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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 1/2016

01-01-2016 | Basic Science

Scleral cross-linking by riboflavin and blue light application in young rabbits: damage threshold and eye growth inhibition

Authors: Hans Peter Iseli, Nicole Körber, Christian Koch, Anett Karl, Anja Penk, Daniel Huster, Andreas Reichenbach, Peter Wiedemann, Mike Francke

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 1/2016

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Abstract

Background

Scleral cross-linking (SXL) by riboflavin and light application has been introduced as a possible treatment to increase scleral tissue stiffness and to inhibit excessive axial elongation of highly myopic eyes. We evaluated an ocular tissue damage threshold for blue light irradiation, and used SXL treatment to induce eye growth inhibition.

Methods

The sclera of 3-week-old rabbits (39 pigmented and 15 albino rabbits) were treated with different blue light intensities (450 ± 50 nm) and riboflavin. Alterations and a damage threshold were detected in ocular tissues by means of light microscopy and immunohistochemistry. The influence of SXL on the eye growth was examined in 21 young rabbits and was measured by using A-scan ultrasonography, micrometer caliper, and for selected eyes additionally by MR imaging.

Results

Light microscopic examinations demonstrated degenerative changes in ocular tissue after irradiation with blue light intensities above 400 mW/cm2 (with and without riboflavin application). Therefore, that light intensity was defined as the damage threshold. Tissue alteration in retina, choroid, and sclera and activation of retinal microglia cells and Müller cells could be earlier observed at blue light intensities of 150 and 200 mW/cm2. Albino rabbits were less sensitive to this SXL treatment. A significant reduction of the eye growth could be detected by SXL treatment with the minimal efficient blue light intensity of 15 mW/cm2 and maintained stable for 24 weeks.

Conclusions

SXL with riboflavin and blue light intensities below a defined damage threshold can induce a long lasting growth inhibitory effect on young rabbit eyes. Therefore, SXL might be a realistic approach to inhibit eye elongation in highly myopic eyes.
Literature
1.
go back to reference Spoerl E, Seiler T (1999) Techniques for stiffening the cornea. J Refract Surg 15:711–713PubMed Spoerl E, Seiler T (1999) Techniques for stiffening the cornea. J Refract Surg 15:711–713PubMed
2.
go back to reference Wu J, Seregard S, Spångberg B, Oskarsson M, Chen E (1999) Blue light induced apoptosis in rat retina. Eye 13:577–583PubMedCrossRef Wu J, Seregard S, Spångberg B, Oskarsson M, Chen E (1999) Blue light induced apoptosis in rat retina. Eye 13:577–583PubMedCrossRef
3.
go back to reference Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE (2008) Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: Long-term results. J Cataract Refract Surg 34:796–801PubMedCrossRef Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE (2008) Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: Long-term results. J Cataract Refract Surg 34:796–801PubMedCrossRef
4.
go back to reference Wollensak G, Iomdina E, Dittert D, Salamatina O, Stoltenburg G (2005) Cross-linking of scleral collagen in the rabbit using riboflavin and UVA. Acta Ophthalmol Scand 83:477–482PubMedCrossRef Wollensak G, Iomdina E, Dittert D, Salamatina O, Stoltenburg G (2005) Cross-linking of scleral collagen in the rabbit using riboflavin and UVA. Acta Ophthalmol Scand 83:477–482PubMedCrossRef
5.
go back to reference Wollensak G, Spoerl E (2004) Collagen crosslinking of human and porcine sclera. J Cataract Refract Surg 30:689–695PubMedCrossRef Wollensak G, Spoerl E (2004) Collagen crosslinking of human and porcine sclera. J Cataract Refract Surg 30:689–695PubMedCrossRef
7.
go back to reference Celorio JM, Pruett RC (1991) Prevalence of lattice degeneration and its relation to axial length in severe myopia. Am J Ophthalmol 111:20–23PubMedCrossRef Celorio JM, Pruett RC (1991) Prevalence of lattice degeneration and its relation to axial length in severe myopia. Am J Ophthalmol 111:20–23PubMedCrossRef
8.
go back to reference Curtin BJ, Karlin DB (1971) Axial length measurements and fundus changes of the myopic eye. Am J Ophthalmol 71:42–53PubMedCrossRef Curtin BJ, Karlin DB (1971) Axial length measurements and fundus changes of the myopic eye. Am J Ophthalmol 71:42–53PubMedCrossRef
9.
10.
go back to reference Wollensak G, Iomdina E (2009) Long-term biomechanical properties of rabbit sclera after collagen crosslinking using riboflavin and ultraviolet A (UVA). Acta Ophthalmol 87:193–198PubMedCrossRef Wollensak G, Iomdina E (2009) Long-term biomechanical properties of rabbit sclera after collagen crosslinking using riboflavin and ultraviolet A (UVA). Acta Ophthalmol 87:193–198PubMedCrossRef
11.
go back to reference Dotan A, Kremer I, Livnat T, Zigler A, Weinberger D, Bourla D (2014) Scleral cross-linking using riboflavin and ultraviolet-A radiation for prevention of progressive myopia in a rabbit model. Exp Eye Res 127:190–195PubMedCrossRef Dotan A, Kremer I, Livnat T, Zigler A, Weinberger D, Bourla D (2014) Scleral cross-linking using riboflavin and ultraviolet-A radiation for prevention of progressive myopia in a rabbit model. Exp Eye Res 127:190–195PubMedCrossRef
12.
go back to reference Iseli HP, Spoerl E, Wiedemann P, Krueger RR, Seiler T (2008) Efficacy and safety of blue-light scleral cross-linking. J Refract Surg 24:S752–S755 Iseli HP, Spoerl E, Wiedemann P, Krueger RR, Seiler T (2008) Efficacy and safety of blue-light scleral cross-linking. J Refract Surg 24:S752–S755
13.
go back to reference Schuldt C, Karl A, Körber N, Koch C, Liu Q, Fritsch AW, Reichenbach A, Wiedemann P, Käs JA, Francke M, Iseli HP (2014) Dose-dependent collagen cross-linking of rabbit scleral tissue by blue light and riboflavin treatment probed by dynamic shear rheology. Acta Ophthalmol 93(5):e328–e336. doi:10.1111/aos.12621 PubMedCrossRef Schuldt C, Karl A, Körber N, Koch C, Liu Q, Fritsch AW, Reichenbach A, Wiedemann P, Käs JA, Francke M, Iseli HP (2014) Dose-dependent collagen cross-linking of rabbit scleral tissue by blue light and riboflavin treatment probed by dynamic shear rheology. Acta Ophthalmol 93(5):e328–e336. doi:10.​1111/​aos.​12621 PubMedCrossRef
14.
go back to reference Iseli HP, Körber N, Karl A, Koch C, Schuldt C, Penk A, Liu Q, Huster D, Käs J, Reichenbach A, Wiedemann P, Francke M (2015) Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application. Exp Eye Res 139:37–47PubMedCrossRef Iseli HP, Körber N, Karl A, Koch C, Schuldt C, Penk A, Liu Q, Huster D, Käs J, Reichenbach A, Wiedemann P, Francke M (2015) Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application. Exp Eye Res 139:37–47PubMedCrossRef
15.
go back to reference Curtin BJ, Karlin DB (1970) Axial length measurements and fundus changes of the myopic eye. I. The posterior fundus. Trans Am Ophthalmol Soc 68:312–334PubMedPubMedCentral Curtin BJ, Karlin DB (1970) Axial length measurements and fundus changes of the myopic eye. I. The posterior fundus. Trans Am Ophthalmol Soc 68:312–334PubMedPubMedCentral
16.
go back to reference Fujiwara T, Imamura Y, Margolis R, Slakter JS, Spaide RF (2009) Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes. Am J Ophthalmol 148:445–450PubMedCrossRef Fujiwara T, Imamura Y, Margolis R, Slakter JS, Spaide RF (2009) Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes. Am J Ophthalmol 148:445–450PubMedCrossRef
18.
go back to reference McBrien NA, Gentle A (2003) Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res 22:307–338PubMedCrossRef McBrien NA, Gentle A (2003) Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res 22:307–338PubMedCrossRef
19.
go back to reference Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Meth 9:671–675CrossRef Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Meth 9:671–675CrossRef
20.
go back to reference Wang M, Zhang F, Liu K, Zhao X (2014) Safety evaluation of rabbit eyes on scleral collagen cross-linking by riboflavin and ultraviolet A. Clin Experiment Ophthalmol 43(2):156–163. doi:10.1111/ceo.12392 PubMedCrossRef Wang M, Zhang F, Liu K, Zhao X (2014) Safety evaluation of rabbit eyes on scleral collagen cross-linking by riboflavin and ultraviolet A. Clin Experiment Ophthalmol 43(2):156–163. doi:10.​1111/​ceo.​12392 PubMedCrossRef
21.
go back to reference Wu J, Seregard S, Algvere PV (2006) Photochemical damage of the retina. Surv Ophthalmol 51:461–481PubMedCrossRef Wu J, Seregard S, Algvere PV (2006) Photochemical damage of the retina. Surv Ophthalmol 51:461–481PubMedCrossRef
22.
go back to reference Rozanowska M, Jarvis-Evans J, Korytowski W, Boulton ME, Burke JM, Sarna T (1995) Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species. J Biol Chem 270:18825–18830PubMedCrossRef Rozanowska M, Jarvis-Evans J, Korytowski W, Boulton ME, Burke JM, Sarna T (1995) Blue light-induced reactivity of retinal age pigment. In vitro generation of oxygen-reactive species. J Biol Chem 270:18825–18830PubMedCrossRef
23.
go back to reference Rozanowska M, Wessels J, Boulton M, Burke JM, Rodgers MA, Truscott TG, Sarna T (1998) Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media. Free Radic Biol Med 24:1107–1112PubMedCrossRef Rozanowska M, Wessels J, Boulton M, Burke JM, Rodgers MA, Truscott TG, Sarna T (1998) Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media. Free Radic Biol Med 24:1107–1112PubMedCrossRef
24.
go back to reference Hunter JJ, Morgan JI, Merigan WH, SLINEY DH, Sparrow JR, Williams DR (2012) The susceptibility of the retina to photochemical damage from visible light. Prog Retin Eye Res 31:28–42PubMedPubMedCentralCrossRef Hunter JJ, Morgan JI, Merigan WH, SLINEY DH, Sparrow JR, Williams DR (2012) The susceptibility of the retina to photochemical damage from visible light. Prog Retin Eye Res 31:28–42PubMedPubMedCentralCrossRef
25.
go back to reference Putting B, van Best J, Vrensen G, Oosterhuis J (1994) Blue-light-induced dysfunction of the blood–retinal barrier at the pigment epithelium in albino versus pigmented rabbits. Exp Eye Res 58:31–40PubMedCrossRef Putting B, van Best J, Vrensen G, Oosterhuis J (1994) Blue-light-induced dysfunction of the blood–retinal barrier at the pigment epithelium in albino versus pigmented rabbits. Exp Eye Res 58:31–40PubMedCrossRef
26.
go back to reference Gorgels TG, van Norren D (1998) Two spectral types of retinal light damage occur in albino as well as in pigmented rat: no essential role for melanin. Exp Eye Res 66:155–162PubMedCrossRef Gorgels TG, van Norren D (1998) Two spectral types of retinal light damage occur in albino as well as in pigmented rat: no essential role for melanin. Exp Eye Res 66:155–162PubMedCrossRef
27.
go back to reference Reichenbach A, Schnitzer J, Friedrich A, Ziegert W, Brückner G, Schober W (1991) Development of the rabbit retina. I. Size of eye and retina, and postnatal cell proliferation. Anat Embryol 183:287–297PubMedCrossRef Reichenbach A, Schnitzer J, Friedrich A, Ziegert W, Brückner G, Schober W (1991) Development of the rabbit retina. I. Size of eye and retina, and postnatal cell proliferation. Anat Embryol 183:287–297PubMedCrossRef
28.
go back to reference Barathi A, Thu MK, Beuerman RW (2002) Dimensional growth of the rabbit eye. Cells Tissues Organs (Print) 171:276–285CrossRef Barathi A, Thu MK, Beuerman RW (2002) Dimensional growth of the rabbit eye. Cells Tissues Organs (Print) 171:276–285CrossRef
29.
go back to reference Bozkir G, Bozkir M, Dogan H, Aycan K, Güler B (1997) Measurements of axial length and radius of corneal curvature in the rabbit eye. Acta Med Okayama 51:9–11PubMed Bozkir G, Bozkir M, Dogan H, Aycan K, Güler B (1997) Measurements of axial length and radius of corneal curvature in the rabbit eye. Acta Med Okayama 51:9–11PubMed
30.
go back to reference Elsheikh A, Phillips JR (2013) Is scleral cross-linking a feasible treatment for myopia control? Ophthalmic Physiol Opt 33:385–389PubMedCrossRef Elsheikh A, Phillips JR (2013) Is scleral cross-linking a feasible treatment for myopia control? Ophthalmic Physiol Opt 33:385–389PubMedCrossRef
Metadata
Title
Scleral cross-linking by riboflavin and blue light application in young rabbits: damage threshold and eye growth inhibition
Authors
Hans Peter Iseli
Nicole Körber
Christian Koch
Anett Karl
Anja Penk
Daniel Huster
Andreas Reichenbach
Peter Wiedemann
Mike Francke
Publication date
01-01-2016
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 1/2016
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-015-3213-x

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