1. UVA/riboflavin for infectious keratitis. Prospective randomized double blind trial. Early experience. Erik Letko, MD 1 ; Francis W. Price, MD 1 ; Carlindo Pereira, MD 1 ; Marianne O. Price, PhD 2 ; Amilia Schrier, MD 3 ; Stephen L. Trokel, MD 3 1 Price Vision Group, 2 Cornea Research Foundation of America, Indianapolis, IN; 3 Edward S. Harkness Institute, Columbia University College of Physicians and Surgeons, New York, NY

2. 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

3. 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

4. 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)

5. Purpose To compare efficacy of UVA/riboflavin application between two different durations of UVA light exposure in patients with infectious keratitis

6. Methods Prospective randomized double blind trial (ongoing) Single site (Price Vision Group) FDA approved physician sponsored IND

7. 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

8. Treatment protocol Remove epithelium (if needed) Saturate cornea with riboflavin (0.1% in 20% dextran) UVA light at 365 nm (3 mW/cm 2 ) (15 or 30 minutes) Routine antibiotics after UVA/riboflavin application

9. Pt Ocular history Culture Resolution of epi defect [days] *Light ø [mm] Notes 1-Fusarium6 (7 after repeat)7.5Repeat UVA/riboflavin at 21 days 2 PKMor/Bac137.5- 3 PKS. aureus77.5Emergency PK at 10 days 4 -S. pneum57.5- 5 DSAEKS. pneum117.5- 6CL, IntacsS. coag-37.5- 7PKMor137.5- 8CLAcnt**48+9.5Culture -, Confocal positive 9-S. aureus37.5- 10Bell’s palsyMor157.5Tarsorrhaphy at 13 days 11CLNegative117.53 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

10. Pt 1 - Day 0

11. Pt 1 - Day 1

12. Pt 1 - Day 5

13. Pt 1 - Day 6

14. Pt 1 - Day 21 - repeat UVA/riboflavin

15. Pt 1 - Day 1/22

16. Pt 1 - Day 5/26

17. Pt 1 - Day 7/28

18. Pt 1 - Day 17/38

19. Pt 3 - Day 0

20. Pt 3 - Day 2

21. Pt 3 - Day 5

22. Pt 3 - Day 6

23. Pt 3 - Day 8

24. Pt 5 - Day 0

26. Pt 5 - Day 11

27. 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