Evaluation of changes in corneal biomechanics in eyes with keratectasia

Purpose. To make a comparative analysis of topographic, tomographic and biomechanical values, measured by Pentacam HR and Corvis ST, in healthy multirefractive cohort versus patients with keratectasia of various severity. Material and methods. The prospective study comprised 237 patients aged from 18 to 47 years, subdivided into three groups. The first group included 174 healthy persons with various refraction (174 eyes). The second and the third group embraced 63 patients with keratoconus: 36 patients (36 eyes) with keratoconus of the I degree and 27 eyes with keratoconus of the II and III degrees. Besides the conventional comprehensive ocular examination the following studies were performed in all the patients: evaluation of topographic, tomographic and biomechanical corneal properties with application of Pentacam HR and Corvis ST (OCULUS Optikgerate GmbH; Wetzlar, Germany). Results. It was revealed that the following biomechanical values, assessed by means of Pentacam HR and Corvis ST, exhibited statistically significant changes (p<0,001) in all degrees of ketatoconus: a relative corneal thickness by Ambrosio, inverted radius of applanation curvature (IntRadius), DA Ratio Coefficient, values of corneal rigidity – SP-A 1 and SSI. Conclusion. The detected parameters may be applied as indicators, allowing to evaluate corneal biomechanics, to define early features of ectatic process, to assess effectiveness of the performed corneal collagen crosslinking and intralamellar keratoplasty with implantation of corneal segments. Key words: keratoconus, corneal biomechanics, pachymetry, index of pachymetric progression, corneal viscoelasticity.

Mechanisms of Collagen Crosslinking in Diabetes and Keratoconus

Collagen crosslinking provides the mechanical strength required for physiological maintenance of the extracellular matrix in most tissues in the human body, including the cornea. Aging and diabetes mellitus (DM) are processes that are both associated with increased collagen crosslinking that leads to increased corneal rigidity. By contrast, keratoconus (KC) is a corneal thinning disease associated with decreased mechanical stiffness leading to ectasia of the central cornea. Studies have suggested that crosslinking mediated by reactive advanced glycation end products during DM may protect the cornea from KC development. Parallel to this hypothesis, riboflavin-mediated photoreactive corneal crosslinking has been proposed as a therapeutic option to halt the progression of corneal thinning by inducing intra- and intermolecular crosslink formation within the collagen fibrils of the stroma, leading to stabilization of the disease. Here, we review the pathobiology of DM and KC in the context of corneal structure, the epidemiology behind the inverse correlation of DM and KC development, and the chemical mechanisms of lysyl oxidase-mediated crosslinking, advanced glycation end product-mediated crosslinking, and photoreactive riboflavin-mediated corneal crosslinking. The goal of this review is to define the biological and chemical pathways important in physiological and pathological processes related to collagen crosslinking in DM and KC.

Reevaluating the Effectiveness of Corneal Collagen Cross-linking and Its True Biomechanical Effect in Human Eyes

ABSTRACT The induction of cross-links in corneal tissue appears to be a promising technique to increase its stiffness and this has been the basis of treatment of keratoconus (KC) and corneal ectatic disease. However, there exists a striking discrepancy between the reported biomechanical effects of corneal collagen cross-linking (CXL) in vitro compared to in vivo, and this has not received much attention in the literature. Despite the documentation of an increase in corneal stiffness in vitro by many investigators, reports that provide evidence of measurable and consistent biomechanical changes in corneal rigidity in vivo after CXL are lacking. Indeed, the absence of documented in vivo biomechanical improvement in CXL-treated corneas is a conundrum, which needs to be further explored. To explain this discrepancy, it has been postulated that biomechanical changes induced by CXL are too subtle to be measured by currently available diagnostic tools or have characteristics not discernible by these technologies. However, the dynamic bidirectional applanation device (Ocular Response Analyzer) and dynamic Scheimpflug analyzer instruments (Corvis ST) have demonstrated the ability to quantify even subtle biomechanical differences in untreated KC corneas of different ectatic degree, and document the reduction in corneal hysteresis (CH) and corneal resistance factor (CRF) in situations where the corneal stiffness is reduced, such as after laser in situ keratomileusis and surface ablation procedures. It has also been possible to demonstrate an altered CH and CRF in patients with diabetes, smoking habit, glaucoma, Fuchs’ dystrophy, and corneal edema. It is puzzling that these diagnostic tools could document subtle biomechanical changes in these situations, yet fail to measure the purported changes induced by CXL on corneas with progressive KC. This failure to document significant and consistent biomechanical changes in corneal rigidity could suggest that CXL does not induce a simple reversal of the particular biomechanical deficits that characterize KC, or make the cornea significantly more resistant to bending forces as has been widely postulated. The absence of measurable biomechanical change in living KC corneas after CXL could be a consequence of biomechanical strengthening which is insignificant compared to the marked weakening caused by preexisting alteration of the collagen structure, disorganization of collagen fiber intertwining, and compromised structural–mechanical homogeneity that are hallmarks of keratoconic disease, especially in corneas with progressive KC. The changes in the cornea induced by CXL that have been described in vivo may instead be driven by a wound healing process in response to the removal of the corneal epithelial layer and subsequent exposure to riboflavin and ultraviolet-A (UVA). This paper will present evidence that sustains this hypothesis. How to cite this article Gatinel D. Reevaluating the Effect­iveness of Corneal Collagen Cross-linking and Its True Biomechanical Effect in Human Eyes. Int J Kerat Ect Cor Dis 2017;6(1):34-41.

Peculiarities of Biomechanical Properties of Ocular Tissue in Keratoconus

Considerable achievements having been recently made in modern diagnostics and treatment of keratoconus have not diminished the urgency of the given problem as the traditional views of the pathogenesis of keratoconus do not always allow to struggle effectively with this difficult and continuously progressing disease.The objective of the research was to study the peculiarities of biomechanical properties of the cornea in keratoconus.Materials and methods. The article presents the analysis of studying biomechanical properties of the cornea in keratoconus. 44 patients (88 eyes) with keratoconus and emmetropic refraction were examined. To calculate biomechanical indicators of the cornea there was carried out the comparative analysis between the measurements obtained with the use of several methods in the same patients, namely the Oculus Pentacam-Scheimpflug imaging device by a standard technique and the indicators calculated using the method proposed by us and the device for in vivo estimation of corneal rigidity.Results. Considerable advantages of using the developed method and the device for estimation of corneal rigidity in vivo in comparison with keratotopography on the Oculus Pentacam-Scheimpflug camera were registered which allowed us not only to reveal the presence of biomechanical disorders of the cornea, but also to differentiate their character. To describe the degree of changes in biomechanical properties of the cornea in vivo the coefficient of corneal rigidity was developed.Conclusions. Loading tests allow receiving more exact information on biomechanical properties of the cornea in comparison with standard researches on the Oculus Pentacam-Scheimpflug camera.

Collagen Cross-linking for the Treatment of Keratoconus in Pediatric Patients

ABSTRACT Keratoconus (KC) is a bilateral noninflammatory, ectatic corneal disorder. It is the most common primary ectasia affecting approximately 1 in 2,000 in the general population. Classically, the disease starts in puberty and progresses throughout the 3rd or 4th decades of life. Ocular signs and symptoms vary depending on disease severity. As the disease progresses, approximately 20% of KC eyes require penetrating keratoplasty. Collagen cross-linking (CXL) with ultraviolet-A (UVA) light and riboflavin is a new treatment that has emerged in the recent years. It is reported to slow the progression of the disease in its early stages, by increasing corneal rigidity and biomechanical stability. As the number of adult KC patients treated using this procedure grew, proving its safety and high efficacy, the pediatric KC patients population has started to receive special attention. In the pediatric KC patients’ eyes, corneas have been shown to be significantly steeper at the time of diagnosis compared to adults, and the severity of KC seems inversely correlated with age. Since treating KC in earlier age may be beneficiary, before developing an advanced disease that may require corneal transplantation, CXL in the pediatric age group has been advocated by many practitioners. The aim of this review is to collect and consolidate all known data regarding the efficacy and safety of CXL in the pediatric population. How to cite this article Hanna R, Berkwitz E, Castillo JH, Tiosano B. Collagen Cross-linking for the Treatment of Keratoconus in Pediatric Patients. Int J Kerat Ect Cor Dis 2015;4(3):94-99.

Imaging Mass Spectrometry by Matrix-Assisted Laser Desorption/Ionization and Stress-Strain Measurements in Iontophoresis Transepithelial Corneal Collagen Cross-Linking

Purpose.To compare biomechanical effect, riboflavin penetration and distribution in transepithelial corneal collagen cross-linking with iontophoresis (I-CXL), with standard cross linking (S-CXL) and current transepithelial protocol (TE-CXL).Materials and Methods.The study was divided into two different sections, considering, respectively, rabbit and human cadaver corneas. In both sections corneas were divided according to imbibition protocols and irradiation power. Imaging mass spectrometry by matrix-assisted laser desorption/ionization (MALDI-IMS) and stress-strain measurements were used. Forty-eight rabbit and twelve human cadaver corneas were evaluated.Results.MALDI-IMS showed a deep riboflavin penetration throughout the corneal layers with I-CXL, with a roughly lower concentration in the deepest layers when compared to S-CXL, whereas with TE-CXL penetration was considerably less. In rabbits, there was a significant increase (by 71.9% andP=0.05) in corneal rigidity after I-CXL, when compared to controls. In humans, corneal rigidity increase was not significantly different among the subgroups.Conclusions.In rabbits, I-CXL induced a significant increase in corneal stiffness as well as better riboflavin penetration when compared to controls and TE-CXL but not to S-CXL. Stress-strain in human corneas did not show significant differences among techniques, possibly because of the small sample size of groups. In conclusion, I-CXL could be a valid alternative to S-CXL for riboflavin delivery in CXL, preserving the epithelium.