1. CROSS LINKING PLUS: COMBINATION TREATMENT FOR KERATOCONUS Andreja Veselica, Franc Šalamun Medical Centre Vid, Nova Gorica, Slovenia

2. CROSS LINKING PLUS Adjuvant REFRACTIVE TREATMENT in combination with CXL TREATMENT IMPROVED FUNCIONAL VISION TISSUE SAVING APPROACHES: 1. CORNEAL RINGS 2. TORIC IOL 3. CONDUCTIVE KERATHOPLASTY TISSUE REMOVAL APPROACHE: PRK CORNEAL BIOMECHANICAL STABILITY

3. CLINICAL OUTCOME AFTER CXL + PRK PROCEDURE  The purpose of our study was to evaluate visual acuity and topographic outcome after the CXL+PRK surgery, and to compare our results with the data from the literature  Retrospective analysis of operating and medical records of patients operated with CXL + PRK between 2008 and 2016

4. CLINICAL OUTCOME AFTER CXL + PRK PROCEDURE - RESULTS  37 eyes were submitted to CXL + PRK procedure between 2008 and 2016  26 eyes with progressive and stable keratoconus were enrolled in the study  Mean age - 32,5 years (from 14 to 56 years)  Mean follow up - 35 mouths (from 5 to 77 mouths)  Pre operative mean cornea thickness at the thinnest point 459,39 µm (393- 543 µm)  Mean ablation stromal depth 28,37 µm ( 15-50 µm )

5. CLINICAL OUTCOME AFTER CXL + PRK PROCEDURE VISUAL ACUITY OUTCOME - UDVA STUDYPRE OPERATIVE UDVA (logMAR) POST OPERATIVE UDVA (logMAR) Salamun et al.0.7 (0.2)0.4 (0.4) Kymionis et al.0.99 (0.1)0.16 (0.7) Kanellopoulus et al.0.8 (0.18)0.3 (0.59) Allesio et al.0.6 (0.25)0.19 (0.6)

6. CLINICAL OUTCOME AFTER CXL + PRK PROCEDURE VISUAL ACUITY OUTCOME - BCVA STUDYPRE OPERATIVE BCDA (logMAR) POST OPERATIVE BCVA (logMAR) Salamun et al.0.5 (0.3)0.1 (0.8) Kymionis et al.0.21 (0.6)0.11(0.8) Kanellopoulus et al.0.2 (0.62)0.1(0.82) Allesio et al.0.06(1.0)0.03 (1.0)

7. TOPOGRAPHIC OUTCOME – reduction in mean K value CXL  Non randomized studies: Between 0.01 AND 3D  Randomized study: between 0.6D AND 2D PRK + CXL  Non randomized studies: between 2.5 and 3.5 D  Randomized studies: 2D Mean reduction in our study: 3.5D No progression – mean follow up 3 years

8. VISUAL ACUITY OUTCOME – CXL + PRK VS. CXL Photorefractive keratectomy followed by cross-linking versus cross-linking alone for management of progressive keratoconus- two-years follow-up (Giovanni Aessio, Milena l’Abbate, Carlo Sborgia, and Maria Gabriella la tegola ) Graph showing change in UDA in logMAR unit during postoperative follow-up in eyes treated by PRK/CXL group; deep gray line; n [ 17) and in eyes treated by CXL alone (CXL group; light gray line; n [ 17) for progressive keratoconus. Graph showing change in manifest refraction spherical equivalent (MRSE) during postoperative follow-up in PRK/CXL group; deep gray line; n [ 17) and in CXL group; light gray line; n [ 17) for progressive keratoconus. Diopters (D) ± standard deviation. mo(s) [ month(s); Preop [ before surgery. CXL + PRK: UDVA 〉 0.5 17.6% to 82.3% CXL: 17% UDVA 〉 0.5 unchanged

9. OUR PROTOCOL - PRK  7mm mechanical removal of the epithelium within the cone  Laser photoablation of 4.5 mm optical zone, flattening the area of the cone – myopic ablation  Ablation depth less then 50 μm  6.0 mm phototherapeutic keratectomy to remove 5 μm of stroma

10.  Impregnation of cornea with 0.1% riboflavin according to standard Dresden protocol Altered Dresden protocol:  Radiation within the cone  Customized 3mW/cm2 UVA (VEGA emitter) radiation reducing the radiation zone from 7 to 5 mm within the cone  oxygen OUR PROTOCOL - CROSS LINKING

11. CLINICAL CASES

12. 6 years follow up UDVA 0.1 0.7 BCVA 0.5 1.0 K mean △ 5.6 stable

13. CONCLUSION  CXL + PRK have shown to be safe and effective – 5 years follow up  CXL + PRK have shown to arrest the progression and improve visual function – topographic regularization and HOA reduction  Simultaneous CXL + PRK have shown better outcome then sequential procedure

14. SUBJECT OF DEBATE  Should we treat progressive and non progressive disease ?  Age?  Simultaneous or sequential procedure  Maximal ablation depth 50 microns  Minimal corneal thickness 400-500 microns

15. 52 years old Stable keratoconus + cataract PRK + CXL + IOL UDVA 0.1 1.0 K mean △ 3D

16. LITERATURE  Kanellopoulos AJ, Binder PS. Collagen cross-linking (CCL) with sequential topography-guided PRK; a temporizing alterna- tive for keratoconus to penetrating keratoplasty. Cornea 2007; 26:891–895  Kymionis GD, Portaliou DM, Diakonis VF, Kontadakis GA, Krasia MS, Papadiamantis AG, Coskunseven E, Pallikaris AI. Posterior linear stromal haze formation after simultaneous pho- torefractive keratectomy followed by corneal collagen cross- linking. Invest Ophthalmol Vis Sci 2010; 51:5030–5033. Available at: http://www.iovs.org/content/51/10/5030.full.pdf. Accessed December 15, 2014  Stojanovic A, Zhang J, Chen X, Nitter TA, Chen S, Wang Q. Topography-guided transepithelial surface ablation followed by corneal collagen cross-linking performed in a single com- bined procedure for the treatment of keratoconus and pellucid marginal degeneration. J Refract Surg 2010; 26:145–152  Alessio G, L’Abbate M, Sborgia C, La Tegola MG. Photorefrac- tive keratectomy followed by cross-linking versus cross- linking alone for management of progressive keratoconus: two-year follow-up. Am J Ophthalmol 2013; 155:54–65  Kymionis GD, Kontadakis GA, Kounis GA, Portaliou DM, Karavitaki AE, Magarakis M, Yoo S, Pallikaris IG. Simulta- neous topography-guided PRK followed by corneal collagen cross-linking for keratoconus. J Refract Surg 2009; 25:S807– S811.  Kanellopoulos AJ. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus. J Refract Surg 2009; 25(9):S812–S818.  O’Brart DPS, Chan E, Samaras K, Patel P, Shah SP. A rando- mised, prospective study to investigate the efficacy of riboflavin/ ultraviolet A (370 nm) corneal collagen cross-linkage to halt the progression of keratoconus. Br J Ophthalmol 2011; 95:1519– 1524. Available at: http://bjo.bmj.com/content/95/11/1519.full. pdf?sidZa585cf27-23ec-4a1a-be48- cdf9597f5584. Accessed December 15, 2014  Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR. A randomized controlled trial of corneal collagen cross-linking in progressive kerato- conus: Preliminary results. J Refract Surg 2008; 24:S720–S725  Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslink- ing for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg 2011; 37:149–160  Wittig-Silva C, Chan E, Islam FMA, Wu T, Whiting M, Snibson GR. A randomized, controlled trial of corneal collagen cross- linking in progressive keratoconus: three-year results. Ophthalmology 2014; 121:812–821

17. THANK YOU FOR YOUR ATTENTION WE HAVE STOPPED THE PROGRESSION YEAH, BUT MY VISION IS STILL BAD