Scleral cross-linking using riboflavin and ultraviolet-A radiation for prevention of progressive myopia in a rabbit model

Dotan, Assaf; Kremer, I; Livnat, Tami; Zigler, A.; Weinberger, Dov; Bourla, Dan

doi:10.1016/j.exer.2014.07.019

Cited by 45 publications

(33 citation statements)

References 28 publications

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“…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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“…Corneal stiffening has become a clinical therapy for keratoconus and other corneal conditions (Iseli et al, 2008; Wollensak et al, 2003). Stiffening of the posterior sclera has also been proposed as a potential treatment for glaucoma (Campbell et al, 2017; Coudrillier et al, 2016; Kimball et al, 2014) and myopia (Dotan et al, 2014; Liu et al, 2016; Wollensak and Spoerl, 2004). It would therefore be interesting to evaluate the level of changes in dynamic IOP that can be expected with localized stiffening of the ocular shell.…”

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confidence: 99%

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Clayson

Pan

Pavlatos

et al. 2017

Experimental Eye Research

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Factors governing the steady-state IOP have been extensively studied; however, the dynamic aspects of IOP are less understood. Clinical studies have suggested that intraocular pressure (IOP) fluctuation may be associated with glaucoma risk. This study aims to investigate how stiffening of corneoscleral biomechanical properties affects IOP spikes induced by rapid microvolumetric change. Porcine eyes (n = 25 in total) were subjected to volumetric infusions before and after external treatment of a circular area (11 mm diameter) in either the central cornea or posterior sclera. The treated area in the control group was immersed in phosphate-buffered saline (PBS) for 40 min, while the treated area of the chemical crosslinking group was immersed in 4% glutaraldehyde/PBS for 40 min. A subset of the sham-treated eyes was also subjected to volumetric infusions at a raised steady-state IOP. The magnitude of IOP spikes increased after localized chemical crosslinking of either the cornea (27.5% increase, p < 0.001) or the sclera (14.3% increase, p < 0.001) with corneal crosslinking having a stronger effect than scleral crosslinking (p = 0.018). We also observed that raising the steady-state IOP from 15 to 25 mmHg resulted in marked increase in IOP spike magnitudes by 63.9% (p < 0.001). These results suggested that an increased corneoscleral stiffness could significantly increase IOP spike magnitudes at the same volumetric change. Corneal stiffness appeared to have a strong impact on the IOP spike magnitude and may play a major role in regulating rapid volume-pressure dynamics. An increase in steady-state IOP also resulted in larger IOP fluctuations due to the increased “apparent” stiffness of the ocular shell, suggesting a potential interaction between the magnitude of IOP and its fluctuations. Corneoscleral properties may represent additional pathways for understanding and managing glaucoma risk and warrant future investigation.

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“…A reduction 3 of the UV light intensity down to 3 mW/cm 2 for 30 min (5.4 J/cm 2 ) of SXL treatment 4 avoided these degenerative side effects and maintained strengthening effects for the 5 scleral tissue(Wollensak and Iomdina, 2009). In another study, a total UVA light dose 6 of 57J/cm 2 and riboflavin were used for the SXL treatment in very young rabbits and 7 no retinal damage was detected(Dotan et al, 2014). The surprising differences in the 8 damage thresholds of approximately 5.4 J/cm 2 or 57 J/cm 2 UVA vs. 240 J/cm 2 blue 9 light (200 mW/cm 2 for 20 min in the presented results) might be explained by different 10 absorption characteristics of the scleral tissue/proteins/molecules for different 11 wavelengths, causing different tissue damaging effects(Wu et al, 2006).…”

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Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application

Iseli

Körber

Karl

et al. 2015

Experimental Eye Research

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Scleral cross-linking using riboflavin and ultraviolet-A radiation for prevention of progressive myopia in a rabbit model

Cited by 45 publications

References 28 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

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application

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