Corneal Rigidity Research Articles

Опыт применения математического моделирования для прогноза результата лечения прогрессирующего кератоконуса

Abstract Original article Experience in the application of mathematical modeling for predicting the outcome of treatment of progressive keratoconus E.G. Solodkova, S.B. Izmailova, B.E. Malyugin, I.N. Zakharov, V.P. Fokin, S.V. Balalin, E.V. Lobanov, V.A. Sivolobov, V.H. Le S. Fyodorov Eye Microsurgery Federal State Institution, Volgograd branch, Volgograd, Russian Federation S. Fyodorov Eye Microsurgery Federal State Institution, Moscow, Russian Federation Volgograd State Technical University, Volgograd, Russian Federation Purpose. To analyze the results of applying mathematical modeling to plan, predict and control the effects of ultraviolet corneal crosslinking (UVCXL), to develop a customized method of local crosslinking and to evaluate its safety and effectiveness in comparison with a standard UVCXL method. Material and methods. COMSOL Multiphysics® was used for modeling of corneal biomechanics in eyes with keratoconus under external diagnostic exposure. 3D-images of stress and strain distribution in reliance to finite elements calculation were obtained. Their correlation with topographic and tomographic maps from Pentacam AXL and Corvis ST allowed defining localization and dimensions of the weakened cornea and elaborating a modified technique of UVCXL with its subsequent application in treatment of 30 persons (30 eyes) with 1st and 2nd stage keratoconus (by Amsler – Krumeich classification). Effectiveness and safety of the proposed approach were evaluated in comparison with a reference group (20 patients, 20 eyes with keratoconus of the 1st and 2nd degree, standard UVCXL). Results. This study represents application of corneal «digital double» for selection of optimal treatment option. Improvement of UCVA and BCVA was observed in all the patients within 6–12 months follow-up (p<0,01). Decrease of maximum keratometric value Kmax along with increase of biomechanical resistance with a reliable improvement of corneal rigidity SP-A1 were achieved in all the cases within 6–12 months follow-up (p<0,01). A credible amelioration of UCVA, BCVA and SP-A1 along with a decrease of an average Kmax were registered one month postoperatively after the standard UVCXL. Effectiveness of the proposed UVCXL technique was confirmed by incurrence of demarcation line in site of UVCXL application at the depth of 242,37±46,27 µm. Conclusion. The proposed personalized topographically and tomographically reliable method of UVCXL provides an evident stabilizing action due to improvement of corneal biomechanical resistance. Key words: corneal biomechanical properties, keratoconus, ultraviolet crosslinking of corneal collagen

The potential application of formulation with pimelic acid as eye drops for corneal collagen cross-linking

Background and aimKeratoconus is a slowly progressive and non-inflammatory disease of eye of unknown etiology characterized by significant structural degeneration, thinning and protrusion of cornea. Collagen cross linking using Riboflavin/ultraviolet A, paraformaldehyde and glutaraldehyde has been widely used to treat keratoconus, but these techniques have several clinical complications. This study aimed to develop a rapid, safer, less toxic and more effective method to increase the corneal stiffness hence treating keratoconus by using EDC/NHS coupling with pimelic acid (PA) as cross-linkers. MethodsThe viability of corneal epithelial and endothelial cells was examined using Alamar blue. The corneal collagen and tissue integrity were evaluated with Masson and hematoxylin and eosin stains respectively. Uniaxial tensile testing was conducted to determine the tissue stiffness. We further assessed the effective penetration depth of cross-linking by fluorescence dye and confocal microscopy. TUNEL assay was performed to detect the damaged DNA fragments in the presence of PA. ResultsThe effect of PA solution on corneal cross-linking showed a significant increase in corneal rigidity without affecting the epithelium integrity under neutralized pH condition, while DEC/NHS alone did not induce the mechanical property. The penetration depth showed consistent results with increased stiffness, which could be affected by the parameters including pH condition, coupling with or without PA. In addition, PA significantly decreased the percentage of TUNEL-positive cells compared to that of EDC/NHS only condition. The cytotoxic effect to endothelium was considered minimal and protected in the presence of PA. ConclusionsWe demonstrated PA as a potential alternative for cross-linking in the model of whole eye with intact epithelium and its protective role on endothelium. The administration of this chemical cross-linker stands as an extremely promising technique for the treatment of corneal keratoconus.

Transglutaminase-induced Cornea Collagen Crosslinking Effect on Central Corneal Thickness and Keratocyte Cell Density

Abstract
 Introduction & Objectives : This research is aimed to evaluate the effect of transglutaminase-induced corneal collagen crosslinking (CXL) on central corneal thickness (CCT) and keratocyte cell density in vivo.
 Methods : Twenty-eight white New Zealand rabbits were divided into four groups: the transglutaminase- induced CXL group, the epithelial-off CXL group, the transepithelial CXL group, and the control group. The ocular surface was treated with a 1 U/mL microbial transglutaminase solution, and both the epithelial-off and transepithelial groups were exposed to clinical ultraviolet A-riboflavin (UVA/RF). The efficacy of each group was evaluated on the 14th day after the procedures. Central corneal thickness was evaluated with Corneal Visualization Scheimpflug Technology (Corvis ST) and keratocyte cell density wad evaluated with histopathology examination.
 Results : Transglutaminase-induced CXL group exhibited the highest mean biomechanical CCT (370.14 ± 38.85) in comparison to the UVA/RF epithelial-off group (368.00 ± 25.48), the UVA/RF transepithelial group (369.86 ± 23.43), and the control group (365.14 ± 28.74). Still, there was no significant differences in both biomechanical CCT (p=0.990). Transglutaminase-induced CXL group had the highest mean of keratocyte cell density (43.26 ± 10.65) compared to UVA/RF epithelial-off (29.99 ± 4.79), UVA/RF transepithelial group (42.03 ± 6.55), and control group (34.36 ± 6.76). There was a significant difference between the group, with a p-value of 0.008.
 Conclusion : Transglutaminase shown that it produces favorable results for CCT and keratocyte density after CXL, which are two factors contributing to corneal rigidity. The outcomes are equivalent to riboflavin used as a conventional element in CXL.

Predictive Value of Dynamic Corneal Response Parameters Evaluated with Scheimpflug High-Speed Video (Corvis ST) on the Visual Field Progression in Prostaglandin Treated Ocular Hypertension and Open-Angle Glaucoma Patients.

The aim of this work is to compare the Corvis ST stress-strain index (SSI) and highest concavity (HC) parameters at baseline and 1month after initiating monotherapy with prostaglandin analogues (PGs) in eyes showing visual field (VF) progression or stability. In this prospective, single-center, observational study, newly diagnosed and treatment-naïve OAG patients were examined at baseline and 1month after beginning monotherapy with topical PGs monotherapy. Goldmann applanation tonometry pressure readings, Corneal Hysteresis (ORA-CH), and the Corvis ST measurements were obtained at both visits. VF progression (Humphrey) was evaluated based on data from 6 years of follow-up after the baseline visit. Stress-strain index (SSI) and HC parameters in progressing (P) and non-progressing (NP) eyes were the main outcome measures. Sixty-three eyes were analyzed; mean age was 64.63 ± 11.26years; 47 eyes were NP and 16 eyes were P according to the event analysis performed by the Humphrey device. There were no significant differences in IOP, CCT, or Corvis parameters between NP and P groups at baseline. Nevertheless, at 1 month, the SSI index was 1.60 ± 0.34 vs. 1.80 ± 0.34 (p = 0.003) in NP vs. P eyes, respectively. HC parameters were different between the groups at 1 month (p < 0.05) suggesting an increased scleral rigidity in the P group. There was no significant difference in IOP between groups at 1 month. The Corvis ST provides a corneal rigidity index (SSI) that seems to be related to VF progression when measured 1 month after initiating PGs monotherapy. Differences in HC parameters, indicative of increased scleral stiffness, are also evident at 1 month on latanoprost in the P eyes.

Safety of transglutaminase-induced corneal collagen cross-linking on the central cornea thickness and intraocular pressure in vivo

Background: Corneal collagen cross-linking (CXL) is a procedure for making bonds that connect polymer chains to one another. Corneal CXL aims to slow or stop the progression of keratoconus by using photooxidative therapy so as to increase stromal rigidity. Transglutaminase enzymes are currently widely used in the food industry. Recent studies have shown that mRNA, fibronectin, and transglutaminase were found to be more abundant in human corneal keratocytes treated with UVA and riboflavin. Transglutaminase is considered to reduce discomfort caused by UVA irradiation. Methods: A total of 21 white New Zealand rabbits were divided into three groups, namely, transglutaminase-induced CXL group, epithelial-off CXL group, and transepithelial CXL group. The ocular surface was treated with a 1 U/mL microbial transglutaminase solution, and both the epithelial-off and transepithelial groups were exposed to clinical ultraviolet A-riboflavin (UVA/RF). The efficacy of each group was evaluated on the 14th day after the procedures. The central corneal thickness (CCT) and intraocular pressure (IOP) were evaluated using Corneal Visualization Scheimpflug Technology (Corvis ST). Results: The transglutaminase-induced CXL group exhibited the highest mean CCT (370.14 ± 38.85) in comparison with the UVA/RF epithelial-off group (368.00 ± 25.48) and the UVA/RF transepithelial group (369.86 ± 23.43). The transglutaminase-induced CXL group had the highest IOP mean (8.50 ± 3.02) compared with the UVA/RF epithelial-off (6.50 ± 3.07) and UVA/RF transepithelial groups (7.00 ± 1.90). There were no significant differences in CCT (p = 0.990) or IOP (p = 0.563) between the groups. Conclusions: The findings of this study suggest that there are no significant differences between the transglutaminase-induced CXL group and the UVA/RF CXL group. The safety of transglutaminase-induced CXL could be comparable to that of UVA/RF CXL in terms of altering CCT and IOP, which are two factors contributing to corneal rigidity.

Short- and mid-term changes in CORVIS ST parameters in successful, adult orthokeratology patients

ABSTRACT Clinical relevance The changes in various biomechanical and tomographic characteristics of the cornea associated with orthokeratology may allow us to identify potential mid- and long-term structural alterations, resulting in a better understanding of the governing mechanisms of this procedure and in its optimisation. Background The study aimed at describing short and mid-term changes in CORVIS ST® parameters and indices in orthokeratology (ortho-k), and their diurnal variations. Methods A prospective observational study was designed in which several CORVIS ST® parameters of 75 new adult participants successfully fitted with overnight ortho-k Seefree® (Conóptica – Hecht Contactlinsen) contact lenses were explored. Measurements were conducted in baseline (BL) conditions and in the morning and evening at the one-night (1 NM/1NT), one-week (1WM/1 WT) and 3-month (3 MM/3MT) follow-up visits. Results Statistically significant differences were found in DARatio_2 mm, IntRad, ARTh, CBI and TBI following overnight ortho-k, when compared with BL values, with most values reaching stability at 1WM or reverting to BL values at 3 MM. The ARTh and CBI parameters showed some of the most significant temporal variations (both p < 0.001), probably reflecting the encountered differences in central corneal thickness between BL and 1WM (p = 0.010) and between BL and 3 MM (p = 0.016). In general, corneal rigidity was higher in the morning at all follow-up visits, and decreased during the day. No statistically significant changes in adjusted intraocular pressure values were found. Conclusion Ortho-k in adults may be considered a safe procedure in terms of short and mid-term changes in CORVIS ST® parameters. The observed alterations in most of the parameters provided by the Corvis ST® probably responded to the well-described changes in corneal pachymetry and tomography, rather than to actual alterations in corneal rigidity.

Corneal cross-linking guards against infectious keratitis: an experimental model

BackgroundPACK-CXL (photo-activated chromophore for keratitis–corneal cross-linking) is an alternative option in treatment of corneal infections. It inhibits corneal melting by increasing the stromal resistance, besides the microbicidal effect of photo-activated riboflavin.MethodsCorneal infection with Pseudomonas aeruginosa and Staph aureus bacteria was induced in 20 eyes of 10 rabbits after 6 weeks of corneal cross-linking in half of the eyes, while the other acted as control group. Clinical and corneal histopathological examination was done to evaluate the extent of inflammation, ulceration, organism penetration, and depth of corneal stromal affection.ResultsThe control eyes developed severe inflammation compared to the cross-linked eyes. Corneal melting occurred in 6 eyes in the control versus none in cross-linked group. Histopathological examination showed that the inflammation was confined to the superficial part of the stroma with localization of the inflammation in the cross-linked eyes in contrast to the control eyes that showed deep infiltration.ConclusionPACK-CXL provides infection localization through increasing the corneal rigidity and resistance to enzymatic digestion, even in the absence of the riboflavin microbicidal role. So, early PACK-CXL is worth to be considered in the IK treatment algorithm.

A Critical Assessment of Friedenwald's Technique for Estimating the Coefficient of Rigidity of the Cornea.

Purpose To determine if Friedenwald's technique for estimating the coefficient of corneal rigidity (Ko, units mmHg/μL), could differentiate between the cornea in keratoconus, normal eyes, and after crosslinking (CXL). Methods Two operators (1 and 2) independently measured Ko in three groups (keratoconus, normal, and post-CXL corneas), and repeated the procedure in some where their care remained unchanged and others after routine CXL (>28 days postop, epi-off treatment, 3.0 mW/cm2, 30 min). The data were subsequently used to quantify interoperator error, test-retest/intersessional reliability for estimation of Ko, the significance of intergroup differences, and the effect of CXL on Ko. Results The major findings were: (i) Ko values were not normally distributed; (ii) mean (±sd, 95% CI) interoperator error was -0.002 (±0.019, −0.006 to 0.003, n = 95) and the limit of agreement between the operators was ±0.039; (iii) RMS differences in the intersessional estimation of Ko values were 0.011 (operator 1) and 0.012 (operator 2); (iv) intergroup differences in Ko were not significant (p > 0.05); (v) intersessional change in Ko (y) was linearly related to Ko estimated (x) at 1st session (for operator 2 y = 1.187x−0.021, r = 0.755, n = 16, p < 0.01); and (vi) change in Ko (y1) after CXL was linearly related to Ko (x1) at preop (for operator 2 y1 = 0.880x1−0.016, r = 0.935, n = 20, p < 0.01). Conclusion Friedenwald's technique for estimating the Ko is prone to substantial interoperator error and intersessional differences. According to the technique, the change in Ko following CXL is on par with the expected intersessional change observed in controls.

Bilateral penetrating keratoplasty revealed advanced glaucoma in a case of mucopolysaccharidosis type VI

Introduction: We report a case of a patient with mucopolysaccharidosis (MPS) type VI disease who underwent bilateral penetrating keratoplasty. The insight into deeper ocular structures after successful keratoplasty enabled the diagnosis of glaucoma. Case Report: A 24-year-old male patient with genetically confirmed MPS VI disease was referred for ophthalmological co-assessment to our Department of Ophthalmology. The patient presented with low visual acuity of 6/200 in both eyes, and increased corneal thickness. The bilateral intraocular pressure was difficult to evaluate in association with the corneal thickness and rigidity. Due to total corneal opacification bilateral penetrating keratoplasty was performed. The successful keratoplasty allowed proper funduscopy and further diagnostic measurements leading to the diagnosis of advanced glaucoma. Conclusion: Although MPS VI is an orphan disease, intravenously applied enzyme replacement therapy with galsulfase has been established as a successful treatment. However, systemically administered therapy with galsulfase does not reduce or affect ocular symptoms and manifestations. The case demonstrates the high impact of early and regularly ophthalmic co-assessment in MPS VI patients, especially keeping in mind that not only corneal involvement can be present in MPS patients. Further-more, preservation of visual acuity is of high importance for participating in social and professional life.

Оценка изменения биомеханических свойств роговицы при кератэктазиях

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&lt;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.

Corneal Crosslinking Biomechanics Evaluated by a Novel and Easily Implemented Differential Tonometry Method

ABSTRACT Purpose: Evaluate potential corneal biomechanical changes following corneal crosslinking (CXL) by paired differential tonometry intraocular pressure (IOP) measurements with a Goldmann tonometer (GAT) prism and corneal compensating, correcting applanation tonometry surface (CATS) prism. Methods: IOP was measured prospectively on 23 unique eyes undergoing CXL for keratoconus with a GAT using a standard flat GAT prism and a curved corneal error correcting CATS prism before treatment and at 2 weeks, 2 months and 6 months after treatment. Concurrent measurements of central corneal thickness (CCT) and corneal hysteresis (CH) were completed. Results: Paired IOP measurements with standard GAT and corneal correcting CATS prisms indicated a significant sustained relative increase in the differential IOP between the two prisms after CXL (p = .002,0.051,0.062). CH initially decreased at two weeks post-CXL then returned to sustained pre-op levels (p = .033,0.20,0.20). CCT progressively decreased following CXL (p = .005). Discussion: Differential tonometry between standard GAT and corneal biomechanical compensating CATS prisms indicates findings consistent with increased corneal rigidity following CXL and may demonstrate a simple and sensitive method for measurement of relative corneal biomechanical changes due to pharmacologic agents and procedures.

The effect of corneal crosslinking on the rigidity of the cornea estimated using a modified algorithm for the Schiøtz tonometer.

Purpose:The aim of this study was to test a method for estimating corneal rigidity before and after cross-linking (CXL) using a Schiøtz tonometer.Methods:The study was performed in the Kyiv City Clinical Ophthalmological Hospital “Eye Microsurgical Center”, Ukraine. This was a prospective, consecutive, randomized, masked, case-by-case, clinical study. Corneal rigidity, indicated by the gradient (G) between lg applied weight and corresponding lg scale reading during Schiøtz tonometry, were obtained by increasing (A-mode) then reducing (D-mode) weights by two operators [A] in keratoconus, post-CXL and control subjects for estimation of (i) interoperator and (ii) intersessional errors, (iii) intergroup differences; [B] before and after CXL. Central corneal thickness CCT was measured by scanning slit pachymetry. ANOVA, t tests, linear regression were the statistical tools used.Results:Average interoperator difference (ΔG) was –0.120 (SD = ±0.294, 95%CI = –0.175 to –0.066). A significant correlation between ΔG and the mean of each pair of G values was found (r = –0.196, n = 112, P = 0.038). Intersessional differences in mean G values were insignificant (P > 0.05). There was a significant correlation between G at first session (X1) and difference between sessions (ΔG) [Operator 1, ΔG = 0.598x1–0.461, r = 0.601, n = 27, P = 0.009]. Significant intergroup differences in G were found (Operator 1, one-way ANOVA, F = 4.489, P = 0.014). The difference (Δ) between the pre-(X2) and post-CXL treatment G values was significantly associated with the pre-CXL treatment value (Operator 1, Δ = 1.970x2-1.622, r = 0.642, n = 18, P = <.001). G values were correlated with CCT in keratoconus and post-CXL.Conclusion:Corneal rigidity (G) estimated using the Schiøtz tonometer can be useful for detecting changes after CXL. However, G values are linked to CCT, can vary from time-to-time and the procedure is operator dependent.

Bruch Membrane Opening Minimum Rim Width Changes During Scleral Lens Wear.

The purpose of this study was to evaluate the change in Bruch membrane opening minimum rim width (BMO-MRW) during scleral lens (SL) wear. Twenty young white subjects were enrolled (10 women and 10 men); preliminary evaluation consisted of serial measurements of intraocular pressure (IOP) using a dynamic noncontact tonometer (Corvis, Oculus), which also yielded a corneal biomechanical index and central corneal thickness, and BMO-MRW using optical coherence tomography imaging (OCT) imaging (Spectralis, Heidelberg) through 6 hrs to establish normative diurnal curves. The next day, participants were fitted with a 16-mm SL on one eye, and OCT measurements were repeated over the same time span. Statistical analysis was carried out with a two-way analysis of variance. Multiple linear regressions were used to identify significant associations. The average diurnal variation for BMO-MRW without lenses was -4.65 μm (95% confidence interval [CI], 0.52-8.77) after 6 hours, whereas it decreased by 8 μm (95% CI, 3.87-12.12; P<0.001) after 6 hours of SL wear. The difference between variations after 6 hours was then -3.35 μm (P=0.029). Variation of the BMO-MRW did not significantly correlate with corneal rigidity (CR), central corneal thickness (CCT), and refractive error (r=-0.224, -0.054 and -0.085, respectively). Scleral lens wear induces a statistically significant decrease in BMO-MRW that could potentially be attributed to a change in IOP. The change in BMO-MRW was not affected by CR, CCT, or refractive error. Further studies are needed to better understand the significance of the observed changes at the optic nerve head during scleral lens wear.

Corneal stromal stem cells restore transparency after N2 injury in mice.

Corneal scarring associated with various corneal conditions is a leading cause of blindness worldwide. The present study aimed to test the hypothesis that corneal stromal stem cells have a therapeutic effect and are able to restore the extracellular matrix organization and corneal transparency in vivo. We first developed a mouse model of corneal stromal scar induced by liquid nitrogen (N2) application. We then reversed stromal scarring by injecting mouse or human corneal stromal stem cells in injured cornea. To characterize the mouse model developed in this study and the therapeutic effect of corneal stromal stem cells, we used a combination of in vivo (slit lamp, optical coherence tomography, in vivo confocal microscopy, optical coherence tomography shear wave elastography, and optokinetic tracking response) and ex vivo (full field optical coherence microscopy, flow cytometry, transmission electron microscopy, and histology) techniques. The mouse model obtained features early inflammation, keratocyte apoptosis, keratocyte transformation into myofibroblasts, collagen type III synthesis, impaired stromal ultrastructure, corneal stromal haze formation, increased corneal rigidity, and impaired visual acuity. Injection of stromal stem cells in N2‐injured cornea resulted in improved corneal transparency associated with corneal stromal stem cell migration and growth in the recipient stroma, absence of inflammatory response, recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored stromal ultrastructure, decreased stromal haze, decreased corneal rigidity, and improved vision. Our study demonstrates the ability of corneal stromal stem cells to promote regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen.

Characterization of In Vivo Biomechanical Properties in Macular Corneal Dystrophy

To measure and compare corneal biomechanics in patients with macular corneal dystrophy (MCD), versus those who underwent penetrating keratoplasty (PK) for MCD, versus normal subjects. Cross-sectional study. This study enrolled 24 eyes with MCD, 25 eyes that underwent PK in patients with preoperative diagnosis of MCD, and 28 normal eyes. The ocular response analyzer was used to measure corneal biomechanical properties, including corneal resistance factor (CRF) and corneal hysteresis (CH). Intraocular pressure (IOP) was measured using a Goldmann applanation tonometer, and central corneal thickness (CCT) was measured using an ultrasonic pachymeter. The CCT, CRF, CH, and IOP were compared among the study group. CCT was significantly lower in the MCD group (423 ± 47 mμ) than in the PK group (541 ± 31 mμ; P < .001) and the controls (540 ± 26 mμ; P < .001). Meanwhile, CCT was comparable between the PK and control groups (P= .98). CRF did not differ between the MCD (8.34 ± 2.12mm Hg) and the PK (8.66 ± 1.66mm Hg) groups (P= .89); however, both of these groups had lower CRF values than the control (9.76 ± 1.83mm Hg, P= .02) group. No significant differences were observed among the 3 groups in CH (P= .13). IOP values did not differ between the MCD (11.25 ± 1.69mm Hg) and PK (12.0 ± 2.67mm Hg) groups (P= .95); however, the IOP values for both of these groups differed significantly from those of the controls (13.46 ± 2.17mm Hg; P= .006). CRF was significantly reduced in MCD and did not return to normal values even after PK. The reduced corneal rigidity could result in underestimating IOP in patients with MCD and in those undergoing PK for this stromal dystrophy.

Corneal pulsation and biomechanics during induced ocular pulse. An ex-vivo pilot study.

The purpose of this study was to ascertain the relationships between the amplitude of the corneal pulse (CP) signal and the parameters of corneal biomechanics during ex-vivo intraocular pressure (IOP) elevation experiments on porcine eyes with artificially induced ocular pulse cycles. Two experiments were carried out using porcine eyes. In the first one, a selected eye globe was subjected to three IOP levels (15, 30 and 45 mmHg), where changes in physical ocular pulse amplitude were controlled by infusion/withdrawal volumes (ΔV). In the second experiment, six eyes were subjected to IOP from 15 mmHg to 45 mmHg in steps of 5 mmHg with a constant ΔV, where corneal deformation parameters were measured using Corvis ST. In both experiments, at each IOP, the CP and IOP signals were acquired synchronically using a non-contact ultrasonic distance sensor and a pressure transmitter, respectively. Based on the amplitudes of the CP and IOP signals ocular pulse based corneal rigidity index (OPCRI) was calculated. Results indicate positive correlations between ΔV and the physical ocular pulse amplitude, and between ΔV and the corneal pulse amplitude (both p < 0.001). OPCRI was found to increase with elevated IOP. Furthermore, IOP statistically significantly differentiated changes in OPCRI, the amplitudes of CP and IOP signals and in most of the corneal deformation parameters (p < 0.05). The partial correlation analysis, with IOP as a control variable, revealed a significant correlation between the length of the flattened cornea during the first applanation (A1L) and the corneal pulse amplitude (p = 0.002), and between A1L and OPCRI (p = 0.003). In conclusion, this study proved that natural corneal pulsations, detected with a non-contact ultrasonic technique, reflect pressure-volume dynamics and can potentially be utilized to assess stiffness of the cornea. The proposed new rigidity index could be a simple approach to estimating corneal rigidity.

Anterior Chamber Angles in Different Types of Mucopolysaccharidoses

To evaluate the anterior chamber angle status and estimate the intraocular pressure (IOP) in patients with mucopolysaccharidoses (MPSs) type I, II, IV, and VI. Prospective cross-sectional study. This study enrolled 27 consecutive MPS patients (8 patients with MPS I, 4 patients with MPSII, 9 patients with MPS IV, and 6 patients with MPS VI) and 20 normal control subjects. Anterior chamber angle status was evaluated by swept-source optical coherence tomography and IOP was estimated by the new-generation tonometer Corvis ST. Twelve eyes (6 patients) of 15 eyes (8 patients) with MPS I had narrow angles or peripheral iridocorneal touches together with elevated IOP (80%). Six eyes (3 patients) of 8 eyes (4 patients) with MPS II had plateau iris configuration, but all 8 eyes had normal IOP. All 18 eyes (9 patients) with MPS IV had normal angle structures, but 8 eyes (4 patients) had elevated IOP (44.4%). Nine eyes (5 patients) of 11 eyes (6 patients) with MPS VI had shallow but not closed angles (81.8%). Among these 9 eyes, 5 eyes had elevated IOP, and 4 of these 5 eyes had IOP >30mm Hg. The trabecular iris angles of MPS types I, II, and VI were smaller than those of MPS type IV and of the control subjects. The angle recess areas of MPS types I and VI were smaller than those of MPS type IV and of the control subjects. MPS type I patients are prone to have glaucoma with narrow or closed angles; MPS type II patients tend to have plateau iris; MPS type IV patients are vulnerable to open-angle glaucoma; MPS type VI patients have narrow angles not as close as those of MPS type I. MPS types I, IV, and VI had higher IOP estimates than the control subjects, but only MPS I and IV had higher corrected IOP estimates than the control subjects. The ordinary IOP estimates in MPS VI patients may be falsely high because of clouded corneas and increased corneal rigidity. Swept-source optical coherence tomography helps ophthalmologist investigate the angle structure and the pathophysiology of glaucoma caused by MPS.

Combined corneal CXL and photorefractive keratectomy for treatment of keratoconus: a review

Keratoconus and iatrogenic keratectasia are the corneal ectatic disorders occurring due to biomechanical weakening of the cornea resulting in distorted images, myopia, and irregular astigmatism. Corneal collagen cross-linking (CXL) is performed to arrest keratoconus successfully. The main aim of this review is to discuss the safety and efficacy of the adjuvant therapies, such as the combination of CXL and photorefractive keratectomy (PRK) for the treatment of corneal ectatic disorders. A comprehensive literature search was performed using PubMed, MEDLINE, and Scopus using keywords 'collagen' 'keratoconus', 'keratectasia', 'collagen cross-linking', and 'photorefractive keratectomy'. Search results were restricted to clinical studies published in English. Corneal CXL effectively arrests the progression of keratoconus by enhancing corneal rigidity. However, functional vision is not improved by cross-linking. Combining CXL to refractive surgeries such as topography-guided PRK or transepithelial PRK is found to be a safe and effective method in providing corneal stability as well as significantly improving functional visual acuity with few minor complications. This combined technique also prevents regression of keratoconus and reduce the risk of keratectasia. CXL combined with PRK is a promising therapeutic approach in ophthalmology that can be successfully used to treat progressive keratoconus and other corneal ectatic disorders and to enhance visual acuity.

Significance of corneal rigidity at measuring of intraocular pressure

AbstractPurposeTo optimize tactics of determination of IOP for emmetropic and myopic eyes by application a correction to the coefficient on cornea rigidity (KER).MethodsThe 160 myopic and 80 emmetropic eyes were included in the study. All eyes were examined with the methods of the measuring of cornea rigidity in vivo (Sergienko N.M., Shargorodska I.V. 2013).ResultsThe results showed no dependence of cornea rigidity was educed from the cornea central thickness (r = 0.04) and sagital front‐back size of eyes for all inspected patients (r = 0.12). Cross‐correlation dependence between these indexes was statistically not reliable (p &gt; 0.05). The results of analysis testified to high the degree of dependence of coefficient cornea rigidity from age and sex of patient (r = 0.53 and r = 0.59 accordingly, p &lt; 0.05), refraction (r = 0.77, p &lt; 0.05), spherical equivalent (r = 0.79, p &lt; 0.05). The most strong cross‐correlation dependence was educed between KER and degree of curvature of cornea in a «steep» meridian (r = 0.78, p &lt; 0.05), elevation of back cornea surface of (r= 0.93, p &lt; 0.05) and exentrisite (r = 0.87).ConclusionThe cornea rigidity index are forward as an integral index that takes into account influence of different factors: age, sex, clinical refraction, spherical equivalent and others. Using of cornea rigidity index for measuring of level IOP will allow more exactly to estimate, removing influence of central cornea thickness on level IOP.ReferencesThe problem of study of biomechanics properties of cornea a long ago attracts attention researchers (Perkins E.S., 1981; Phillips J.R., 1990; Iomdina E.N., 2006; Svetlova O.V., 2010). The functional features of co‐operation of biomechanical properties of cornea with other eye regulator systems of eye can play substantial influence on exactness to measuring of ophthalmotonus (Young F.A., Leary G.A., 1991; Koshitz I.N., 2001).

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.