Optimization of Oxygen Dynamics, UV-A Delivery, and Drug Formulation for Accelerated Epi-On Corneal Crosslinking

References

• Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620–27. doi:10.1016/S0002-9394(02)02220-1.
   PubMed Web of Science ®Google Scholar
• Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998 Jan;66(1):97–103. doi:10.1006/exer.1997.0463.
   PubMed Web of Science ®Google Scholar
• Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK. United States multicenter clinical trial of corneal collagen crosslinking for keratoconus treatment. Ophthalmology. 2017;124(9):1259–70. doi:10.1016/j.ophtha.2017.03.052.
   PubMed Web of Science ®Google Scholar
• Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK. U.S. multicenter clinical trial of corneal collagen crosslinking for treatment of corneal ectasia after refractive surgery. Ophthalmology. 2017;124(10):1475–84. doi:10.1016/j.ophtha.2017.05.036.
   PubMed Web of Science ®Google Scholar
• Kanellopoulos AJ. Novel myopic refractive correction with transepithelial very high fluence cross-linking applied in a customized pattern: early results of a feasibility study. Clin Ophthalmol. 2014;8:1–6.
   PubMedGoogle Scholar
• Lim WK, Da Soh Z, Choi HKY, Theng JTS. Epithelium-on photorefractive intrastromal cross-linking (PiXL) for reduction of low myopia. Clin Ophthalmol. 2017;11:1205–11. doi:10.2147/OPTH.S137712.
   PubMed Web of Science ®Google Scholar
• Elling M, Kersten-gomez I, Dick HB. Photorefractive intrastromal corneal cross-linking for the treatment of refractive errors: six-month interim findings. J Cart Refract Surg. 2017;43(6):789–95. doi:10.1016/j.jcrs.2017.03.036.
   PubMed Web of Science ®Google Scholar
• Febo ME, Kersten-gomez I, Dick HB. Photorefractive intrastromal corneal crosslinking for treatment of myopic refractive error: findings from 12-month prospective study using an epithelium-off protocol. J Cart Refract Surg. 2018;44(4):487–95. doi:10.1016/j.jcrs.2018.01.022.
   PubMed Web of Science ®Google Scholar
• El Hout S, Cassagne M, Sales de Gauzy T, Galiacy S, Malecaze F, Fournié P. Transepithelial photorefractive intrastromal corneal crosslinking versus photorefractive keratectomy in low myopia. J Cataract Refract Surg. 2019;45(4):427–36. doi:10.1016/j.jcrs.2018.11.008.
   PubMed Web of Science ®Google Scholar
• Nordström M, Schiller M, Fredriksson A, Behndig A. Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br J Ophthalmol. 2017 Jul;101(7):920–925. doi:10.1136/bjophthalmol-2016-309210.
   Web of Science ®Google Scholar
• Cassagne M, Pierné K, Galiacy SD, Asfaux-Marfaing M-P, Fournié P, Malecaze F. Customized topography-guided corneal collagen cross-linking for keratoconus. J Refract Surg. 2017;33(5):290–97. doi:10.3928/1081597X-20170201-02.
   PubMed Web of Science ®Google Scholar
• Mazzotta C, Moramarco A, Traversi C, Baiocchi S, Iovieno A, Fontana L. Accelerated corneal collagen cross-linking using topography-guided UV-A energy emission: preliminary clinical and morphological outcomes. J Ophthalmol. 2016;2016:1–10. doi:10.1155/2016/2031031.
   Web of Science ®Google Scholar
• Seiler TG, Fischinger I, Koller T, Zapp D, Frueh BE, Seiler T. Customized corneal cross-linking: one-year results. Am J Ophthalmol. 2016;166:14–21. doi:10.1016/j.ajo.2016.02.029.
   PubMed Web of Science ®Google Scholar
• ShettyR, PahujaN, RoshanT, DeshmukhR, FrancisM, GhoshA, Sinha RoyA. Customized corneal crosslinking using different UVA beam profiles customized corneal crosslinking using different UVA beam profiles. J Refract Surg. 2017;33(10):676–82. doi:10.3928/1081597X-20170621-07.
   PubMed Web of Science ®Google Scholar
• Koppen C, Wouters K, Mathysen D, Rozema J, Tassignon M-J. Refractive and topographic results of benzalkonium chloride-assisted transepithelial crosslinking. J Cataract Refract Surg. 2012 Jun;38(6):1000–05. doi:10.1016/j.jcrs.2012.01.024.
   PubMed Web of Science ®Google Scholar
• Alhamad TA, O’Brart DPS, O’Brart NAL, Meek KM. Evaluation of transepithelial stromal riboflavin absorption with enhanced riboflavin solution using spectrophotometry. J Cataract Refract Surg. 2012 May;38(5):884–89. doi:10.1016/j.jcrs.2011.11.049.
   PubMed Web of Science ®Google Scholar
• Raiskup F, Pinelli R, Spoerl E. Riboflavin osmolar modification for transepithelial corneal cross-linking. Curr Eye Res. 2012;37(3):234–38. doi:10.3109/02713683.2011.637656.
   PubMed Web of Science ®Google Scholar
• Gatzioufas Z, Sabatino F, Angunawela R. Tetracaine-enhanced transepithelial corneal collagen crosslinking. J Cataract Refract Surg. 2016;42(7):1106. doi:10.1016/j.jcrs.2016.06.021.
   PubMed Web of Science ®Google Scholar
• Torricelli AAM, Ford MR, Singh V, Santhiago MR, Dupps WJ, Wilson SE. BAC-EDTA transepithelial riboflavin-UVA crosslinking has greater biomechanical stiffening effect than standard epithelium-off in rabbit corneas. Exp Eye Res. 2014 Aug;125:114–17. doi:10.1016/j.exer.2014.06.001.
   PubMed Web of Science ®Google Scholar
• Spadea L, Mencucci R. Transepithelial corneal collagen cross-linking in ultrathin keratoconic corneas. Clin Ophthalmol. 2012;6(1):1785–92. doi:10.2147/OPTH.S37335.
   PubMedGoogle Scholar
• Lesniak SP, Hersh PS. Transepithelial corneal collagen crosslinking for keratoconus: six-month results. J Cataract Refract Surg. 2014 Dec;40(12):1971–79. doi:10.1016/j.jcrs.2014.03.026.
   PubMed Web of Science ®Google Scholar
• Touboul D, Efron N, Smadja D, Praud D, Malet F, Colin J. Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus. J Refract Surg. 2012;28(11):769–76. doi:10.3928/1081597X-20121016-01.
   PubMed Web of Science ®Google Scholar
• Al Fayez MF, Alfayez S, Alfayez Y. Transepithelial versus epithelium-off corneal collagen cross-linking for progressive keratoconus: a prospective randomized controlled trial. Cornea. 2015;34 Suppl 1(10):S53–6. doi:10.1097/ICO.0000000000000547.
   Web of Science ®Google Scholar
• Filippello M, Stagni E, Buccoliero D, Bonfiglio V, Avitabile T. Transepithelial cross-linking in keratoconus patients: confocal analysis. Optom Vis Sci. 2012 Oct;89(10):e1–7. doi:10.1097/OPX.0b013e318264cc62.
   PubMed Web of Science ®Google Scholar
• Zhang X, Sun L, Chen Y, Li M, Tian M, Zhou X. One-year outcomes of pachymetry and epithelium thicknesses after accelerated (45 mW/cm2) transepithelial corneal collagen cross-linking for keratoconus patients. Sci. Rep. 2016 Sep 6;6:32692. doi: 10.1038/srep32692..
   Google Scholar
• Artola A, Ruiz-fortes P, Soto-negro R. Clinical outcomes at one year following keratoconus treatment with accelerated transepithelial cross-linking. Int J Ophthalmol. 2017;10(4):652–55. doi:10.18240/ijo.2017.04.10.
   PubMed Web of Science ®Google Scholar
• Shen Y, Jian W, Sun L, Li M, Han T, Son J, Zhou X. One-year follow-up of changes in corneal densitometry after accelerated (45 mW/cm2) transepithelial corneal collagen cross-linking for keratoconus: a retrospective study. Cornea. 2016;35(11):1434–40. doi:10.1097/ICO.0000000000000801.
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhao J, Li M, Tian M, Shen Y, Zhou X. Conventional and transepithelial corneal cross-linking for patients with keratoconus. PLoS One. 2018;13:1–15.
   Web of Science ®Google Scholar
• Kır MB, Türkyılmaz K, Öner V. Transepithelial high-intensity cross-linking for the treatment of progressive keratoconus: 2-year outcomes. Curr Eye Res. 2017;42(1):28–31. doi:10.3109/02713683.2016.1148742.
   PubMed Web of Science ®Google Scholar
• Vinciguerra P, Randleman JB, Romano V, Legrottaglie EF, Rosetta P, Camesasca FI, Piscopo R, Azzolini C, Vinciguerra R. Transepithelial Iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg. 2014;30(11):746–53. doi:10.3928/1081597X-20141021-06.
   PubMed Web of Science ®Google Scholar
• Torres-Netto EA, Kling S, Hafezi N, Vinciguerra P, Randleman JB, Hafezi F. Oxygen diffusion may limit the biomechanical effectiveness of Iontophoresis-assisted transepithelial corneal cross-linking. J Refract Surg. 2018;34(11):768–74. doi:10.3928/1081597X-20180830-01.
   PubMed Web of Science ®Google Scholar
• Mazzotta C, Bagaglia SA, Vinciguerra R, Ferrise M, Vinciguerra P. Enhanced-fluence pulsed-light iontophoresis corneal cross-linking: 1-year morphological and clinical results. J Refract Surg. 2018;34(7):438–44. doi:10.3928/1081597X-20180515-02.
   PubMed Web of Science ®Google Scholar
• Cassagne M, Laurent C, Rodrigues M, Galinier A, Spoerl E, Galiacy SD, Soler V, Fourni P, Malecaze F. Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Investig Ophthalmol Vis Sci. 2016;57(2):594–603. doi:10.1167/iovs.13-12595.
   PubMed Web of Science ®Google Scholar
• Gore DM, O’Brart DP, French P, Dunsby C, Allan BD. A comparison of different corneal iontophoresis protocols for promoting transepithelial riboflavin penetration. Invest Ophthalmol Vis Sci. 2015;56(13):7908–14. doi:10.1167/iovs.15-17569.
   PubMed Web of Science ®Google Scholar
• Arboleda A, Kowalczuk L, Savoldelli M, Klein C, Ladraa S, Naud MC, Aguilar MC, Parel JM, Behar-Cohen F. Evaluating in vivo delivery of riboflavin with Coulomb-controlled iontophoresis for corneal collagen cross- linking: a pilot study. Investig Ophthalmol Vis Sci. 2014;55(4):2731–38. doi:10.1167/iovs.14-13931.
   PubMed Web of Science ®Google Scholar
• Kamaev P, Friedman MD, Sherr E, Muller D. Photochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci. 2012 Mar;53(4):2360–67. doi:10.1167/iovs.11-9385.
   PubMed Web of Science ®Google Scholar
• Muller D, Kamaev P, Friedman M, Sherr E, Eddington W. Accelerated UVA-RF corneal cross-linking through pulsed UVA Illumination and oxygen rich environments. Invest Ophthalmol Vis Sci. 2013 Jun;54(15):5281.
   PubMed Web of Science ®Google Scholar
• Kamaev P, Smirnov M, Friedman M, Sherr E, Muller D. Aggregation and photoreduction in anaerobic solutions of flavin mononucleotide. J Photochem Photobiol A Chem. 2015;310:60–65. doi:10.1016/j.jphotochem.2015.04.025.
   Web of Science ®Google Scholar
• Richoz O, Hammer A, Tabibian D, Gatzioufas Z, Hafezi F. The biomechanical effect of corneal collagen cross-linking (CXL) with Riboflavin and UV-A is oxygen dependent. Transl Vis Sci Technol. 2013 Nov;2(7):6. doi:10.1167/tvst.2.7.6.
   PubMed Web of Science ®Google Scholar
• Kling S, Richoz OO, Hammer A, Tabibian D, Jacob S, Agarwal A, Hafezi F. Increased biomechanical efficacy of corneal cross-linking in thin corneas due to higher oxygen availability. J Refract Surg. 2015;31(12):840–46. doi:10.3928/1081597X-20151111-08.
   PubMed Web of Science ®Google Scholar
• Stulting RD, Trattler WB, Woolfson JM, Rubinfeld RS. Corneal crosslinking without epithelial removal. J Cataract Refract Surg. 2018;44(11):1363–70.
   PubMed Web of Science ®Google Scholar
• Rubinfeld RS, Stulting RD, Gum GG, Talamo JH. Quantitative analysis of corneal stromal riboflavin concentration without epithe- lial removal. J Cataract Refract Surg. 2018 Feb;44(2):237–242.
   Web of Science ®Google Scholar
• Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Epithelial thickness in the normal cornea: three-dimensional display with very high frequency ultrasound. J Refract Surg. 2008;24(6):571–81. doi:10.3928/1081597X-20080601-05.
   PubMed Web of Science ®Google Scholar
• Freeman RD. Oxygen consumption by the component layers of the cornea. J Physiol. 1972;225:15–32. doi:10.1113/jphysiol.1972.sp009927.
   PubMed Web of Science ®Google Scholar
• Diakonis VF, Likht NY, Yesilirmak N, Delgado D, Karatapanis AE, Yesilirmak Y, Fraker C, Yoo SH, Ziebarth NM. Corneal elasticity after oxygen enriched high intensity corneal cross linking assessed using atomic force microscopy. Exp Eye Res. 2016 Dec;153:51–55. doi:10.1016/j.exer.2016.10.013.
   PubMed Web of Science ®Google Scholar
• Kolozsva L, No A, Bor Z. UV absorbance of the human cornea in the 240- to 400-nm. Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2165–8.
   Google Scholar
• Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007 May;26(4):385–89. doi:10.1097/ICO.0b013e3180334f78.
   PubMed Web of Science ®Google Scholar
• Wollensak G, Aurich H, Wirbelauer C, Sel S. Significance of the riboflavin film in corneal collagen crosslinking. J Cataract Refract Surg. 2010 Jan;36(1):114–20. doi:10.1016/j.jcrs.2009.07.044.
   PubMed Web of Science ®Google Scholar