Fibril density reduction in keratoconic corneas

Zhou, Dong; Abass, Ahmed; Lopes, Bernardo; Eliasy, Ashkan; Hayes, Sally; Boote, Craig; Meek, Keith Michael Andrew; Movchan, A. B.; Movchan, N. V.; Elsheikh, Ahmed

doi:10.1098/rsif.2020.0900

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…In addition, knowing the transmittance of the normal corneal layers can help us to know the influence of ultraviolet absorption in patients with certain corneal pathologies or after some surgical procedures. For instance, corneal diseases such as keratoconus, which may result in a progressive thinning of the corneal and cells composition [ 18 ], might affect corneal spectral transmission, and it would be important to protect the cornea, the lens, and the retina from the UV radiation that would normally be blocked by a healthy cornea.…”

Section: Introductionmentioning

confidence: 99%

Spectral Transmission of the Human Corneal Layers

Peris-Martínez

García-Domene

Penadés

et al. 2021

JCM

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We have assessed the spectral transmittance of the different layers of the human cornea in the ultraviolet (UV), visible, and near-infrared (IR) spectral ranges. Seventy-four corneal sample donors were included in the study. Firstly, the corneal transmittance was measured using a spectrophotometer. Then, all samples were fixed for histopathological analysis, which allowed us to measure the thickness of each corneal layer. Finally, the absorption coefficients of the corneal layers were computed by a linear model reproducing total transmittance. The results show that corneal transmission was almost in unity at the visible and IR ranges but not at the UV range, in which the layer with higher transmission is Descemet’s membrane, whereas the stroma showed the lowest transmittance. Regarding the absorption coefficient, the most absorptive tissue was Bowman’s layer, followed by the endothelium. Variations on transmittance due to changes in the stroma, Bowman’s layer, or Descemet layer were simulated, and important transmission increases were found due to stroma and Bowman changes. To conclude, we have developed a method to measure the transmittance and thickness for each corneal layer. All corneal layers absorb UV light to a greater or lesser extent. The absorption coefficient is higher for Bowman’s layer, while the stroma is the layer with the lowest transmittance due to its thickness. Variations in stroma thickness or changes in the corneal tissue of Bowman’s layer or the endothelium layer due to some pathologies or surgeries could affect, to a greater or lesser degree, the total transmission of the cornea. Thus, obtaining accurate absorption coefficients for different layers would help us to predict and compensate these changes.

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Section: Introductionmentioning

confidence: 99%

Spectral Transmission of the Human Corneal Layers

Peris-Martínez

García-Domene

Penadés

et al. 2021

JCM

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“…These results are in line with ex vivo experimental results using electron microscopy and x-ray scattering in which the collagen fibrils’ organisation was significantly altered inside the keratoconic KC area of pathology but remained unaffected outside it ( Radner et al, 1998 ; Meek et al, 2005 ). Using x-ray scattering, Zhou et al observed that the magnitude of collagen fibril density reduction inside the cone area was up to 35% in advanced KC cases ( Zhou et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Another limitation is that the validation of the mapping method relied on comparing the numerically-predicted, SSI-based deformation of the cornea along only the cornea’s principal temporal-nasal meridian to that measured clinically by the Corvis ST ( Zhang et al, 2021 ). Further, the method to relate the fibril density reduction inside the cone with the cone morphology was based on information obtained from only 7 KC corneas ( Zhou et al, 2021 ). On the clinical side, it is important to note that the relatively small sample used in the study and the lack of cases in which there was a small progression extent represented other limitations, which will be addressed in prospective studies.…”

Section: Discussionmentioning

confidence: 99%

“…In brief, the process begins by estimating three KC cone features: apex location, cone height and KC area of pathology, based on a method proposed by Eliasy et al that was later clinically validated ( Eliasy et al, 2020 ; Lopes B. et al, 2021 ). The fibril density reduction inside the cone was then estimated based on these KC cone features using the method proposed by Zhou et al ( Zhou et al, 2021 ). Using the tomography data of the corneas under study, eye-specific 3D finite element (FE) models were built using fifteen-noded continuum solid elements, described in detail, including an integrated mesh convergence study, elsewhere ( Eliasy, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

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In vivo Assessment of Localised Corneal Biomechanical Deterioration With Keratoconus Progression

Lopes

Padmanabhan

Eliasy

et al. 2022

Front. Bioeng. Biotechnol.

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Purpose: To evaluate the regional corneal biomechanical deterioration with keratoconus (KC) progression as measured by the Stress-Strain Index (SSI) maps.Methods: The preoperative examinations of 29 progressive KC cases that were submitted to corneal cross-linking (CXL) were evaluated. The examinations included the tomography and the SSI measured by the Pentacam HR and the Corvis ST (Oculus, Wetzlar, Germany), respectively. The results were recorded twice, the latter of which was at the last visit before the CXL procedure. The patient-specific SSI maps were built, using data at each examination, based on finite element modelling and employing inverse analysis to represent the regional variation of biomechanical stiffness across the cornea.Results: All cases presented significant shape progression (above the 95% CI of repeatability) in anterior and posterior curvatures and minimum thickness. The overall corneal stiffness as measured by the SSI within the central 8 mm-diameter area underwent slight but significant reductions from the first to the last examination (−0.02 ± 0.02, range: −0.09 to 0, p < 0.001). In all 29 cases, the reduction in stiffness was localised and concentred in the area inside the keratoconus cone. The SSI values inside the cone were significantly lower in the last examination (by 0.15 ± 0.09, range: −0.42 to −0.01, p < 0.001), while the SSI outside the cone presented minimal, non-significant variations (0 ± 0.01, range: −0.04 to 0.01, p = 0.999).Conclusion: It has been observed through the SSI maps that the regional deterioration in stiffness was concerted inside the area of pathology, while only mild non-significant alterations were observed outside the area of pathology.

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“…The posterior lamellae also exhibit thinning, splitting, and distortion along with Vogt’s striae, which run anteriorly from the deep posterior stroma: while normal corneas also have these striae, they are more numerous and longer in keratoconus. Other notable changes in keratoconus are thinning and fragmentation of Bowman’s membrane, thickening of the epithelial layer to fill the void left by the shrunken stroma, and in end-stage disease, rupture of Descemet’s membrane and the onset of hydrops [ 3 , 6 , 12 , 13 , 17 – 23 ]. These changes are all largely concentrated in the region where the cone forms ( Fig 1D ).…”

Section: Introductionmentioning

confidence: 99%

Biomechanics of keratoconus: Two numerical studies

et al. 2023

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Background The steep cornea in keratoconus can greatly impair eyesight. The etiology of keratoconus remains unclear but early injury that weakens the corneal stromal architecture has been implicated. To explore keratoconus mechanics, we conducted two numerical simulation studies. Methods A finite-element model describing the five corneal layers and the heterogeneous mechanical behaviors of the ground substance and lamellar collagen-fiber architecture in the anterior and posterior stroma was developed using the Holzapfel-Gasser-Ogden constitutive model. The geometry was from a healthy subject. Its stroma was divided into anterior, middle, and posterior layers to assess the effect of changing regional mechanical parameters on corneal displacement and maximum principal stress under intraocular pressure. Specifically, the effect of softening an inferocentral corneal button, the collagen-based tissues throughout the whole cornea, or specific stromal layers in the button was examined. The effect of simply disorganizing the orthogonally-oriented posterior stromal fibers in the button was also assessed. The healthy cornea was also subjected to eye rubbing-like loading to identify the corneal layer(s) that experienced the most tensional stress. Results Conical deformation and corneal thinning emerged when the corneal button or the mid-posterior stroma of the button underwent gradual softening or when the collagen fibers in the mid-posterior stroma of the button were dispersed. Softening the anterior layers of the button or the whole cornea did not evoke conical deformation. Button softening greatly increased and disrupted the stress on Bowman’s membrane while mid-posterior stromal softening increased stress in the anterior layers. Eye rubbing profoundly stressed the deep posterior stroma while other layers were negligibly affected. Discussion These observations suggest that keratoconus could be initiated, at least partly, by mechanical instability/damage in the mid-posterior stroma that then imposes stress on the anterior layers. This may explain why subclinical keratoconus is marked by posterior but not anterior elevation on videokeratoscopy.

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Fibril density reduction in keratoconic corneas

Cited by 9 publications

References 43 publications

Spectral Transmission of the Human Corneal Layers

Spectral Transmission of the Human Corneal Layers

In vivo Assessment of Localised Corneal Biomechanical Deterioration With Keratoconus Progression

Biomechanics of keratoconus: Two numerical studies

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