1. Paradox of Corneal CXL and Infectious Keratitis: To Do or Not to Do? None of the authors have any financial disclosure to make Vishal Vohra,MS (Presenting Author), Rohit Shetty, DNB, FRCS; Harsha Nagaraj, MS; Luci Kaweri, MD; Chetna Sharma, MS; Natasha K. Pahuja, DOMS Narayana Nethralaya, Bangalore, INDIA

2. PURPOSE To evaluate the dual role of crosslinking both as a treatment modality and a pathogenic factor for microbial keratitis Group 1 To evaluate the efficacy and safety of corneal collagen cross-linking (CXL) in infectious keratitis Group 2 To analyse the profile of microbial keratitis occurring after CXL Group 2 To analyse the profile of microbial keratitis occurring after CXL

3. Riboflavin + UV A radiation Irreversible breaks in DNA / RNA strands Increases the corneal thermal shrinkage temperature Effect on leucocytes Effect on immune response KXL in infectious keratitis: Mechanism Kills microbes Arrests stromal melting Reduces pain and inflammation Reactive Oxygen species

4. Non-healing microbial keratitis Phase 1 of study Conventional CXL 15 eyes of 15 patients Phase 1 of study Conventional CXL 15 eyes of 15 patients Phase 2 of study (ongoing) Accelerated CXL 3 eyes of 3 patients Phase 2 of study (ongoing) Accelerated CXL 3 eyes of 3 patients Not responding to 2 weeks of topical therapy ongoing Prospective, interventional ongoing study METHODOLOGY – GROUP1

5. Soak period 0.1% Riboflavin drops (Medio-Cross D) every 2 minutes for 30 minutes Soak period 0.1% Riboflavin drops (Medio-Cross D) every 2 minutes for 30 minutes Accelerated CXL in 3 patients 9mW/cm 2 for 10 min PROCEDURE Conventional CXL – 15 patients 3mW/cm 2 for 30 minutes Riboflavin + UV-A (365nm) Irradiation Riboflavin + UV-A (365nm) Irradiation

6. RESULTS Total resolution: Seen in 18 patients 8 out of 11 bacterial keratitis (72.73%) showed resolution 3 out of 6 fungal keratitis (50%) showed resolution Acanthoemeba keratitis:  Favourable result but recurrence noted  Can repeat CXL be effective??? Superficial and anterior stromal infiltrates- better response  1 st POD- significantly reduced/ no pain in all patients  ‘Chemical denervation’  Mean time for epithelial healing- 23 days  Mean time for resolution of corneal infiltrate was 33 days

7. Not every story has a Happy Ending…. It is interesting that CXL itself might be a precipitating factor in causing keratitis

8. Group 2 To analyse the profile of microbial keratitis occurring after CXL infectious keratitis post CXL 4 eyes developed infectious keratitis post CXL Etiology - MXRSA) Etiology - moxifloxacin resistant Staphylococcus aureus (MXRSA) These eyes were studied 1715 CXL, 310 TE-CXL and 325 A-CXL over 7 years who underwent CXL 2350 progressive KC patients A Retrospective analysis

9. CaseClinical picture Associated conditions TreatmentProcedureManagement 1Bronchial asthmaInhalational /oral steroids Conventional CXL Femtosecond Endothelial Keratoplasty 2Vernal catarrhTopical steroidsConventional CXL Rigid gas permeable contact lens 3EczemaOral Cyclophospha- mide Conventional CXL Penetrating Keratoplasty 4Vernal catarrhTopical steroidsConventional CXL Amniotic membrane graft, under follow-up Keratitis after CXL - Clinical profile of patients

10. The Question Arises… Cross –linking is treatment of infectious keratitis Cross-linking predisposing to keratitis

11. Pre –operative steroids: ? altered flora Ermis SS, Aktepe OC, Inan UU, Ozturk F, Altindis M. Effect of topical dexamethasone and ciprofloxacin on bacterial flora of healthy conjunctiva. Eye (Lond). 2004 Mar; 18(3):249-52 SYSTEMIC IMMUNOSUPPRESSION LOCAL STEROID THERAPY LOCAL STEROID THERAPY UVA induced: ? Moxifloxacin resistance Ince D, Zhang X, Hooper DC. Activity of and resistance to moxifloxacin in Staphylococcus aureus. Antimicrob Agents Chemother. 2003 Apr;47(4):1410-5