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Fernando Faria-Correia,1–5 Bernardo T Lopes,5,6 Isaac C Ramos,5,6 Tiago Monteiro,1,2 Nuno Franqueira,1 Renato Ambrósio Jr5–8 1Ophthalmology Department, Hospital de Braga, Braga, Portugal; 2Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 3ICVS/3B’s - PT Government Associate Laboratory, Braga, Portugal; 4ICVS/3B’s - PT Government Associate Laboratory, Guimarães, Portugal; 5Rio de Janeiro Corneal Tomography and Biomechanics Study Group, Rio de Janeiro, Brazil; 6Instituto de Olhos Renato Ambrósio, Rio de Janeiro, Brazil; 7VisareRio, Rio de Janeiro, Brazil; 8Department of Ophthalmology and Visual Sciences, Federal University of São Paulo, São Paulo, Brazil Purpose: To evaluate the correlations between preoperative Scheimpflug-based lens densitometry metrics and phacodynamics. Methods: The Lens Opacities Classification System III (LOCS III) was used to grade nuclear opalescence (NO), along with different methods of lens densitometry evaluation (absolute scale from 0% to 100%): three-dimensional (3D), linear, and region of interest (ROI) modes. Cumulative dissipated energy (CDE) and total ultrasound (US) time were recorded and correlated with the different methods of cataract grading. Significant correlations were evaluated using Pearson or Spearman correlation coefficients according to data normality. Results: A positive correlation was detected between the NO score and the average density and the maximum density derived from the 3D mode (r=0.624, P

Purpose: To investigate the potential improvement in visual acuity and subjective perception of image quality in patients with keratoconus using non-orthogonal correction (NOC) cylinder trial lenses where the steep and flat power meridians are set at angles less or greater than 90°., Methods: A set of NOC plano/cylindrical trial lenses, where the axes between the power meridians were set at a range of non-orthogonal angles, were used to refract 18 participants with keratoconus in whom 23 eyes were used for testing. Corneal elevation data were processed by bespoke MATLAB code from Pentacam Scheimpflug tomographer scans. Each participant first underwent subjective refraction using standard orthogonal cylinder trial lenses, and the monocular best-corrected visual acuity (BCVA, logMAR) was recorded for each eye. They then underwent a second subjective refraction using NOC cylinder trial lenses created for the study and completed a questionnaire to elicit their subjective appraisal of letter clarity and ghosting., Results: Fourteen (61%) eyes demonstrated an increase in objective BCVA with the NOC versus the orthogonal correction; seven (30%) eyes showed no change and in two (9%) eyes, the BCVA was slightly worse. Further, 87% and 79% experienced an increase in letter clarity and a reduction in ghosting, respectively, independent of changes in BCVA. The majority of non-orthogonal angles were in the range of 80°-85°, and it was possible to refine the cylinder and axis of the NOC further compared with the orthogonal correction. All but one of the participants said they would be interested in trying non-orthogonal spectacles if the opportunity arose., Conclusions: Correcting irregular astigmatism in keratoconic individuals with non-orthogonal spectacle correction may provide benefit in terms of increased visual acuity, improvements in letter clarity and a reduction of ghosting effects. This type of correction has the potential to improve the overall quality of life for patients with keratoconus., (© 2024 The Author(s). Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Accurate detection of post-refractive ectasia susceptibility is essential during preoperative evaluation for laser vision correction (LVC) due to the risk of progressive corneal ectasia and vision decline post-surgery. Despite improved screening and a reduced incidence from 0.66 to 0.033%, iatrogenic ectasia remains a concern due to the severe vision loss it can cause, highlighting the need for more accurate detection tools. A new optimized version of the Belin/Ambrósio Enhanced Ectasia Display version 4 (BAD-D v4) was developed and validated across 26 international centers to enhance the detection of keratoconus and very asymmetric ectasia and to assess the risk of post-refractive ectasia. Analyzing a dataset of 3,886 eyes from 3,351 patients, including normal, keratoconus (KC), and cases with very asymmetric ectasia (VAE) categories, having one eye with normal topography (VAE-NT and the fellow eye with clinical ectasia (VAE-E). The study utilized an optimized logistic regression algorithm improving diagnostic accuracy. The BAD-D v4 showed superior efficacy in differentiating normal eyes from ectatic conditions, with Area Under the Receiver Operating Characteristic Curve (AUROC) scores of 0.997 and 0.998 in training and testing samples for normal versus clinical ectasia. Additionally, in Normal vs. Disease (KC + VAE), the AUROC was 0.974 and 0.966, and in the challenging Normal vs. VAE-NT diverse group, it scored 0.905 and 0.858. These results outperformed the current version (BAD-D v3) and were comparable to the Pentacam Random Forest Index in all tested scenarios, highlighting the potential of BAD-D v4 in early ectasia detection, without altering the index scale or the end-user experience., Competing Interests: Declarations. Competing interests: BL, MB and RA are consultants for Oculus GmbH (Wetzlar, Germany), MH, LI and TK declare no potential conflict of interest., (© 2024. The Author(s).)

Purpose: This article introduces the Pentacam ® Cornea OCT (optical coherence tomography). This advanced corneal imaging system combines rotating ultra-high-resolution spectral domain OCT with sub- 2-micron axial resolution and Scheimpflug photography. The purpose of this study is to present the first experience with the instrument and its potential for corneal diagnostics, including optical biopsy., Methods: In this prospective study, the Pentacam ® Cornea OCT was used to image the corneas of seven patients. The novel wide-angle pericentric scan system enables optimal OCT imaging performance for the corneal layer structure over the entire width of the cornea, including the limbal regions. A detailed analysis of the resulting images assessed the synergism between the OCT and Scheimpflug photography., Results: The Pentacam ® Cornea OCT demonstrated significantly improved image resolution and ability to individualize corneal layers with high quality. There is a synergism between the OCT high-definition signal to individualize details on the cornea and Scheimpflug photography to detect and quantify corneal scattering. The noncontact exam was proven safe, user-friendly, and effective for enabling optical biopsy., Conclusions: Pentacam ® Cornea OCT is an advancement in corneal imaging technology. The ultra-high-resolution spectral domain OCT and Scheimpflug photography provide unprecedented detail and resolution, enabling optical biopsy and improving the understanding of corneal pathology. Further studies are necessary to compare and analyze the tomographic reconstructions of the cornea with the different wavelengths, which may provide helpful information for diagnosing and managing corneal diseases.

Introduction: The study aims to demonstrate and estimate the prevalence of clinical corneal ectasia and keratoconus (KC) in patients with relatively low keratometry (low-K KC)., Methods: In a retrospective, analytical, and non-interventionist study, one eye was randomly selected from 1054 patients from the original Tomographic Biomechanical Index (TBIv1) study and the external validation (from Rio de Janeiro, Brazil, and Milan, Italy clinics). Patients were stratified into three groups. Group 1 included 736 normal patients, and groups 2 and 3 included 318 patients with clinical KC in both eyes, divided into low-K KC (90 patients) and high-K KC (228 patients), respectively. All patients underwent a comprehensive ophthalmological evaluation along with Pentacam and Corvis ST (Oculus, Wetzlar, Germany) examinations. Cases with maximum mean zone 3 mm keratometry (Kmax zone mean 3 mm) lower than 47.6 diopters (D) were considered as low-keratometry keratoconus, and cases with Kmax zone mean 3 mm higher than 47.6 D were regarded as high-keratometry keratoconus., Results: Ninety (28.30%) of the 318 KC group presented ectasia with low-keratometric values (low-Kmax). The average age in the normal group was 39.28 years (range 6.99-90.12), in the low-Kmax KC group it was 37.49 (range 13.35-78.45), and in the high-Kmax KC group it was 34.22 years (range 12.7-80.34). Mean and SD values and median (range), respectively, of some corneal tomographic and biomechanical parameters evaluated from the low-Kmax KC group were as follows: Belin-Ambrósio enhanced ectasia display (BAD-D) 3.79 ± 1.62 and 3.66 (0.83-9.73); Pentacam random forest index (PRFI) 0.78 ± 0.25 and 0.91 (0.05-1); corneal biomechanical index (CBI) 0.58 ± 0.43 and 0.75 (0-1); TBI 0.93 ± 0.17 and 1 (0.35-1); and stiffness parameter at A1 (SP-A1) 86.16 ± 19.62 and 86.05 (42.94-141.66)., Conclusion: Relatively low keratometry, with a Kmax lower than 47.6 D, can occur in up to 28.30% of clinical keratoconus. These cases have a less severe presentation of the disease. Future studies involving larger populations and prospective designs are necessary to confirm the prevalence of keratoconus with low keratometry and define prognostic factors in such cases., (© 2024. The Author(s).)

Purpose: To investigate corneal densitometry artefacts found in Pentacam Scheimpflug scans and their potential effect on assessing keratoconic (KC) corneas compared to normal (N) corneas., Methods: The current study utilises Pentacam data of 458 N eyes, aged 35.6 ± 15.8 (range 10-87), referred to as the "N group", and 314 KC eyes, aged 31.6 ± 10.8 (range 10-72), referred to as the "KC group", where densitometry data were extracted and analysed via a custom-built MATLAB code. Radial summations of the densitometry were calculated at diameters ranging from 0.5 mm to 5.0 mm. The minimum normalised radial summation of densitometry (NRSD) value and angle were determined at each diameter and then linked. KC cone locations and areas of pathology were determined, and a comparison between N and KC groups was carried out both within the averaged area of pathology and over the corneal surface., Results: Joining minimum NRSD trajectory points marked a clear distortion line pointing to the nasal-superior direction at 65° from the nasal meridian. The findings were found to be independent of eye laterality or ocular condition. Consistency was detected in the right and left eyes among both the N and KC groups. The location of the KC cone centre and the area of pathology were determined, and the densitometry output was compared both within the area of pathology and over the whole cornea. When the average densitometry was compared between N and KC eyes within the KC area of pathology, the N group recorded a 16.37 ± 3.15 normalised grey-scale unit (NGSU), and the KC group recorded 17.74 ± 3.4 NGSU ( p = 0.0001). However, when the whole cornea was considered, the N group recorded 16.71 ± 5.5 NGSU, and the KC group recorded 15.72 ± 3.98 NGSU ( p = 0.0467). A weak correlation was found between the Bad D index and NGSU when the whole measured cornea was considered (R = -0.01); however, a better correlation was recorded within the KC area of pathology (R = 0.21)., Conclusions: Nasal-superior artefacts are observed in the densitometry Pentacam maps, and analysis shows no significant differences in their appearance between N or KC corneas. When analysing KC corneas, it was found that the cone positions are mostly on the temporal-inferior side of the cornea, opposite to the densitometry artefact NRSD trajectory. The analysis suggests that the corneal densitometry artefacts do not interfere with the KC area of pathology as it reaches its extreme in the opposite direction; therefore, weighting the densitometry map to increase the contribution of the inferior-temporal cornea and decreasing that of the superior-nasal area would improve the classification or identification of KC if densitometry is to be used as a KC metric.

Different diagnostic approaches for ectatic corneal diseases (ECD) include screening, diagnosis confirmation, classification of the ECD type, severity staging, prognostic evaluation, and clinical follow-up. The comprehensive assessment must start with a directed clinical history. However, multimodal imaging tools, including Placido-disk topography, Scheimpflug three-dimensional (3D) tomography, corneal biomechanical evaluations, and layered (or segmental) tomography with epithelial thickness by optical coherence tomography (OCT), or digital very high-frequency ultrasound (dVHF-US) serve as fundamental complementary exams for measuring different characteristics of the cornea. Also, ocular wavefront analysis, axial length measurements, corneal specular or confocal microscopy, and genetic or molecular biology tests are relevant for clinical decisions. Artificial intelligence enhances interpretation and enables combining such a plethora of data, boosting accuracy and facilitating clinical decisions. The applications of diagnostic information for individualized treatments became relevant concerning the therapeutic refractive procedures that emerged as alternatives to keratoplasty. The first paradigm shift concerns the surgical management of patients with ECD with different techniques, such as crosslinking and intrastromal corneal ring segments. A second paradigm shift involved the quest for identifying patients at higher risk of progressive iatrogenic ectasia after elective refractive corrections on the cornea. Beyond augmenting the sensitivity to detect very mild (subclinical or fruste) forms of ECD, ectasia risk assessment evolved to characterize the inherent susceptibility for ectasia development and progression. Furthermore, ectasia risk is also related to environmental factors, including eye rubbing and the relational impact of the surgical procedure on the cornea., (© 2023. The Author(s).)

Chagas disease (CD) is a neglected disease caused by the protozoan Trypanosoma cruzi. It has high morbidity and mortality rates and mainly affects socially vulnerable populations. This is a cross-sectional study, with retrospective and prospective data collection. Using questionnaires applied to environmental surveillance coordinators, we characterized the status of CD surveillance activities in municipalities endemic for the disease in Northern Minas Gerais State (MG) and Jequitinhonha Valley (Vale do Jequitinhonha). Moreover, we spatialized the vulnerability index for chronic CD in the study area. The population consisted of 22 environmental surveillance coordinators, active in 2020, from Northern MG and Jequitinhonha Valley, 21 municipalities included in the SaMi-Trop research project, and Montes Claros municipality. After applying the questionnaires to the coordinators, a descriptive analysis of the variables was performed. To characterize the active municipalities, the explanatory variables collected in the questionnaire were compared with the dichotomous variable. Bivariate descriptive analysis was performed. Finally, geoprocessing techniques were used to spatialize the data and prepare maps. Regarding the team of endemic combat agents (ECA), 90.9% reported the lack of a specific team for CD vector control actions. Of the 22 municipalities participating in this study, nine were active (41.1%). Only 25% (n=2) of active municipalities (9% of the municipalities studied) met the target of visiting 50% of households per year. Finally, 81.1% of the coordinators stated that in their municipality, they developed actions linked to primary health care (PHC). The implementation of CD surveillance activities weakened in the endemic region. Few municipalities have a surveillance team, with low regularity of active surveillance and noncompliance with the program's goal. The results suggest insufficient recording of activities in the information system, considering that there are municipalities that report performing the activities, but no production record was observed in the system.

Purpose: To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection., Design: Multicenter cross-sectional case-control retrospective study., Methods: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy., Results: The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001)., Conclusions: AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society., (Copyright © 2022. Published by Elsevier Inc.)

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.

In recent decades, waves of yellow fever virus (YFV) from the Amazon Rainforest have spread and caused outbreaks in other regions of Brazil, including the Cerrado, a savannah-like biome through which YFV usually moves before arriving at the Atlantic Forest. To identify the vectors involved in the maintenance of the virus in semiarid environments, an entomological survey was conducted after confirmation of yellow fever (YF) epizootics at the peak of the dry season in the Cerrado areas of the state of Minas Gerais. In total, 917 mosquitoes from 13 taxa were collected and tested for the presence of YFV. Interestingly, mosquitoes of the Sabethes genus represented 95% of the diurnal captured specimens, displaying a peak of biting activity never previously recorded, between 4:30 and 5:30 p.m. Molecular analysis identified three YFV-positive pools, two from Sabethes chloropterus -from which near-complete genomes were generated-and one from Sa. albiprivus , whose low viral load prevented sequencing. Sa. chloropterus was considered the primary vector due to the high number of copies of YFV RNA and the high relative abundance detected. Its bionomic characteristics allow its survival in dry places and dry time periods. For the first time in Brazil, Sa. albiprivus was found to be naturally infected with YFV and may have played a role as a secondary vector. Despite its high relative abundance, fewer copies of viral RNA were found, as well as a lower Minimum Infection Rate (MIR). Genomic and phylogeographic analysis showed that the virus clustered in the sub-lineage YFV PA-MG , which circulated in Pará in 2017 and then spread into other regions of the country. The results reported here contribute to the understanding of the epidemiology and mechanisms of YFV dispersion and maintenance, especially in adverse weather conditions. The intense viral circulation, even outside the seasonal period, increases the importance of surveillance and YFV vaccination to protect human populations in affected areas.

Recent advances, specifically in the understanding of the biomechanical properties of the cornea and its response to diseases and surgical interventions, have significantly improved the safety and surgical outcomes of corneal refractive surgery, whose popularity and demand continue to grow worldwide. However, iatrogenic keratectasia resulting from the deterioration in corneal biomechanics caused by surgical interventions, although rare, remains a global concern. On one hand, in vivo biomechanical evaluation, enabled by clinical imaging systems such as the ORA and the Corvis ST, has significantly improved the risk profiling of patients for iatrogenic keratectasia. That is despite the fact the biomechanical metrics provided by these systems are considered indicators of the cornea's overall stiffness rather than its intrinsic material properties. On the other hand, new surgical modalities including SMILE were introduced to offer superior biomechanical performance to LASIK, but this superiority could not be proven clinically, creating more myths than answers. The literature also includes sound evidence that tPRK provided the highest preservation of corneal biomechanics when compared to both LASIK and SMILE. The aim of this review is twofold; to discuss the importance of corneal biomechanical evaluation prior to refractive surgery, and to assess the current understanding of cornea's biomechanical deterioration caused by mainstream corneal refractive surgeries. The review has led to an observation that new imaging techniques, parameters and evaluation systems may be needed to reflect the true advantages of specific refractive techniques and when these advantages are significant enough to offer better protection against post-surgery complications.

Purpose: To prospectively review the importance of biomechanical assessment in the screening, diagnosis, prognosis, individualized planning, and clinical follow-up for ectatic corneal diseases. Methods: We demonstrate two commercially available devices to assess the corneal biomechanics in vivo , the Ocular Response Analyzer (ORA, Reichester, NY, USA) and the Corvis ST (Oculus, Wetzlar, Germany). Novel devices have been demonstrated to provide in vivo biomechanical measurements, including Brillouin optical microscopy and OCT elastography. Conclusion: The integration of biomechanical data and other data from multimodal refractive imaging using artificial intelligence demonstrated the ability to enhance accuracy in diagnosing ectatic corneal diseases.

The study of corneal stiffness in vivo has numerous clinical applications such as the measurement of intraocular pressure, the preoperative screening for iatrogenic ectasia after laser vision correction surgery and the diagnosis and treatment of corneal ectatic diseases such as keratoconus. The localised aspect of the microstructure deterioration in keratoconus leading to local biomechanical softening, corneal bulging, irregular astigmatism and ultimately loss of vision boosted the need to map the corneal stiffness to identify the regional biomechanical failure. Currently, two methods to map the corneal stiffness in vivo are integrated into devices that are either already commercially available or about to be commercialised: the stress-strain index (SSI) maps and the Brillouin Microscopy (BM). The former method produces 2D map of stiffness across the corneal surface, developed through numerical simulations using the corneal shape, its microstructure content, and the deformation behaviour under air-puff excitation. It estimates the whole stress-strain behaviour, making it possible to obtain the material tangent modulus under different intraocular pressure levels. On the other hand, BM produces a 3D map of the corneal longitudinal modulus across the corneal surface and thickness. It uses a low-power near-infrared laser beam and through a spectral analysis of the returned signal, it assesses the mechanical compressibility of the tissue as measured by the longitudinal modulus. In this paper, these two techniques are reviewed, and their advantages and limitations discussed.

The study aims to investigate the likelihood of Zernike polynomial being used for reconstructing rabbit corneal surfaces as scanned by the Pentacam segment tomographer, and hence evaluate the accuracy of corneal power maps calculated from such Zernike fitted surfaces. The study utilised a data set of both eyes of 21 rabbits using a reverse engineering approach for deductive reasoning. Pentacam raw elevation data were fitted to Zernike polynomials of orders 2 to 20. The surface fitting process to Zernike polynomials was carried out using randomly selected 80% of the corneal surface data points, and the root means squared fitting error (RMS) was determined for the other 20% of the surface data following the Pareto principle. The process was carried out for both the anterior and posterior surfaces of the corneal surfaces that were measured via Pentacam scans. Raw elevation data and the fitted corneal surfaces were then used to determine corneal axial and tangential curvature maps. For reconstructed surfaces calculated using the Zernike fitted surfaces, the mean and standard deviation of the error incurred by the fitting were calculated. For power maps computed using the raw elevation data, different levels of discrete cosine transform (DCT) smoothing were employed to infer the smoothing level utilised by the Pentacam device. The RMS error was not significantly improved for Zernike polynomial orders above 12 and 10 when fitting the anterior and posterior surfaces of the cornea, respectively. This was noted by the statistically non-significant increase in accuracy when the order was increased beyond these values. The corneal curvature calculations suggest that a smoothing process is employed in the corneal curvature maps outputted by the Pentacam device; however, the exact smoothing method is unknown. Additionally, the results suggest that fitting corneal surfaces to high-order Zernike polynomials will incur a clinical error in the calculation of axial and tangential corneal curvature of at least 0.16 ± 01 D and 0.36 ± 0.02 D, respectively. Rabbit corneal anterior and posterior surfaces scanned via the Pentacam were optimally fitted to orders 12 and 10 Zernike polynomials. This is essential to get stable values of high-order aberrations that are not affected by Zernike polynomial fittings, such as comas for Intracorneal Ring Segments (ICRS) adjustments or spherical aberration for pre-cataract operations. Smoothing was necessary to replicate the corneal curvature maps outputted by the Pentacam tomographer, and fitting corneal surfaces to Zernike polynomials introduces errors in the calculation of both the axial and tangential corneal curvatures.

There are different fundamental diagnostic strategies for patients with ectatic corneal diseases (ECDs): screening, confirmation of the diagnosis, classification of the type of ECD, severity staging, prognostic assessment, and clinical follow-up. The conscious application of such strategies enables individualized treatments. The need for improved diagnostics of ECD is related to the advent of therapeutic refractive procedures that are considered prior to keratoplasty. Among such less invasive procedures, we include corneal crosslinking, customized ablations, and intracorneal ring segment implantation. Besides the paradigm shift in managing patients with ECD, enhancing the sensitivity to detect very mild forms of disease, and characterizing the inherent susceptibility for ectasia progression, became relevant for identifying patients at higher risk for progressive iatrogenic ectasia after laser vision correction (LVC). Moreover, the hypothesis that mild keratoconus is a risk factor for delivering a baby with Down's syndrome potentially augments the relevance of the diagnostics of ECD. Multimodal refractive imaging involves different technologies, including Placido-disk corneal topography, Scheimpflug 3-D tomography, segmental or layered tomography with layered epithelial thickness using OCT (optical coherence tomography), and digital very high-frequency ultrasound (VHF-US), and ocular wavefront. Corneal biomechanical assessments and genetic and molecular biology tests have translated to clinical measurements. Artificial intelligence allows for the integration of a plethora of clinical data and has proven its relevance in facilitating clinical decisions, allowing personalized or individualized treatments.

Purpose: To investigate the relationship between Ortho-K contact lens design parameters and refractive power change of the eye through a parametric mathematical representation., Methods: The current study utilises fully anonymized records of 249 eyes, 132 right eyes, and 117 left eyes from subjects aged 14.1 ± 4.0 years on average (range 9-38 years) which were selected for secondary analysis processing. The data were split into 3 groups (G1 up to 35 days wear, from 10 to 35 days, G2 up to 99 days wear, more than 35-99 days & G3 more than 100 days wear) according to the length of time, in days, that the lenses were worn. Corneal shape was measured before and after contact lens wear using the Medmont E300 topographer, from which height and distance files were read by a custom-built MATLAB code to construct the corneal anterior surface independently. Changes in refractive power pre and post-Ortho-K wear were determined using constructed tangential refractive power maps from which both centrally flattened and annular steepened zones were automatically bounded, hence used to determine the refractive power change., Results: On average, flat Sim-K and steep Sim-K were reduced after Ortho-K lens wear by 1.6 ± 1.3 D and 1.3 ± 1.4 D respectively. The radius of the base curve was correlated with the mean central flattened zone power change strongly in G1 (R = 0.7, p < 0.001) and moderately in G2 (R = 0.4) and G3 (R = 0.4, p < 0.001). Hence, a strong correlation with the base curve was recorded in group G1 and moderate in G2 and G3. The reverse curve was very strongly correlated to the mean central flattened zone power change in G1 (R = 0.8, p < 0.001) and strongly correlated with G2 (R = 0.6, p < 0.001) and G3 (R = 0.7, p < 0.001). The reverse curve was also strongly correlated with the mean annular steepened zone power change among all groups G1, G2, and G3 (R = 0.7, R = 0.6 and R = 0.6) respectively (p < 0.001)., Conclusions: Although the central corneal refractive power change was strongly correlated to the Ortho-K lens base curve, it characterized only 50% of the target power change. However, the annular steepened zone refractive power change appears to be a clearer predictor of target power change, as there appears to be a one-to-one inverse relationship with the target refractive power correction. Differences between these results and the literature may be a result of the topography software smoothing effect., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

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., (Copyright © 2022 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: To assess the efficiency of an index derived from multiple logistic regression analysis (MLRA) to measure differences in corneal tomography findings between subclinical keratoconus (KC) in 1 eye, corneal ectasia, and healthy corneas., Setting: 2 private Brazilian ophthalmological centers., Design: Multicenter case-control study., Methods: This study included 187 eyes with very asymmetric ectasia and with normal corneal topography and tomography (VAE-NTT) in the VAE-NTT group, 2296 eyes with healthy corneas in the control group (CG), and 410 eyes with ectasia in the ectasia group. An index, termed as Boosted Ectasia Susceptibility Tomography Index (BESTi), was derived using MLRA to identify a cutoff point to distinguish patients in the 3 groups. The groups were divided into 2 subgroups with an equal number of patients: validation set and external validation (EV) set., Results: 2893 patients with 2893 eyes were included. BESTi had an area under the curve (AUC) of 0.91 with 86.02% sensitivity (Se) and 83.97% specificity (Sp) between CG and the VAE-NTT group in the EV set, which was significantly greater than those of the Belin-Ambrósio Deviation Index (BAD-D) (AUC: 0.81; Se: 66.67%; Sp: 82.67%; P < .0001) and Pentacam random forest index (PRFI) (AUC: 0.87; Se: 78.49%; Sp: 79.88%; P = .021)., Conclusions: BESTi facilitated early detection of ectasia in subclinical KC and demonstrated higher Se and Sp than PRFI and BAD-D for detecting subclinical KC., Competing Interests: Disclosures: R. Ambrósio Jr is a consultant for Oculus Optikgeräte GmbH. The other authors do not have any conflict of interest., (Copyright © 2022 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

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.

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., Competing Interests: AhE is a consultant for Oculus. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lopes, Padmanabhan, Eliasy, Zhang, Abass and Elsheikh.)

Purpose: To determine the effectiveness of parameters and indices based on biomechanical measures at discriminating fellow eyes with topographically and tomographically normal corneas in patients with keratoconus from normal control corneas., Methods: The study included 47 keratoconus suspect eyes, defined as the topographically and tomographically normal fellow eyes of patients with frank keratoconus in the other eye. Eyes were imaged using the Pentacam HR and Corvis ST (both Oculus Optikgeräte GmbH). Fellow eyes were then categorized as topographically/tomographically normal fellow eyes (TNF) and topographically/tomographically borderline fellow eyes (TBF). The ability of each of the Corvis Biomechanical Index (CBI), Tomographic and Biomechanical Index (TBI), stiffness parameter at applanation 1 (SP-A1), and stress-strain index (SSI) at discriminating between normal controls and keratoconus suspects was assessed., Results: The TBI had the best discriminative ability with the greatest area under the receiver operating characteristic (AUROC) curve value of 0.946 for normal controls versus TBF eyes, and 0.824 for normal controls versus TNF eyes. Compared to the TBI AUROC curves, SP-A1 and CBI had AUROC curve values of 0.833 ( P = .09) and 0.822 ( P = .01) for normal controls versus TBF eyes, respectively, and AUROC curve values of 0.822 ( P = .96) and 0.550 ( P = .0002) for normal controls versus TNF eyes, respectively. The TBI had the best positive predictive value for TNF and TBF eyes, followed by CBI and SP-A1., Conclusions: The TBI and the purely biomechanical parameter SP-A1 were of moderate utility in distinguishing between normal and keratoconus suspect eyes. In the absence of topographic/tomographic evidence of keratectasia, an independently abnormal biomechanical parameter may suggest an increased risk of ectasia. [ J Refract Surg . 2022;38(5):318-325.] .

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., Competing Interests: Author AE is a consultant to Oculus Optikgeräte GmbH. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xin, Lopes, Wang, Wu, Zhu, Jiang, Miao, Lin, Cao, Zheng, Eliasy, Chen, Wang, Ye, Bao and Elsheikh.)

Background: Several non-drug treatment approaches for systemic arterial hypertension have been studied aimed at reducing the adverse effects of this clinical condition. In addition to exercise training, which already has many of its modalities consolidated in the scientific field, body and mind practices have gained strength and deserve attention in the science and treatment of hypertension. The literature shows that meditation practices have numerous health benefits, one of which is blood pressure (BP) control., Objective: This study aimed to evaluate the acute effects of a single mindfulness-based meditation on BP in adults with hypertension., Methods: Research was developed that evaluated the BP of 5 adult women with controlled hypertension. As a data collection instrument, we used 2 sessions of ambulatory BP monitoring (ABPM): the first was a control session and the second a meditation session. Systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) were evaluated at the pre- and post-session in addition to heart rate (HR), with clinical and ambulatorial measurements, during the day, night, morning surge and a 24-hour period. Data analysis was performed using one-way analysis of variance (ANOVA) for the ABPM data and two-way ANOVA to analyze blood pressure., Results: The main results found were a statistically significant reduction in SBP in the morning and a tendency toward a significant decrease in MBP during the same period (P = .057). There were no significant changes in the other variables analyzed., Conclusion: Therefore, we concluded that a single meditation session was effective only in reducing morning SBP.

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., (© 2021 The Authors.)

Purpose: To investigate the capability of Zernike polynomials fitting to reconstruct corneal surfaces as measured by Pentacam HR tomographer, Medmont E300 Placido-disc and Eye Surface Profiler (ESP)., Methods: The study utilised a collection of clinical data of 527 participants. Pentacam HR raw elevation data of 660 eyes (430 healthy and 230 keratoconic) were fitted to Zernike polynomials of order 2 to 20. Same analyses were carried out on 158 eyes scanned by Medmont E300 Placido-disc and 236 eyes were scanned by ESP for comparison purposes. The Zernike polynomial ​fitting was carried out using a random 80% of each individual eye surface's data up to a corneal radius of 5 mm and the root means squared fitting error (RMS) was calculated for the unused 20% portion of the surface data. The process was carried out for the anterior and posterior surfaces of the corneal measurements of the Pentacam HR and the anterior surfaces only with the ESP and the Medmont E300 measurements., Results: Statistical significances in reduction of RMS were noticed up to order 14 among healthy participants (p < 0.0001 for right eyes, p = 0.0051 for left eyes) and up to order 12 (p < 0.0001 for right eyes, p = 0.0002 for left eyes) in anterior surfaces measured by the Pentacam. Among keratoconic eyes, statical significance was noticed up to order 12 in both eyes (p < 0.0001 for right eyes, p = 0.0003 for left eyes). The Pentacam posterior corneal data, both right and left, healthy and keratotic eyes recorded significance (p < 0.0001) in reduction of RMS up to order 10 with same RMS values of 0.0003 mm with zero standard deviation. RMS of fitting Zernike polynomials to Medmont data up to order 20 showed a consistent reduction in RMS with the increase of the fitting order with no rise at high fitting orders. Minimum RMS = 0.0047 ± 0.0021 mm, 0.0046 ± 0.0019 mm for right and left eyes respectively were recorded at order 20 and were more than 15 times the minimum RMS of the Pentacam. RMS of fitting Zernike polynomials to ESP data also showed a consistent reduction in RMS with the increase of the fitting order with no sign of any rise at high fitting orders. Similar to the Medmont, minimum RMS of 0.0005 ± 0.0003 mm, 0.0006 ± 0.0003 mm was recorded at order 20 for right and left eyes respectively and was 2 times the minimum RMS of the Pentacam for right eyes and 1.7 times the minimum RMS of the Pentacam for left eyes., Conclusions: Orders 12 and 10 Zernike polynomials almost perfectly matched the raw-elevation data collected from Pentacam for anterior and posterior surfaces, respectively for either healthy or keratoconic corneas. The Zernike fitting could not perfectly match the data collected from Medmont E300 and ESP., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

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., Competing Interests: AE is a consultant to Oculus Optikgeräte GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ye, Li, Zhu, Abu Said, Nguelemo Mayopa, Akiti, Huang, Lopes, Eliasy, Miao, Wang, Zheng, Chen, Bao and Elsheikh.)

Purpose: To quantify the effect of levelling the corneal surface around the optical axis on the calculated values of corneal asphericity when conic and biconic models are used to fit the anterior corneal surface. Methods: This cross-sectional study starts with a mathematical simulation proving the concept of the effect that the eye's tilt has on the corneal asphericity calculation. Spherical, conic and biconic models are considered and compared. Further, corneal asphericity is analysed in the eyes of 177 healthy participants aged 35.4 ± 15.2. The optical axis was determined using an optimization procedure via the Levenberg-Marquardt nonlinear least-squares algorithm, before fitting the corneal surface to spherical, conic and biconic models. The influence of pupil size (aperture radii of 1.5, 3.0, 4.0 and 5.0 mm) on corneal radius and asphericity was also analysed. Results: In computer simulations, eye tilt caused an increase in the apical radii of the surface with the increase of the tilt angle in both positive and negative directions and aperture radii in all models. Fitting the cornea to spherical models did not show a significant difference between the raw-measured corneal surfaces and the levelled surfaces for right and left eyes. When the conic models were fitted to the cornea, changes in the radii of the cornea among the raw-measured corneal surfaces' data and levelled data were not significant; however, significant differences were recorded in the asphericity of the anterior surfaces at radii of aperture 1.5 mm ( p < 0.01). With the biconic model, the posterior surfaces recorded significant asphericity differences at aperture radii of 1.5 mm, 3 mm, 4 mm and 5 mm ( p = 0.01, p < 0.01, p < 0.01 & p < 0.01, respectively) in the nasal temporal direction of right eyes and left eyes ( p < 0.01, p < 0.01, p < 0.01 & p < 0.01, respectively). In the superior-inferior direction, significant changes were only noticed at aperture radii of 1.5 mm for both right and left eyes ( p = 0.05, p < 0.01). Conclusions: Estimation of human corneal asphericity from topography or tomography data using conic and biconic models of corneas are affected by eyes' natural tilt. In contrast, the apical radii of the cornea are less affected. Using corneal asphericity in certain applications such as fitting contact lenses, corneal implant design, planning for refractive surgery and mathematical modelling when a geometrical centre of the eye is needed should be implemented with caution.

Background: Corneal refractive surgery has become reliable for correcting refractive errors, but it can induce unintended ocular changes that alter refractive outcomes. This study is to evaluate the unintended changes in ocular biometric parameters over a 6-month follow-up period after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE)., Methods: 156 consecutive myopic patients scheduled for FS-LASIK and SMILE were included in this study. Central corneal thickness (CCT), mean curvature of the corneal posterior surface (K pm ), internal anterior chamber depth (IACD) and the length from corneal endothelium to retina (ER) were evaluated before and after surgery over a 6-month period., Results: Both the FS-LASIK and SMILE groups (closely matched at the pre-surgery stage) experienced flatter K pm , shallower IACD and decreased ER 1 week post-surgery (P < 0.01), and these changes were larger in FS-LASIK than in SMILE group. During the 1 week to 6 months follow up period, K pm , IACD and ER remained stable unlike CCT which increased significantly (P < 0.05), more in the FS-LASIK group., Conclusions: During the follow up, the posterior corneal surface became flatter and shifted posteriorly, the anterior chamber depth and the length from the corneal endothelium to retina decreased significantly compared with the pre-surgery stage. These unintended changes in ocular biometric parameters were greater in patients undergoing FS-LASIK than SMILE. The changes present clear challenges for IOL power calculations and should be considered to avoid affecting the outcome of cataract surgery.

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., Competing Interests: The authors have read the journal’s policy and have the following competing interests: LW is a paid employee of Ultravision CLPL, which also provided raw materials for this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Consumption of synthetic cathinones, the second largest class of new psychoactive substances (NPS) reported worldwide, represents a serious public health risk. One of the biggest challenges created by the rapid spread of NPS on the illegal drug market is the discovery of selective biomarkers for their detection in biological matrices, which is only possible through the study of their metabolic profile. The synthetic cathinones 4'-methyl- N , N -dimethylcathinone ( 4-MDMC ), 4'-methyl- N , N -diethylcathinone ( 4-MDEC ), 4'-chloro-α-pyrrolidinovalerophenone ( 4Cl-PVP ), and 4'-chloroethylcathinone ( 4-CEC ) are NPS recently seized in Europe, and, with the exception of 4-CEC , no metabolism study was reported for these cathinones. With the ultimate goal of overcoming this gap, these cathinones were incubated in vitro in human and rat liver microsomes in the presence of Phase I and II (glucuronidation) co-factors, using α-pyrrolidinovalerophenone (α-PVP) as positive control. The metabolite identification was performed by liquid chromatography coupled to tandem high resolution mass spectrometry (LC-HRMS/MS). This allowed the identification of multiple Phase I and glucuronide metabolites of the selected cathinones. Additionally, a new glucuronide conjugate, derived from the recreational drug α-PVP, was herein identified for the first time. Importantly, we have demonstrated that 4-MDMC and 4-MDEC can act as prodrugs of the controlled substances 4-MMC and 4-MEC , respectively. The metabolites herein identified are expected to play an important role not only by acting as potential selective biomarkers of the intake of the synthetic cathinones selected for this study but also to understand their potential adverse effects and link these causative agents to toxicities, thereby helping in the treatment of non-fatal intoxications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lopes, Caldeira, Gaspar and Antunes.)

Purpose: This study investigates how both the peripheral zone design and corneal shape affect the behaviour of soft contact lenses on-eye., Methods: In this study, soft contact lenses of varying nominal cylindrical powers and peripheral zone designs-a single-prism gravity-based stabilised lens (G1P), two-prism blink-based stabilised lens (B2P) and four-prism blink-based stabilised lens (B4P)-were generated as finite element models. The on-eye simulation results were analysed to identify the impact of each peripheral zone design (Each with different volume ratios) on the effective power change (EPC) when worn by a subject. Topographies of three eyes of varying average simulated anterior corneal curvature (flat, average & steep) were used in this study., Results: The volume of the lens's peripheral zone as a ratio of the total lens volume (Vp) recorded very weak correlations with the effective power change (EPC) among the three investigated designs when they were fitted to the flat eye (R = -0.19, -0.15 & -0.22 respectively), moderate correlations with the average eye (R = 0.42, 0.43 & 0.43 respectively) and strong correlations with the steep eye (R = 0.91, 0.9 & 0.9 respectively). No significant differences were noticed among the three investigated designs and none of the cylindrical lenses designed with axis 90° recorded EPC values outside the acceptance criteria range (ACR) of ±0.25 D. No significant differences in EPC were recorded among the three designs G1P, B2P and B4P (p>0.6) when they were designed with three axes at 90°, 45° and 0°. Moving the toric lens axis away from 90° dragged the EPC to the negative side and most of the investigated lenses with axes at 45° and 0° recorded EPCs outside the ±0.25D range., Conclusions: In all cases, the shape of the cornea had a more dominant effect on EPC when compared to the peripheral zone design. Corneal shape influences the soft toric contact lens's on-eye power change more than the lens design., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: Ultravision CLPL provided support in the form of salaries for author LW. All other authors declare no potential financial or non-financial competing interests including employment, consultancy, patents, products in development, or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Estimates of completeness of death registration are crucial to produce estimates of life tables and population projections and to estimate the burden of disease. They are an important step in assessing the quality of data. In the case of subnational data analysis in Brazil, it is important to consider spatial and temporal variation in the quality of mortality data. There are two main sources of data quality evaluation in Brazil, but there are few comparative studies and how they evolve over time. The aim of the paper is to compare and discuss alternative estimates of completeness of death registration, adult mortality (45q15) and life expectancy estimates produced by the National Statistics Office (IBGE), Institute for Health Metrics and Evaluation (IHME), and estimates presented in Queiroz et al. (2017) and Schmertmann and Gonzaga (2018), for 1980 and 2010., Methods: We provide a descriptive and comparative analysis of aforementioned estimates from four (4) sources of estimates at subnational level (26 states and one Federal District) in Brazil from two different points in time., Results: We found significant differences in estimates that affect both levels and trends of completeness of adult mortality in Brazil and states. IHME and Queiroz et al. (2017) estimates converge by 2010, but there are large differences when compared to estimates from the National Statistics Office (IBGE). Larger differences are observed for less developed states. We have showed that the quality of mortality data in Brazil has improved steadily overtime, but with large regional variations. However, we have observed that IBGE estimates show the lowest levels of completeness for the Northern of the country compared to other estimates. Choice of methods and approaches might lead to very unexpected results., Conclusion: We produced a detailed comparative analysis of estimates of completeness of death registration from different sources and discuss the main results and possible explanations for these differences. We have also showed that new improved methods are still needed to study adult mortality in less developed countries and at a subnational level. More comparative studies are important in order to improve quality of estimates in Brazil.

Purpose: To assess the axial, radial and tangential limbus position misrepresentation when parametric models are used to represent the cornea and the sclera., Methods: This retrospective study included 135 subjects aged 22 to 65 years (36.5 mean ±9.8 STD), 71 females and 64 males. Topography measurements were taken using an Eye Surface Profiler topographer and processed by a custom-built MATLAB code. Eye surfaces were freed from edge-effect artefacts and fitted to spherical, conic and biconic models., Results: When comparing the radial position of the limbus, average errors of -0.83±0.19mm, -0.76±0.20mm and -0.69±0.20mm were observed within the right eye population for the spherical, conic and biconic models fitted up to 5mm. For the same fitting radius, the average fitting errors were -0.86±0.23mm, -0.78±0.23mm and -0.73±0.23mm for the spherical, conic and biconic models respectively within the left eye population. For the whole cornea fit, the average errors were -0.27±0.12mm and -0.28±0.13mm for the spherical models, -0.02±0.29mm and -0.05±0.27mm for the conic models, and -0.22±0.16mm and 0.24±0.17mm for the biconic models in the right and left eye populations respectively., Conclusions: Through the use of spherical, conic and biconic parametric modelling methods, the eye's limbus is being mislocated. Additionally, it is evident that the magnitude of fitting error associated with the sclera may be propagating through the other components of the eye. This suggests that a corneal nonparametric model may be necessary to improve the representation of the limbus., Competing Interests: CV has received payments or expenses for acting as the clinical chair for NHS England Commissioning through Evaluation for SDR. MP has received personal fees from Merck. The other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: This paper presents and clinically validates two algorithms for estimating intraocular pressure (IOP) and corneal material behavior using numerical models that consider the fluid-structure interaction between the cornea and the air-puff used in non-contact tonometry. Methods: A novel multi-physics fluid-structure interaction model of the air-puff test was employed in a parametric numerical study simulating human eyes under air-puff pressure with a wide range of central corneal thickness (CCT = 445-645 μm), curvature ( R = 7.4-8.4 mm), material stiffness and IOP (10-25 mmHg). Models were internally loaded with IOP using a fluid cavity, then externally with air-puff loading simulated using a turbulent computational fluid dynamics model. Corneal dynamic response parameters were extracted and used in development of two algorithms for IOP and corneal material behavior; fIOP and fSSI, respectively. The two algorithms were validated against clinical corneal dynamic response parameters for 476 healthy participants. The predictions of IOP and corneal material behavior were tested on how they varied with CCT, R, and age. Results: The present study produced a biomechanically corrected estimation of intraocular pressure (fIOP) and a corneal material stiffness parameter or Stress-Strain Index (fSSI), both of which showed no significant correlation with R ( p > 0.05) and CCT ( p > 0.05). Further, fIOP had no significant correlation with age ( p > 0.05), while fSSI was significantly correlated with age ( p = 0.001), which was found earlier to be strongly correlated with material stiffness. Conclusion: The present study introduced two novel algorithms for estimating IOP and biomechanical material behavior of healthy corneas in-vivo . Consideration of the fluid structure interaction between the cornea and the air puff of non-contact tonometry in developing these algorithms led to improvements in performance compared with bIOP and SSI., (Copyright © 2020 Maklad, Eliasy, Chen, Wang, Abass, Lopes, Theofilis and Elsheikh.)

A novel method to locate the centre of keratoconus (KC) and the transition zone between the pathological area and the rest of the corneal tissue is proposed in this study. A spherical coordinate system was used to generate a spherical height map measured relative to the centre of the optimal sphere fit, and normal to the surface. The cone centre was defined as the point with the maximum height. Second derivatives of spherical height were then used to estimate the area of pathology in an iterative process. There was mirror symmetry between cone centre locations in both eyes. The mean distance between cone centre and corneal apex was 1.45 ± 0.25 mm (0.07-2.00), the mean cone height normal to the surface was 37 ± 23 µm (2-129) and 75 ± 45 µm (5-243) in the anterior and posterior surfaces, respectively. There was a significant negative correlation between the cone height and the radius of the sphere of optimal fit ( p < 0.05 for both anterior and posterior surfaces). On average, posterior cone height was larger than the corresponding anterior cone height by 37 ± 24 µm (0-158). The novel method proposed can be used to estimate the cone centre and area, and explore the changes in anterior and posterior corneal surfaces that take place with KC progression. It can help improve understanding of keratoconic corneal morphology and assist in developing customized treatments.

Purpose: To test the performance of 4 tonometers in estimating intraocular pressure (IOP) after 3 forms of refractive surgery., Setting: Eye Hospital, Wenzhou Medical University, China., Design: Prospective case series., Methods: Patients matched for preoperative age, corneal thickness, and myopic correction enrolled for femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), small-incision lenticule extraction (SMILE), or transepithelial photorefractive keratectomy (tPRK) were included in the study. For each patient, 4 measurements of IOP were obtained preoperatively and 3 months postoperatively, using the Goldmann applanation tonometer (GAT-IOP), the Dynamic Contour Tonometer (DCT-IOP), corneal-compensated IOP (IOPcc) from the Ocular Response Analyzer, and biomechanically corrected IOP (bIOP) from the Corvis ST. Overall corneal stiffness was also estimated based on the stiffness parameter (SP-A1) provided by the Corvis ST., Results: The study included 144 eyes of 144 patients. Among the 3 procedures, the smallest variances between preoperative and postoperative IOP estimates and SP-A1 values were observed with the tPRK, followed by SMILE and FS-LASIK. In the tPRK group, no significant differences were observed in both bIOP (-0.18 ± 1.63 mm Hg) and DCT-IOP (-.64 ± 2.34 mm Hg), whereas they were larger and significant in GAT-IOP (-1.78 ± 2.29 mm Hg) and IOPcc (-2.77 ± 1.84 mm Hg). In FS-LASIK and SMILE groups, although there were similar significant reductions in IOP postoperatively, these reductions were still lower in bIOP and DCT-IOP than those in GAT-IOP and IOPcc., Conclusions: The bIOP and DCT-IOP were the least affected IOP estimates between the 3 refractive surgery procedures considered. It was evident that tPRK produced significantly smaller reductions in IOP readings than did FS-LASIK and SMILE.

Purpose: To compare clinical outcomes between topography-guided customized ablation treatment (TCAT) and wavefront-optimized (WFO) photorefractive keratectomy (PRK) in fellow eyes of myopic patients., Methods: Forty-six eyes of 23 patients who underwent PRK were included. WFO ablation was performed in one eye (WFO group) and TCAT in the fellow eye (TCAT group). The customized treatment plan was based on the Topolyzer Vario topography system (Alcon Laboratories, Inc) data. The patients were observed for 12 months after the procedure., Results: One year after the surgery, there was no significant difference in the manifest refraction spherical equivalent, sphere, or cylinder variables between the two groups (P > .05). In both groups, 96% of eyes achieved an uncorrected distance visual acuity of 20/20 or better at 12 months postoperatively. Accuracy, safety, and efficacy of the refractive and visual outcomes were similar in the two groups. The postoperative higher order aberrations magnitude was lower in the TCAT group, but this was not statistically significant (P > .05). During the 12-month follow-up, no patient described any symptoms related to glare, halos, or starbursts in either eye. Other postoperative complications, such as infection or cor-neal infiltrates, did not occur in either group., Conclusions: TCAT and WFO ablations provided similar outcomes after PRK for myopia and myopic astigmatism correction. There were no statistically significant differences in postoperative corneal wavefront analysis. [J Refract Surg. 2020;36(6):358-365.]., (Copyright 2020, SLACK Incorporated.)

Corneal ectasia is a complication of refractive surgery, and keratoconus is a contraindication to this type of procedure. Surface ablation may be an option for selected cases of mild keratoconus, with patient education being fundamental to this treatment as well as a complete evaluation of the cornea and optical properties of the patient. Here we report the clinical outcome of a patient 15 years after advanced surface ablation in a case of mild (fruste) keratoconus.

Corneal biomechanics has been a hot topic for research in contemporary ophthalmology due to its prospective applications in diagnosis, management, and treatment of several clinical conditions, including glaucoma, elective keratorefractive surgery, and different corneal diseases. The clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia after laser vision correction. This review discusses the latest developments in the detection of corneal ectatic diseases. These developments should be considered in conjunction with multimodal corneal and refractive imaging, including Placido-disk based corneal topography, Scheimpflug corneal tomography, anterior segment tomography, spectral-domain optical coherence tomography (SD-OCT), very-high-frequency ultrasound (VHF-US), ocular biometry, and ocular wavefront measurements. The ocular response analyzer (ORA) and the Corvis ST are non-contact tonometry systems that provide a clinical corneal biomechanical assessment. More recently, Brillouin optical microscopy has been demonstrated to provide in vivo biomechanical measurements. The integration of tomographic and biomechanical data into artificial intelligence techniques has demonstrated the ability to increase the accuracy to detect ectatic disease and characterize the inherent susceptibility for biomechanical failure and ectasia progression, which is a severe complication after laser vision correction., Competing Interests: Competing interestsBL, PV, RV, AE and RA are consultants for Oculus (Wetzlar, Germany). The authors declare that they have no competing interests., (© The Author(s). 2020.)

Purpose: To evaluate the variation in the optical power achieved following soft contact lens eye fitting for spherical and cylindrical lenses with differing hydrogel material properties., Methods: Uniaxial tensile tests were performed on four hydrogel materials 77% water-content (w-c) hydrogel, 74% w-c blue silicone hydrogel, 74% w-c clear silicone hydrogel, and 64% w-c clear hydrogel (shortly referred to as H77p0, SiH74p5-blue, SiH74p5-clear, and H64p0-clear), under loading conditions that would be expected in vivo. Finite element models of the cornea and contact lens interaction were generated using spherical and cylindrical lenses with powers varying from -10 to +20 D; overall diameters of either 13.5, 14.0, or 14.5 mm; and with material properties matching those determined through experimental testing., Results: The moduli of elasticity for each of the tested hydrogel materials were 0.195 ± 0.027 MPa, 0.277 ± 0.019 MPa, 0.279 ± 0.01 MPa, and 0.457 ± 0.013 MPa for H77p0, SiH74p5-blue, SiH74p5-clear, and H64p0 respectively. The calculated values of effective power change (EPC) showed strong negative correlations with lens power. This was particularly apparent in the higher end of the lens power spectrum (over +5 D), where each of the materials demonstrated a highly linear reduction in EPC with increased lens power., Conclusions: Soft contact lenses composed of a stiffer hydrogel are far more resilient to changes in EPC across the lower end of the lens power spectrum (-10 to +5 D). Beyond this range, the material choice does not have a significant effect on the EPC.

Purpose: To introduce and clinically validate a new method of estimating intraocular pressure (IOP) in patients with keratoconus and soft corneas with the aim of significantly reducing dependence on corneal biomechanics., Setting: Vincieye Clinic, Milan, Italy, and Rio de Janeiro Corneal Tomography and Biomechanics Study Group, Brazil., Design: Retrospective case series., Method: This study comprised participants enrolled at two hospitals on two continents. Numerical analysis based on the finite element method was performed to simulate the effect of tonometric air pressure of the Corvis ST dynamic Scheimpflug analyzer on eye globes with wide variations in thickness, geometry, and tissue. The numerical predictions of ocular behavior were used to develop a new algorithm to produce predictions of the biomechanically corrected IOP (bIOP) in eyes with a soft cornea (bIOP s ). Predictions of the bIOP s were assessed in the keratoconic clinical datasets (because on average these corneas are softer) and compared with the previously developed bIOP algorithm predictions obtained for normal healthy eyes., Results: The study comprised 722 eyes (722 participants). The main outcome was the absence of a significant difference in IOP between healthy eyes and keratoconic eyes when the bIOP and bIOP s algorithms were used (P > .05). There was, however, a significant difference with the uncorrected Scheimpflug analyzer IOP in both groups (P < .001). Furthermore, the bIOP s predictions were significantly less affected by corneal thickness and patient age than the Scheimpflug analyzer IOP., Conclusion: The bIOP s algorithm was more reliable at estimating the IOP in eyes with a soft cornea and was validated for use in eyes with keratoconus., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To present a three-dimensional non-parametric method for detecting scleral asymmetry using corneoscleral topography data that are free of edge-effect artefacts., Methods: The study included 88 participants aged 23 to 65 years (37.7±9.7), 47 women and 41 men. The eye topography data were exported from the Eye Surface Profiler software in MATLAB binary data container format then processed by custom built MATLAB codes entirely independent from the profiler software. Scleral asymmetry was determined initially from the unprocessed topography before being determined again after removing the edge-effect noise. Topography data were levelled around the limbus, then edge-effect was eliminated using a robust statistical moving median technique. In addition to comparing raw elevation data, scleral elevation was also compared through fitting a sphere to every single scleral surface and determining the relative elevation from the best-fit sphere reference surface., Results: When considering the averaged raw topography elevation data in the scleral section of the eye at radius 8 mm, the average raw elevations of the right eyes' sclera were -1.5±1.77, -1.87±2.12, -1.36±1.82 and -1.57±1.87 mm. In the left eyes at the same radius the average raw elevations were -1.62±1.78, -1.82±2.07, -1.28±1.76 and -1.68±1.93 mm. While, when considering the average raw elevation of the sclera after removing the edge effect, the average raw elevations of the right eyes were -3.71±0.25, -4.06±0.23, -3.95±0.19 and -3.95±0.23 mm. In the left eyes at the same radius the average raw elevations were -3.71±0.19, -3.97±0.22, -3.96±0.19 and -3.96±0.18 mm in the nasal, temporal, superior and inferior sides respectively. Maximum raw elevation asymmetry in the averaged scleral raw elevation was 1.6647±0.9015 mm in right eyes and 1.0358±0.6842 mm in left eyes, both detected at -38° to the nasal side. Best-fit sphere-based relative elevation showed that sclera is more elevated in three main meridians at angles -40°, 76°, and 170° in right eyes and -40°, 76°, and 170° in left eyes, all measured from the nasal meridian. Maximum recorded relative elevation asymmetries were 0.0844±0.0355 mm and 0.068±0.0607 mm at angular positions 76° and 63.5° for right and left eyes in turn., Conclusions: It is not possible to use corneoscleral topography data to predict the scleral shape without considering a method of removing the edge-effect from the topography data. The nasal side of the sclera is higher than the temporal side, therefore, rotationally symmetric scleral contact lenses are more likely to be translated towards the temporal side. The scleral shape is best described by levelled raw elevation rather than relative elevation., Competing Interests: L W, the clinical director of UltraVision CLPL, may use the results in this manuscript to improve the design of soft contact lenses. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare no potential financial or non-financial competing interests.

Purpose : To present a novel design method for non-orthogonal lenses to reduce the problem of residual astigmatism in non-orthogonal, astigmatic eyes Methods : A method to create spectacle trial lenses with non-orthogonal power axes was developed based on a novel optimised light ray-tracing algorithm rather than conventional lens design methods which could not fully eliminate spherical aberration. Using this method, three sets of refraction trial lenses were made with the angles between power axes of each set controlled at 80°, 70° and 60°, respectively. Within each set, the cylindrical power varied from -1.00 D to -6.00 D in 1.00 D steps in addition to a -0.50 D lens. Computer-based numerical simulation of the lenses optical performance was carried out to apply orthogonal and non-orthogonal lenses on simulated astigmatic eyes. Subsequently, three clinical trial cases were investigated. Results : Computer-simulated optical performance of non-orthogonal lenses showed the ability to achieve high performance in correcting non-orthogonal astigmatism. Subsequently, three patients with irregular astigmatism were refracted with the non-orthogonal lens sets, and clinically observed improvement at least two lines in the LogMAR chart was achieved in all three cases, compared with correction with orthogonal lenses, along with subjective improvement in image quality. Conclusions : Non-orthogonal astigmatism, which is commonly ignored by current eye prescription systems, is taken into account in this study in the design of spectacle and soft contact lenses. The new approach considers the possible non-orthogonal positions of the eye's two optical power meridians and appears to be better able to correct the vision of irregular astigmatic eyes and significantly reduce residual astigmatism.

Purpose: This study aims to introduce and clinically validate a new algorithm that can determine the biomechanical properties of the human cornea in vivo . Methods: A parametric study was conducted involving representative finite element models of human ocular globes with wide ranges of geometries and material biomechanical behavior. The models were subjected to different levels of intraocular pressure (IOP) and the action of external air puff produced by a non-contact tonometer. Predictions of dynamic corneal response under air pressure were analyzed to develop an algorithm that can predict the cornea's material behavior. The algorithm was assessed using clinical data obtained from 480 healthy participants where its predictions of material behavior were tested against variations in central corneal thickness (CCT), IOP and age, and compared against those obtained in earlier studies on ex-vivo human ocular tissue. Results: The algorithm produced a material stiffness parameter (Stress-Strain Index or SSI) that showed no significant correlation with both CCT ( p > 0.05) and IOP ( p > 0.05), but was significantly correlated with age ( p < 0.01). The stiffness estimates and their variation with age were also significantly correlated ( p < 0.01) with stiffness estimates obtained earlier in studies on ex-vivo human tissue. Conclusions: The study introduced and validated a new method for estimating the in vivo biomechanical behavior of healthy corneal tissue. The method can aid optimization of procedures that interfere mechanically with the cornea such as refractive surgeries and introduction of corneal implants.

Purpose: To evaluate the impact of soft contact lens eye-fit on optical power by computational modelling and to produce correction maps for reversing this impact during the design process., Methods: Finite element models of spherical and toric hydrogel contact lenses at varying nominal powers of -20 D to +20 D, base curves radii (R1b) of 8.2, 8.5, 8.8 mm, and overall diameters (d3) of 14.5, 15.0, 15.5 mm were generated. Lenses were fitted to computational eye models generated with human eyes' topography data. Combined eye-lens simulations were run under the boundary conditions of the tears' surface tension between the contact lens and the eye in addition to the eyelid blink pressure. Lens optical zone power changes were calculated through computational light-ray tracing methods following each simulation., Results: Effective power changes (EPC) were affected negatively for all toric simulated lenses with power varying from -20 D to +20 D. Spherical lenses demonstrated similar behaviour, however with some positive EPC over the power range from -20 D to -10 D for spherical power (SPH) lenses. EPC assessment was between +0.25 D and -0.5 D for most lenses, however, lenses with prescriptions from +10 D to +20 D incurred EPC outside this range. The spherical lenses showed a maximum effective power change of +1.046 ± 0.338 D (Average Eye), and a minimum of -3.278 ± 0.731 D (Steep Eye). Similarly, the toric lenses showed a maximum of +1.501 ± 0.338 D (Average Eye), and a minimum of -3.514 ± 0.731 D (Steep Eye). EPC trends, along with minimum and maximum power, generally increased negatively as nominal lens prescription increased positively. Contact lens base curve selection affected the assessed effective power change for both spherical and toric lenses. The effect from lens total diameter for spherical lenses was less substantial than that for toric lenses., Conclusions: This study considered the impact of soft contact lens design parameters on effective optical power changes (EPC) after eye-fit. Spherical lenses experienced more EPC of clinical significance (>0.25 D) than toric lenses. Both types of lenses, spherical and toric (simple astigmatism), demonstrated similar trends in EPC on fitting from -20 D to +20 D, with lenses in the extremely positive and the extremely negative prescriptions demonstrating the highest EPCs. The lens base curve impacted the extent of EPC observed, with flatter base curves experiencing less power change. Diameter proved to impact toric lenses more than spherical ones, however generally the diameter has less effect on power change than base curve selection., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: AA was a paid employee of an Innovate UK Knowledge Transfer Partnership Programme Grant till November 2017. AS, CEO of Eaglet Eye BV, and both IF and RS, the clinicians in Eaglet Eye BV, may use the figures in this manuscript to improve the performance of the Eye Surface Profiler (ESP). All other authors declare no potential financial or non-financial competing interests including employment, consultancy, patents, products in development, or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To test the accuracy of the Tomographic and Biomechanical Index (TBI) for ectasia detection in an independent population from the original study., Design: Retrospective case-control study., Methods: Subjects: Patients were grouped according to clinical diagnosis including corneal topography (front-surface curvature): Normal group, including 1 eye randomly selected from 312 patients with normal corneas; Keratoconus group, including 1 eye randomly selected from 118 patients with keratoconus; a nonoperated ectatic eye from 57 patients with very asymmetric ectasia (57 eyes, VAE-E group), and the nonoperated fellow eye with normal topography (57 eyes, VAE-NT group)., Main Outcome Measures: The ability of TBI to distinguish normal and ectatic corneas; and comparison with other indexes, including the Belin/Ambrósio Deviation Index (BAD-DI) and the Corvis Biomechanical Index (CBI), considering the areas under receiver operating characteristic curves (AUCs)., Results: The AUC of the TBI was statistically higher than all other tested parameters (DeLong, P < .001). Considering all cases, the cut-off value of 0.335 for the TBI provided a sensitivity of 94.4% and a specificity of 94.9% (AUC = 0.988; 95% confidence interval [CI] 0.982-0.995). Considering the VAE-NT group, optimized TBI cut-off value of 0.295 provided a sensitivity of 89.5% and a specificity of 91.0% (AUC = 0.960; 95% CI 0.937-0.983)., Conclusion: The TBI was more accurate than all parameters tested for differentiating normal from ectatic corneas. The TBI may epitomize ectasia susceptibility and distinguish cases with fruste disease from true unilateral cases among the eyes with normal-topography VAE., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To present a novel non-parametric algorithm for detecting the position of the human eye limbus in three dimensions and a new dynamic method for measuring the full 360° visible iris boundary known as white-to-white distance along the eye horizontal line., Methods: The study included 88 participants aged 23 to 65 years (37.7±9.7), 47 females and 41 males. Clinical characteristics, height data and the apex coordinates and 1024×1280 pixel digital images of the eyes were taken by an Eye Surface Profiler and processed by custom-built MATLAB codes. A dynamic light intensity frequency based white-to-white detection process and a novel three-dimensional method for limbus detection is presented., Results: Evidence of significant differences (p<0.001) between nasal-temporal and superior-inferior white-to-white distances in both right and left eyes were found (nasal-temporal direction; 11.74±0.42 mm in right eyes and 11.82±0.47 mm in left eyes & superior-inferior direction; 11.52±0.45 mm in right eyes and 11.55±0.46 mm in left eyes). Average limbus nasal-temporal diameters were 13.64±0.55 mm for right eyes, and 13.74±0.40 mm for left eyes, however the superior-inferior diameters were 13.65±0.54 mm, 13.75±0.38 mm for right and left eyes, respectively. No significant difference in limbus contours has been observed either between the nasal-temporal direction (p = 0.91) and the superior-inferior direction (p = 0.83) or between the right (p = 0.18) and left eyes (p = 0.16). Evidence of tilt towards the nasal-temporal side in the three-dimensional shape of the limbus was found. The right eyes mean limbus contour tilt around the X-axis was -0.3±1.35° however, their mean limbus contour tilt around the Y-axis was 1.76±0.9°. Likewise, the left eyes mean limbus contour tilt around the X-axis was 0.77±1.25° and the mean limbus contour tilt around the Y-axis was -1.54±0.89°., Conclusions: The white-to-white distance in the human eye is significantly larger in the nasal-temporal direction than in the superior-inferior direction. The human limbus diameter was found not to vary significantly in these directions. The 3D measures show that the limbus contour does not lay in one plane and tends to be higher on the nasal-inferior side of the eye., Competing Interests: JC, Joint CEO and CTO of UltraVision CLPL, may use the computing in this manuscript to improve the clinical measurement of the limbus position. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. All other authors declare no potential financial or non-financial competing interests.

Purpose: To identify the relative positions of geometrical and visual axes of the eye and present a method to locate the visual center when the geometrical axis is taken as a reference., Methods: Topography elevation data was collected using a Pentacam HR ® topographer from 2040 normal eyes of 1020 healthy participants in Brazil, China and Italy. A three-dimensional, rotation algorithm, a first-order Zernike polynomial fit and a nonlinear least-squares error function was used within an optimization function to locate the geometrical axis and the visual center of each eye., Results: The right eyes of participants were significantly more tilted than left eyes throughout the topography scanning process (p < 0.001). The visual centers were always located in the nasal-superior quadrant, although the visual centers of fellow eyes were not symmetrically located. Mean distances between the visual center and the geometrical center in right eyes were 0.8 ± 0.29 mm, 0.56 ± 0.18 mm and 0.91 ± 0.34 mm among Brazilian, Chinese and Italian participants, respectively, and located at angular positions of 38.7 ± 24.5°, 23.0 ± 29.8° and 23.1 ± 28.1° from the nasal side. However, in left eyes, mean distances were 0.76 ± 0.33 mm, 0.45 ± 0.12 mm and 0.75 ± 0.33 mm at polar angles from the nasal side of 59.3 ± 29.0°, 50.6 ± 44.5° and 61.8 ± 34.1°, respectively., Conclusions: Fellow eyes do not perform similarly during the fixation process, with right eyes tending to tilt more than left eyes, and the visual centers of the fellow eyes positioned differently relative to the geometrical centers.