PACK-CXL. for infectious keratitis. Farhad Hafezi, MD PhD. Professor of Ophthalmology Keck School of Medicine USC Los Angeles, USA

Transcription

1 PACK-CXL for infectious keratitis Farhad Hafezi, MD PhD Professor of Ophthalmology University of Geneva Geneva, Switzerland Medical Director ELZA Institute Zurich, Switzerland Research Group Leader Lab. for Ocular Cell Biology University of Zurich, Switzerland Professor of Ophthalmology Keck School of Medicine USC Los Angeles, USA

2 Financial disclosures Named co-inventor on PCT applications CH2012/ and PCT2014/CH Chief Scientific Officer EMAGine SA

3 AMR (Antimicrobial resistance), a global problem

4 AMR, a global problem ANTIMICROBIAL RESISTANCE Global Report on surveillance 2014 What you need to know WHO s first global report on antimicrobial resistance, with a focus on antibiotic resistance, reveals that it is no longer a prediction for the future. Antibiotic resistance - when bacteria change and antibiotics fail - is happening right now, across the world The report is the most Looking at 7 common High levels of Significant gaps comprehensive picture to bacteria that cause serious resistance found in all exist in tracking of date, with data provided by diseases from bloodstream regions of the world antibiotic resistance 114 countries infections to gonorrhoea Over the last 30 years, no major new types of antibiotics have been developed Discovery void Penicillin Cephalosporin Carbapenem Fluoroquinolones What does this mean? Without urgent action we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill What you can do Use antibiotics only when prescribed by a health professional How can infections be prevented in the first place to reduce the need for antibiotics? Better hygiene Complete the full prescription, even if you feel better Access to Infection control clean water in healthcare and sanitation facilities or use leftover prescriptions Vaccination Never share antibiotics with others More information at WHO report 2014

5 with a focus on antibiotic resistance, reveals that it is no longer a prediction for the future. Antibiotic resistance - when bacteria change and antibiotics fail - is happening right now, across the world The report is the most comprehensive picture to Looking at 7 common bacteria that cause serious High levels of resistance found in all Significant gaps exist in tracking of date, with data provided by diseases from bloodstream regions of the world antibiotic resistance 114 countries infections to gonorrhoea Over the last 30 years, no major new types of antibiotics have been developed Discovery void Penicillin Cephalosporin Carbapenem Fluoroquinolones What does this mean? Without urgent action we are heading for a post-antibiotic era, in which common infections and minor injuries can once again kill How can infections be prevented in the first place to reduce the need for antibiotics? Better Access to Infection control Vaccination hygiene clean water in healthcare and sanitation facilities What you can do Use antibiotics only when prescribed Complete the full prescription, Never share antibiotics with others

6 AMR, a global problem

7 Diagnostic dilemma, therapeutic dilemma

8 Infectious keratitis - Silent epidemic (WHO) Antibiotic resistance Mixed infections Developed countries High costs 6-8 Million new cases / year Developing countries ophthalmologists

9 PACK-CXL Hafezi et al, Journal of Refractive Surgery, Need gap: AMR 3. Need gap: Corneal infection 4. Alternative: PACK- Cross-Linking Kills both bacteria and fungi Reduce diagnostic and therapeutic dilemma Alternative to antibiotics

10 Zurich, Switzerland: 2004 IROC (Seiler, Mrochen, Hafezi, Iseli) ETH Swiss Federal Institute of Technology

11 Cross-Linking effects 32 Steric hindrance 3 DNA/RNA intercalation 4 Oxidative stress

12 2008. Switzerland. Proof of principle. 2. First Results Post-LASIK keratitis Ten days after PACK-CXL Iseli et al, 2008, Cornea

13 Laboratory Staph aureus growth inhibition by 97% in 30 minutes (Dresden keratoconus protocol) 2. First Results Schrier et al., IOVS,2008 Martins et al., IOVS, 2008

14 Veterinary ophthalmology. 2. First Results 1 dy 13 dys 3 mo Pot and Hafezi, Vet Ophthalmol, 2013 Mortensen et al., Vet Ophthalmol, 2013

15 2011 Phase 2 Clinical Trial No antibiotics 2. First Results Before PACK-CXL Two weeks after PACK-CXL Makdoumi et al., Curr Eye Res, 2011

16 Kill bacteria and fungi simultaneously BACTERIA Up to 98% in vitro With fluence currently used in clinical setting 2. Results 3. Optimize FUNGI 60-70% in vitro With high fluence currently used in clinical setting (7.2 J/cm 2 ) MSSA MRSA P. aeruginosa S. epidermidis C. albicans Fusarium 5.4 J/cm 2 ( ) ( ) 98% 99% 98% 97% 60-70% 60-70% Schrier et al., IOVS,2008 Martins et al., IOVS, 2008 Richoz et al., JRS, 2014 Richoz et al., unpublished data

17 Future treatment needs 2. Results 3. Optimize Simplify Accelerate Access to all

18 Simplify 2. Results 3. Optimize

19 : Advanced ulcers 2. Results 3. Optimize Ophthalmology, 2014

20 Treat Early Infiltrate / Early ulcer? Advanced ulcer? 2. Results 3. Optimize Price et al., JRS, 2012 Said et al., Ophthalmology, 2014

21 Accelerate: bactericidal effect 2. First Results 3. Optimize 150 seconds, 98% killing Richoz et al, JRS, 2014

22 Accelerate: enzymatic digestion 2. First Results 3. Optimize Kanellopoulos et al, Cornea, 2016

23 Phase 2 trial: accelerated PACK-CXL mw/cm 2 Adjuvant to antibiotics 2. Results 3. Optimize Knyazer et al., in preparation

24 Phase 2 trial: accelerated PACK-CXL mw/cm 2 Adjuvant to antibiotics 2. Results 3. Optimize Knyazer et al., in preparation

25 Swiss PACK-CXL multicenter trial Phase 3 prospective, randomized, multicenter trial 2. First Results Non-inferiority study Infiltrates and small ulcers < 2 mm, < 300 µm depth n = Optimize 4. Clinical data 11 sites 10 countries

26 Introduction at ESCRS 2016 Copenhagen 2. First Results 3. Optimize 4. Clinical data 5. CXL at the slit lamp C-Eye device

27 Conclusions PACK-CXL 2. First Results 3. Optimize 4. Clinical data Accelerated to 3 minutes Highly efficient in bacteria and fungi CXL at the slit lamp: access to all 5. CXL at the slit lamp 6. Conclusions

28 Conclusions 74 MedLine Results 1200 Papers on CXL for keratoconus 3. Optimize 4. Swiss PACK-CXL Multicenter trial Papers on PACK-CXL for infectious keratitis 5. CXL at the slit lamp 6. Conclusions PACK-CXL is a new technology, do not use as a routine procedure (yet)

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