1. Corneal collagen cross-linking: 2015 and beyond Dr Elsie Chan Consultant Ophthalmologist, Royal Victorian Eye and Ear Hospital Honorary Fellow, CERA, University of Melbourne November, 2015

2. Treatment Improving vision – Spectacles – Contact lenses – Corneal transplant Most advanced cases KC is leading indication for transplants in Australia But these do not stop worsening of keratoconus

3. Cross-linking for keratoconus ‘A chemical bond between……complex molecule’ CXL of the cornea for keratoconus first published in 1997 Cross-links may stiffen cornea, increasing its stability which may slow progression of disease

4. CXL procedure – Dresden protocol Step 1 – remove epithelium Step 2 – riboflavin (vitamin B 2 ) drops (30 minutes) Step 3 – UVA + riboflavin (30 minutes)

5. CXL procedure – Dresden protocol Step 1 – remove epithelium Step 2 – riboflavin (vitamin B 2 ) drops (30 minutes) Step 3 – UVA + riboflavin (30 minutes)

6. CXL procedure – Dresden protocol Step 1 – remove epithelium Step 2 – riboflavin (vitamin B 2 ) drops (30 minutes) Step 3 – UVA + riboflavin (30 minutes)

7. Pre-clinical testing Increased stiffness by over 300% Endothelial damage when corneal thickness less than 400µm (0.4mm) Wollensak et al, AJO 2003

8. Results First study in patients in 2003 Widespread adoption of CXL into clinical practice around the world 5 randomised, controlled trials – Compare treated versus untreated eyes – Tests the effectiveness of the treatment – Australia, UK, USA, India, Germany Melbourne (CERA/ RVEEH) trial is the one with the longest follow-up Courtesy of Faye Mach-Phung

9. Melbourne CXL trial 100 eyes of 76 patients randomised to CXL treatment or no treatment (control group) Followed up yearly for 5 years Inclusion criteria – Progressive keratoconus over 12 months – Corneal thickness >400µm

10. 5 years: Corneal curvature (average results) Control +1.85D CXL -1.29D Δ K steep (D) 1 yr2 yrs 3 yrs4 yrs steeper (worse) flatter (better) 5 yrs

11. 5 years: Corneal curvature (individual results) Number of eyes

12. Thin corneas Using standard treatment in cornea <400µm – Endothelial cell damage can occur – Irreversible corneal swelling and reduced vision Use of hypotonic riboflavin to swell the cornea – Cornea still needs to be >400µm during the UVA stage

13. Thin corneas - Melbourne Randomised, controlled trial Corneal thickness: 330-400µm CXL group - 8 eyes Control - 10 eyes 4 year results analysed – Progression >1D Control group: 5 out of 10 eyes CXL group: 0 out of 8 eyes

14. 4 years: thin corneas – corneal curvature Control +1.76D CXL -1.16D Δ K steep (D) 1 yr2 yrs3 yrs4 yrs steeper (worse) flatter (better)

15. RVEEH paediatric study 9 eyes of 8 patients aged < 16 years old – Average 14 years old Follow-up > 12 months (average 2 years, 4 months) 2 progressed (increased corneal curvature) – Although only one person lost one line of vision

16. Other publications Overall, about 70-90% success rate in stabilising keratoconus Corneal curvature (keratometry) – Small improvements (ranging from mean -0.62 to -2.57D) Vision – About 80% studies report improvement in vision about 1-2 lines Paediatric patients – same vs not as sustainable improvement? Thin corneas - limited results in the scientific literature suggest stabilises KC after at least 12 months

17. COMPLICATIONS

18. Complications Scarring Infections Irreversible corneal swelling MedPIC Royal Victorian Eye & Ear Hospital

19. Acknowledgements Christine Wittig-Silva Grant Snibson Mark Whiting Laurence Sullivan Ben Connell Richard Lindsay Mario Constantinou Tony Wu Kiera Young Ecosse Lamauroux Amirul Islam Keratoconus Australia IROC (Switzerland) Emagin (Sydney) Eye Research Australia Foundation RVEEH Research Committee Contact Lens Society of Australia Private donors RVEEH Medical Photography and Imaging Centre RVEEH Pharmacy