Corneal Response Research Articles

A corneo-retinal hypercitrullination axis underlies ocular injury to nitrogen mustard

The vesicant sulfur mustard (SM) is a chemical warfare agent that causes acute and chronic injury to the cornea and proximal anterior segment structures. Despite clinical evidence of SM-exposure causing unexplained retinal deficits, there have been no animal studies conducted to examine the retinal toxicity of this vesciant. The cardinal hallmark of retinal response to stressors or injury is the activation of reactive gliosis, a cellular process largely governed by Müller glia. Previously we showed that corneal exposure to sodium hydroxide elicits rapid induction of reactive gliosis and results in retinal degeneration in a dose-related manner. Based on this evidence, we hypothesized that the vesicant nitrogen mustard (NM), an analog of SM, may also elicit reactive gliosis. To test this idea, we developed a mouse model of NM ocular injury and investigated corneal and retinal effects focusing on citrullination, a posttranslational modification (PTM) of proteins. This PTM was recently linked to alkali injury and has also been shown to occur in retinal degenerative conditions. Here, we demonstrate that corneal exposure to 1% NM causes a synchronous activation of citrullination in both the cornea and retina with hypercitrullination becoming apparent temporally and manifesting with altered cellular expression characteristics. A key finding is that ocular citrullination occurs acutely as early as 1-h post-injury in both the cornea and retina, which underscores a need for expeditious interception of this acute corneal and retinal response. Moreover, exploiting dose response and temporal studies, we uncoupled NM-induced retinal citrullination from its induction of retinal gliosis. Our findings demonstrate that hypercitrullination is a common corneo-retinal mechanism that sensitizes the eye to NM injury and suggests that counteracting hypercitrullination may provide a suitable countermeasure to vesicant injury.

The corneal fibroblast: The Dr. Jekyll underappreciated overseer of the responses to stromal injury

PurposeTo review the functions of corneal fibroblasts in wound healing. MethodsLiterature review. ResultsCorneal fibroblasts arise in the corneal stroma after anterior, posterior or limbal injuries and are derived from keratocytes. Transforming growth factor (TGF) β1 and TGFβ2, along with platelet-derived growth factor (PDGF), are the major modulators of the keratocyte to corneal fibroblast transition, while fibroblast growth factor (FGF)-2, TGFβ3, and retinoic acid are thought to regulate the transition of corneal fibroblasts back to keratocytes. Adequate and sustained levels of TGFβ1 and/or TGFβ2, primarily from epithelium, tears, aqueous humor, and corneal endothelium, drive the development of corneal fibroblasts into myofibroblasts. Myofibroblasts have been shown in vitro to transition back to corneal fibroblasts, although apoptosis of myofibroblasts has been documented as a major contributor to the resolution of fibrosis in several in situ corneal injury models. Corneal fibroblasts, aside from their role as a major progenitor to myofibroblasts, also perform many critical functions in the injured cornea, including the production of critical basement membrane (BM) components during regeneration of the epithelial BM and Descemet's membrane, production of non-basement membrane-associated stromal collagen type IV to control and downregulate TGFβ effects on stromal cells, release of chemotactic chemokines that attract bone marrow-derived cells to the injured stroma, production of growth factors that modulate regeneration and maturation of the overlying epithelium, and production of collagens and other ECM components that contribute to stromal integrity after injury. ConclusionsCorneal fibroblasts are major contributors to and overseers of the corneal response to injuries.

Development and validation of an intuitive biomechanics-based method for intraocular pressure measurement: a modal analysis approach

BackgroundCurrent intraocular pressure (IOP) measurements based on non-contact tonometry are derived from statistics-driven equations and lack biomechanical significance, which often leads to under-estimation in post-refractive surgery cornea. This study aims to introduce and validate modal analysis-derived intraocular pressure (mIOP) as a novel method generated through Legendre-based modal decomposition of the anterior corneal contour; it provides an accurate and intuitive IOP measurement from an energy-based perspective.MethodsThis retrospective study included 680 patients. Healthy participants were divided into reference (n = 385) and validation (n = 142) datasets, and the others underwent either femtosecond-assisted laser in situ keratomileusis (FS-LASIK, n = 58) or transepithelial photorefractive keratectomy (TPRK, n = 55). Corneal curvature of the right eyes was extracted from raw serial cross-sectional images of the cornea generated by Corvis ST, a noncontact tonometer with a high-speed Scheimpflug-camera. Legendre expansion was then applied to the corneal curvature to obtain the modal profiles (i.e., temporal changes of the coefficient for each basis polynomial [modes]). Using the reference dataset, feature selection on the modal profiles generated a final mIOP model consisting of a single parameter: total area under curve (frames 1–140) divided by the area under curve of the rising phase (frames 24–40) in the fourth mode, i.e. the M4 ratio. Validation was performed in both the healthy validation and postoperative datasets. IOP-Corvis, pachymetry-corrected IOP, biomechanically corrected IOP, and mIOP values were compared. For the FS-LASIK and TPRK groups, pairwise postoperative IOP changes were analyzed through repeated measures analysis of variance, and agreement was examined through Bland–Altman analysis. Using a finite element analysis based three-dimensional model of the human cornea, we further compared the M4 ratio with the true intraocular pressure within the physiological range.ResultsThe M4 ratio-based mIOP demonstrated weak to negligible association with age, radius of corneal curvature, and central corneal thickness (CCT) in all validation analyses, and performed comparably with biomechanically corrected IOP (bIOP) in the refractive surgery groups. Both remained nearly constant postoperatively and were not influenced by CCT changes. Additionally, M4 ratio accurately represented true intraocular pressure in the in silico model.ConclusionsmIOP is a reliable IOP measurement in healthy and postrefractive surgery populations. This energy-based, ratio-derived approach effectively filters out pathological, rotational, misaligned movements and serves as an interpatient self-calibration index. Modal analysis of corneal deformation dynamics provides novel insights into regional corneal responses against pressure loading.

Comparison of corneal biomechanical properties in healthy thin corneas with matched keratoconus eyes.

To compare corneal biomechanical parameters of normal thin corneas with matched keratoconus eyes. Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Cross-sectional comparative study. Dynamic corneal response parameters of Corvis ST were compared in 61 eyes with keratoconus with 61 matched healthy thin corneas (corneal thinnest point <500 μm), while corneal thickness, biomechanically corrected intraocular pressure, and age were considered covariates. The receiving operator sensitivity curve analysis was used to determine the cutoff point with the highest sensitivity and specificity, and the area under the curve (AUC) for each parameter. All biomechanical parameters were statistically significant between the 2 groups except for the first ( P = .947) and second ( P = .582) applanation length, first ( P = .783) and second ( P = .301) applanation velocity, and deformation amplitude in the highest concavity phase ( P = .106). The highest mean difference between groups (12.89 ± 2.03 mm Hg/mm) was related to the stiffness parameter at the first applanation (SPA1). Although the Corvis biomechanical index and tomographic biomechanical index had the highest detection ability based on their AUC (0.912 and 0.959, respectively), among the standard and combined biomechanical parameters except for keratoconus screening parameters, the highest discriminative ability was related to SPA1 with AUC, sensitivity, and specificity of 0.793, 60.66%, and 90.16%, respectively. Keratoconus corneas were significantly softer compared with healthy thin corneas of matched thickness. Optimal cutoff points close to the maximum value defined for screening parameters limit their clinical use for differentiation purposes in these particular types of cases.

Change in the corneal material mechanical property for small incision lenticule extraction surgery.

Purpose: To assess the distribution characteristics and related factors of stress-strain index (SSI) values and discuss changes in biomechanical parameters, including SSI, after small incision lenticule extraction (SMILE) surgery. Methods: This study included 253 patients who underwent SMILE (253 eyes). SSI and other biomechanical parameters were measured using corneal visualization Scheimpflug technology before and 3months after surgery. The data collected included SSI, central corneal thickness (CCT), and eight other dynamic corneal response parameters. The Kolmogorov-Smirnov test, Pearson and partial correlation analyses, and paired-sample t-tests were used for statistical analyses. Results: Both pre-op SSI and ΔSSI follow a normal distribution, while post-op SSI does not follow a normal distribution. The decline in SSI after SMILE surgery was not statistically significant, and the data dispersion of SSI after SMILE surgery was close to that before surgery (p > 0.05). No statistical correlation was noted between SSI values and age and pre-op CCT (all p > 0.05). However, both pre- and post-op SSI values decreased with increasing degree of myopia (all p < 0.05), and weakly correlated with preoperative intraocular pressure and biomechanically corrected intraocular pressure (all p < 0.05). Other biomechanical parameters changed significantly after surgery (all p < 0.001). After SMILE, the magnitude of the deformation at the highest concave, deformation ratio, and integral radius increased significantly (all p < 0.001), while the Ambrosio relational thickness horizontal, stiffness parameter A1, and Corvis biomechanical index decreased significantly (p < 0.001). Conclusion: SSI, which reflects essential corneal material attributes, differs from other corneal biomechanical parameters and remains stable before and after SMILE surgery, and can be used as an indicator to evaluate changes in corneal material properties after SMILE surgery.

The Yin and Yang of Mesenchymal Cells in the Corneal Stromal Fibrosis Response to Injury: The Cornea as a Model of Fibrosis in Other Organs.

Mesenchymal cells (keratocytes, corneal fibroblasts, and myofibroblasts), as well as mesenchymal progenitor bone marrow-derived fibrocytes, are the major cellular contributors to stromal fibrosis after injury to the cornea. Corneal fibroblasts, in addition to being major progenitors to myofibroblasts, also have anti-fibrotic functions in (1) the production of non-basement membrane collagen type IV that binds activated transforming growth factor (TGF) beta-1 and TGF beta-2 to downregulate TGF beta effects on cells in the injured stroma, (2) the production of chemokines that modulate the entry of bone marrow-derived cells into the stroma, (3) the production of hepatocyte growth factor and keratinocyte growth factor to regulate corneal epithelial healing, (4) the cooperation with the epithelium or corneal endothelium in the regeneration of the epithelial basement membrane and Descemet's membrane, and other functions. Fibrocytes also serve as major progenitors to myofibroblasts in the corneal stroma. Thus, mesenchymal cells and mesenchymal cell progenitors serve Yin and Yang functions to inhibit and promote tissue fibrosis depending on the overall regulatory milieu within the injured stroma.

Ultrasonographic measured optic nerve sheath diameter as a bedside prognostication tool in patients with severe traumatic brain injury

Rise in intracranial pressure (ICP) after the severe traumatic brain injury (TBI) has been associated with poor outcomes in patients. Measuring ONSD on ultrasonography is an emerging noninvasive bedside tool that can reliably and rapidly detect raised ICP. 30-year-old patient sustained a head injury in a road traffic accident. On examination it was found that GCS was 7/15, 4 mm bilaterally fixed pupils, negative corneal response and ONSD was 6.38 mm on the ultrasound. The raised intracranial pressure was detected and management was immediately started. Patient was immediately taken up for surgery after a CT scan was done. This case report highlights the potential of rapidly identifying raised intracranial pressure at the patients’s bedside by measuring ONSD by ultrasonography.

The link between anterior scleral thickness, corneal biomechanical response and ocular parameters

AbstractPurpose: to assess anterior scleral thickness (AST) across diverse scleral meridians and to evaluate the relationship with corneal biomechanical response and several ocular parameters.Methods: This prospective non‐randomized study comprised 50 eyes of 50 patients (mean age, 29.02 ± 9.48 years). Anterior scleral thickness was measured meridionally at three scleral locations (1‐, 2‐, and 3‐mm posterior to the scleral spur) using swept‐source optical coherence tomography. A multivariate model was created to associate AST with several ocular parameters. Principal component analysis (PCA) was used to reduce linearly the dimensionality of seven biomechanical input metrics to two significant components, C1 and C2. Two multivariate analyses were performed to associate C1 and C2 with AST and ocular parameters.Results: AST was thickest in the inferior (581 ± 52 μm) and thinnest in the superior meridian (441 ± 42 μm) when compared to all meridians (p &lt; 0.001), and similar in the nasal (529 ± 53 μm) and temporal (511 ± 59 μm) meridians (p &gt; 0.05). The sclera exhibited the thinnest point 2 mm posterior to the scleral spur (p &lt; 0.001). The AST was significantly linked with axial length, central corneal thickness, and intraocular pressure (p &lt; 0.001). The PCA showed that C1 accounts for 53.84% whereas C2 for the 16.51% of the total variance in the original variables. The C1 model was significantly associated with AST along all meridians (p &lt; 0.001). The partial correlation was moderate in the nasal (r = −0.36, p &lt; 0.001) and inferior (r = −0.26, p = 0.004) meridians whereas weak in the temporal (r = −0.14, p = 0.05) and superior (r = −0.15, p = 0.05) meridians.Conclusions: The relationship between the new biomechanical component and the AST provides the first evidence of the association of AST with the corneal response parameters which should be considered in corneal response interpretation. Tissue thickness varied significantly among meridians supporting the asymmetrical expansion of the ocular globe. The AST was associated with several ocular parameters.

Changes in Stress-Strain Index and Corneal Biomechanics in Granular Corneal Dystrophy.

The aim of this study was to assess stress-strain index (SSI) and corneal biomechanical parameters in eyes with granular corneal dystrophy (GCD). This case-control study included 12 eyes of 12 patients with GCD (mean age 45.2 ± 18.7 years) and 20 eyes of 20 healthy individuals (mean age 54.4 ± 3.8 years). In addition to SSI, dynamic corneal response (DCR) parameters were assessed at the first and second applanation, including length (AL1, AL2), velocity (AV1, AV2), time (AT1, AT2), and deformation amplitude (DA A1, DA A2), and at the highest concavity (HC) phase, including DA, peak distance (PD), radius (HCR), and DA ratio (DAR 1 and 2 mm), by Corvis ST. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were considered covariates in comparing DCR parameters between the two groups. SSI was statistically significantly lower in eyes with GCD than in normal eyes (p = 0.04). The corneal velocity towards the first applanation was 0.02 m/s faster in the GCD eyes AV1 (0.15 ± 0.02 vs. 0.13 ± 0.02 m/s, p &lt; 0.001) and IR (7.48 ± 1.01 vs. 6.80 ± 1.22 mm, p = 0.003) parameters were significantly higher in the GDC group, while AT1 (7.33 ± 0.66 vs. 7.47 ± 0.36 ms, p = 0.002) and HCR (7.42 ± 0.76 vs. 8.20 ± 1.08 mm, p = 0.014) were significantly lower in the normal group. GCD led to a change in biomechanical properties of the cornea. SSI refers to fewer stiff corneas in GDC than normal.

Evaluation of Dynamic Corneal Response Parameters and the Biomechanical E-Staging After Accelerated Corneal Cross-Linking in Keratoconus.

This study evaluated the biomechanical E-staging in progressive keratoconus (KC) corneas before and after epithelium-off accelerated corneal cross-linking (CXL, 9mW/cm2, 10min, 5.4J/cm2). German university-based retrospective longitudinal cohort study. The biomechanical E-staging for ectatic corneal diseases was applied retrospectively on 49 progressive KC corneas of 41 patients who underwent CXL. Main outcome parameters included the Corvis Biomechanical Factor (CBiF, the linearized Corvis Biomechanical Index), the biomechanical E-staging (E1 to E4 result of dividing the CBiF value range into 5 groups), maximal anterior keratometry (Kmax), anterior radius of curvature (ARC), and thinnest corneal thickness (TCT). They were evaluated at 2.1±2.0 months preoperatively (n=49 corneas, 41 patients) and postoperatively after 5.4±1.4, 11.3±1.8, and 23.4±1.6 months. The CBiF decreased (5.1±0.5 | 5.0±0.5, P=0.0338) and the E-staging increased significantly (2.4±0.9 | 2.6±0.8, P=0.0035) from preoperatively to the first postoperative follow-up. The difference was not significant after 11 months and there were same values after 23 months. Kmax, ARC, and TCT slightly decreased (Kmax: 56.9±6.3, 54.3±5.1, 56.2±6.6, 54.0±5.2; ARC: 49.8±3.5, 48.9±3.2, 50.8±5.6, 49.0±3.7; TCT: 470±34, 454±36, 459±35, 466±39; preoperatively and 5, 11, and 23 months postoperatively). A postoperatively decreased TCT was associated with an increased E-stage, whereas an equal or increased TCT measurement after CXL was associated with equal or lower E-staging results. The biomechanical E-staging in KC corneas is influenced by TCT measurements and increases within the first postoperative months after CXL. On the long term, it indicates a postoperative KC stabilization, with comparable E-values to preoperatively at 11 and 23 months after CXL.

A detailed methodology to model the Non Contact Tonometry: a Fluid Structure Interaction study.

Understanding the corneal mechanical properties has great importance in the study of corneal pathologies and the prediction of refractive surgery outcomes. Non-Contact Tonometry (NCT) is a non-invasive diagnostic tool intended to characterize the corneal tissue response in vivo by applying a defined air-pulse. The biomarkers inferred from this test can only be considered as indicators of the global biomechanical behaviour rather than the intrinsic biomechanical properties of the corneal tissue. A possibility to isolate the mechanical response of the corneal tissue is the use of an inverse finite element method, which is based on accurate and reliable modelling. Since a detailed methodology is still missing in the literature, this paper aims to construct a high-fidelity finite-element model of an idealized 3D eye for in silico NCT. A fluid-structure interaction (FSI) simulation is developed to virtually apply a defined air-pulse to a 3D idealized eye model comprising cornea, limbus, sclera, lens and humors. Then, a sensitivity analysis is performed to examine the influence of the intraocular pressure (IOP) and the structural material parameters on three biomarkers associated with corneal deformation. The analysis reveals the requirements for the in silico study linked to the correct reproduction of three main aspects: the air pressure over the cornea, the biomechanical properties of the tissues, and the IOP. The adoption of an FSI simulation is crucial to capture the correct air pressure profile over the cornea as a consequence of the air-jet. Regarding the parts of the eye, an anisotropic material should be used for the cornea. An important component is the sclera: the stiffer the sclera, the lower the corneal deformation due to the air-puff. Finally, the fluid-like behavior of the humors should be considered in order to account for the correct variation of the IOP during the test which will, otherwise, remain constant. The development of a strong FSI tool amenable to model coupled structures and fluids provides the basis to find the biomechanical properties of the corneal tissue in vivo.

Magic Bullets: The Coming Age of Meaningful Pharmacological Control of the Corneal Responses to Injury and Disease.

Corneal injuries from chemical burns, mechanical trauma, infections, immunological rejections, surgical complications, and some diseases are commonly associated with persistent epithelial defects (PED), neurotrophic epitheliopathy, scarring fibrosis, corneal neovascularization (CNV), and/or corneal endothelial damage that lead to vision loss. Several Food and Drug Administration (FDA) approved medications have recently become available, are currently in clinical trials, or are likely to enter clinical trials in the near future. For example, a 2-week course of topical human recombinant nerve growth factor is frequently an effective treatment for corneal neurotrophic epitheliopathy associated with PEDs. Topical losartan, an angiotensin converting enzyme II receptor antagonist that also inhibits TGF beta signaling, has been shown to effectively decrease myofibroblast generation and scarring fibrosis in alkali burn injury and Descemetorhexis rabbit models. Small molecule topical tyrosine kinase inhibitors, such as sunitinib and axitinib, FDA approved as chemotherapeutic agents to treat specific cancers, have also been found to be effective topical inhibitors of CNV in animal and human trials. Rho-kinase inhibitors, such as ripasudil and netarsudil, that are currently approved agents for the treatment of glaucoma in some countries, have been shown to stimulate corneal endothelial proliferation in animal studies and human trials, and may accelerate the regeneration of Descemet's membrane. These agents, as well as other drugs in development, will be used in targeted combinations to treat corneal pathophysiology associated with epithelial healing disorders, stromal scarring fibrosis, CNV, and corneal endothelial injury during the next decade.

S1.5c Proteomics in fungal keratitis research: a road map to personalized treatment

S1.5 Mycotic Keratitis, September 21, 2022, 11:00 AM - 12:30 PMResearch becomes very significant and meaningful when it addresses a significant public health problem of a region. Fungal keratitis, ulceration of the cornea due to fungal infection, is one such serious problem. This infection that results in monocular blindness affects primarily the agrarian population and is considered to be a silent epidemic in India.The current treatment for fungal keratitis is the topical application of antifungal drugs such as natamycin and voriconazole. Nearly 40% of the patients do not respond to this treatment and require corneal transplantation. Treatment with antifungal drugs is not a holistic approach as it addresses only killing the fungus. The exaggerated inflammatory response at the site of infection may be a crucial factor in the disease outcome. And, this is not taken into account during the treatment due to the lack of knowledge of the host response during the fungal infection. This was the starting point of our research in fungal keratitis—to understand the corneal immune response to fungal infection.Using mass-spectrometry-based proteomics studies on a tear from keratitis patients, we identified that in response to the fungal infection, the complement and coagulation pathways were activated along with neutrophil-mediated defense responses, notably the neutrophil extracellular traps. These pathways and their cross-talk with each other were primarily responsible for the exaggerated immune response at the site of infection. We selected five tear proteins that were significantly altered and validated them to serve as indicators of the inflammatory status of the ulcer in keratitis patients. Further, we developed a predictive logistic regression model that incorporates tear biomarker levels and ulcer characteristics to identify the subset of patients who are unlikely to respond to the antifungal treatment. We are currently exploring the possibility of using tear-derived EVs or their cargo as adjuvant therapy to modulate the inflammatory response in these non-responder patients.Through our efforts using proteomics approaches, we now have five tear proteins as indicators of the inflammatory status in keratitis patients. These proteins along with the clinical features can identify the subset of patients who are unlikely to respond to antifungal treatment. Additionally, we showed that keratitis patient tear-derived extracellular vesicles are enriched with proteasomes. As proteasomes have an established role in immune modulation, EVs with proteasomes are thus promising candidates for adjuvant therapy, which we are currently exploring. Thus, our journey of over a decade of research on fungal keratitis started with the basic research to understand the host response that in turn provided the leads for translational research, which is now advancing towards personalized treatment for these patients.

Repeatability of a Scheimpflug tonometer to measure biomechanical parameters before and after myopic refractive surgery

To assess the repeatability of several corneal biomechanical parameters with a Scheimpflug tonometer (Corvis ST) in myopic eyes and eyes that underwent transepithelial photorefractive keratectomy (transPRK), small-incision lenticule extraction (SMILE), or femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery. Eye Hospital of Wenzhou Medical University, Wenzhou, China. Prospective randomized controlled study. 315 eyes from 315 patients (135 myopes, 58 post-transPRK, 52 post-SMILE, and 70 post-FS-LASIK) were included. 3 consecutive scans were performed to evaluate the repeatability of the 40 parameters examined. 315 eyes were included. In all eyes, the coefficient of variation (CoV) for intraocular pressure (IOP) and biomechanical-corrected IOP (bIOP) ranged from 7.29% to 9.47% and 6.11% to 7.75%, respectively; the CoV of pachymetry was <0.8%. The intraclass correlation coefficient of Corvis Biomechanical Index-Laser Vision Correction (LVC) was 0.680 for post-transPRK, 0.978 for post-SMILE, and 0.911 for post-FS-LASIK. The CoV of Stress-Strain Index (SSI) was 204.93% for post-transPRK, 91.92% for post-SMILE, and 171.72% for post-FS-LASIK. The CoV of the 6 clinically important dynamic corneal response parameters ranged from 2.0% to 7.8% for myopia, 1.8% to 11.1% for post-transPRK, 2.1% to 8.7% for post-SMILE, and 1.8% to 8.8% for post-FS-LASIK. Excellent intrameasurement repeatability of IOP, bIOP, and pachymetry was observed in all groups; SSI measurement in post-LVC corneas displayed more variation. Caution is warranted when assessing SSI in post-LVC corneas for the purpose of diagnosing iatrogenic ectasia or evaluating biomechanical remodeling of postoperative refractive corneas.

Effect of fluence levels on prophylactic corneal cross-linking for laser in situ keratomileusis and transepithelial photorefractive keratectomy.

The purpose of this study is to assess the effect of various fluence levels on prophylactic corneal cross-linking (CXL) combined with femtosecond laser in situ keratomileusis (FS-LASIK-Xtra) or transepithelial photorefractive keratectomy (TransPRK-Xtra) on biomechanics, demarcation line (DL), and stromal haze. Prospective analysis where two prophylactic CXL protocols (lower/higher fluence [LF/HF]: 30 mw/cm2 , 60/80 s, 1.8/2.4J/cm2 ) were performed as part of either an FS-LASIK-Xtra or TransPRK-Xtra procedure. Data were collected preoperatively and at 1week and 1, 3, and 6months postoperatively. Main outcome measures were (1) dynamic corneal response parameters and the stress-strain index (SSI) from Corvis, (2) actual DL depth (ADL), and (3) stromal haze on OCT images analysed by a machine learning algorithm. Eighty-six eyes from 86 patients underwent FS-LASIK-Xtra-HF (21 eyes), FS-LASIK-Xtra-LF (21 eyes), TransPRK-Xtra-HF (23 eyes), and TransPRK-Xtra-LF (21 eyes). SSI increased similarly by around 15% in all groups 6months postoperatively (p=0.155). All other corneal biomechanical parameters were statistically significant worsening postoperatively, but the change was similar in all groups. At 1month postoperatively, there was no statistical difference in mean ADL among four groups (p=0.613), mean stromal haze was similar between the two FS-LASIK-Xtra groups, but higher in the TransPRK-Xtra-HF group compared with the TransPRK-Xtra-LF group. FS-LASIK-Xtra and TransPRK-Xtra lead to a similar ADL and improve SSI equally. Lower fluence prophylactic CXL might be recommended as it achieves similar mean ADL with potentially less induced stromal haze, especially in TransPRK. The clinical relevance and applicability of such protocols remains to be assessed.

Comparison of Scheimpflug Derived Biomechanical and Tomographical Indices to Detect Corneal Ectasia - A Cross Sectional Study

Objective: To compare Corvis ST (Oculus Wetzlar, Germany) and Pentacam (Oculus) derived indices to detect normal cornea, keratoconus and for mefruste keratoconus.&#x0D; Study Design: Comparative cross sectional study.&#x0D; Place and Duration of Study: Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi, from Feb to Jul 2019.&#x0D; Methodology: Following strict inclusion criteria 90 patients were enrolled that were divided into 3 equal groups of normal, Keratoconus and Formefruste kertoconus. One eye of the patient was selected and underwent ophthalmic examination followed by assessment of Corvis ST (Oculus Wetzlar, Germany) and Pentacam (Oculus). Classification analysis between normal, keratoconus and formefruste keratoconus was evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) was compared.&#x0D; Results: Several corneal response parameters generated by Corvis St (Oculus Wetzlar, Germany) were statistically significant (p-value &lt;0.05) in keratoconus group. The Area under the curve (AUC) ROC values for the keratoconus and normal comparison were 0.84(SPA1), 0.864 (BAD-D), 0.865 (PRFI), 0.92 (CBI), 0.96 (TBI). Among the combined indices TBI showed increase sensitivity of 98.3 % and 94.7% specificity to detect keratoconus. The AUC ROC value for the formefruste and normal control comparison were 0.75 (SPA1), 0.81 (BAD-D), 0.82 (PRFI), 0.81 (CBI), 0.91 (TBI) with 94% sensitivity and 90% specificity to detect formefruste keratoconus.&#x0D; Conclusion: Our study concluded that among the combined indices TBI demonstrated greater precision to detect keratoconus and formefruste keratoconus thus aiding and augmenting the recent technology.

Measuring Human Corneal Stromal Biomechanical Properties Using Tensile Testing Combined With Optical Coherence Tomography.

Purpose: To investigate the ex vivo elastic modulus of human corneal stroma using tensile testing with optical coherence tomography (OCT) imaging and its correlation with in vivo measurements using corneal visualization Scheimpflug technology. Methods: Twenty-four corneal specimens extracted from stromal lenticules through small incision lenticule extraction were cut into strips for uniaxial tensile tests. In vivo corneal biomechanical responses were evaluated preoperatively using the corneal visualization Scheimpflug technology (CorVis ST). The correlation of the elastic modulus with clinical characteristics and dynamic corneal response parameters were analyzed using Spearman’s correlation analysis. Results: The mean low strain tangent modulus (LSTM) of the human corneal stroma was 0.204 ± 0.189 (range 0.010–0.641) MPa, and high strain tangent modulus (HSTM) 5.114 ± 1.958 (range 2.755–9.976) MPa. Both LSTM (r = 0.447, p = 0.029) and HSTM (r = 0.557, p = 0.005) were positively correlated with the stress-strain index (SSI). LSTM was also positively correlated with the A1 deflection length (r = 0.427, p = 0.037) and A1 deflection area (r = 0.441, p = 0.031). HSTM was positively correlated with spherical equivalent (r = 0.425, p = 0.038). Conclusions: The correlation of corneal elastic modulus with A1 deflection parameters and SSI may indicate a relationship between these parameters and tissue elasticity. The HSTM decreased with the degree of myopia. Combining tensile test with OCT may be a promising approach to assess corneal biomechanical properties.

The low-density lipoprotein receptor-related protein 1 (LRP1) interactome in the human cornea

The human cornea is responsible for approximately 70% of the eye's optical power and, together with the lens, constitutes the only transparent tissue in the human body. Low-density lipoprotein receptor-related protein 1 (LRP1), a large, multitalented endocytic receptor, is expressed throughout the human cornea, yet its role in the cornea remains unknown. More than 30 years ago, LRP1 was purified by exploiting its affinity for the activated form of the protease inhibitor alpha-2-macroblulin (A2M), and the original purification protocol is generally referred to in studies involving full-length LRP1. Here, we provide a novel and simplified LRP1 purification protocol based on LRP1's affinity for receptor-related protein (RAP) that produces significantly higher yields of authentic LRP1. Purified LRP1 was used to map its unknown interactome in the human cornea. Corneal proteins extracted under physiologically relevant conditions were subjected to LRP1 affinity pull-down, and LRP1 ligand candidates were identified by LC-MS/MS. A total of 28 LRP1 ligand candidates were found, including 22 novel ligands. The LRP1 corneal interactome suggests a novel role for LRP1 as a regulator of the corneal immune response, structure, and ultimately corneal transparency.

In Vivo Corneal Biomechanical Properties in a Selected Chinese Population, Measured Using the Corneal Visualization Scheimpflug Technology.

Purpose: To evaluate the repeatability and reproducibility of recalculated dynamic corneal response (DCR) parameters and the biomechanical-compensated intraocular pressure (bIOP) derived from the Corneal Visualization Scheimpflug Technology (Corvis ST), as well as to study the variations of DCR parameters and their relationship with demographic, and ocular characteristics. Methods: A total of 544 healthy subjects were recruited in this study and a series of ophthalmological examinations were performed on their right eyes. Three repeated measurements were obtained at 3-min intervals for 291 of the participants to ensure repeatability. A sum of 100 participants was examined twice within 2-h intervals using two different Corvis ST in the reproducibility study. The repeatability and reproducibility of 37 parameters, including 36 DCR parameters and bIOP, were assessed by the coefficient of repeatability (CR), coefficient of variation (CV), intraclass correlation coefficient (ICC), and within-subject standard deviation (sw). Pearson’s correlation coefficients and stepwise multivariate linear regression models were performed to investigate whether the DCR parameters were related to demographic and ocular characteristics. Results: Of all the 37 parameters, 34 showed excellent (ICC ≥0.90) or good (ICC ≥0.75) repeatability while 27 of the 37 parameters showed excellent (ICC ≥0.90) or good (ICC ≥0.75) reproducibility. In particular, a CV of less than 20% was found for all DCR parameters and bIOP. A fraction of 14 out of 36 DCR parameters was selected for correlation analysis, based on measurement reliability and clinical relevance in referring to previous literature. Age was negatively associated with the Highest concavity delta arc length (HCdArcL) and peak distance (PD) but it positively correlated with the Whole Eye Movement Max Length (WEMML). Intraocular pressure (IOP) and central corneal thickness (CCT) were negatively associated with the deformation amplitude ratio (DARM) [1 mm], A1 Velocity (A1V), and PD, while positively related to the stiffness parameter at applanation 1 (SP-A1). The bIOP was negatively associated with A1V but positively associated with A2 Velocity (A2V). The anterior chamber volume (ACV) was negatively associated with the pachy slope (PS), WEMML, and SP-A1. Conclusion. The Corvis ST showed good precision for the repeatability and reproducibility of 36 DCR parameters and bIOP parameters in healthy eyes. The IOP, CCT, bIOP, Km, and ACV significantly influenced the DCR parameters of the eyes.

Corneal Response to Scleral Contact Lens Wear in Keratoconus.

To verify corneal alterations in patients with keratoconus who wear scleral contact lenses (ScCLs), focusing on corneal endothelial assessment. Scleral contact lenses were fitted in 22 patients with keratoconus. During a 90-day follow-up, patients were assessed in three visits: at baseline, after 30 days, and after 90 days. Patients underwent visual acuity measurement, slitlamp biomicroscopy of the anterior segment, specular microscopy of the corneal endothelium, corneal pachymetry, measurement of the clearance between the cornea and the lens, and follow-up of ectasia. Variables related to endothelial morphology and pachymetry values did not change significantly over time. Central clearance measurements decreased in the 90-day period. No progression of corneal ectasia was observed, neither were infectious or inflammatory processes in the same period. Daily wear of ScCLs in patients with keratoconus was not associated with adverse effects on the cornea or endothelium over a period of 90 days nor was there evidence of disease progression. Central clearance values diminished over that period, but the significance of this observation remains unclear.