Safety evaluation of rabbit eyes on scleral collagen cross‐linking by riboflavin and ultraviolet <scp>A</scp>

Wang, Meng Meng; Zhang, Fengju; Liu, Kegao; Zhao, Xu

doi:10.1111/ceo.12392

Cited by 29 publications

(21 citation statements)

References 27 publications

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“…Previous attempts at scleral crosslinking (sCXL) using UVA-riboflavin–mediated photochemical crosslinking (CXL) also were reported, although difficulty accessing the posterior sclera with an ultraviolet (UV) light source was a concern 3,4 as well as changes in electroretinographic (ERG) amplitudes following CXL in rabbit sclera. 5 More recently, the “CXL” approach has been used successfully to halt axial elongation in visually form-deprived rabbits (by tarsorrhaphy), although multiple regions of posterior sclera required separate irradiation zones. 6 …”

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confidence: 99%

Evaluation of Therapeutic Tissue Crosslinking (TXL) for Myopia Using Second Harmonic Generation Signal Microscopy in Rabbit Sclera

Zyablitskaya

Takaoka

Munteanu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeSecond harmonic generation signals (SHG) are emitted preferentially from collagenous tissue structures and have been used to evaluate photochemically-induced (CXL) crosslinking changes in the cornea. Since therapeutic tissue crosslinking (TXL) using sodium hydroxymethylglycinate (SMG) of the sclera is a potential treatment for high myopia, we explored the use of SHG microscopy to evaluate the effects.MethodsSingle sub-Tenon's (sT) injections (400 μL) using SMG (40–400 mM) were made at the equatorial 12 o'clock position of the right eye of cadaveric rabbit heads (n = 16 pairs). After 3.5 hours, confocal microscopy (CM) was performed using 860 nm two-photon excitation and 400 to 450 nm emission. Pixel density and fiber bundle “waviness” analyses were performed on the images. Crosslinking effects were confirmed using thermal denaturation (Tm) temperature. Comparison experiments with riboflavin photochemical crosslinking were done.ResultsTherapeutic tissue crosslinking localization studies indicated that crosslinking changes occurred at the site of injection and in adjacent sectors. Second harmonic generation signals revealed large fibrous collagenous bundled structures that displayed various degrees of waviness. Histogram analysis showed a nearly 6-fold signal increase in 400 mM SMG over 40 mM. This corresponded to a ΔTm = 13°C for 400 mM versus ΔTm = 4°C for 40 mM. Waviness analysis indicated increased fiber straightening as a result of SMG CXL.ConclusionsSecond harmonic generation signal intensity and fiber bundle waviness is altered by scleral tissue crosslinking using SMG. These changes provide insights into the macromolecular changes that are induced by therapeutic crosslinking technology and may provide a method to evaluate connective tissue protein changes induced by scleral crosslinking therapies.

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confidence: 99%

Evaluation of Therapeutic Tissue Crosslinking (TXL) for Myopia Using Second Harmonic Generation Signal Microscopy in Rabbit Sclera

Zyablitskaya

Takaoka

Munteanu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…The surgical technique to enforce the equator is already clinically approved, for example, the cerclage technique for retinal detachment. Previously described SXL approaches use either a UV-A lamp, 40 a fiber-optic probe, 13,14 or a dental blue light source connected to plastic tubing 12,21 to deliver light to scleral tissue. Not only do these approaches provide uneven illumination by treating only a few target regions of the eye, but also the illumination area is relatively small owing to the limited probe size, typically covering an area of 10 to 100 mm 2 .…”

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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“…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). When human sclera is cross-linked in vitro, the response is similar to that observed in vivo, with a skew towards thicker collagen fibril diameters and an overall increase in spread of fibril diameters (55,56).…”

Section: Collagen Cross-linkingmentioning

confidence: 99%

“…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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Safety evaluation of rabbit eyes on scleral collagen cross‐linking by riboflavin and ultraviolet A

Abstract: According to the electrophysiological and histopathological results, the current scleral CXL laboratory technique is not safe enough for the postoperative visual function of rabbit eyes.

Cited by 29 publications

References 27 publications

Evaluation of Therapeutic Tissue Crosslinking (TXL) for Myopia Using Second Harmonic Generation Signal Microscopy in Rabbit Sclera

Evaluation of Therapeutic Tissue Crosslinking (TXL) for Myopia Using Second Harmonic Generation Signal Microscopy in Rabbit Sclera

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

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