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

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

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

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)

Purpose

• To compare efficacy of UVA/riboflavin

application between two different durations of

UVA light exposure in patients with infectious

keratitis

Methods

• Prospective randomized double blind trial (ongoing)

• Single site (Price Vision Group)

• FDA approved physician sponsored IND

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

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

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

Pt 1 - Day 0

Pt 1 - Day 1

Pt 1 - Day 5

Pt 1 - Day 6

Pt 1 - Day 21 - repeat UVA/riboflavin

Pt 1 - Day 1/22

Pt 1 - Day 5/26

Pt 1 - Day 7/28

Pt 1 - Day 17/38

Pt 3 - Day 0

Pt 3 - Day 2

Pt 3 - Day 5

Pt 3 - Day 6

Pt 3 - Day 8

Pt 5 - Day 0

Pt 5 - Day 0

Pt 5 - Day 11

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