Transepithelial Crosslinking vs. Corneal Pocket Crosslinking Christoph Kranemann MD Anna Yu OD Rome 2013
We have no financial interests in this presentation.
Corneal collagen cross linking Creates new covalent cross-links between collagen fibrils in the stroma Riboflavin (photo sensitizer) Shield for UVA penetration to underlying tissue Increase corneal uv absorption from 30 to 95% In reaction with 370nm wavelength UV light and oxygen produce a photo-oxidative reaction Up to four fold increase in inter-collagen connections Stiffens anterior cornea more than posterior Significant refractive effect when applied as full Cxl Minimum corneal thickness (bed) 400 microns vs. 325 microns (Avedro) Wollensak et al., Salgado et al.
Traditional Indications Keratoconus Iatrogenic corneal ectasia Pellucid Marginal degeneration Bullous Keratopathy Infectious keratitis (melting) Used in combination with topography-guided PRK to reshape and stabilize the cornea in keratoconus patients Suggested as additional treatment for patients with fruste keratoconus, undergoing refractive surgery or patients with greater 8 diopter correction
Side effects Prolonged healing of epithelium often longer than post primary PRK Prolonged stromal haze and steroid use 3/12 Risk of steroid induced IOP spike at least 20-40% Postop infection risk including herpetic keratitis Postop sterile corneal opacities 2.2-2.8% Progressive corneal melts requiring PKP Koller et al., Kanellopoulos
Transepithelial Crosslinking No need for epithelial restoration Minimal if any infection risk Minimal if any corneal haze Much shorter steroid use 2-3/52 No sterile opacities and much lower if any infection risk Use of some chemical epithelial bond disruptor to improve riboflavin dye penetration Epithelial dye uptake and UV uptake Less oxygen availability in stroma for crosslinking action Fillippello et. al., Spadea et al., Magli et al.
Corneal Pocket Crosslinking (CPC) Femtosecond pocket at 100 to 120 microns with 3 mm sidecut superiorly Standard protocol of dye placed into pocket with cannula Minimal if any dye absorbtion of epithelium Slightly greater potential for oxygen availability Pulsed energy delivery to optimize oxygen availability Seeking to preserve advantages of transepithelial crosslinking yet obtaining greater treatment effect more akin to epithelium-off crosslinking
Methods Prospective and consecutive cohort of patients who underwent transepithelial crosslinking or pocket crosslinking Pockets 100 to 120 microns Minimum corneal Thickness 350 microns The treatment involved a 12 min exposure to riboflavin 0.25% solution with 1% Proparacain/HPMC/BAC/EDTA/TRIS and exposed to UVA with 45 mw/cm² for 2:40 min OR 5:20 min for pulsed. For a total energy of 7.40 J/cm² Preop topography itrace and Galilei, wavefront itrace Riboflavin 0.25%, 1% proparacaine, HPMC, BAC, EDTA, TRIS every 30 seconds for 12 minutes PF OU qid for 2/52 and Tobradex ung OU qhs x 1/52 Postop Vision corrected and uncorrected and topographies were recorded At day 1, week 1, month 1, 3, 6, 12 and 18
Transepithelial crosslinking versus pocket crosslinking Transepithelial Cxl Pocket Cxl 20 eyes Mean age 24.75 years old Range 11 to 52 years old Diagnosis KC 15 PMD 4 KERATOECTASIA 1 10 eyes Mean age 29.5 years old Range 18 to 46 years old Diagnosis KC 8 PMD 1 KERATOECTASIA 1
Preop Transepithelial Mean uncorrected Va 20/150 Mean corrected Va 20/50 Mean K 50.54 +/- 4.48 Steep K 53.02 +/- 5.25 Flat K 48.12 +/- 3.96 Pocket Mean uncorrected Va 20/200 Mean corrected Va 20/50 Mean K 51.22 +/- 4.25 (NS) Steep K 53.70 +/- 4.95 Flat K 48.54 +/- 4.12 (NS)
Results 1 month Transepithelial Mean uncorrected Va 20/60 Mean corrected Va 20/28 Mean K s 49.72 +/- 4.05 Steep K 52.38 +/- 4.95 Flat K 47.96 +/- 4.04 Pocket Mean uncorrected Va 20/200 Corrected Va 20/40 Mean K s 50.72 +/- 4.05 Steep K s 53.30 +/- 4.55 Flat K s 48.34 +/- 4.22
Results 12 months Transepithelial Mean uncorrected Va 20/70 Corrected Va 20/32 Mean K s 49.95 +/- 4.55 Steep K 52.58 +/- 5.05 Flat K 48.15 +/- 4.04 Pocket Mean uncorrected Va 20/70 Corrected Va 20/30 Mean K s 49.84 +/- 4.20 Steep K 52.32 +/- 4.25 Flat K 47.98 +/- 4.12
18 months results Transepithelial Mean uncorrected Va 20/100 Mean corrected Va 20/50 Mean K s 50.68 +/- 4.25 Steep K 53.24 +/- 4.02 Flat K 48.34 +/- 4.04 Pocket Not yet available
Results 51.5 51 50.5 50 Series 1 49.5 Series 2 49 48.5 Column1 Series 2 Column1 preop 1 month 12 months 18 months Series 1
Results K E Epithelium on/ K P Pocket/ K C Epithelium off 60 59 58 57 56 55 54 53 52 51 50 49 48 47 46 45 44 43 42 41 40 Preop Month 1 Month 12 Month 18 K E K P K C
Differences Transepithelial No haze 5/12 mild SPK x 1/52 Effectively back to normal at 1/52 Largely lost treatment effect at 18 months Initially better effect but not maintained too superficial Pocket Initial haze up to 8 weeks Steroids x 8 weeks 1/10 steroid responder Microstriae in pocket roof Treatment effect increasing over time Treatment effect likely deeper and prolonged
Conclusion Epithelium on crosslinking has an excellent safety profile Longterm efficacy of pure epithelium on crosslinking has to be questioned and corneal pocket crosslinking (CPC) holds promise Tradeoff is reappearance of haze and microstriae Alternative repeat Epi-on Crosslinkings every 18-24 months still safest for pediatric population Potential role for pulsed crosslinking with either approach Potential for increasing soak time and possibly treatment time with Epi-on approach We need long term studies
References Filippello,M, Stagni,E, O Brart,D. Transepithelial corneal collagen crosslinking:bilateral study. J Cataract Refrct Surg 2012. 38: 283-291; Filippelll, Stagni,E, Bucco,Maoliero,D, Bonfiglio,V, Avitabile,T. Transepithelial cross-linking in keratoconus patients:confocanalysis. Optom Vis Sci 2012. 89: e1-e7; Kanellopoulos, AJ. Long term results of a prospective randomized bilateral eye comparion trial of higher fluence, shorter duration ultraviolet A radiation, and riboflavin collagen cross linking for progressive keratoconus. Clinical Ophthalmology 2012; Koller,T, Mrochen,M, Seiler,T. Complication and failure rates after corneal crosslinking. J Cataract Refract surg 2009. 35:1358-136; Magli,A, Forte,R, Tortori,A, Capasso,L, Marsico,G, Piozzi,E. Epithilium-off collagen cross-linking versus transepithelial cross-linking for pediatric keratoconus. Cornea 2012. 0:1-5; Salgado,JP, Khoramnia,R, Lohmann, CP, Winkler von Mohrenfels,C. Corneal collagen crossliking in post-lasik keratectasia. Br J Ophthalmol 2001. 95:493-497 Spadea,L, Mencucci,R. Transepithelial corneal collagen cross-linking in ultrathin keratoconic corneas. Clinical Ophthalmology 2012 6:1785-1892 Wollensak,G, Spoerl,E, Seiler,T. Riboflavin/ultraviolet-A-induced cross-linking for the treatment of keratoconus. Am J Ophthalmol 2003. 135:620-627