Effect of corneal cross-linking on biomechanical changes following transepithelial photorefractive keratectomy and femtosecond laser-assisted LASIK.

Purpose: To evaluate the change in corneal biomechanics in patients with postoperative ectasia risk when combining two common laser vision correction procedures (tPRK and FS-LASIK) with cross-linking (in tPRK Xtra and FS-LASIK Xtra). Methods: The study included 143 eyes of 143 myopic, astigmatic patients that were divided into non-cross-linked refractive surgery groups (non-Xtra groups, tPRK and FS-LASIK) and cross-linked groups (Xtra groups, tPRK Xtra and FS-LASIK Xtra) according to an ectasia risk scoring system. The eyes were subjected to measurements including the stress-strain index (SSI), the stiffness parameter at first applanation (SP-A1), the integrated inverse radius (IIR), the deformation amplitude at apex (DA), and the ratio of deformation amplitude between apex and 2 mm from apex (DARatio2mm). The measurements were taken preoperatively and at 1, 3, and 6 months postoperatively (pos1m, pos3m, and pos6m). Posterior demarcation line depth from the endothelium (PDLD) and from the ablation surface (DLA) were recorded at pos1m. Results: SP-A1 significantly decreased, while IIR, deformation amplitude, and DARatio2mm increased significantly postoperatively in all four groups (p < 0.01)-all denoting stiffness decreases. In the FS-LASIK group, the changes in IIR, DA, and DARatio2mm were 32.7 ± 15.1%, 12.9 ± 7.1%, and 27.2 ± 12.0% respectively, which were significantly higher (p < 0.05) compared to 20.1 ± 12.8%, 6.4 ± 8.2%, and 19.7 ± 10.4% in the FS-LASIK Xtra group. In the tPRK group, the change in IIR was 27.3 ± 15.5%, significantly larger than 16.9 ± 13.4% in the tPRK Xtra group. The changes of SSI were minimal in the tPRK (-1.5 ± 21.7%, p = 1.000), tPRK Xtra (8.4 ± 17.9%, p = 0.053), and FS-LASIK Xtra (5.6 ± 12.7%, p = 0.634) groups, but was significant in the FS-LASIK group (-12.1 ± 7.9%, p < 0.01). After correcting for baseline biomechanical metrics, preoperative bIOP and the change in central corneal thickness (△CCT) from pre to pos6m, the changes in the IIR in both FS-LASIK and tPRK groups, as well as DA, DARatio2mm and SSI in the FS-LASIK group remained statistically greater than their corresponding Xtra groups (all p < 0.05). Most importantly, after correcting for these covariates, the changes in DARatio2mm in the FS-LASIK Xtra became statistically smaller than in the tPRK Xtra (p = 0.017). Conclusion: The statistical analysis results indicate that tPRK Xtra and FS-LASIK Xtra effectively reduced the biomechanical losses caused by refractive surgery (tPRK and FS-LASIK). The decrease in corneal overall stiffness was greater in FS-LASIK than in tPRK, and the biomechanical enhancement of CXL was also higher following LASIK than after tPRK.

Performance of Corvis ST Parameters Including Updated Stress-Strain Index in Differentiating Between Normal, Forme-Fruste, Subclinical, and Clinical Keratoconic Eyes.

PURPOSE: This study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus at different disease stages and normal eyes. DESIGN: Diagnostic accuracy analysis to distinguish disease stages. METHODS: 1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-Ⅰ, 175 eyes), moderate clinical keratoconus (CKC-Ⅱ, 204 eyes), and severe clinical keratoconus (CKC-Ⅲ, 199 eyes). Each eye was subjected to a Corvis ST examination to determine the central corneal thickness (CCT), biomechanically corrected intraocular pressure (bIOP), SSIv2 (updated stress-strain index), and other 8 Corvis parameters including the stress-strain index (SSIv1), stiffness parameter at first applanation (SP-A1), first applanation time (A1T), Ambrósio relational thickness to the horizontal profile (ARTh), integrated inverse radius (IIR), maximum deformation amplitude (DAM), ratio between deformation amplitude at the apex and at 2 mm nasal and temporal (DARatio2), and Corvis biomechanical index (CBI). The sensitivity and specificity of these parameters in diagnosing keratoconus were analyzed through receiver operating characteristic curves. RESULTS: Before and after correction for CCT and bIOP, SSIv2 and ARTh were significantly higher and IIR and CBI were significantly lower in the normal group than in the FFKC group, SKC group and the 3 CKC groups (all P < .05). There were also significant correlations between the values of SSIv2, ARTh, IIR, CBI, and the CKC severity (all P < .05). AUC of SSIv2 was significantly higher than all other Corvis parameters in distinguishing normal eyes from FFKC, followed by IIR, ARTh and CBI. CONCLUSION: Corvis ST's updated stress-strain index, SSIv2, demonstrated superior performance in differentiating between normal and keratoconic corneas, and between corneas with different keratoconus stages. Similar, but less pronounced, performance was demonstrated by the IIR, ARTh and CBI.

Effect of intrastromal corneal ring segments on in vivo corneal biomechanics in keratoconus: 1-year results.

PURPOSE: To evaluate the 1-year effects of the implantation of intrastromal corneal ring segments (ICRS) in keratoconus (KC) on the dynamic corneal response (DCR) parameters obtained with the Corvis. SETTING: Fernández-Vega Ophthalmological Institute, Oviedo, Spain. DESIGN: Prospective, single-center, clinical study. METHODS: Included were patients who underwent ICRS implantation for KC over a period of 1 year. On the day of the surgery and at least 6 months after ICRS implantation, the following measurements were made: corrected distance and uncorrected distance visual acuity, corneal tomography indices with the Pentacam, biomechanically corrected intraocular pressure and the Corvis DCRs (integrated inverse concave radius, deformation amplitude ratio, stiffness parameter at first applanation, stress-strain index [SSI] and the highest concavity radius). RESULTS: 30 eyes were included with a mean follow-up time of 15 months. Statistical analysis showed that ICRS implantation induced significant improvements in corneal biomechanics measurements between preoperative and long-term follow-up as demonstrated by a significant increase in SSI (P = .003). To confirm that this difference was actually induced due to a stiffening between early postoperative (previously published) and long-term an additional t-test was done between month 1 and late follow-up which confirmed a significant stiffening in the value of SSI (P = .01). CONCLUSIONS: Patients implanted with ICRS alone for KC showed a significantly stiffer response due to increased structural support compared with preoperative values and 1 month postoperative.

Assessment of the specificity of corvis biomechanical index-laser vision correction (CBI-LVC) in stable corneas after phototherapeutic keratectomy.

PURPOSE: The Corvis Biomechanical Index-Laser Vision Correction (CBI-LVC) is a biomechanical index to detect ectasia in post-refractive surgery patients (PRK, LASIK, SMILE). This study aims to evaluate the distribution of the CBI-LVC in stable patients who underwent Phototherapeutic Keratectomy (PTK) compared to PRK patients. METHODS: Patients who underwent PRK and PTK performed between 2000 and 2018 in Humanitas Research Hospital, Rozzano, Milan, Italy and remained stable for at least four years post-surgery were included. All eyes were examined with the Corvis ST (Oculus, Germany), whose output allows the calculation of the CBI-LVC. The distribution and specificity of the CBI-LVC in the two populations were estimated using a Wilcoxon Mann-Whitney test and compared. RESULTS: 175 eyes of 148 patients were included (85 eyes of 50 PTK patients and 90 eyes of 90 PRK patients). The distribution of CBI-LVC in the two groups showed a minor difference, with a median value in PRK patients of 0.000 (95% CI 0.000; 0.002) and 0.008 (95% CI 0.000; 0.037) in PTK patients (Mann-Whitney U test p = 0.023). The statistical analysis showed that the CBI-LVC provided a specificity of 92.22% in the PRK group, while in the PTK group it was 82.35%. Nevertheless, this difference was not statistically significant (Chi-squared test with Yates, p = 0.080). CONCLUSION: CBI-LVC provided similar specificity in stable PTK patients compared to those who underwent PRK. These results suggest that the CBI-LVC could be a useful tool to aid corneal surgeons in managing PTK patients.

Introduction and Clinical Validation of an Updated Biomechanically Corrected Intraocular Pressure bIOP (v2).

PURPOSE: To improve the stability of the Corvis ST biomechanically-corrected intraocular pressure measurements (bIOP) after refractive surgery and its independence of corneal biomechanics. METHODS: A parametric study was carried out using numerical models simulating the behavior of the eye globe under the effects of IOP and Corvis ST external air pressure and used to develop a new algorithm for bIOP; bIOP(v2). It was tested on 528 healthy participants to evaluate correlations with CCT and age. Its ability to compensate for the geometrical changes was tested in 60 LASIK and 80 SMILE patients with six months follow up. The uncorrected Corvis ST IOP (CVS-IOP) and the two versions of biomechanically corrected IOP; bIOP(v1) and bIOP(v2), were compared. RESULTS: In the healthy dataset, bIOP(v2) had weak and non-significant correlation with both CCT (R = -0.048, p = .266) and age (R = 0.085, p = .052). For bIOP(v1), the correlation was non-significant with CCT (R = -0.064, p = .139) but significant with age (R = -0.124, p < .05). In both LASIK and SMILE groups, the median change in bIOP(v2) following surgery was below 1 mmHg at follow-up stages and the interquartile range was smaller than both bIOP(v1) and CVS-IOP. CONCLUSION: The bIOP(v2) algorithm performs better than bIOP(v1) and CVS-IOP in terms of correlation with CCT and age. The bIOP(v2) also demonstrated the smallest variation after LASIK and SMILE refractive surgeries indicating improved ability to compensate for geometrical changes.

Long-term Effects of Riboflavin Ultraviolet-A-Induced CXL With Different Irradiances on the Biomechanics of In Vivo Rabbit Corneas.

PURPOSE: To evaluate the long-term effects of ultraviolet-A corneal cross-linking (CXL) with different irrandiances on the biomechanical properties of rabbit corneas and the corresponding changes in stromal microstructure. METHODS: The study involved the left eyes of 85 healthy white Japanese rabbits, randomly divided into five groups (n = 16 to 18 each). After removing the epithelium, the first four groups were exposed to riboflavin (0.22% concentration by volume) and ultraviolet-A (370 nm) at different CXL irradiations but with the same total dose (5.4 J/cm2). The four groups were defined as standard CXL (SCXL; 3 mW/cm2 for 30 minutes, n = 17), accelerated CXL1 (ACXL1; 9 mW/cm2 for 10 minutes, n = 16), accelerated CXL2 (ACXL2; 18 mW/cm2 for 5 minutes, n = 17), and accelerated CXL3 (ACXL3; 30 mW/cm2 for 3 minutes, n = 17). The control group (n = 18) was treated with riboflavin without ultraviolet-A exposure. Nine months after CXL, 10 corneas from each group were tested ex vivo under inflation, and the tangent modulus (Et) was estimated using an inverse analysis process. The remaining six to eight specimens in each group were examined by electron microscopy to determine the mean fibril diameter and interfibrillar spacing. RESULTS: The SCXL and ACXL1 groups showed statistically significant differences in Et at all stresses (0.005, 0.010, and 0.015 MPa) analyzed compared to the control group (all P < .01), but the differences were non-significant in the ACXL3 group (P = 1.000, .785, and .679, respectively). For the ACXL2 group, there was no statistical difference in Et under the low stress of 0.005 MPa (P = .155), but the differences became significant at 0.010 and 0.015 MPa when compared with the control group (all P < .05). CONCLUSIONS: CXL had a significant effect on corneal biomechanics in both standard and accelerated procedures. However, standard CXL was the most effective, and this effectiveness decreased gradually with increasing ultraviolet-A power intensity. [J Refract Surg. 2022;38(6):389-397.].

In vivo Assessment of Localised Corneal Biomechanical Deterioration With Keratoconus Progression.

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.

The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics.

BACKGROUND: Knee joint injuries, common in athletes, have a high risk of developing post-traumatic osteoarthritis (PTOA). Ligaments, matrix-rich connective tissues, play important mechanical functions stabilising the knee joint, and yet their role post-trauma is not understood. Recent studies have shown that ligament extracellular matrix structure is compromised in the early stages of spontaneous osteoarthritis (OA) and PTOA, but it remains unclear how ligament matrix pathology affects ligament mechanical function. In this study, we aim to investigate both structural and mechanical changes in the anterior cruciate ligament (ACL) in a mouse model of knee trauma. METHODS: Knee joints were analysed following non-invasive mechanical loading in male C57BL/6 J mice (10-week-old). Knee joints were analysed for joint space mineralisation to evaluate OA progression, and the ACLs were assessed with histology and mechanical testing. RESULTS: Joints with PTOA had a 33-46% increase in joint space mineralisation, indicating OA progression. Post-trauma ACLs exhibited extracellular matrix modifications, including COL2 and proteoglycan deposition. Additional changes included cells expressing chondrogenic markers (SOX9 and RUNX2) expanding from the ACL tibial enthesis to the mid-substance. Viscoelastic and mechanical changes in the ACLs from post-trauma knee joints included a 20-21% decrease in tangent modulus at 2 MPa of stress, a decrease in strain rate sensitivity at higher strain rates and an increase in relaxation during stress-relaxation, but no changes to hysteresis and ultimate load to failure were observed. CONCLUSIONS: These results demonstrate that ACL pathology and viscoelastic function are compromised in the post-trauma knee joint and reveal an important role of viscoelastic mechanical properties for ligament and potentially knee joint health.

Biomechanical Effects of tPRK, FS-LASIK, and SMILE on the Cornea.

Purpose: The objective of this study is to evaluate the in vivo corneal biomechanical response to three laser refractive surgeries. Methods: Two hundred and twenty-seven patients who submitted to transepithelial photorefractive keratectomy (tPRK), femtosecond laser-assisted in-situ keratomileusis (FS-LASIK), or small-incision lenticule extraction (SMILE) were included in this study. All cases were examined with the Corvis ST preoperatively (up to 3 months) and postoperatively at 1, 3, and 6 months, and the differences in the main device parameters were assessed. The three groups were matched in age, gender ratio, corneal thickness, refractive error corrections, optical zone diameter, and intraocular pressure. They were also matched in the preoperative biomechanical metrics provided by the Corvis ST including stiffness parameter at first applanation (SP-A1), integrated inverse radius (IIR), deformation amplitude (DA), and deformation amplitude 2 mm away from apex and the apical deformation (DARatio2mm). Results: The results demonstrated a significant decrease post-operation in SP-A1 and significant increases in IIR, DA, and DARatio2mm (p < 0.05), all of which indicated reductions in overall corneal stiffness. Inter-procedure comparisons provided evidence that the smallest overall stiffness reduction was in the tPRK group, followed by the SMILE, and then the FS-LASIK group (p < 0.05). These results remained valid after correction for the change in CCT between pre and 6 months post-operation and for the percentage tissue altered. In all three surgery groups, higher degrees of refractive correction resulted in larger overall stiffness losses based on most of the biomechanical metrics. Conclusion: The corneal biomechanical response to the three surgery procedures varied significantly. With similar corneal thickness loss, the reductions in overall corneal stiffness were the highest in FS-LASIK and the lowest in tPRK.

The Effect of Intracorneal Ring Segments Implantation for Keratoconus on In Vivo Corneal Biomechanics Assessed With the Corvis ST.

PURPOSE: To evaluate the effect of the implantation of intracorneal ring segments (ICRS) in keratoconus on the dynamic corneal response (DCR) parameters obtained with the Corvis ST (Oculus Optikgeräte GmbH). METHODS: This prospective clinical study included patients who underwent ICRS implantation for keratoconus over a period of 1 year. On the day of the surgery and at least 1 month after ICRS implantation, the following measurements were made: corrected and uncorrected distance visual acuity, corneal tomography indices with the Pentacam (Oculus Optikgeräte GmbH), biomechanically corrected intraocular pressure (bIOP), Corvis ST DCR parameters, integrated inverse concave radius (1/R), deformation amplitude ratio (DA ratio), stiffness parameter at first applanation (SP-A1), stress-strain index (SSI), and highest concavity radius (HRC). RESULTS: Fifty-one eyes of 40 patients were included with a median follow-up time of 3 months (interquartile ratio [IQR]: 2 to 6 months). Statistical analysis showed that ICRS implantation did not affect corneal biomechanical measurements evaluated with the Corvis ST, which was demonstrated by non-significant changes in the SP-A1 (P = .637), 1/R (P = .647), HRC (P = .177), DA ratio (P = .735), and SSI (P = .501). Additionally, the results showed that bIOP measurements were not significantly affected by ICRS implantation (P = .113). CONCLUSIONS: ICRS implantation does not affect corneal biomechanical measurements in early follow-up. [J Refract Surg. 2022;38(4):264-269.].

In Vivo Biomechanical Changes Associated With Keratoconus Progression.

PURPOSE: To assess the biomechanical deterioration arising from keratoconus progression in-vivo. METHODS: The preoperative examinations of 32 progressive KC cases that were submitted to corneal cross-linking were evaluated. The examinations included the corneal tomography using the Pentacam HR and biomechanical parameters assessed by the Corvis ST (Oculus, Wetzlar, Germany). The results were recorded at two time points, the latter of which was at the last visit before the CXL procedure. Keratoconus progression was characterised by a significant change in the ABCD system. RESULTS: At the last follow-up visit (41.4 ± 40.9 months) all morphological parameters of the ABCD grading system showed significant deterioration (p < 0.001). The comparative analyses revealed a significant reduction in corneal stiffness expressed by a significant reduction in the stress-strain index (SSI: -0.10 ± 0.06, p < 0.001), the Stiffness parameter A1 (SP-A1: -6.1 ± 12.0 mmHg/mm, p = 0.011), by a significant increase in the integrated Inverse Radius (IIR: 0.95 ± 1.04 mm-1, p < 0.001) and in the deflection amplitude (DA) ratio (0.23 ± 0.58, p = 0.034). A barely significant increase in the DA also pointed towards corneal stiffness reduction. (0.04 ± 0.13 mm, p = 0.056). The SSI and the IIR were the indices with the smallest overlaps between the two examinations. CONCLUSIONS: It has been demonstrated in-vivo that corneal biomechanical deterioration occurs with keratoconus progression. The larger changes observed in the SSI and the IIR when compared to the remaining biomechanical parameters suggests that these parameters could be suitable to assess the corneal stiffness reduction in keratoconus natural progression.

Evaluation of corneal biomechanical behavior in vivo for healthy and keratoconic eyes using the stress-strain index.

PURPOSE: To evaluate the characteristics of corneal material properties in healthy individuals and keratoconic patients using the stress-strain index (SSI). SETTING: Vincieye Clinic in Milan, Italy, and Instituto de Olhos Renato Ambrósio in Rio de Janeiro, Brazil. DESIGN: Retrospective observational cross-sectional study. METHODS: Records of 1221 patients were divided into 3 groups: healthy corneas (n = 728), bilateral keratoconus (KC, n = 388), and very asymmetric ectasia (VAE, n = 105) when patients presented with clinical ectasia in 1 eye and normal topography (VAE-NT) in the fellow eye. All patients were examined with Pentacam HR and Corvis ST. Severity of KC cases was stratified according to the Pentacam topographic KC classification. The SSI distribution across the different groups and its correlation with age, biomechanically corrected intraocular pressure (bIOP), and central corneal thickness (CCT) were assessed. RESULTS: A statistically significant difference between healthy individuals and each of the keratoconic groups ( P < .001) was observed, and a progressive reduction in the SSI was observed across the groups. A significant correlation was observed between the SSI and age in all groups ( P < .010) but KC severe subgroup ( P = .361). No correlation between the SSI and bIOP and CCT was observed in all KC subgroups and VAE-NT groups ( P > .050). Among healthy eyes, there was only a mild correlation between the SSI and bIOP ( R = 0.12, P = .002) and CCT ( R = 0.13, P = .001). CONCLUSIONS: This study estimates the in vivo corneal material properties in healthy individuals and patients with KC using a new method. The SSI showed a progressive deterioration within the advance in disease stages while being relatively independent of bIOP and CCT but positively correlated with age.

Effect of Mydriasis-Caused Intraocular Pressure Changes on Corneal Biomechanical Metrics.

Purpose: To evaluate the dependence of biomechanical metrics on intraocular pressure (IOP). Methods: 233 refractive surgery patients were included in this study-all were examined 3 times with the Corvis ST before and after dilation, and the differences (∆) in the main device parameters were assessed. The data collected included the biomechanically corrected IOP (bIOP), the central corneal thickness (CCT), and six dynamic corneal response (DCR) parameters, namely DA, DARatio2mm, IIR, SP-A1, CBI, and SSI. Participants were divided into three groups according to the changes in patients' bIOP after mydriasis. Results: Intra-operator repeatability was generally high in most of the DCR parameters obtained before and after dilation. The mean changes in bIOP and CCT after dilation were -0.12 ± 1.36 mmHg and 1.95 ± 5.23 µm, respectively. Only ∆DARatio2mm, ∆IIR, and ∆CBI exhibited a statistically significant correlation with ∆CCT (p < 0.05). The changes in all DCR parameters, especially ∆DA and ∆SP-A1 were also correlated with ∆bIOP (p < 0.01)-a 1-mmHg change in bIOP was associated, on average, with 5.612 and -0.037 units of change in SP-A1 and DA, respectively. In contrast, the weakest correlation with ∆bIOP was exhibited by ∆SSI. Conclusion: Most corneal DCR parameters, provided by the Corvis ST, were correlated with IOP, and more weakly with CCT. Changes experienced in CCT and IOP should therefore be considered in studies on corneal biomechanics and how it is affected by disease progression and surgical or medical procedures.

A new approach for quantifying epithelial and stromal thickness changes after orthokeratology contact lens wear.

The aim of the study was to develop an automatic segmentation approach to optical coherence tomography (OCT) images and to investigate the changes in epithelial and stromal thickness profile and radius of curvature after the use of orthokeratology (Ortho-K) contact lenses. A total of 45 right eyes from 52 participants were monitored before, and after one month of, uninterrupted overnight Ortho-K lens wear. The tomography of their right eyes was obtained using optical OCT and rotating Scheimpflug imaging (OCULUS Pentacam). A custom-built MATLAB code for automatic segmentation of corneal OCT images was created and used to assess changes in epithelial thickness, stromal thickness, corneal and stromal profiles and radii of curvature before, and after one month of, uninterrupted overnight wear of Ortho-K lenses. In the central area (0-2 mm diameter), the epithelium thinned by 12.8 ± 6.0 µm (23.8% on average, p < 0.01) after one month of Ortho-K lens wear. In the paracentral area (2-5 mm diameter), the epithelium thinned nasally and temporally (by 2.4 ± 5.9 µm, 4.5% on average, p = 0.031). The stroma thickness increased in the central area (by 4.8 ± 16.1 µm, p = 0.005). The radius of curvature of the central corneal anterior surface increased by 0.24 ± 0.26 mm (3.1%, p < 0.01) along the horizontal meridian and by 0.34 ± 0.18 mm (4.2%, p < 0.01) along the vertical meridian. There were no significant changes in the anterior and posterior stromal radius of curvature. This study introduced a new method to automatically detect the anterior corneal surface, the epithelial posterior surface and the posterior corneal surface in OCT scans. Overnight wear of Ortho-K lenses caused thinning of the central corneal epithelium. The anterior corneal surface became flattered while the anterior and posterior surfaces of the stroma did not undergo significant changes. The results are consistent with the changes reported in previous studies. The reduction in myopic refractive error caused by Ortho-K lens wear was mainly due to changes in corneal epithelium thickness profile.

Clinical Validation of the Automated Characterization of Cone Size and Center in Keratoconic Corneas.

PURPOSE: To evaluate an automated method for detecting the cone shape characteristics and to assess the cornea specialists' subjective variability of these measures using different maps. METHODS: Topographic images of the anterior and posterior surface of each eye were presented to 12 clinicians in two different types of map: tangential curvature and relative elevation to the best-fit sphere. They were asked to mark the cone center and its boundaries in the two maps without knowing that they belonged to the same patient. The results between the maps were compared to assess the subjective variability dependent on the map type and the automated method was compared against both estimations to assess its accuracy. RESULTS: Considering the results of anterior and posterior surfaces, there was low agreement between the cone center estimations using different types of maps for 10 of the 12 cases (P < .05), whereas the comparison between the automated method and the two map estimations did not show differences in 11 of the 12 cases (P > .05). There was high variability, up to 55%, among clinicians' estimations of the cone area. The results of the automated method were within the range of the expert's estimations. CONCLUSIONS: An objective, mathematically derived method of determining morphological dimensions of the cone was consistent with clinicians' evaluations. Although there was high variability among the experts' subjective estimates, which were highly influenced by the type of map, the objective method provided a reliable evaluation of the keratoconus shape independent of maps or color scale. [J Refract Surg. 2021;37(6):414-421.].

Stress-Strain Index Map: A New Way to Represent Corneal Material Stiffness.

PURPOSE: To introduce a new method to map the mechanical stiffness of healthy and keratoconic corneas. METHODS: Numerical modeling based on the finite element method was used to carry out inverse analysis of simulated healthy and keratoconic corneas to determine the regional variation of mechanical stiffness across the corneal surface based on established trends in collagen fibril distribution. The Stress-Strain Index (SSI), developed and validated in an earlier study and presented as a parameter that can estimate the overall stress-strain behavior of corneal tissue, was adopted in this research as a measure of corneal stiffness. The regional variation of SSI across the corneal surface was estimated using inverse analysis while referring to the common features of collagen fibrils' distribution obtained from earlier x-ray scattering studies. Additionally, for keratoconic corneas, a method relating keratoconic cone features and cornea's refractive power to the reduction in collagen fibril density inside the cone was implemented in the development of SSI maps. In addition to the simulated cases, the study also included two keratoconus cases, for which SSI maps were developed. RESULTS: SSI values varied slightly across corneal surface in the simulated healthy eyes. In contrast, both simulated and clinical keratoconic corneas demonstrated substantial reductions in SSI values inside the cone. These SSI reductions depended on the extent of the disease and increased with more considerable simulated losses in fibril density in the cone area. SSI values and their regional variation showed little change with changes in IOP, corneal thickness, and curvature. CONCLUSION: SSI maps provide an estimation of the regional variation of biomechanical stiffness across the corneal surface. The maps could be particularly useful in keratoconic corneas, demonstrating the dependence of corneal biomechanical behavior on the tissue's microstructure and offering a tool to fundamentally understand the mechanics of keratoconus progression in individual patients.

Detection of postlaser vision correction ectasia with a new combined biomechanical index.

PURPOSE: To validate and evaluate the use of a new biomechanical index known as the Corvis biomechanical index-laser vision correction (CBI-LVC) as a method for separating stable post-LVC eyes from post-LVC eyes with ectasia. SETTING: 10 clinics from 9 countries. DESIGN: Retrospective, multicenter, clinical study. METHODS: The study was designed with 2 purposes: to develop the CBI-LVC, which combines dynamic corneal response (DCR) parameters provided by a high-speed dynamic Scheimpflug camera (CorVis ST; OCULUS Optikgeräte GmbH) and then to evaluate its ability to detect post-LVC ectasia. The CBI-LVC includes integrated inverse radius, applanation 1 (A1) velocity, A1 deflection amplitude, highest concavity and arclength, deformation amplitude ratio of 2 mm, and A1 arclength in millimeters. Logistic regression with Wald forward stepwise approach was used to identify the optimal combination of DCRs to create the CBI-LVC and then separate stable from LVC-induced ectasia. Eighty percentage of the database was used for training the software and 20% for validation. RESULTS: 736 eyes of 736 patients were included (685 stable LVC and 51 post-LVC ectasia). The receiver operating characteristic curve analysis showed an area under the curve of 0.991 when applying CBI-LVC in the validation dataset and 0.998 in the training dataset. A cutoff of 0.2 was able to separate stable LVC from ectasia with a sensitivity of 93.3% and a specificity of 97.8%. CONCLUSIONS: The CBI-LVC was highly sensitive and specific in distinguishing stable from ectatic post-LVC eyes. Using CBI-LVC in routine practice, along with topography and tomography, can aid the early diagnosis of post-LVC ectasia and allow intervention prior to visually compromising progression.

Fibril density reduction in keratoconic corneas.

This study aims to estimate the reduction in collagen fibril density within the central 6 mm radius of keratoconic corneas through the processing of microstructure and videokeratography data. Collagen fibril distribution maps and topography maps were obtained for seven keratoconic and six healthy corneas, and topographic features were assessed to detect and calculate the area of the cone in each keratoconic eye. The reduction in collagen fibril density within the cone area was estimated with reference to the same region in the characteristic collagen fibril maps of healthy corneas. Together with minimum thickness and mean central corneal refractive power, the cone area was correlated with the reduction in the cone collagen fibrils. For the corneas considered, the mean area of keratoconic cones was 3.30 ± 1.90 mm2. Compared with healthy corneas, fibril density in the cones of keratoconic corneas was lower by as much as 35%, and the mean reduction was 17 ± 10%. A linear approximation was developed to relate the magnitude of reduction to the refractive power, minimum corneal thickness and cone area (R2 = 0.95, p < 0.001). Outside the cone area, there was no significant difference between fibril arrangement in healthy and keratoconic corneas. The presented method can predict the mean fibril density in the keratoconic eye's cone area. The technique can be applied in microstructure-based finite-element models of the eye to regulate its stiffness level and the stiffness distribution within the areas affected by keratoconus.

Compressive behaviour of soft contact lenses and its effect on refractive power on the eye and handling off the eye.

PURPOSE: To investigate the stress-strain behaviour of 9 soft contact lens materials, that are commonly used in the market, under uniaxial compression loading. METHODS: Seven types of hydrogel and two types of silicone-hydrogel soft contact lens materials were hydrated in phosphate-buffered saline (PBS) solution then subjected to uniaxial compression loads. The load rate was set to 16.0 N/min starting with two consecutive initial 5.0 N loading cycles followed by three relaxation periods of 4.0 min within which there were two more 5.0 N loading cycles and eventually, a full loading cycle that stopped at a load of 49.0 N. The load and contraction data obtained experimentally were analysed to derive the stress-strain behaviour. Finite Element (FE) analysis was then utilised to evaluate the performance of soft contact lenses on the human eye and handling lenses off the eye. RESULTS: Unlike tensile tests, all tested materials showed nonlinear behaviour when tested under compression. When fitted to first-order Ogden hyperelastic model, parameter µ was found to be varying in the range 0.12 to 0.74 MPa and material parameter α was found to be varying in the range 8.2 to 20.326 among the nine tested materials. Compression modulus of elasticity was 2.2 times higher than the tensile modulus of elasticity on average. FE simulation with nonlinear Ogden constitutive model showed a limited change (8%~12%) in the optical performance when compared to other material models, however, it predicted higher stress when the lens was simulated under bending during off-eye handling. CONCLUSIONS: Compression tests revealed slightly nonlinear behaviour when materials were strained under compression stress down to 15% ~ 30% of their nominal heights. Considering the physiological compression loading range of 8 mmHg, secant moduli of elasticity were 1.5% to 6.9% higher than the tension moduli of elasticity depending on the material. Tensile-based moduli of elasticity could be used in FE analysis as a step towards simulating the optical performance of soft contact lenses on-eye. However, nonlinear compression-based material models are recommended for FE analysis of soft contact lenses when lens-handling is investigated off-eye.

Experimental evaluation of the viscoelasticity of porcine vitreous.

This study aims to estimate the material properties of the porcine vitreous while testing it in close to its natural physiological conditions. Eighteen porcine eyes were tested within 48 h post-mortem. A custom-built computer-controlled test rig was designed to support, load and monitor the behaviour of eye globes while being subjected to dynamic rotation cycles mimicking saccade eye movement. Specimens were glued to the base of a container, surrounded by gelatin, frozen and cut in half to expose the vitreous. After thawing, the container was subjected to concentric dynamic rotations of up to 5°, 10° or 15°, while taking 50 MP photos of the specimen every 2 ms. The images were analysed by a digital image correlation algorithm to trace the movement of marked points on the vitreous surface with different radii from the centre of the posterior chamber. The initial camera image was used in building a finite-element model of the test set-up, which was used in an inverse analysis exercise to estimate the material properties of the vitreous. Angular displacements of the monitored points were up to 3.3°, 4.1° and 3.9° in response to eye rotations of 5°, 10° and 15°, respectively. With the experimental relationships between eye rotation and angular displacements used as target behaviour, the inverse analysis exercise estimated the initial shear modulus, the long-term shear modulus and the viscoelastic decay constant of the porcine vitreous as 2.10 ± 0.15 Pa, 0.50 ± 0.04 Pa and 1.20 ± 0.09 s-1, respectively. Consideration of the viscoelasticity of the vitreous was essential to represent its experimental behaviour. Testing the vitreous in close to its normal physiological conditions produced estimations of the initial shear modulus and long-term shear modulus that were, respectively, smaller and larger than reported values (Zimberlin et al. 2010 Soft Matter 6, 3632-3635. (doi:10.1039/b925407b), Liu et al. 2013 J. Biomech. 46, 1321-7. (doi:10.1016/j.jbiomech.2013.02.006), Rossi et al. 2011 Invest. Ophthalmol. Vis. Sci. 52, 3994-4002. (doi:10.1167/iovs.10-6477)).