New Vision Inc., Taipei 103, China(Juiteng Lin); China Medical University, Taichung 404, China (Da-chuan Cheng); Taipei Nobel Eye Institute, Taipei 101, China (Chaokai Chang); Department of Ophthalmology, Shandong Provincial Hospital, Shandong University, Jinan 250021, China (Zhang Yong)
Objective To discuss the critical issues of the dynamics of UV-light-photoinitiated cross-linking in corneal collagen (CXL) and to confirm the dynamics of riboflavin (vitamin-B2) absorption under UV light. Methods Coupled dynamic equations are numerically solved and analytic formulas are derived for three critical parameters: the safe depth (z*), the safe dose (E*) and the cross-linking time (t*). Time-dependent absorption of UV light due to the depletion of the initiator is measured and shown by a dynamic spectrum of riboflavin. The critical issues of CXL are explored by seven parameters: the extinction coefficient, concentration, the penetration depth of the riboflavin, the UV light intensity and dose, irradiation duration, and corneal thickness. Results The safe dose (E*) has a wide range from 2.3 to 8.2 (J/cm2) for riboflavin concentrations of 0.1% to 0.2% and penetration depths of 0.02 to 0.04 cm. It is shown by mathematical modeling that a higher light intensity and extinction coefficient lead to shorter t* for a given cross-linking depth, while t* increases with corneal thickness (z*). The safety depth decreases as a function of the extinction coefficient and initiator concentration. Conclusion A new cross-linking protocol is suggested based on new findings, which include the safe depth (z*), the safe dose (E*), the cross-linking time (T*), and the safe riboflavin concentration.
Odian G. Principles of Polymerization[M]. New York: Wiley,1991.
[2]
Miller GA, Gou L, Narayanan V, et al. Modeling of photobleaching for the photoinitiation of thick polymerization systems[J]. J Polym Sci Pol Chem,2002,40(6):793-808.
[3]
Terrones G, Pearlstein AJ. Effects of optical attenuation and consumption of a photobleaching initiator on local initiation rates in photopolymerizations[J]. Macromolecules.,2001,34(10):3195-3204.
[4]
Stephenson N, Kriks D, El-Maazawi M, et al. Spatial and temporal evolution of the photo initiation rate for thick polymer systems illuminated on both sides[J]. Polym Int,2005,54(10):1429-1439.
[5]
Meek KM, Hayes S. Corneal cross-linking—A review[J]. Ophthalmic Physiol Opt,2013,33(2):78-93.
[6]
Kamaev P, Friedman MD, Sherr E, et al. Photochemical kinetics of corneal cross-linking with riboflavin[J]. Invest Ophthalmol Vis Sci,2012, 53(4):2360-2367.
[7]
Sondergaard AP, Hjortdal J, Breitenbach T, et al. Corneal distribution of riboflavin prior to collagen cross-linking[J]. Curr Eye Res,2010,35(2):116-121.
[8]
Chai D, Gaster RN, Roizenblatt R, et al. Quantitative assessment of UVA-riboflavin corneal cross-linking using nonlinear optical microscopy[J]. Invest Ophthalmol Vis Sci,2011,52(7):4231-4238.
[9]
Spoerl E, Mrochen M, Sliney D, et al. Safety of UVA-riboflavin cross-linking of the cornea[J]. Cornea,2007,26(4):385-389.
[10]
Lamy R, Chan E, Zhang H, et al. Ultrasound-enhanced penetration of topical riboflavin into the corneal stroma[J]. Invest Ophthalmol Vis Sci,2013,54(8):5908-5912.
[11]
Wollensak G, Spoerl E, Wilsch M, et al. Endothelial cell damage after riboflavin-ultraviolet-A treatment in the rabbit[J]. J Cataract Refract Surg,2003,29(29):1786-90.
[12]
Wernli J, Schumacher S, Spoer E, et al. The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time[J]. Invest Ophthalmol Vis Sci,2013,54(2):1176-1180.
[13]
Schumacher S, Mrochen M, Spoerl E. Absorption of UV-light by riboflavin solutions with different concentration[J]. J Refract Surg,2012,28(2):91-92.
[14]
Koppen C, Gobin L, Tassignon MJ. The absorption characteristics of the human cornea in ultraviolet-a crosslinking[J]. Eye Contact Lens,2010,36(2):77-80.
Schumacher S, Mrochen M, Wernli J, et al. Optimization model for UV-riboflavin corneal cross-linking[J]. Invest Opthalmol Vis Sci,2012,53(2):762-769.
[17]
Lin JT, Liu HW, Cheng DC. Modeling the kinetics of enhanced photo-polymerization by a collimated and a reflecting focused UV laser[J]. Polymers,2014,6(5):1489-1501.
[18]
Lin JT, Cheng DC. Optimal focusing and scaling law for uniform photo-polymerization in a thick medium using a focused UV laser[J]. Polymers,2014,6(2):552-564.
[19]
Lin JT. Analysis on the critical issues of UV light induced corneal cross linking[J]. Int J Latest Res Eng Comp,2013,1:104-110.
[20]
Lin, JT, Liu HW, Cheng DC. On the dynamic of UV-light initiated corneal cross linking[J]. Med Biolog Eng,2014,34(3):247-250.
[21]
Tian C, Peng X, Fan Z, et al. Corneal collagen cross-linking in keratoconus: A systematic review and meta-analysis[J]. Sci Rep,2014,4:5652.
[22]
Mazzotta C, Traversi C, Caragiuli S, et al. Pulsed vs continuous light accelerated corneal collagen crosslinking: In vivo qualitative investigation by confocal microscopy and corneal OCT[J]. Eye,2014,28(10):1179-1183.
[23]
Freidman MD, et al. Systems and methods for corneal cross-linking with pulsed light[P]. US Patent Publication number WO2014014521 A1(2014).
[24]
Balidis M, Konidaris VE, Ioannidis G, et al. Femtosecond-assisted intrastromal corneal cross-linking for early and moderate keratoconus[J]. Eye,2014,28(10):1258-1260.
[25]
Bikbova G1, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin[J]. Acta Ophthalmol,2014,92(1):e30-34.
[26]
Muller D, Marshall J, Friedman MD, et al. Controlled cross-linking initiation and corneal topography feedback systems for directing cross-linking[P]. US Patent Publication number EP2712311A1(2014).
[27]
Kamaev P, Friedman MD, Sherr E, et al. Photochemical Kinetics of corneal cross-linking with riboflavin[J]. Invest Ophthalmol Vis Sci,2012, 53(4):2360-2367.