First spanish presentation about Keraflex an crosslinking KXL done by Dr. Barraquer in SEO 2011

1. Simposio IMEX Nueva opción en elQueratocono Dr. Rafael I. Barraquer Titular de la Cátedra “J. Barraquer” IUB - UAB - Barcelona

2. Tratamiento del Queratocono Opciones actuales (Gafas), LC (RGP, especiales…) Implantes anulares (SAIC) Reticulación colágeno (CXL) Téc. combinadas (SAIC+CXL, PRK, LIOf, etc…) … Trasplantes (queratoplastia) Penetrante Laminar profunda (DALK) Prevención Evitar frotamiento ocular Genética… Opciones tradicionales (Gafas), LC clásicas (RGP) LC especiales, piggyback Queratoplastia penetrante Prevención ?

3. 3 ¿En quéconsiste el proc. Avedro? Una técnica combinada de moldeo corneal: Termoqueratoplastia anular por microondas “Keraflex” (Avedro - Vedera) Crosslinking acelerado x10 (Avedro KXL)

4. 4 La Termoqueratoplstia… Una técnica clásica… Con cauterio (1975…) Radiofrecuencia (“Queratoplastia conductiva”) Láser de Holmio … Microondas  Keraflex

5. Árbol de la Cirugía Querato-Refractiva Ambas Sustraer PRK, LASIK, etc Espesores Curvatura Queratofaquia Añadir Lentes Intracorn. REFRACCIÓN Queratotomías Relajar Retirar suturas Biomecánica Resección (suturada) Índice de Refracción Suturas compresivas Ocupación (Anillos) Tensar Retracción tejido (Termo, CK…) Lentes IC Polisulfona

6. 6 Termoqueratoplastia: mecanismo Retracción del colágeno por calentamiento Lo contrario de las técnicas relajantes: Si en periferia  aumenta la curvatura central (ttos. hipermetropía x Ls.Holmio) lo contrario a una Q.Radial Si en el centro (anillo pericentral)  aplana la curvatura central (Keraflex) lo contrario a un Intracor

7. 7 Termoqueratoplastia: problemas Tª de acción: crítica Si es escasa: no tendrá efecto Si es excesiva: desnaturaliza el colágeno  cede Seguridad: posible daño endotelial  Solventado con tecnologías dosificables: (calor < RF < MW < láser) Tendencia a la regresión se solventa asociando CXL

9. Keraflex treats myopia and keratoconus by the trans-epithelial application of a continuous ring of microwave energy applied in a toroidal pattern to the periphery of the cornea.

10. Alteration of the collagen in the periphery applies stress to the central cornea, causing flattening and the reduction of myopia.© Avedro 2009 MA-00005, Rev. A

11. The Vedera KXS for Performing Keraflex Touch screen for procedure programming and device operation Microwave energy applied for less than a second No loss of biomechanical integrity because there is no incision and no flap created during a Keraflex procedure Vedera KXS Patient Interface Pod (PIP) © Avedro 2009 MA-00005, Rev. A

12. Applicator and Targeting Stage With Disposables Applicator Targeting Stage Disposable Micro-tube Suction Set Disposable Applicator Cover Disposable Alignment Reticle © Avedro 2009 MA-00005, Rev. A

13. Cross-Sectional View Applicator End View Inner conductor Outer conductor Inner conductor Outer conductor Gap spacing Microwave energy Gap spacing Cornea Keraflex Applicator Design © Avedro 2009 MA-00005, Rev. A

14. Inner conductor Outer conductor Treatment lesion is Outside the visual axis Keraflex induces peripheral steepening causing central corneal flattening Microwave energy Courtesy of Prof. John Marshall SEMs of Keraflex Effect MA-00005, Rev. A

15. Keraflex Stromal lesion Keraflex Stromal lesion Post-Keraflex Lesion …SEM and Histology Histology Courtesy of Prof. John Marshall © Avedro 2009 MA-00005, Rev. A

16. Keraflex Procedure Once the patient’s prescription is entered, the Targeting Stage is centered on the pre-marked corneal apex and the vacuum is engaged © Avedro 2009 MA-00005, Rev. A

17. Keraflex Procedure With vacuum applied to the Targeting Stage, the Alignment Reticle is placed into the Targeting Stage and finely aligned to the corneal apex; once the Reticle is aligned to the apex, the Targeting Stage is locked Microscope view of the Reticle within the Targeting Stage and in position over the pre-marked corneal apex Knob motions to align Targeting Stage to apex: (Top) rotate for up-down alignment (Bottom) move up-down for side-to-side alignment © Avedro 2009 MA-00005, Rev. A

18. Keraflex Procedure With the Reticle removed, the Applicator is inserted into the Targeting Stage Applicator © Avedro 2009 MA-00005, Rev. A

19. Keraflex Procedure The Applicator is engaged and locked under software control © Avedro 2009 MA-00005, Rev. A

20. Keraflex Procedure The energy delivery unit within the Applicator is Advanced onto the eye under microprocessor control © Avedro 2009 MA-00005, Rev. A

21. Keraflex Procedure Internal control systems determine when proper mechanicaland electrical contact have been made © Avedro 2009 MA-00005, Rev. A

22. Keraflex Procedure Once the footswitch is depressed, micro-pulses of coolant are dispersed onto the eye providing thermal protection To the outer layer of the cornea © Avedro 2009 MA-00005, Rev. A

23. Keraflex Procedure In less than a second, microwave energy is applied to the cooled zone © Avedro 2009 MA-00005, Rev. A

24. Keraflex Procedure The resulting toroidal ring of collagen shrinkage causes the central cornea to flatten © Avedro 2009 MA-00005, Rev. A

25. 23

26. Immediately Post Keraflex Procedure © Avedro 2009

27. One-Day Post Keraflex Procedure © Avedro 2009

28. Keraflex for Keratoconus © Avedro 2009

29. Avedro’s KXL System for Accelerated Cross-Linking UVA light source with programmability from standard to accelerated power KXL Specifications CE Mark - Yes UV-A Wavelength - 365 nm Power Output - 3mW/cm2 to 30 mW/cm2 Energy density - Controlled to 5.4J/cm2 Beam Diameter – 9mm Other Features: Touch screen monitor Wireless remote control in the x, y, and z axis Battery or wall power Riboflavin: Isotonic 0.1% riboflavin Touch screen monitor for procedure programming and device operation Wireless X, Y, Z beam positioning and adjustable beam diameter Multi-position UVA light stable UVA light positioning MA-00057, Rev. A

31. Safety: 5-10 minute time soak time (depending on corneal thickness)

32. Predictability: Uniform beam profile (Consistent energy delivered across the cornea with superior depth of focus)MA-00057, Rev. A

33. Comparison of Cross-linking Times Speed Typical UVA Light source in current use Avedro KXL System 30 mW/cm2 3 min exposure 3 mW/cm2 30 min exposure 5J/cm2 Same Energy on Cornea MA-00057, Rev. A

34. Speed Corneal Biomechanics Wollensack G et al Others Avedro Increasing Stiffness Corneal Young’s Modulus/MPa UVA Cross-linked 3 mW/cm² UVA Cross-linked 30 mW/cm² Courtesy of Prof. John Marshall MA-00057, Rev. A

35. Equi-dose Extensiometry: Stress/Strain Speed There are no statistically significant biomechanical differences when Equi-dosing high UVA with shorter exposure time Adapted from Krueger, Spoerl, Herekar, Rapid vs. Standard Collagen CXL with Equivalent Energy Dosing. Original online presentation link: http://www.slideshare.net/Iogen/krueger-herekar-rapid-cross-linking MA-00057, Rev. A

36. Keratocyte and Endothelial Cell Viability Safety Endothelial cells show similar or better cell viability at higher irradiance for shorter time vs. lower irradiance for a longer time 30mW/cm2 – 3 Min 3mW/cm2 – 30 Min Courtesy of Prof. John Marshall Courtesy of Prof. John Marshall *Optical Density MA-00057, Rev. A

37. Endothelium Safety Concerns are Related to … UVA & Riboflavin Interaction, NOT UVA Alone Safety CXL: 30 minute pre-soak; 30 minute UVA @ 3 mW/cm² KXL: 10 minute pre-soak; 3 minute UVA @ 30 mW/cm² KXL: 5 minute pre-soak; 3 minute UVA @ 30 mW/cm² Two important considerations when performing cross-linking: Have enough riboflavin in the anterior stroma for cross-link formation 2. Limit the UVA absorption by the riboflavin adjacent to the endothelium KXL accelerated crosslinking at 300-325 μm has the same relative absorption as standard cross-linking at 400-425μm MA-00057, Rev. A

38. Uniformity is Key to Consistent Cross-linking Predictability 3 mW/cm2 typical UVA light in current use 30 mW/cm2 KXLSystem 9 mm Aperture Bowman’s Center to edge beam uniformity insures consistent results Cool edges provide no cross-linking Endothelium MA-00057, Rev. A

39. Beam Profiles for KXL and UV-X Light Sources Predictability +5mm Out of Plane At Focus -5mm Out of Plane Avedro KXL UV-X MA-00057, Rev. A

40. Beam Profiles for KXL and UV-X Light Sources Predictability +5mm Out of Plane At Focus -5mm Out of Plane Avedro KXL UV-X MA-00057, Rev. A

41. Impact of Beam Profile and Riboflavin Shielding Predictability UV-X - Treatment 30 minute pre-soak; 30:00 Min. @ 3mW/cm2 KXL Treatment: 10 minute presoak; 3:00Min. @ 30 mW/cm2 Avedro KXL System UVA Dose Absorbed by Riboflavin vs. Corneal Depth In Various Radial Zones Nominally Focused Conventional UVX System UVA Dose Absorbed by Riboflavin vs. Corneal Depth In Various Radial Zones Nominally Focused Central 3 mm zone: Irradiance 30 mW/cm² Central 3 mm zone + shielding due to Riboflavin/Dextran layer 3 mm - 7 mm zone: Irradiance 30 mW/cm² 3 mm – 7 mm zone + shielding due to Riboflavin/Dextran layer 7mm – 9 mm zone: Irradiance 30 mW/cm² 7 mm – 9 mm zone + shielding due to Riboflavin/Dextran layer MA-00057, Rev. A

42. 38 Caso 1 (GhO HC 1.030.371) Mujer 28 a. no ve bien desde 5-6 a. antes Usa LC RGP d. hace 1 a. (mala tolerancia) Dx de “Queratocono” reciente OD: AVSC= 0,1 165º-5 -3= 0,5 Nº1 O I: AVSC= 0,02 5º-12-9= 0,3 Nº2 Indicación: OD: Ks = 47-52 D  SAIC (2x 6mm 120ºx 200mm) O I: Ks = 48-60 D Querato?  Keraflex+KXL

43. 39 Preoperatorio

44. 40 Preoperatorio C Rx: Keraflex -5 D + KXL 30mW x 3 min

45. 41 Postop 1 día

46. 42 Postop 1 día

47. 43 Postop 1 semana

48. 44 Postop 1 semana

49. 45 Postop 1 semana

50. 46 Postop 1 semana

53. Discusión 49 Comparado con Segmentos IC, Keraflex presenta: Más simple / rápido(>eficiencia) Menor manipulación(<invasividad ?) Mayor capacidad de cambio (queratométrico) No es reversible (sí dosificable) Menos versátil (sólo anillo 360º)

54. Perspectivas 50 AvedroKeraflex +KXL se perfila como una nueva alternativa en el tratamiento conservador del queratocono. Su versatilidad podría mejorarse habilitando tratamientos sectoriales (180º, 120º, 90º…) que permitiesen combinaciones comparables a las de los segmentos IC. La Avedro-KXL acelerada parece mejorar en gran medida la eficiencia del procedimiento clásico sin perder eficacia ni seguridad. Se proponen aplicaciones novedosas de la KXL como la profilaxis inmediata de la ectasia tras LASIK en córneas finas (“LASIK Xtra”: 1,25 min UVA tras 1 min Riboflavina)

55. Muchas Gracias