Photochemically Induced Crosslinking of Tarsal Collagen as a Treatment for Eyelid Laxity: Assessing Potentiality in Animal Tissue

Smith, Tai; Suzuki, Shuko; Cronin, Brendan G.; Haghighatpanah, Mohammadreza; Petcu, Eugen Bogdan; Philippa, Christopher; Chirilă, Traian V.

doi:10.1097/iop.0000000000001063

Cited by 18 publications

(19 citation statements)

References 27 publications

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“…They found no significant effects of low levels of irradiance (3–6 mW/cm 2 ) on stiffness. However, at much higher levels of irradiance (30 and 45 mW/cm 2 ), cross-linked samples significantly stiffened 7. The higher levels of irradiance used by Smith and colleagues7 cannot be used safely in humans.…”

Section: Discussionmentioning

confidence: 95%

“…However, at much higher levels of irradiance (30 and 45 mW/cm 2 ), cross-linked samples significantly stiffened 7. The higher levels of irradiance used by Smith and colleagues7 cannot be used safely in humans. However, in the current human study, lower irradiance (6 mW/cm 2 ) significantly stiffened tarsal plates.…”

Section: Discussionmentioning

confidence: 95%

“…Smith and colleagues7 reviewed the efficacy of collagen cross-linking for increasing the stiffness of the tarsal plates of sheep. They found no significant effects of low levels of irradiance (3–6 mW/cm 2 ) on stiffness.…”

Section: Discussionmentioning

confidence: 99%

“…Smith and colleagues7 recently reviewed the use of photochemical cross-linking with ultraviolet A (UVA) and riboflavin (vitamin B 2 ) for the stiffening of ovine tarsal plates. They did not find a significant stiffening effect from this treatment.…”

Section: Introductionmentioning

confidence: 99%

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Biomechanical and Morphologic Effects of Collagen Cross-Linking in Human Tarsus

Ugradar

Lesgart

et al. 2019

Trans. Vis. Sci. Tech.

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PurposeTo investigate the feasibility of increasing the stiffness of human tarsal tissue following treatment with riboflavin and ultraviolet A (UVA) to induce cross-linking of collagen fibers.MethodsIn this case control study, 18 right and left upper eyelids were excised en bloc from 18 fresh-frozen cadavers. One side served as the control while the samples from the opposite side were cross-linked. Four 2 × 6-mm vertical strips of central tarsus were cut from the superior to inferior border of each tarsal plate. Sample tissue was irradiated with UVA at 6 mW/cm2 for 18 minutes. A microtensile load cell and an optical coherence tomography scanner allowed calculation of stiffness (Young's modulus). Six cross-linked samples and corresponding controls were stained with hematoxylin and eosin (H&E) and Masson trichrome stains. Four controls and four cross-linked samples were also reviewed with a transmission electron microscope.ResultsMean Young's modulus in the linear region for controls was 28 ± 9 MPa and was much higher at 138 ± 8 MPa for cross-linked samples (P < 0.001), yielding a 493% mean stiffness increase. Staining with H&E and Masson did not reveal any histologic changes. Transmission electron microscopy showed a decrease in average diameter of 50 randomly selected collagen fibers from 47.2 ± 1.9 nm prior to cross-linking to 34.2 ± 1.1 nm post cross-linking (P < 0.001). Qualitatively, the collagen fibers appeared more closely packed following cross-linking.ConclusionsThe findings of this study suggest that collagen cross-linking is a viable and effective modality for increasing the stiffness of human tarsal plates.Translational RelevanceThis work provides proof that collagen cross-linking produces stiffening of the human tarsal plate and may be used in disorders that cause eyelid laxity.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biomechanical and Morphologic Effects of Collagen Cross-Linking in Human Tarsus

Ugradar

Lesgart

et al. 2019

Trans. Vis. Sci. Tech.

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“…Riboflavin, a photosensitizer applied directly to the corneal stromal collagen, is exposed to UVA (ultraviolet A) radiation, inducing bond formation between collagen fibers (primarily type I and III) and increasing corneal stiffness [19, 20]. In addition, a recent study demonstrated significant stiffening of sheep tarsal plate tissue following collagen crosslinking [21].…”

Section: Introductionmentioning

confidence: 99%

Effects of collagen crosslinking on porcine and human tarsal plate

et al. 2019

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BackgroundFloppy eyelid syndrome is a disorder in which the tarsal plate is easily distensible and is currently treated with conservative or surgical measures. Human tarsal plate contains type I collagen, which is crosslinked in corneal tissue as a treatment for keratoconus. We hypothesized that collagen crosslinking would similarly stiffen tarsal plate tissue and investigated this in porcine and human tarsal plate specimens.MethodsRiboflavin-sensitized porcine and human tarsus samples were irradiated with ultraviolet-A light. Porcine experiments were analyzed with gross photographs, anterior segment optical computed tomography (AS-OCT) imaging, and tensile testing. A prospective study of human tarsus was performed on samples from patients undergoing wedge resection for floppy eyelid syndrome and was analyzed with AS-OCT and tensile testing.Results73 porcine adnexa and 9 patients (16 eyelids) who underwent wedge excision were included in the study. Grossly, greater stiffness was observed in crosslinked porcine tissue. AS-OCT imaging in porcine tissue showed a distinct hyperreflective band in crosslinked specimens whose area and intensity increased with longer treatment time (P = 0.003); this band was also visible in crosslinked human specimens. Tensile testing was performed, but results were not statistically significant.ConclusionsAS-OCT imaging, which has not been previously described for tarsal plate, showed a characteristic change in crosslinked porcine and human specimens. Tissue stiffness was increased grossly, but changes in tensile properties were not statistically significant. Further study is warranted to determine relevance as a potential treatment for floppy eyelid syndrome.

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The Floppy Eyelid Syndrome

Ramesh

2022

Foundational Papers in Oculoplastics

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Photochemically Induced Crosslinking of Tarsal Collagen as a Treatment for Eyelid Laxity: Assessing Potentiality in Animal Tissue

Abstract: These findings indicate that irradiation of tarsal collagen leading to tissue stiffening could be a safe procedure for treating lax eyelid conditions in human patients.

Cited by 18 publications

References 27 publications

Biomechanical and Morphologic Effects of Collagen Cross-Linking in Human Tarsus

Biomechanical and Morphologic Effects of Collagen Cross-Linking in Human Tarsus

Effects of collagen crosslinking on porcine and human tarsal plate

The Floppy Eyelid Syndrome

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