Scleral crosslinking using genipin can compromise retinal structure and function in tree shrews

Hamdaoui, Mustapha El; Levy, Alexander; Stuber, Aaron B; Girkin, Christopher A.; Kraft, Timothy W.; Samuels, Brian C; Grytz, Rafael

doi:10.1016/j.exer.2022.109039

Cited by 7 publications

(3 citation statements)

References 43 publications

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“… 91 A recent study in tree shrews using retrobulbar injections of the crosslinking agent genipin did show effectiveness against form deprivation myopia 92 but was associated with significant retinal pathology. 93 Pathologic changes were also seen with scleral cross-linking in the guinea pig. 94 Previous studies in rabbits have suggested that using a blue light–riboflavin combination to induce scleral cross-linking can increase scleral stiffness with no pathologic effects.…”

Section: Imi Digest—experimental Models Of Emmetropization and Myopiamentioning

confidence: 97%

IMI 2023 Digest

Sankaridurg

Berntsen

Bullimore

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Myopia is a dynamic and rapidly moving field, with ongoing research providing a better understanding of the etiology leading to novel myopia control strategies. In 2019, the International Myopia Institute (IMI) assembled and published a series of white papers across relevant topics and updated the evidence with a digest in 2021. Here, we summarize findings across key topics from the previous 2 years. Studies in animal models have continued to explore how wavelength and intensity of light influence eye growth and have examined new pharmacologic agents and scleral cross-linking as potential strategies for slowing myopia. In children, the term premyopia is gaining interest with increased attention to early implementation of myopia control. Most studies use the IMI definitions of ≤−0.5 diopters (D) for myopia and ≤−6.0 D for high myopia, although categorization and definitions for structural consequences of high myopia remain an issue. Clinical trials have demonstrated that newer spectacle lens designs incorporating multiple segments, lenslets, or diffusion optics exhibit good efficacy. Clinical considerations and factors influencing efficacy for soft multifocal contact lenses and orthokeratology are discussed. Topical atropine remains the only widely accessible pharmacologic treatment. Rebound observed with higher concentration of atropine is not evident with lower concentrations or optical interventions. Overall, myopia control treatments show little adverse effect on visual function and appear generally safe, with longer wear times and combination therapies maximizing outcomes. An emerging category of light-based therapies for children requires comprehensive safety data to enable risk versus benefit analysis. Given the success of myopia control strategies, the ethics of including a control arm in clinical trials is heavily debated. IMI recommendations for clinical trial protocols are discussed.

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Section: Imi Digest—experimental Models Of Emmetropization and Myopiamentioning

confidence: 97%

IMI 2023 Digest

Sankaridurg

Berntsen

Bullimore

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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“…However, a stiffer scleral may increase the strain experienced by the OHN by directing stress to the weakest point in the eye wall. Multiple scleral stiffening compounds such as glyceraldehyde, glutaraldehyde, and genipin have failed to demonstrate RGC protection in rodent models or tree shrews thus far [ 121 , 122 , 123 ] and may be harmful to the retina as well [ 124 ]. Alternatively, perhaps reducing scleral stiffness could alleviate certain cases of glaucoma through the application of collagenase or other compounds that break down glycosaminoglycans [ 125 , 126 , 127 ].…”

Section: Discussionmentioning

confidence: 99%

Remodeling of the Lamina Cribrosa: Mechanisms and Potential Therapeutic Approaches for Glaucoma

Strickland

Garner

Gross

et al. 2022

IJMS

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Glaucomatous optic neuropathy is the leading cause of irreversible blindness in the world. The chronic disease is characterized by optic nerve degeneration and vision field loss. The reduction of intraocular pressure remains the only proven glaucoma treatment, but it does not prevent further neurodegeneration. There are three major classes of cells in the human optic nerve head (ONH): lamina cribrosa (LC) cells, glial cells, and scleral fibroblasts. These cells provide support for the LC which is essential to maintain healthy retinal ganglion cell (RGC) axons. All these cells demonstrate responses to glaucomatous conditions through extracellular matrix remodeling. Therefore, investigations into alternative therapies that alter the characteristic remodeling response of the ONH to enhance the survival of RGC axons are prevalent. Understanding major remodeling pathways in the ONH may be key to developing targeted therapies that reduce deleterious remodeling.

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“…This is especially true for soft tissues that are often heterogeneous as well as very small. [4][5][6][7] Traditional test methods, such as uniaxial tensile-compression testing, may not capture the heterogeneity of the tissue, as these tests tend to interrogate only the bulk of the material and do not capture spatial variations. 8 Moreover, traditional test methods often require significant extra sample space for clamping, 9 which proves difficult or impossible when working with small biological samples.…”

Section: Introductionmentioning

confidence: 99%