The ultrastructure of rabbit sclera after scleral crosslinking with riboflavin and blue light of different intensities

Karl, Anett; Makarov, F. N.; Koch, Christian; Körber, Nicole; Schuldt, Carsten; Krüger, Melanie; Reichenbach, Andreas; Wiedemann, Peter; Bringmann, Andreas; Iseli, Hans Peter; Francke, Mike

doi:10.1007/s00417-016-3393-z

Cited by 15 publications

(8 citation statements)

References 26 publications

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“…Using 450-nm blue light, a damage threshold of 200 to 400 mW/cm 2 for 20 minutes has been established for rabbit sclera. 21,27 In our study, we used 25 to 50 mW/cm 2 irradiation for 30 minutes, much lower than the damage threshold, and yet achieved an increase of greater than 80% in the Young's modulus at 8% strain. SXL-induced changes in elastic moduli can depend greatly on sample preparation and analysis procedure, but our results are generally consistent with previous studies using riboflavin and porcine eyes.…”

Section: Discussionmentioning

confidence: 99%

Flexible Optical Waveguides for Uniform Periscleral Cross-Linking

Kwok

Kim

Lin

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeScleral cross-linking (SXL) with a photosensitizer and light is a potential strategy to mechanically reinforce the sclera and prevent progressive axial elongation responsible for severe myopia. Current approaches for light delivery to the sclera are cumbersome, do not provide uniform illumination, and only treat a limited area of sclera. To overcome these challenges, we developed flexible optical waveguides optimized for efficient, homogeneous light delivery.MethodsWaveguides were fabricated from polydimethylsiloxane elastomer. Blue light (445 nm) is coupled into the waveguide with an input fiber. Light delivery efficiency from the waveguide to scleral tissue was measured and fit to a theoretical model. SXL was performed on fresh porcine eyes stained with 0.5% riboflavin, using irradiances of 0, 25, and 50 mW/cm2 around the entire equator of the eye. Stiffness of scleral strips was characterized with tensiometry.ResultsLight delivery with a waveguide of tapered thickness (1.4–0.5 mm) enhanced the uniformity of light delivery, compared to a flat waveguide, achieving a coefficient of variation of less than 10%. At 8% strain, sclera cross-linked with the waveguides at 50 mW/cm2 for 30 minutes had a Young's modulus of 10.7 ± 1.0 MPa, compared to 5.9 ± 0.5 MPa for no irradiation, with no difference in stiffness between proximally and distally treated halves. The stiffness of waveguide-irradiated samples did not differ from direct irradiation at the same irradiance.ConclusionsWe developed flexible waveguides for periscleral cross-linking. We demonstrated efficient and uniform stiffening of a 5-mm-wide equatorial band of scleral tissue.

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Section: Discussionmentioning

confidence: 99%

Flexible Optical Waveguides for Uniform Periscleral Cross-Linking

Kwok

Kim

Lin

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…In eyes treated with scleral cross-linking, but no myopia induction, an inhibition of eye growth is present, further demonstrating the role of scleral cross-links on eye growth cessation (51). In contrast to myopic eyes, when scleral cross-linking is performed in vivo without myopia induction the scleral collagen fibre bundles also become skewed towards smaller diameters (52) and increased variability in fibre bundle composition (53). Biomechanically, the crosslinked sclera shows increased elastic and viscous modulus (53)(54)(55), and increased stiffness (53).…”

Section: Collagen Cross-linkingmentioning

confidence: 89%

“…Increasing levels of irradiation provide, in most cases, greater scleral stiffening, but increasing irradiation levels increase the risk of complications. Scleral inflammation (58), collagen destruction or disorganisation (52,53,55), reduction in dark-adapted electroretinogram (ERG) (54), and retinal cell death and layer disruption (51-54,58) have all been observed following cross-linking procedures, particularly with higher irradiance levels. Given that the biomechanical changes required to prevent myopia progression require higher irradiances to achieve, the potential for serious side effects to occur with current procedures warrants careful further investigation before starting human cross-linking trials.…”

Section: Collagen Cross-linkingmentioning

confidence: 99%

Scleral remodelling in myopia and its manipulation: a review of recent advances in scleral strengthening and myopia control

Backhouse¹,

Gentle²

2018

Ann. Eye Sci

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The biological mechanisms of eye growth and refractive development are increasingly well characterised, a result of many careful studies that have been carried out over many years. As the outer coat of the eye, the sclera has the ultimate impact on the restraint or facilitation of eye growth, thus any changes in its biochemistry, ultrastructure, gross morphology and/or biomechanical properties are critical in refractive error development and, in particular, the development of myopia. The current review briefly revisits our basic understanding of the structure and biomechanics of the sclera and how these are regulated and modified during eye growth and myopia development. The review then applies this knowledge in considering recent advances in our understanding of how the mechanisms of scleral remodelling may be manipulated or controlled, in order to constrain eye growth and limit the development of myopia, in particular the higher degrees of myopia that lead to vision loss and blindness. In doing so, the review specifically considers recent approaches to the strengthening of the sclera, through collagen cross-linking, scleral transplantation, implantation or injection of biomaterials, or the direct therapeutic targeting and manipulation of the biochemical mechanisms known to be involved in myopia development. These latest approaches to the control of scleral changes in myopia are, where possible, placed in the context of our understanding of scleral biology, in order to bring a more complete understanding of current and future therapeutic interventions in myopia, and their consequences.

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“…Xia et al 11 used polarized light microscopy and observed a microscopically detectable corneal haze with a significant increase in type III collagen fibrils between 30 and 90 days after crosslinking therapy with riboflavin and ultraviolet light. Karl et al 22 used electron microscopy to examine how the fibrils change after crosslinking and found similar changes in structure with blue light treatment.…”

Section: Discussionmentioning

confidence: 99%

Changes in Collagen Structure and Permeability of Rat and Human Sclera After Crosslinking

Guo

Miao

Yang

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose To use second harmonic generation imaging and fluorescence recovery after photobleaching to demonstrate alterations in scleral collagen structure and permeability after crosslinking in rat and human eyes. Methods Excised rat and human scleras were imaged ex vivo with an inverted two-photon excitation fluorescence microscope before and after photochemical crosslinking using riboflavin and 405-nm laser light. Fluorescence recovery after photobleaching was applied to measure the diffusion of fluorescein isothiocyanate–dextran across the sclera. Results Crosslinking caused scleral collagen fibers to become wavier and more densely packed, with surface collagen being more affected than deeper collagen fibers. Crosslinked sclera showed significantly decreased permeability in the irradiation zone and also extended as far as 250 µm outside the irradiation zone. Conclusions Photochemical crosslinking induced changes in scleral structure and permeability that extended to tissue even outside the irradiation zone. Translational Relevance Ultrastructural changes associated with the emerging clinical technique of photochemical scleral crosslinking have not been well characterized. We demonstrate not only changes in scleral collagen by second harmonic generation imaging but also the associated functional changes in tissue permeability by fluorescence recovery after photobleaching. We report the novel finding of reduced permeability extending well beyond the direct irradiation zone. This has implications for control in the clinical setting.

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The ultrastructure of rabbit sclera after scleral crosslinking with riboflavin and blue light of different intensities

Cited by 15 publications

References 26 publications

Flexible Optical Waveguides for Uniform Periscleral Cross-Linking

Flexible Optical Waveguides for Uniform Periscleral Cross-Linking

Scleral remodelling in myopia and its manipulation: a review of recent advances in scleral strengthening and myopia control

Changes in Collagen Structure and Permeability of Rat and Human Sclera After Crosslinking

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