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Purpose: This study aimed to employ the incremental digital image correlation (DIC) method to obtain displacement and strain field data of the cornea from Corvis ST (CVS) sequences and access the performance of embedding these biomechanical data with machine learning models to distinguish forme fruste keratoconus (FFKC) from normal corneas. Methods: 100 subjects were categorized into normal (N = 50) and FFKC (N = 50) groups. Image sequences depicting the horizontal cross-section of the human cornea under air puff were captured using the Corvis ST tonometer. The high-speed evolution of full-field corneal displacement, strain, velocity, and strain rate was reconstructed utilizing the incremental DIC approach. Maximum (max-) and average (ave-) values of full-field displacement V, shear strain γxy, velocity VR, and shear strain rate γxyR were determined over time, generating eight evolution curves denoting max-V, max-γxy, max-VR, max-γxyR, ave-V, ave-γxy, ave-VR, and ave-γxyR, respectively. These evolution data were inputted into two machine learning (ML) models, specifically Naïve Bayes (NB) and Random Forest (RF) models, which were subsequently employed to construct a voting classifier. The performance of the models in diagnosing FFKC from normal corneas was compared to existing CVS parameters. Results: The Normal group and the FFKC group each included 50 eyes. The FFKC group did not differ from healthy controls for age (p = 0.26) and gender (p = 0.36) at baseline, but they had significantly lower bIOP (p < 0.001) and thinner central cornea thickness (CCT) (p < 0.001). The results demonstrated that the proposed voting ensemble model yielded the highest performance with an AUC of 1.00, followed by the RF model with an AUC of 0.99. Radius and A2 Time emerged as the best-performing CVS parameters with AUC values of 0.948 and 0.938, respectively. Nonetheless, no existing Corvis ST parameters outperformed the ML models. A progressive enhancement in performance of the ML models was observed with incremental time points during the corneal deformation. Conclusion: This study represents the first instance where displacement and strain data following incremental DIC analysis of Corvis ST images were integrated with machine learning models to effectively differentiate FFKC corneas from normal ones, achieving superior accuracy compared to existing CVS parameters. Considering biomechanical responses of the inner cornea and their temporal pattern changes may significantly improve the early detection of keratoconus. [ABSTRACT FROM AUTHOR]

This study aims to compare meibomian gland (MG) dropout and MG dysfunction (MGD) between patients with diabetes mellitus (DM) with moderate–severe non-proliferative diabetic retinopathy (NPDR) and patients with no diabetes (NDM). This prospective, transversal, age, and gender-matched case–control study included 98 DM and 106 NDM eyes. Dry eye disease (DED) and MGD evaluations were performed, including meibography (Keratograph 5M®). The objective MG dropout percentage was obtained by analyzing meibography images with ImageJ software (v. 1.52o, National Institutes of Health, Bethesda, MD, USA) and was subsequently graded with Arita's meiboscore. The DM duration was 18 ± 9 years. The mean meiboscore (3.8 ± 0.8 vs. 3.4 ± 1.0, p = 0.001), meiboscore severity (p = 0.016), and MG dropout (45.1 ± 0.1% vs. 39.0 ± 0.4%, p < 0.001) were greater in DM than in NDM. All patients showed MG dropout (meiboscore > 1). Lower eyelids showed greater MG dropout in both groups. A correlation with age (r = 0.178, p = 0.014) and no correlations with DM duration or gender (p > 0.005) were observed. Patients with diabetes showed greater corneal staining (1.7 ± 1.3 vs. 0.9 ± 1.1; p < 0.001), reduced corneal sensitivity (5.4 ± 1.1 vs. 5.9 ± 0.4; p < 0.001), lower MG expressibility (3. 9 ± 1.6 vs. 4.4 ± 2.1; p = 0.017), and worse meibum quality (1.9 ± 0.8 vs. 1.7 ± 0.5; p = 0.019). Tear breakup time, osmolarity, MMP-9, Schirmer, and the Ocular Surface Disease Index showed no significant differences. In conclusion, patients with DM with NPDR have greater MG dropout and meiboscore, as well as more severe MGD and DED parameters than persons with NDM. [ABSTRACT FROM AUTHOR]

The aim of our study is to investigate the feasibility and outcomes of using a femtosecond laser (FSL) platform (Ziemer LDV Z8) for deep anterior lamellar keratoplasty (DALK), enabling the creation of mushroom-shaped graft–host junctions, lamellar cuts, and intrastromal tunnels, to facilitate the big bubble, in one step. We included wet lab experiments on nine porcine eyes to assess the laser accuracy and cuts depth using an anterior segment (AS) OCT. This was followed by an interventional prospective case series on 10 eyes with variant corneal pathologies. The Z8 system, with in-built intraoperative optical coherence tomography (iOCT), guided corneal scans and directed the cuts. ASOCT showed visible mushroom configurations, lamellar cuts, and tunnels. Deviations from the target were 1.6%, 2.6%, and 3.5%. Anterior lamellar removal was easy in all clinical cases, including corneal scarring. The intrastromal tunnel was found at the preset location and the mushroom configuration was acquired. A big bubble was achieved in all cases. Type 1, 2, and 3 bubbles were formed in eight, one, and one case, respectively. We describe a new approach to DALK in which the in-built iOCT-guided FSL enables safe, precise, controlled, and reproducible desired cuts in one step. The preliminary clinical outcomes were favorable. [ABSTRACT FROM AUTHOR]

Fuchs endothelial corneal dystrophy (FECD) is a complex genetic disorder characterized by the slow and progressive degeneration of corneal endothelial cells. Thus, it may result in corneal endothelial decompensation and irreversible corneal edema. Moreover, FECD is associated with alterations in all corneal layers, such as thickening of the Descemet membrane, stromal scarring, subepithelial fibrosis, and the formation of epithelial bullae. Hence, anterior segment imaging devices that enable precise measurement of functional and anatomical changes in the cornea are essential for the management of FECD. In this review, the authors will introduce studies on the application of various imaging modalities, such as anterior segment optical coherence tomography, Scheimpflug corneal tomography, specular microscopy, in vitro confocal microscopy, and retroillumination photography, in the diagnosis and monitoring of FECD and discuss the results of these studies. The application of novel technologies, including image processing technology and artificial intelligence, that are expected to further enhance the accuracy, precision, and speed of the imaging technologies will also be discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To improve the effectivity of patient-specific finite element analysis (FEA) to predict refractive power change (RPC) in rigid Ortho-K contact lens fitting. Novel eyelid boundary detection is introduced to the FEA model to better model the effects of the lid on lens performance, and stress and strain outcomes are investigated to identify the most effective FEA components to use in modelling. Methods: The current study utilises fully anonymised records of 249 eyes, 132 right eyes, and 117 left eyes from subjects aged 14.1 ± 4.0 years on average (range 9 to 38 years), which were selected for secondary analysis processing. A set of custom-built MATLAB codes was built to automate the process from reading Medmont E300 height and distance files to processing and displaying FEA stress and strain outcomes. Measurements from before and after contact lens wear were handled to obtain the corneal surface change in shape and power. Tangential refractive power maps were constructed from which changes in refractive power pre- and post-Ortho-K wear were determined as the refractive power change (RPC). A total of 249 patient-specific FEA with innovative eyelid boundary detection and 3D construction analyses were automatically built and run for every anterior eye and lens combination while the lens was located in its clinically detected position. Maps of four stress components: contact pressure, Mises stress, pressure, and maximum principal stress were created in addition to maximum principal logarithmic strain maps. Stress and strain components were compared to the clinical RPC maps using the two-dimensional (2D) normalised cross-correlation and structural similarity (SSIM) index measure. Results: On the one hand, the maximum principal logarithmic strain recorded the highest moderate 2D cross-correlation area of 8.6 ± 10.3%, and contact pressure recorded the lowest area of 6.6 ± 9%. Mises stress recorded the second highest moderate 2D cross-correlation area with 8.3 ± 10.4%. On the other hand, when the SSIM index was used to compare the areas that were most similar to the clinical RPC, maximum principal stress was the most similar, with an average strong similarity percentage area of 26.5 ± 3.3%, and contact pressure was the least strong similarity area of 10.3 ± 7.3%. Regarding the moderate similarity areas, all components were recorded at around 34.4% similarity area except the contact pressure, which was down to 32.7 ± 5.8%. Conclusions: FEA is an increasingly effective tool in being able to predict the refractive outcome of Ortho-K treatment. Its accuracy depends on identifying which clinical and modelling metrics contribute to the most accurate prediction of RPC with minimal ocular complications. In terms of clinical metrics, age, Intra-ocular pressure (IOP), central corneal thickness (CCT), surface topography, lens decentration and the 3D eyelid effect are all important for effective modelling. In terms of FEA components, maximum principal stress was found to be the best FEA barometer that can be used to predict the performance of Ortho-K lenses. In contrast, contact pressure provided the worst stress performance. In terms of strain, the maximum principal logarithmic strain was an effective strain barometer. [ABSTRACT FROM AUTHOR]

We investigated the bioavailability and stability of a C-Clear artificial cornea in a rabbit chemical burn model. Thirty-six rabbits were divided into a control group (n = 16) and a chemical burn group that used NaOH solution (n = 20). After lamellar dissection, the central posterior lamella was excised using a 3 mm diameter trephine, and an artificial cornea was transplanted into the lamellar pocket. After 2 weeks, the central anterior lamella was excised using a 3 mm diameter trephine to secure a clean visual axis. We examined the anterior segment of the eyes weekly for 12 weeks after transplantation. Successful subjects whose artificial corneas were maintained stably for 12 weeks were euthanized and underwent histologic examinations. Artificial corneas remained stable for up to 12 weeks in 62.5 and 50% of rabbits in the control and chemical burn groups, respectively. Two rabbits in the chemical burn group showed the formation of a retroprosthetic membrane, and one rabbit with visual axis blockage underwent membrane removal using a Nd:YAG laser. In histologic examinations, adhesion between artificial cornea and peripheral corneal stoma was observed. In conclusion, we confirmed structural stability and biocompatibility of the C-Clear artificial cornea for up to 12 weeks after implantation in control and chemical burn groups. [ABSTRACT FROM AUTHOR]

Keratoconus is a bilateral progressive degenerative corneal disease characterized by localized corneal thinning and dilatation. The pathogenesis of keratoconus is not fully elucidated. To gain a better understanding of the pathophysiology of this disease and to explore potential treatments, animal models are essential for basic research. Several attempts have been made to establish animal models of corneal ectasia by using collagenase. However, continuous changes of the cornea have not been well-tracked for the model. In this study, corneal morphology and biomechanical behavior in vivo were determined before and after collagenase Ⅱ treatment at 2, 4, and 8 weeks. The elastic modulus and histology of cornea tissues ex vivo were measured at 8 weeks postoperatively. The results showed that the posterior corneal curvature (Km B) increased and central corneal thickness (CCT) decreased after collagenase treatment. The mechanical properties of ectatic corneas weakened significantly and the collagen fiber interval in the stromal layer was increased and disorganized. This study provides insights into the changes of corneal morphology and biomechanical properties in a rabbit model of corneal ectasia. Changes observed at 8 weeks indicated that the cornea was still undergoing remodeling. [ABSTRACT FROM AUTHOR]

The corneal epithelium is composed of nonkeratinized stratified squamous cells and has a significant turnover rate. Limbal integrity is vital to maintain the clarity and avascularity of the cornea as well as regeneration of the corneal epithelium. Limbal epithelial stem cells (LESCs) are located in the basal epithelial layer of the limbus and preserve this homeostasis. Proper functioning of LESCs is dependent on a specific microenvironment, known as the limbal stem cell niche (LSCN). This structure is made up of various cells, an extracellular matrix (ECM), and signaling molecules. Different etiologies may damage the LSCN, leading to limbal stem cell deficiency (LSCD), which is characterized by conjunctivalization of the cornea. In this review, we first summarize the basics of the LSCN and then focus on current and emerging bioengineering strategies for LSCN restoration to combat LSCD. [ABSTRACT FROM AUTHOR]

Platelet concentrates (PCs), including platelet-rich plasma (PRP) gel and platelet-rich fibrin (PRF), are autologous blood-derived biomaterials containing numerous growth factors. This study aimed to evaluate the initial healing effects of PRP gel and PRF on deep corneal wounds. Thirty-three eyes from New Zealand white rabbits were divided into four groups: group 1, lamellar keratectomy (LK); group 2, LK + commercial porcine small intestinal submucosal membrane (SIS); group 3, LK + SIS + PRP gel; and group 4, LK + SIS + PRF. Postoperative clinical and histological findings were observed for eight weeks. Group 1 showed no neovascularization during the observation period, and incompletely recovered with a thin cornea. Group 2 showed active healing through neovascularization, and a thick cornea was regenerated through the sufficient generation of myofibroblasts. Although group 3 showed a healing effect similar to that of group 2, angiogenesis and subsequent vessel regression were promoted, and corneal opacity improved more rapidly. In group 4, angiogenesis was promoted during initial healing; however, the incidence of complications, such as inflammation, was high, and myofibroblasts were hardly generated in the corneal stroma, which adversely affected remodeling. In conclusion, while PRP gel is a safe surgical material for promoting remodeling through vascular healing and myofibroblast production in deep corneal wounds, the use of PRF is not recommended. [ABSTRACT FROM AUTHOR]

The anterior segment of the eye is a complex set of structures that collectively act to maintain the integrity of the globe and direct light towards the posteriorly located retina. The eye is exposed to numerous physical and environmental insults such as infection, UV radiation, physical or chemical injuries. Loss of transparency to the cornea or lens (cataract) and dysfunctional regulation of intra ocular pressure (glaucoma) are leading causes of worldwide blindness. Whilst traditional therapeutic approaches can improve vision, their effect often fails to control the multiple pathological events that lead to long-term vision loss. Regenerative medicine approaches in the eye have already had success with ocular stem cell therapy and ex vivo production of cornea and conjunctival tissue for transplant recovering patients' vision. However, advancements are required to increase the efficacy of these as well as develop other ocular cell therapies. One of the most important challenges that determines the success of regenerative approaches is the preservation of the stem cell properties during expansion culture in vitro. To achieve this, the environment must provide the physical, chemical and biological factors that ensure the maintenance of their undifferentiated state, as well as their proliferative capacity. This is likely to be accomplished by replicating the natural stem cell niche in vitro. Due to the complex nature of the cell microenvironment, the creation of such artificial niches requires the use of bioengineering techniques which can replicate the physico-chemical properties and the dynamic cell-extracellular matrix interactions that maintain the stem cell phenotype. This review discusses the progress made in the replication of stem cell niches from the anterior ocular segment by using bioengineering approaches and their therapeutic implications. [ABSTRACT FROM AUTHOR]

Walking support systems are essential for blind people. In this study, the presentation of phosphene position is focused on as a method to detect obstacles for blind people. When the phosphene is used in a walking support system, it is necessary to accurately present the phosphene in at least three directions of the visual field. Controlling the presentation of phosphene position has been reported in several previous studies. However, methodologies to present phosphene in multiple directions without any electric interference have not as yet been investigated. In this study, therefore, appropriate stimulation factors are clarified by the simulation of electric field on the eyeball surface which is strongly related to the presentation of phosphene position in the visual field. As a result of the simulation, it was revealed that the distance of each electrode does not give a significant effect to the eyeball surface. However, the phase of alternating current significantly changed the electric field on the eyeball surface. From investigation of the simulation results, it was clarified that the transition of the electric field on the eyeball surface can be controlled using anti-phase stimulation. In addition, the methodology to present the phosphene at least in two directions was verified. [ABSTRACT FROM AUTHOR]

The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstruction of LSCN and artificial stem cells for self-renewal. [ABSTRACT FROM AUTHOR]

Corneal transplantation remains the ultimate treatment option for advanced stromal and endothelial disorders. Corneal tissue engineering has gained increasing interest in recent years, as it can bypass many complications of conventional corneal transplantation. The human cornea is an ideal organ for tissue engineering, as it is avascular and immune-privileged. Mimicking the complex mechanical properties, the surface curvature, and stromal cytoarchitecure of the in vivo corneal tissue remains a great challenge for tissue engineering approaches. For this reason, automated biofabrication strategies, such as bioprinting, may offer additional spatial control during the manufacturing process to generate full-thickness cell-laden 3D corneal constructs. In this review, we discuss recent advances in bioprinting and biomaterials used for in vitro and ex vivo corneal tissue engineering, corneal cell-biomaterial interactions after bioprinting, and future directions of corneal bioprinting aiming at engineering a full-thickness human cornea in the lab. [ABSTRACT FROM AUTHOR]

The cornea is avascular, which makes it an excellent model to study matrix protein expression and tissue stiffness. The corneal epithelium adheres to the basement zone and the underlying stroma is composed of keratocytes and an extensive matrix of collagen and proteoglycans. Our goal was to examine changes in corneas of 8- and 15-week mice and compare them to 15-week pre-Type 2 diabetic obese mouse. Nanoindentation was performed on corneal epithelium in situ and then the epithelium was abraded, and the procedure repeated on the basement membrane and stroma. Confocal imaging was performed to examine the localization of proteins. Stiffness was found to be age and obesity dependent. Young's modulus was greater in the epithelium from 15-week mice compared to 8-week mice. At 15 weeks, the epithelium of the control was significantly greater than that of the obese mice. There was a difference in the localization of Crb3 and PKCζ in the apical epithelium and a lack of lamellipodial extensions in the obese mouse. In the pre-Type 2 diabetic obese mouse there was a difference in the stiffness slope and after injury localization of fibronectin was negligible. These indicate that age and environmental changes incurred by diet alter the integrity of the tissue with age rendering it stiffer. The corneas from the pre-Type 2 diabetic obese mice were significantly softer and this may be a result of changes both in proteins on the apical surface indicating a lack of integrity and a decrease in fibronectin. [ABSTRACT FROM AUTHOR]

The cornea is the most external layer of the eye and serves two important roles in (1) the refraction of light and (2) protection from the outside environment, both of which are highly dependent on the collagen assembly of the corneal stroma. This study sought to determine the collagen fiber arrangement of the canine corneal stroma and correlate the stromal organization with tissue stiffness in the anterior and posterior cornea. Collagen organization of the canine cornea was visualized through second-harmonic generation (SHG) imaging, and tissue stiffness of the anterior and posterior corneal stroma was determined by atomic force microscopy. Analysis of the canine anterior corneal stroma using SHG imaging documented intertwining of the collagen fibers with a high degree of fiber branching, with a more lamellar and non-branching posterior stroma. The anterior stroma had significantly higher tissue stiffness in both dogs and humans, when compared with the posterior corneal stroma (canine median: 1.3 kPa vs. 0.3 kPa; human median: 14.6 kPa vs. 2.1 kPa, respectively). There was a direct correlation between corneal collagen stromal organization and tissue stiffness in the dog, which was consistent with other mammalian species previously examined and likely reflects the need for maintenance of rigidity and corneal curvature. [ABSTRACT FROM AUTHOR]