorhexidine versus natamycin60 71 Fungal No significant difference Econazole versus natamycin53 116 Fungal No significant difference Moxifloxacin versus ofloxacin

• r fortified

tobramycin/cephazolin51 229 Bacterial No significant difference Povidone-iodine as adjunctive therapy versus standard therapy61 358 All microbial No significant difference PHMB versus chlorhexidine as monotherapy55 56 Acanthamoeba No significant difference Natamycin versus voriconazole6 120 Fungal No significant difference Corticosteroid versus placebo as adjunctive therapy with moxifloxacin50 500 Bacterial No significant difference

Corneal Ulcer RCTs with >50 Ulcers

Survey of Cornea Specialists

Most preferred antifungal in an ideal world? voriconazole 79%

Loh et al, Cornea 2009

Mycotic Ulcer Treatment Trial I

Natamycin versus Voriconazole

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MUTT I

Which topical agent, voriconazole or natamycin, is more effective in the treatment of filamentous fungal keratitis?

NEI U10 EY018573

MUTT I (N=323)

Prajna et al., Archives of Ophthalmology 2013

3-month Acuity

2-lines better with Natamycin

(P=0.006)

3-month Acuity Fusarium species

4-lines better with Natamycin

(P<0.001)

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Do NOT use voriconazole monotherapy for Fusarium species

Comparison Authors N Etiology Results Ofloxacin versus cefazolin and tobramycin O’Brien et al Archives 1995 248 Bacterial No significant difference Ofloxacin versus gentamicin and cefuroxime Ofloxacin Study Group Ophthalmology 1997 122 All microbial No significant difference Chlorhexidine versus natamycin Rahman et al BJO 1998 71 Fungal No significant difference Econazole versus natamycin Prajna et al BJO 2003 116 Fungal No significant difference Povidone-iodine as adjunctive therapy versus standard Katz et al BJO 2004 358 All microbial No significant difference Moxifloxacin versus ofloxacin or tobramycin and cephazolin Constantinou et al Ophthalmology 2007 229 Bacterial No significant difference PHMB versus chlorhexidine Lim et al AJO 2008 56 Acanthamoeba No significant difference Natamycin versus voriconazole Prajna et al Archives 2010 120 Fungal No significant difference Steroid versus placebo with moxifloxacin Srinivasan et al Archives 2011 500 Bacterial No significant difference Natamycin versus voriconazole Prajna et al Archives 2013 323 Fungal ?

Corneal Ulcer RCTs with >50 Ulcers

Comparison Authors N Etiology Results Ofloxacin versus cefazolin and tobramycin O’Brien et al Archives 1995 248 Bacterial No significant difference Ofloxacin versus gentamicin and cefuroxime Ofloxacin Study Group Ophthalmology 1997 122 All microbial No significant difference Chlorhexidine versus natamycin Rahman et al BJO 1998 71 Fungal No significant difference Econazole versus natamycin Prajna et al BJO 2003 116 Fungal No significant difference Povidone-iodine as adjunctive therapy versus standard Katz et al BJO 2004 358 All microbial No significant difference Moxifloxacin versus ofloxacin or tobramycin and cephazolin Constantinou et al Ophthalmology 2007 229 Bacterial No significant difference PHMB versus chlorhexidine Lim et al AJO 2008 56 Acanthamoeba No significant difference Natamycin versus voriconazole Prajna et al Archives 2010 120 Fungal No significant difference Steroid versus placebo with moxifloxacin Srinivasan et al Archives 2011 500 Bacterial No significant difference Natamycin versus voriconazole Prajna et al Archives 2013 323 Fungal Natamycin better

Corneal Ulcer RCTs with >50 Ulcers

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MUTT II

Does adjunctive oral voriconazole help in severe fungal ulcers?

NEI U10 EY018573

MUTT II (N=240) MUTT II (N=240)

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MUTT II (N=240) Corneal cross-linking? New with fungal ulcers?

experts are moderately expert natamycin better than voriconazole

• ral voriconazole not necessary

metagenomic deep sequencing corneal cross-linking