Financial disclosures Named co-inventor on PCT applications CH2012/0000090 and PCT2014/CH000075 Chief Scientific Officer EMAGine SA
Historical decision in 2004 1. Future: extremely thin corneas Dresden ( 3 mw/cm 2 for 30 min) = 330 µm effect Recommendation: only treat if 400 µm 300 µ Wollensak et al., 1998 Seiler & Hafezi, 2006
Treat thin corneas 1. Future: extremely thin corneas JCRS, 2009
Other techniques 1. Future: extremely thin corneas Hypoosmolar CXL Contact-lens-assisted Transepithelial CXL Epithelial island CXL
Modify depth of effect 1. Future: extremely thin corneas Modify Modify Riboflavin Modify UV Thickness concentration intensity Hypoosmolar CXL Transepithelial CXL Contact-lens-assisted Epithelial island CXL
New model 1. Future: extremely thin corneas Modify UV intensity Riboflavin diffusion kinetics Oxygen diffusion kinetics
Fixed fluence (5.4 J/cm 2 ) 1. Future: extremely thin corneas 400 µm 300 µm
Fixed fluence (5.4 J/cm 2 ) 1. Future: extremely thin corneas 400 µm 300 µm Hypoosmolar Contact lens-assisted
Adapted fluence 1. Future: extremely thin corneas 400 µm 300 µm 250 µm 3 mw/cm 2 for 30 3 mw/cm 2 for xx 3 mw/cm 2 for xx 5.4 J/cm 2 xx J/cm 2 xx J/cm 2
New model to adapt CXL effect between 1. Future: extremely thin corneas Kling & Hafezi., JRS, in press
Treat corneas thinner between 200 and 400 µm 1. Future: extremely thin corneas Currently 32 eyes Depth of demarcation line at 1 month Treated so far: 270 µm to 395 µm
Simplified protocol 1. Future: extremely thin corneas 1. Perform abrasio 2. Instill riboflavin with speculum in place 3. Measure thickness after hypoosmolar riboflavin installation 4. Adapt the total fluence and treat
Conclusions 1. Future: extremely thin corneas The future: customized settings for every corneal thickness Use one single riboflavin solution: no more confusion with multiple different riboflavin solutions Can the CXL effect stabilize a 250 µm cornea?
AMR (Antimicrobial resistance), a global problem
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 comprehensive picture to date, with data provided by 114 countries Looking at 7 common bacteria that cause serious diseases from bloodstream infections to gonorrhoea High levels of resistance found in all regions of the world Significant gaps exist in tracking of antibiotic resistance Over the last 30 years, no major new types of antibiotics have been developed 1910 1920 1930 1940 1950 1960 1970 1990 1980 2000 2010 Penicillin Cephalosporin Carbapenem Fluoroquinolones Discovery void 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 clean water and sanitation Infection control in healthcare facilities Vaccination Never share antibiotics with others or use leftover prescriptions More information at www.who.int/drugresistance WHO report 2014
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 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 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
AMR, a global problem
AMR, a global problem
Diagnostic dilemma, therapeutic dilemma
Major geographic variations Whitcher et al., Int Ophthalmol Clin 2002
1. Introduction 2. Problem
Problem Treatment success depends on time/access to vision care specialists type of treatment funding compliance
Scenario 1 + AB +
Scenario 2 24h 72h CDVA 20/200
Zurich, Switzerland: 2004 IROC (Seiler, Mrochen, Hafezi, Iseli) ETH Swiss Federal Institute of Technology
Cross-Linking effects 32 Steric hindrance 3 DNA/RNA intercalation 4 Oxidative stress
UV-A + riboflavin = disinfectant Goodrich et al, 2000, Vox Sang Reddy et al, 2008, Transfusion Med Rev Heaselgrave et al., Appl Environ Microbiol, 2010
2008. Switzerland. Proof of principle. 2. First Results Post-LASIK keratitis Ten days after PACK-CXL Iseli et al, 2008, Cornea
PACK-CXL Hafezi et al, Journal of Refractive Surgery, 2013 2. 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
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
2008-2013. Veterinary ophthalmology. 2. First Results 1 dy 13 dys 3 mo Pot and Hafezi, Vet Ophthalmol, 2013 Mortensen et al., Vet Ophthalmol, 2013
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
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
Future treatment needs Optimize 2. Results Accelerate 3. Optimize Access to all
Simplify 2. Results 3. Optimize
2010-2012: Early ulcers 2. Results JRS, 2012 3. Optimize Prospective clinical study 40 eyes. All stages of ulcer, 0-12 mm Bacterial, fungal, mixed Overall: 15% required additional treatment Early ulcers alone: none required additional treatment
2010-2012: Early ulcers 2. Results 3. Optimize
2010-2013: Advanced ulcers 2. Results 3. Optimize Ophthalmology, 2014 Prospective randomised clinical study 40 patients with therapy-resistant end-stage ulcer Bacterial, fungal, mixed Arm 1: Medication only, 21 eyes Arm 2: Medication plus CXL, 19 eyes Healing time comparable
2010-2013: Advanced ulcers 2. Results 3. Optimize Ophthalmology, 2014
Treat Early Infiltrate / Early ulcer? Advanced ulcer? 2. Results 3. Optimize Price et al., JRS, 2012 Said et al., Ophthalmology, 2014
Accelerate 2. Results 3. Optimize For keratoconus? No Hammer et al, IOVS, 2014
Accelerate: bactericidal effect 2. First Results 3. Optimize 150 seconds, 98% killing Richoz et al, JRS, 2014
Phase 2 trial: accelerated PACK-CXL 180 seconds @ 30 mw/cm 2 2. Results 3. Optimize Arm 1: antibiotics alone (n=28) Arm 2: antibiotics & CXL (n=32) Difference in healing 12 vs 7 days (p=0.001) Knyazer et al., in preparation
Phase 2 trial: accelerated PACK-CXL 180 seconds @ 30 mw/cm 2 2. Results 3. Optimize Arm 1: antibiotics alone (n=28) Arm 2: antibiotics & CXL (n=32) Difference in healing 12 vs 7 days (p=0.001) Knyazer et al., in preparation
Swiss PACK-CXL RCT Phase 3 prospective RCT Non-inferiority study Infiltrates and small ulcers < 4 mm, < 350 µm depth 2. First Results 3. Optimize 4. Clinical data 13 sites 10 countries
Introduction at ESCRS 2016 Copenhagen 2. First Results 3. Optimize 4. Clinical data 5. CXL at the slit lamp C-Eye device
Introduction at ESCRS 2016 Copenhagen 2. First Results 3. Optimize 4. Clinical data 5. CXL at the slit lamp C-Eye device
C-Eye device Sterile tip Intensities delivered 2. First Results 3 mw/cm 2 9 mw/cm 2 18 mw/cm 2 30 mw/cm 2 Keratoconus Corneal Ulcer 3. Optimize 4. Clinical data 5. CXL at the slit lamp Beam optimization Safety mechanism
C-Eye Device 1 2. First Results 3. Optimize 2 4. Clinical data 5. CXL at the slit lamp 3 PACK-CXL EMAGine s product line offers a one-time treatment using basic equipment and infrastructure of any vision care specialist.* The use of UV light and a proprietary chromophore solution would be effective in killing all harmful pathogens in one treatment, including mixed infections. * Prophylatic anti-microbials can be administered after treatment.
Benefits Current PACK-CXL + 2. First Results 3. Optimize ( ) 4. Clinical data 5. CXL at the slit lamp Compliance-independent approach Diagnostic-independent approach
Why do PACK-CXL, antibiotics are cheap In the future: antimicrobial resistance will increase 2. First Results PACK-CXL does not only kill, but increases resistance to digestion = lesser scar 3. Optimize 4. Clinical data 5. CXL at the slit lamp Many areas of the world: doctor s costs are limiting PACK-CXL independent of diagnostic look and experience in infection assessment Less compliance issues
2013 2017
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