Background
description
Transcript of Background
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UVA/riboflavin for infectious keratitis. Prospective randomized double blind trial.
Early experience.
Erik Letko, MD1; Francis W. Price, MD1; Carlindo Pereira, MD1; Marianne O. Price, PhD2; Amilia Schrier, MD3; Stephen L. Trokel, MD3
1Price Vision Group, 2Cornea Research Foundation of America, Indianapolis, IN; 3Edward S. Harkness Institute, Columbia University
College of Physicians and Surgeons, New York, NY
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Background
• UVA – 320-400 nm– Damage to DNA/RNA– Disinfection of drinking water– Air/surface disinfection
• Riboflavin (vit. B2)– Photosensitizer– Rapidly passing through lipid membranes– Intercalates with nucleic acids– In cornea protects deeper layers from UVA
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Background
• Riboflavin/UVA oxidation of nucleic acid residues ROS damage to RNA/DNA
– Kills microorganisms• Used to sterilize blood products
– Collagen crosslinking• Strengthens the cornea to prevent progression of ulceration
– Inactivates white blood cells• ?Reduction of scarring
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UVA/riboflavin in vitro
• Inactivates– Bacteria
• S. epidermidis • S. aureus (including MRSA)• S. pneumoniae (drug resistant)• E. coli• P. aeruginosa (multidrug resistant)
– Viruses• West Nile • Parvovirus (porcine) • HIV
– Parasites• Trypanosoma cruzi• Leishmania• Malaria
• Ineffective – Candida albicans (Martins et al, IOVS, 2008)
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Purpose
• To compare efficacy of UVA/riboflavin
application between two different durations of
UVA light exposure in patients with infectious
keratitis
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Methods
• Prospective randomized double blind trial (ongoing)
• Single site (Price Vision Group)
• FDA approved physician sponsored IND
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Methods
• Inclusion criteria• Subjects must be 18 years of age or older
• Diagnosis of (presumed) infectious keratitis
• Corneal scraping sent for cultures and sensitivities
• Exclusion criteria• Descemetocele or perforated cornea
• Breastfeeding or pregnant women
• Immunocompromised status
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Treatment protocol
• Remove epithelium (if needed)• Saturate cornea with riboflavin (0.1% in 20%
dextran)• UVA light at 365 nm (3 mW/cm2) (15 or 30 minutes)
• Routine antibiotics after UVA/riboflavin application
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PtOcular history
CultureResolution of epi
defect [days]*Light ø
[mm]Notes
1 - Fusarium 6 (7 after repeat) 7.5 Repeat UVA/riboflavin at 21 days
2 PK Mor/Bac 13 7.5 -
3 PK S. aureus 7 7.5 Emergency PK at 10 days
4 - S. pneum 5 7.5 -
5 DSAEK S. pneum 11 7.5 -
6 CL, Intacs S. coag- 3 7.5 -
7 PK Mor 13 7.5 -
8 CL Acnt **48+ 9.5 Culture -, Confocal positive
9 - S. aureus 3 7.5 -
10 Bell’s palsy Mor 15 7.5 Tarsorrhaphy at 13 days
11 CL Negative 11 7.5 3 days on atb prior to culture
Results
Pt - patient, epi - epithelial, *UVA light aperture PK - penetrating keratoplasty, Mor - Moraxella, Bac - Bacillus (non-anthracis), DSAEK - Descemet’s stripping endothelial keratoplasty, CL - contact lens, Acnt - Acanthamoeba, **patient currently followed
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Pt 1 - Day 0
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Pt 1 - Day 1
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Pt 1 - Day 5
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Pt 1 - Day 6
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Pt 1 - Day 21 - repeat UVA/riboflavin
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Pt 1 - Day 1/22
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Pt 1 - Day 5/26
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Pt 1 - Day 7/28
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Pt 1 - Day 17/38
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Pt 3 - Day 0
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Pt 3 - Day 2
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Pt 3 - Day 5
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Pt 3 - Day 6
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Pt 3 - Day 8
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Pt 5 - Day 0
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Pt 5 - Day 0
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Pt 5 - Day 11
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Conclusions
• Application of UVA/riboflavin appears to be safe
and might be effective for treatment of infectious
keratitis
• Longer or repeat treatments might be needed at
least in some cases
• Further investigation is warranted