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Infectious keratitis is a leading cause of corneal blindness worldwide with little information known about causative etiologies in Malawi, Africa. This area is resource-limited with ophthalmologist and microbiology services. The Department of Ophthalmology at the Kamuzu College of Health Sciences in Blantyre, Malawi, is a participating site of an international corneal ulcer consortium, capriCORN (Comprehensive Analysis of Pathogens, Resistomes, and Inflammatory-markers in the CORNea). In this study, 50 patients with corneal ulcers were swabbed for pathogen identification using RNA-sequencing. Corneal trauma was reported in 41% and 19% of the patients worked in agriculture. A pathogen was identified in 58% of the cases. Fungal pathogens predominated, followed by viruses and bacteria. Aspergillus, Fusarium, HSV-1, and Gardnerella were the most common pathogens detected. 50% of patients reported treatment with an antibiotic before presentation. Pathogens unusual for infectious keratitis, such as Subramaniula asteroids, Aureobasidium pullulans, and Gardnerella vaginalis, were also detected.

PURPOSE: We determined interblink corneal surface-temperature decline and tear-film evaporation rates of localized tear breakup cold regions (LCRs) and localized tear unbroken warm regions (LWRs) of the corneal surface, as well as that of the overall average corneal surface. METHODS: Each subject underwent 4 inter-day visits where the interblink corneal surface-temperature history of the right eye was measured using a FLIR A655sc infrared thermographer. Corneal surface temperature history was analyzed to determine the overall, LCR, and LWR temperature-decline rates. Evaporation rates of LCR and LWR regions were determined from the measured LCR and LWR temperature data using the physical model of Dursch et al. RESULTS: Twenty subjects completed the study. Mean (SD) difference of LCR temperature-decline rate was -0.08 (0.07)°C/s faster than LWR (P < 0.0001). Similarly, evaporation rates of LCR and LWR were statistically different (P < 0.0001). At ambient temperature, mean LCR and LWR evaporation rates were 76% and 27% of pure water evaporation flux, respectively. There was no statistically significant difference between the inter-day measured temperature-decline rates and the interblink starting temperature. CONCLUSIONS: Significant differences in corneal temperature-decline rate and evaporation rate between LCR and LWR were quantified using infrared thermography. In agreement with literature, LCRs and LWRs correlate directly with fluorescein break-up areas and unbroken tear areas, respectively. Because lipid-evaporation protection is diminished in breakup areas, higher local evaporation rates and faster local cooling rates occur in LCRs relative to LWRs. Our results confirm this phenomenon clinically for the first time.

Refractive errors remain a global health concern, as a large proportion of the world's population is myopic. Current ablative approaches are costly, not without risks, and not all patients are candidates for these procedures. Electromechanical reshaping (EMR) has been explored as a viable cost-effective modality to directly shape tissues, including cartilage. In this study, stromal collagen structure and fibril orientation was examined before and after EMR with second-harmonic generation microscopy (SHG), a nonlinear multiphoton imaging method that has previously been used to study native corneal collagen with high spatial resolution. EMR, using a milled metal contact lens and potentiostat, was performed on the corneas of five extracted rabbit globes. SHG was performed using a confocal microscopy system and all images underwent collagen fibril orientation analysis. The collagen SHG signal in controls is uniform and is similarly seen in samples treated with pulsed potential, while continuous EMR specimens have reduced, nonhomogeneous signal. Collagen fibril orientation in native tissue demonstrates a broad distribution with suggestion of another peak evolving, while with EMR treated eyes a bimodal characteristic becomes readily evident. Pulsed EMR may be a means to correct refractive errors, as when comparing its SHG signal to negative control, preservation of collagen structures with little to no damage is observed. From collagen fiber orientation analysis, it can be inferred that simple DC application alters the structure of collagen. Future studies will involve histological assessment of these layers and multi-modal imaging analysis of dosimetry.

Purpose of reviewThis study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs).Recent findingsADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity.SummaryThree of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.

PurposeDiabetes mellitus causes diabetic keratopathy (DK). This and other ocular surface disorders are underdiagnosed and problematic for affected patients as well as recipients of diabetic donor corneas. Thus, it is important to find noninvasive means to facilitate determination of the potentially vision-threatening DK. It has been reported that diabetic corneas uptake significantly less oxygen (O2) than healthy controls. However, an integral assessment of the ocular surface is missing.MethodsUsing an optic-fiber O2 micro-sensor (optrode) we demonstrated recently that the healthy ocular surface displays a unique spatiotemporal map of O2 consumption. We hypothesize that diabetes impairs the spatiotemporal profile of O2 uptake at the ocular surface.ResultsUsing streptozotocin (STZ)-induced diabetic mice, we found diminished O2 uptake and loss of the unique pattern across the ocular surface. A diabetic cornea consumes significantly less O2 at the bulbar conjunctiva and limbus, but not the central and peripheral cornea, compared to controls. Further, we show that, contrary to the healthy cornea, the diabetic cornea does not increase the O2 consumption at the limbus in the evening as the normal control.ConclusionsAltogether, our measurements reveal a previously unknown impairment in O2 uptake at the diabetic cornea, making it a potential tool to diagnose ocular surface abnormalities and suggesting a new etiology mechanism.

PURPOSE: Contact lens wear induces corneal parainflammation involving increased immune cell numbers after 24 hours (CD11c+, Lyz2+, γδ-T cells) and six days (Ly6G+ cells) wear. We investigated the time course of onset and resolution of these responses. METHODS: LysMcre or C57BL/6J mice were fitted with a contact lens (four to 48 hours). Contralateral eyes did not wear lenses. After lens removal, Lyz2+, MHC-II+ or Ly6G+ cells were examined by quantitative imaging. RT-qPCR determined cytokine gene expression. RESULTS: Lens wear for 24 hours increased corneal Lyz2+ cells versus contralateral eyes approximately two-fold. Corneas remained free of visible pathology. The Lyz2+ response was not observed after four or 12 hours wear, nor after 12 hours wear plus 12 hours no wear. Lens removal after 24 hours wear further increased Lyz2+ cells (∼48% after one day), which persisted for four days, returning to baseline by seven days. Lyz2+ cells in contralateral eyes remained at baseline. MHC-II+ cells showed a similar response but without increasing after lens removal. Lens wear for 48 hours showed reduced Lyz2+ cells versus 24 hours wear with one day discontinuation, correlating with reduced IL-1β and IL-18 gene expression. Lens wear for 24 hours did not induce Ly6G+ responses six days after removal. CONCLUSIONS: Lens-induced corneal parainflammation involving Lyz2+ cells requires 24 hours wear but persists after lens discontinuation, requiring seven days for reversal. Lens wear for 48 hours may suppress initial Lyz2+ cell and cytokine responses. The significance of parainflammation during and after lens wear remains to be determined.

The cornea, as a dynamic and responsive tissue, constantly interacts with mechanical forces in order to maintain its structural integrity, barrier function, transparency and refractive power. Cells within the cornea sense and respond to various mechanical forces that fundamentally regulate their morphology and fate in development, homeostasis and pathophysiology. Corneal cells also dynamically regulate their extracellular matrix (ECM) with ensuing cell-ECM crosstalk as the matrix serves as a dynamic signaling reservoir providing biophysical and biochemical cues to corneal cells. Here we provide an overview of mechanotransduction signaling pathways then delve into the recent advances in corneal mechanobiology, focusing on the interplay between mechanical forces and responses of the corneal epithelial, stromal, and endothelial cells. We also identify species-specific differences in corneal biomechanics and mechanotransduction to facilitate identification of optimal animal models to study corneal wound healing, disease, and novel therapeutic interventions. Finally, we identify key knowledge gaps and therapeutic opportunities in corneal mechanobiology that are pressing for the research community to address especially pertinent within the domains of limbal stem cell deficiency, keratoconus and Fuchs' endothelial corneal dystrophy. By furthering our understanding corneal mechanobiology, we can contextualize discoveries regarding corneal diseases as well as innovative treatments for them.

BACKGROUND: It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial. METHODS: A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness. RESULTS: The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods. CONCLUSION: DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.

In this study, we conducted stress and strain analyses on the eyeball under pressure using the finite element simulation software Ansys. The eyeball model was constructed using SolidWorks, and additionally, it simulates a contact-type tonometer, applying pressure to the eyeball through probe force variations and calculating the pressure changes inside the eyeball. Initially, the cornea, sclera, ciliary body, suspensory ligaments, aqueous humor, and vitreous humor were combined using SolidWorks. Subsequently, the model was imported into Ansys for meshing, boundary setting, and simulation calculation. Finally, the analysis results were extracted using the Ansys postprocessor and the simulated data were validated against actual measurement data to ensure accuracy. Material properties necessary for the eyeball under pressure analyses were configured, with the Mooney-Rivlin hyperelastic material being selected. During compression, the cornea and sclera primarily absorbed the concentrated load after compression. Pressure was applied using a probe to observe variations in stress and strain concerning the applied force and intraocular pressure. Three probe materials (rubber, titanium alloy, and glass) were chosen for comparative simulation analyses. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to illustrate the changes in ocular findings, meibography, and tear break-up time (TBUT) values in pediatric patients with ocular rosacea following a standardized treatment. Methods: The study included consecutive patients diagnosed with ocular rosacea, referred to a tertiary hospital between 2021 and 2023. Each patient underwent biomicroscopic examinations, non-invasive TBUT assessments, corneal fluorescein staining (evaluated using the Oxford scoring system), and meibography. The standard treatment protocol involved warm compresses, eyelid hygiene, preservative-free sodium hyaluronate eye drops (administered four times daily), topical azithromycin 1.5% (twice daily for 3 days), topical steroids (loteprednol 0.5%, four times daily for 2 weeks), and either doxycycline 100 mg/day for 14 days or oral suspension of azithromycin 10 mg/kg for 3 days followed by an additional three-day course of treatment administered 10 days later (for patients above and below 14 years of age, respectively). Results: The study included 18 patients, with 10 (55.5%) being female and 8 (44.4%) being male, with a mean age of 9.7 ± 4.5 years (range: 3–18). Four patients displayed cutaneous involvement. The treatments resulted in significant improvements in the Oxford scores, reduction in corneal neovascularization, and increased TBUT (p < 0.001, p = 0.016, p < 0.001, respectively). Meibomian gland loss area also significantly improved post-treatment (27.4 ± 6.7% vs 39.2 ± 13.4%, p = 0.001). Conclusion: This study demonstrated that pediatric ocular rosacea patients may exhibit improved meibomian gland function, regression of corneal neovascularization, and enhanced tear film parameters following a standardized treatment protocol that includes both topical and systemic approaches. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis are the most common ocular diseases caused by CMV infections in immunocompetent patients. The incidence of CMV corneal endotheliitis is relatively high in middle-aged men. CMV corneal endotheliitis presents with mild anterior chamber inflammation, corneal edema, keratic precipitates, and elevated intraocular pressure. It resembles Posner–Schlossman syndrome and Fuchs uveitis because of the elevated intraocular pressure. Without proper diagnosis and treatment, it may progress to bullous keratopathy or glaucoma, necessitating keratoplasty or glaucoma surgery. Therefore, early diagnosis and treatment are important for a good prognosis. Aqueous humor analysis can facilitate the diagnosis of CMV corneal endotheliitis, and early antiviral treatment can decrease the risk of corneal compensation or glaucomatous optic atrophy. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of CMV corneal endotheliitis along with the evidence for early clinical diagnosis and active antiviral treatment. [ABSTRACT FROM AUTHOR]

Purpose: Corneal epithelial defects from trauma or surgery heal as new epithelial cells grow centripetally from the limbus and replenish the epithelium. Corneal wound healing requires cell signalling molecules. However, a topical treatment with these components is not available. Human breast milk (HBM) offers a potential, novel treatment as it contains bioactive molecules important in epithelial cell healing. This study seeks to investigate the potential of HBM in cornea wound healing. Methods: Balb/c mice, 8–12 weeks old, were anesthetized prior to creating a 2 mm central cornea epithelial defect. Mice were randomly assigned to a treatment group: HBM, ophthalmic ointment containing neomycin, polymyxin B, dexamethasone (RxTx), or saline and treated 4x/day for 2 days. Wound area was quantified by fluorescein and ImageJ at 0, 8, 24, and 48 h post wounding and eyes used for histology, RT-qPCR, and ELISA. Results: Wounded corneas treated with HBM demonstrated increased re-epithelialization at 8 h post injury compared to saline treatments. ELISA showed significantly higher Ki67 in HBM treated eyes vs. saline control at 8 h (p = 0.0278). Additionally, immunohistology revealed more Ki67 positive cells in the HBM group compared to saline at 8 h and 24 h (p = 0.0063 8 h; p = 0.0007 24 h). For inflammatory analysis, HBM group IL-1β levels were similar to the saline group, and higher than RxTx treated eyes (p < 0.05). Immunohistochemical staining for CD11b (macrophage marker) revealed HBM-treated eyes had significantly more positive cells vs. saline. RT-qPCR of limbal stem cell markers (LESCs) revealed upregulation of Integrin αV at 8 h with HBM vs. saline. Conclusions: HBM treatment on corneas with debridement of epithelium demonstrated improved healing, cellular proliferation, and upregulation of the LESC gene transcript, integrin αV, after wounding. Future studies could investigate LESC response to different signalling molecules in HBM to better understand the efficacy of this potential therapy. [ABSTRACT FROM AUTHOR]

Purpose: Corneal collagen cross-linking (CXL) can halt corneal ectasia. Leaving corneal epithelium intact during treatment may reduce the incidence of complications. However, it is under debate whether this reduces efficacy and if oxygen supplementation may be necessary to optimize the cross-linking effect. This study aimed to investigate the impact of hyperbaric oxygenation (HBO) on intracorneal oxygen concentrations during epi-off and epi-on CXL. Methods: CXL was performed using riboflavin and ultraviolet-A (UV-A) irradiance (3 mW/cm2 for 30 min) on porcine corneas under normobaric and hyperbaric conditions, with and without supplemented oxygen, with and without epithelium. Intracorneal oxygen concentrations were continuously monitored before and during irradiation. Biomechanical properties were assessed through tensile strength testing. Results: HBO alone did not cause perceivable changes in stromal oxygen concentrations. Oxygen supplementation resulted in higher oxygen concentration in corneal stroma during CXL. HBO may cause a further increase in oxygen levels, although this was not statistically significant in this study. Notably, a tendency of oxygen levels to rise continuously during UV-irradiation was observed using HBO. Biomechanical properties showend no statistically significant differences between any groups. Conclusions: In this ex-vivo model, HBO increased stromal oxygen levels during CXL, regardless of the presence of corneal epithelium. The dynamics in oxygen concentrations in corneal stromal tissue during CXL suggest that time is an important factor to consider in modifications of established protocols. Also, we hypothesize that stromal levels of riboflavin and UV-A irradiance may be more critical to the CXL effect when oxygen is supplemented and epithelium is not removed. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare early changes in classified higher-order aberrations (HOAs) pre- and postsurgery in patients who received nontoric versus toric implantable collamer lenses (ICL; ICL Model V4c; STAAR Surgical, Monrovia, CA, USA). Methods: This prospective study included 124 eyes of 64 patients: 49 eyes were treated using a nontoric implantable collamer lens (ICL), and 75 eyes were treated using a toric implantable collamer lenses (TICL). Refractive parameters and ocular aberrations were examined before and 1 month after surgery. Results: At one month, the safety indices were 1.24 ± 0.17 in the ICL group and 1.20 ± 0.25 in the TICL group (p = 0.39). The efficacy indices were 1.07 ± 0.17 in the ICL group and 1.15 ± 0.26 in the TICL group (p = 0.02). The root mean square (RMS) values of whole-eye total HOAs, trefoil, corneal total HOAs, spherical aberration, and intraocular spherical aberration significantly increased postoperatively in both groups. The RMS of intraocular total HOAs in the TICL group significantly increased 1 month postoperatively. No statistically significant differences were observed in HOA changes between the ICL and TICL groups. Conclusions: The dominant increases in short-term aberrations after ICL and TICL V4c implantation were in corneal trefoil and intraocular spherical aberrations, which were related to the corneal incision and implanted lens. The HOA changes post-surgery were not statistically different between the two lens types. [ABSTRACT FROM AUTHOR]

Purpose: To compare safety and efficacy of isolated and combined UV‐light corneal crosslinking (CXL) and fine‐needle diathermy (FND) to regress pathological corneal vessels in vivo. Methods: Mice with inflamed and pathologically vascularized corneas received CXL or FND as monotherapy or a combination of both treatments. Corneal pathological blood and lymphatic vessels, immune cells and the morphology of anterior segment structures were evaluated. Results: All three approaches were able to regress blood and lymphatic vessels in mice. A comparative analysis of the three methods revealed that the FND monotherapy and the CXL + FND combination were significantly more effective than the CXL monotherapy, one and 2 weeks after therapy and especially in regressing lymphatic vessels. Furthermore, the combination therapy induced significantly less immune cell recruitment compared to the monotherapies. All three methods were safe to use in regards of corneal integrity. Conclusions: A combination of FND and CXL led to regression of pathological corneal lymphatic and blood vessels and reduced the infiltration of immune cells into inflamed murine corneas. This approach offers a new effective, safe and clinically usable strategy to treat eyes with mature pathological blood vessels and even more so for lymphatic vessels, for example prior to high‐risk corneal transplantation. [ABSTRACT FROM AUTHOR]

Purpose: To propose the optimal value of baseline corneal astigmatism and pterygial morphological profiles for primary pterygium surgery to restore the corneal optical properties. Methods: We analysed 93 eyes from 84 subjects with nasal‐only primary pterygium who underwent pterygium excision with conjunctival‐limbal autograft and were assessed perioperatively using anterior segment swept‐source optical coherence tomography (AS SS‐OCT). We collected data on anterior corneal astigmatism (ACA) and root mean square (RMS) values for anterior corneal lower‐ (LoA) and higher‐order aberrations (HoA) as corneal optical properties using AS SS‐OCT. Using preoperative ACA and four pterygial morphological profiles (horizontal invasion length [HIL], height, thickness and the ratio of residual corneal thickness [RCT] to central corneal thickness [CCT]) measured in AS SS‐OCT, we plotted receiver operating characteristic (ROC) curves. These curves aimed to determine cut‐off values predicting a perioperative decrease exceeding 50% in ACA, RMS LoA and RMS HoA, as well as postoperative residual ACA higher than 1.25D. Results: Preoperative ACA > 1.42D (AUC = 0.934) and >3.60D (AUC = 0.946) proved most effective in identifying subjects with perioperative decrease exceeding in ACA and RMS LoA, respectively. HIL > 3.34 mm (AUC = 0.941) was most effective in distinguishing subjects with perioperative reduction exceeding 50% in RMS HoA. Preoperative ACA > 5.78D (AUC = 0.776) and HIL > 5.03 mm (AUC = 0.700) significantly distinguished subjects with postoperative residual ACA higher than 1.25D. Conclusion: Optimizing the restoration of corneal astigmatism and aberrations after pterygium surgery may be facilitated by determining the optimal surgical timing based on preoperative ACA and HIL values. [ABSTRACT FROM AUTHOR]

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A ocorrência de ectasia corneana após ceratectomia fotorrefrativa é uma complicação rara, porém grave, em cirurgia refrativa. Os possíveis fatores de risco não são bem avaliados, mas a opinião atual é que a falha na detecção de ceratocone pré-operatório possa ser o principal motivo. Neste relato, descrevemos um caso de ectasia corneana após ceratectomia fotorrefrativa em paciente apresentando padrão tomográfico suspeito no pré-operatório, mas sem alterações degenerativas associadas a ceratocone patológico, conforme revelado por microscopia confocal in vivo da córnea. Além disso, revisamos, na literatura, relatos de casos elegíveis de ectasia pós-ceratectomia fotorrefrativa para encontrar características semelhantes. [ABSTRACT FROM AUTHOR]

Background: To analyze the difference and agreement between measurements obtained by a new fully automatic optical biometer, the SW-9000 μm Plus, based on optical low-coherence reflectometry (OLCR) and a commonly used optical biometer (Pentacam AXL) based on Scheimpflug imaging with partial coherence interferometry (PCI). Methods: The central corneal thickness (CCT), anterior chamber depth (ACD, from epithelium to anterior lens surface), lens thickness (LT), mean keratometry (Km), corneal astigmatism, corneal diameter (CD), pupil diameter (PD), and axial length (AL) of 74 eyes (from 74 healthy subjects) were measured using the SW-9000 μm Plus and the Pentacam AXL to determine the agreement. Double angle plots were used for astigmatism vector analysis. Bland–Altman and 95% limits of agreement (LoA) were calculated. Results: Statistically significant differences were detected for all parameters but J0 vector. The Bland–Altman analysis of AL, CCT, ACD, Km, CD, J0 and J45 indicated a high level of agreement between the two devices. Among AL, CCT, ACD, Km, J0, J45, CD, and PD, the 95% LoA ranged from -0.07 to 0.05 mm, -9.67 to 7.34 mm, -0.11 to 0.04 mm, -0.25 to 0.50 D, -0.22 to 0.20 D, -0.15 to 0.20 D, -0.23 to 0.35 mm and 1.55 to 3.77 mm, respectively. Conclusions: The measurements of AL, CCT, ACD, Km, corneal astigmatism, and CD showed a narrow LoA and may be used interchangeably in healthy subjects between the new OLCR optical biometer and the Scheimpflug/PCI biometer; however, a poor agreement was noted for PD values. [ABSTRACT FROM AUTHOR]

Laser assisted in situ keratomileusis (LASIK) surgery is the leading and most performed refractive surgery nowadays. A possible complication of LASIK surgery is infectious keratitis which can lead to disastrous corneal damage and result in permanent loss of vision. LASIK procedures have become increasingly accessible, and the demand for refractive surgery has risen among patients, challenging the medical field to improve the prevention of post-operative infections. Nevertheless, a wide range of pathogens have been described as responsible for post-LASIK keratitis. However, non-tuberculous mycobacterial keratitis remains an infrequent occurrence and is poorly described in the literature. To the best of our knowledge, this is the first ever reported case of post-LASIK keratitis caused by Mycobacterium wolinskyi. We describe the clinical and microbial characteristics, leading to its challenging treatment choice. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions 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°.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.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.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. [ABSTRACT FROM AUTHOR]

Background: Linarine is a natural chemical component widely found in Buddleja officinalis Maxim., Chrysanthemum indicum L., Mentha canadensis L., and other medicinal plants. Modern pharmacological studies have shown that linarine with good anti-inflammatory and antioxidant activities can inhibit the proliferation and induce apoptosis of many kinds of tumor cells. Moreover, linarine showed protective effect on the liver, kidneys, and other organs. Methods: Inflammation model of human corneal epithelial cell (HCEC) was constructed using NaCl induction, and cytotoxicity was detected by the CCK8 assay. The levels of inflammatory factors tumor necrosis factor-a (TNF-a) and interleukin 1b (IL-1b) were measured using Enzyme-linked immunoassay (ELISA). Chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops in a desiccator established a mouse model of dry eye disease (DED). The following parameters were recorded: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. The levels of inflammatory factors mitogen activated protein kinase (MAPK), nuclear factor kappa-B (NF-kB), c-Jun N-terminal kinase (JNK), IL-1b, Interleukin 18(IL-18), A2A, A3, P2X4, P2X7, P2Y1 were measured by using immunofluorescence (IF) staining. Results: Linarine can inhibit the secreation of TNF-a, and IL-1b in HCECs. Linarine prolonged tear film rupture time, promoted tear secretion, repaired corneal damage, and reduced the levels of inflammatory factors of MAPK, NF-kB, JNK, IL-1b, IL-18, and modulated the levels of the purinergic receptor. Conclusions: Linarine is effective in treating dry eye in mice by inhibiting purinergic receptors-mediated inflammatory response. [ABSTRACT FROM AUTHOR]

We aimed to investigate the repeatability of various corneal measurements according to topographical location in the entire cornea measured by dual rotating Scheimpflug-Placido camera and to explore the differences in repeatability between patients with mild dry eye and those with normal eyes. In both the normal and dry eye groups, divided based on BUT or the height of the tear film, there were no statistically significant differences in the ratio of unacceptable variation (RUV) and ICC. The consistency of the examination of the anterior and posterior refractive values and corneal thickness according to the corneal location, measured three times repeatedly using the Galilei anterior segment camera, was high. There was no difference based on the height of the tear film or the tear film break-up time. However, caution is needed when interpreting the values of the anterior corneal refractive values, as there can be changes of more than 0.5D within 3 mm of the central area. [ABSTRACT FROM AUTHOR]

Background: This study aims to determine the incidence of conjunctival chemosis during phacoemulsification and to explore the possible mechanism and treatments. Methods: Patients with or without chemosis during phacoemulsification by the same operator within two years were included. The initial site of chemosis, the chemosis originated time, and the degree of chemosis at the end of the surgery were recorded. The differences in phacoemulsification energy/time and irrigation volume were compared between two groups. Meanwhile, the distance between the clear corneal incision (CCI) and the end of the Bowman's layer, surgically induced astigmatism (SIA), intraocular pressure and central corneal thickness were also compared between the two groups. Results: The incidence of intraoperative chemosis was 9.17% (66/720). The distance between CCI and the end of the Bowman's layer in the chemosis group was significantly longer than that in the non-chemosis group postoperatively (P < 0.0001). The initial sites of chemosis were located on both sides of the external opening of the CCI. The average time from the phacoemulsification probe introducing into the anterior chamber to the originating of chemosis was 30.23 ± 49.23s. Conclusion: Intraoperative chemosis is related to the distance from CCI to the end of Bowmen's layer. The residual conjunctiva around the incision wraps the phacoemulsification probe sleeve to form a passage, the leakage fluid enters the subconjunctiva through this passage, forming chemosis. Conjunctival incision on both sides of CCI can effectively prevent the development of chemosis. [ABSTRACT FROM AUTHOR]

Objective Animals Studied Procedures Results Conclusions To determine the replication kinetics and cytopathic effect (CPE) of feline calicivirus (FCV) in feline corneal epithelial cells (FCEC).Seven archived FCV isolates and one archived feline herpesvirus type 1 (FHV‐1) isolate, previously obtained from eight domestic short hair cats.FCV RNA was extracted for sequencing using Illumina MiSeq, to identify three genomically diverse isolates for further testing. Following reference‐based assembly, viral genomes were annotated and assessed. Superficial keratectomies were performed to isolate the corneal epithelium of cats and the cells were cultured in vitro. FCEC were infected with the three chosen FCV isolates and one FHV‐1 isolate at two different multiplicity of infection ratios (MOIs, 0.1 and 0.01 PFU/cell) and virus titration was assessed at 0, 2, 6, 12, 24, and 48 h post‐infection (hpi). Viral identity was confirmed by RT‐qPCR.Three genomically diverse FCV isolates were chosen for further assessment in the FCEC model. All infections of FCEC with FCV led to visible CPE, characterized by epithelial cell rounding and detachment from the plate by 24 hpi, while FHV‐1 led to visible CPE within 48 hpi. All three of the FCV isolates replicated effectively in FCEC at both 0.1 and 0.01 MOI, with a peak increase in titer approximately 12–24 hpi.The results support the possible role of FCV as a primary pathogen of the feline ocular surface. FCV replicates in FCEC in vitro, leading to profound CPE. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionsTo compare the impact of 8 mm versus 9 mm optical zone (OZ) diameters on corneal astigmatism correction and to evaluate the impact of incision depth percentage after femtosecond laser corneal relaxing incisions (CRIs) combined with cataract surgery.Thirty-nine eyes from 39 patients were enrolled and randomly assigned to two groups based on the OZ diameter: 8 mm and 9 mm. Corneal astigmatism and CRI depth were measured using Pentacam and anterior segment optical coherence tomography. Vector analysis was performed using Alpins method.In the 8 mm group, postoperative corneal astigmatism was reduced by 0.77 ± 0.61 diopters (D), significantly greater than the reduction of 0.42 ± 0.40 D in the 9 mm group (p < 0.05). The 8 mm group exhibited greater surgically induced astigmatism (SIA), net corneal changes, and a smaller angle of error (AE) (p < 0.05). At 3 months postsurgery, the correction index (CI) values were 0.84 ± 0.39 for the 8 mm group, exceeding the 0.52 ± 0.32 observed in the 9 mm group (p < 0.05). The mean incision depth percentage was significantly higher in the 9 mm group (79.30 ± 10.76%) compared to the 8 mm group (72.58 ± 8.73%) (p < 0.05). In the 8 mm group, CI values closer to 1.00 were associated with lower percentages of incision depth.CRIs with an 8 mm OZ diameter demonstrated superior efficacy in correcting corneal astigmatism with shallower incision depths compared to those with a 9 mm diameter. [ABSTRACT FROM AUTHOR]

Purpose: To review the clinical features, risk factors, microbiological profile, and treatment regimens of fungal keratitis in Galicia, a region in Northwestern Spain with temperate humid weather. Patients and methods: A retrospective case series was employed, including patients with fungal keratitis from nine hospitals within the region of Galicia, Spain, between 2010 and 2020. Data obtained from clinical records were analysed. Results: Out of 654 cases of infectious keratitis, 77 cases (9.9%) were identified as fungal keratitis. The median age of affected patients was 68.0 years, with a higher incidence in rural areas (62.3%). Candida spp. infections were the most frequent type (55.8%) and were associated with a higher median age than were the non-dermatophyte mould infections. The primary risk factors included steroid eyedrop use (29.9%), recent keratoplasty (18.2%), ocular trauma (19.5%), and contact with vegetable matter (11.7%). Most ulcers displayed stromal involvement, and 37.7% presented corneal thinning. The median duration of infection was longer in fungal than in bacterial keratitis, and surgical intervention was required in 48.1% of cases. Conclusions: Fungal keratitis, mainly involving Candida spp., accounted for 9.9% of microbial keratitis cases in Galicia, Spain, with significant risk factors being topical steroid use, ocular trauma, and contact with vegetable matter. Delayed diagnosis often resulted in poor outcomes, highlighting the need for early detection through awareness and new technologies to improve prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared with a commercially available hydrogel canalicular plug (Form Fit). Setting: 5 sites in the United States. Design: Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug). Methods: Adults (=22 years) with the Schirmer test (with anesthesia) =10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of =23 with =3 responses of "not applicable," patent lacrimal drainage system, and bilateral corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was noninferiority of the mean within subject change from baseline to month 3 in Schirmer score for patients receiving filler compared with plugs. The key secondary effectiveness endpoint was noninferiority of the proportion of patients with filler achieving improvement from baseline to month 3 in OSDI by a minimal clinically important difference. Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear breakup time, and safety. Results: 157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was noninferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI. Conclusions: Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the changing patterns of corneal endothelial cells and the associated factors in children with congenital ectopia lentis (CEL) after scleral-fixated intraocular lens (SF IOL) surgery. Setting: Zhongshan Ophthalmic Center, Guangzhou, China. Design: Retrospective study. Methods: Patients were divided into the surgery group and the control group. Central endothelial cell density (ECD), coefficient of variation in cell size, the percentage of hexagonal cells (hexagonality), average cell size (AVG), and central corneal thickness were analyzed for both groups at baseline and each follow-up visit. Clinic characteristic, ocular parameters, IOL decentration, and IOL tilt of patients in the surgery group were collected. Multiple linear regression was performed to assess the potential associated factors for the postoperative changes in corneal endothelial cells in the surgery group. Results: After 2-year follow-up, the decline of ECD was 17.8% (95% CI, -21.8 to -13.9) in the surgery group and -3.1% (95% CI, -5.2 to -1.0) in the control group (P < .001), while the increase of AVG was 24.3% (17.1-31.6) in the surgery group and 2.7% (1.0 to 4.5) in the control group (P < .001). Multivariate analysis showed that axial length (AL) =24 mm and white-to-white (WTW) <12.2 mm were significantly associated with greater loss of ECD (b = -241.41, 95% CI, -457.91 to -24.91, P = .030 and b = 251.63, 95% CI, 42.10-461.17, P = .020, respectively) and AL =24 mm was significantly positively associated with the increase of AVG (b = 34.81, 95% CI, 0.90-68.71, P = .044). Conclusions: The SF IOL had a significant impact on corneal endothelium in children with CEL. More attention should be paid to monitor postoperative corneal endothelium change during longterm follow-up in CEL children, especially for those with longer AL and smaller WTW. [ABSTRACT FROM AUTHOR]

Purpose: To describe the Shammas-Cooke formula, an updated no-history (NH) formula for IOL calculation in eyes with prior myopic laser vision correction (M-LVC), and to compare the results with the Shammas PL, Haigis-L, and Barrett True-K NH formulas. Setting: Bascom Palmer Eye Institute (BPEI), The Lennar Foundation Medical Center, University of Miami, Miami, Florida; Dean A. McGee Eye Institute (DMEI), University of Oklahoma, Oklahoma City, Oklahoma; and private practice, Lynwood, California, and St Joseph, Michigan. Design: Retrospective observational study. Methods: We analyzed 2 large series of cataractous eyes with prior M-LVC. The training set (BPEI series of 330 eyes) was used to derive the new corneal power conversion equation to be used in the new Shammas-Cooke formula and the testing set (165 eyes of 165 patients in the DMEI series) to compare the updated formula with 3 other M-LVC NH formulas on the ASCRS calculator: Shammas PL, Haigis-L, and Barrett True-K NH. Results: Mean prediction error was 0.09 ± 0.56 diopters (D), -0.44 ± 0.61 D, -0.47 ± 0.59 D, and -0.18 ± 0.56 D and the mean absolute error was 0.43 D, 0.60 D, 0.61 D, and 0.45 D for the Shammas-Cooke, Shammas PL, Haigis-L, and Barrett True-K NH, respectively. The percentage of eyes within ±0.50 D was 66.7% vs 47.9%, 48.5%, and 65.5%, respectively. Conclusions: The Shammas-Cooke formula performed better than the Shammas PL and Haigis-L (P < .001 for both) and as well as the Barrett True-K NH formula (P = .923). [ABSTRACT FROM AUTHOR]

Purpose: To protect the corneal endothelium, various ophthalmical viscoelastic devices (OVDs) are used during cataract surgery. In this study, we compared two sodium hyaluronate-based OVD, the bacteria-derived FIDIAL PLUS OVD (test) with the animal-derived IAL®-F OVD (reference) during the surgical procedure. Methods: Fifty patients with bilateral cataract participated in the study: 50 eyes randomly received FIDIAL PLUS and 50 eyes received IAL®-F (ratio 1:1). Noninferior efficacy of FIDIAL PLUS compared with reference OVD (first objective) was evaluated using a paired t-test comparing the mean percent loss of corneal endothelial cells (CECs) with FIDIAL PLUS against the mean percent loss with IAL®-F. Corneal endothelial protection during cataract surgery with FIDIAL PLUS without significant (≥30 mmHg) postoperative intraocular pressure (IOP) increase (main secondary objective) was assessed using a repeated measures logistic model comparing the incidence of significant postoperative IOP elevation between the two groups. Safety, tolerability, and efficacy were also evaluated by assessing secondary endpoints before and after surgery. Results: FIDIAL PLUS showed a statistically noninferior efficacy compared with IAL®-F; there was no significant increase in IOP in either group or different trends of the secondary endpoints were observed between the OVD groups. The safety profile was similar in both OVD groups and no adverse device effects were reported. Conclusions: This study demonstrates the equivalent efficacy, tolerability, and safety of the bacteria-derived FIDIAL PLUS compared with the animal-derived IAL®-F, confirming the clinical value of this product. [ABSTRACT FROM AUTHOR]

Purpose: Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma. However, pharmacokinetic data are lacking. This study aims to describe the pharmacokinetics of topical acetaminophen and its metabolite [N-arachidonoylaminophenol (AM404)] when administered individually and in combination, and to determine its effect on IOP in the ocular normotensive adult New Zealand White Rabbit (NZWR). Methods: A randomized control trial was conducted using topical 1% acetaminophen and 1% AM404. The study was divided into two sub-studies using both paired-eye and two-eye designs. Results: The mean [95% confidence interval of the mean (95% CI)] concentration of acetaminophen detected in the aqueous humor (AH) was 4.09 ppm (3.18–5.00) at 2 h and 0.92 ppm (0.60–1.24) at 4 h after an immediate dose of topical acetaminophen. The integral IOP, defined as the integral of IOP change from baseline over time, was −5.1 mmHg⋅h (95% CI: −10 to 0.41) for control,−7.5 mmHg⋅h (95% CI: −14 to −1.1) for half-hourly acetaminophen, and −4.4 mmHg⋅h (95% CI: −14 to 5.5) for hourly acetaminophen over a 4-h period. When comparing topical acetaminophen with AM404 dosed half-hourly over a 4-h period, the integral IOP was −2.3 mmHg⋅h (95% CI: −5.9 to 1.3) for control,−2.0 mmHg⋅h (95% CI: −5.6 to 1.7) for AM404, −1.7 mmHg⋅h (95% CI: −4.5 to 1.2) for acetaminophen, and −3.2 mmHg⋅h (95% CI: −5.4 to −0.96) for acetaminophen/AM404 combined. Conclusions: Acetaminophen, but not its metabolite AM404, penetrated the multilayered cornea via passive diffusion in a dose-dependent fashion. There was a nonsignificant tendency to cause a lowering of IOP over the 4-h dosing period with higher AH concentrations of acetaminophen. Topical AM404 did not show a significant IOP-lowering effect. [ABSTRACT FROM AUTHOR]

Objectives: This pilot ex vivo study and first clinical experience in Italy evaluate the impact of using pre-implantation crosslinking on all-femtosecond laser-cut corneal allogenic intracorneal ring segments (AFXL CAIRSs). Methods: Six human donor eye-bank corneas were used for this preclinical ex vivo human study. Three donor (D) corneas were used for AFXL CAIRSs. First, they were prepared with an IntraLase™ femtosecond laser (Johnson & Johnson, New Brunswick, NJ, USA). The allogenic tissue rings were crosslinked before implantation with Riboflavin–UV-A accelerated crosslinking protocol (ACXL) with a 0.1% HPMC Riboflavin isotonic solution (Vibex Rapid, Glaukos-Avedro, Burlington, MA, USA) and a new KXL UV-A emitter (Glaukos-Avedro, USA). Three corneas were used as recipients (Rs) of the AFXL CAIRSs. After completing the ex vivo phase, IRB approval and signing a specific informed consent, the first two Italian patients were treated. A single ACXL CAIRS was implanted in a 51-year-old male with 53.53 D K steep, 363 μm minimum corneal thickness (MCT) and a double ACXL CAIRS was implanted in a 46-year-old male patient with 58.30 D K steep, 443 μm MCT. The longest follow-up was at three months. Results: Crosslinking of the segments enhanced tissue stiffness and grip, facilitating manipulation and CAIRS insertion into the recipient tunnels, and the yellowish color of the crosslinked segments improved visibility. The segment's thickness and volume remained unaltered during the follow-up. Both patients improved UDVA and BSCVA. K steep and High-Order Aberrations (HOAs) were reduced and MCT increased. Conclusions: Pre-implantation ACXL facilitated CAIRS insertion preserving dimensions and volume during the follow-up, rendering this important step a promising candidate in method standardization. Functional data and MCT improved significantly without adverse events. [ABSTRACT FROM AUTHOR]

The synthetic peptide of lumican C-terminal 13 amino acids with the cysteine replaced by an alanine, hereafter referred to as lumikine (LumC13C-A: YEALRVANEVTLN), binds to TGFβ type I receptor/activin-like kinase5 (TBR1/ALK5) in the activated TGFβ receptor complex to promote corneal epithelial wound healing. The present study aimed to identify the minimum essential amino acid epitope necessary to exert the effects of lumikine via ALK5 and to determine the role of the Y (tyrosine) residue for promoting corneal epithelium wound healing. This study also aimed to determine the signaling pathway(s) triggered by lumican–ALK5 binding. For such, adult Lum knockout (Lum−/−) mice (~8–12 weeks old) were subjected to corneal epithelium debridement using an Agerbrush®. The injured eyes were treated with 10 µL eye drops containing 0.3 µM synthetic peptides designed based on the C-terminal region of lumican for 5–6 h. To unveil the downstream signaling pathways involved, inhibitors of the Alk5 and EGFR signaling pathways were co-administered or not. Corneas isolated from the experimental mice were subjected to whole-mount staining and imaged under a ZEISS Observer to determine the distance of epithelium migration. The expression of EGFR ligands was determined following a scratch assay with HTCE (human telomerase-immortalized cornea epithelial cells) in the presence or not of lumikine. Results indicated that shorter LumC-terminal peptides containing EVTLN and substitution of Y with F in lumikine abolishes its capability to promote epithelium migration indicating that Y and EVTLN are essential but insufficient for Lum activity. Lumikine activity is blocked by inhibitors of Alk5, EGFR, and MAPK signaling pathways, while EGF activity is only suppressed by EGFR and MAPK inhibitors. qRT-PCR of scratched HTCE cells cultures treated with lumikine showed upregulated expression of several EGFR ligands including epiregulin (EREG). Treatment with anti-EREG antibodies abolished the effects of lumikine in corneal epithelium debridement healing. The observations suggest that Lum/lumikine binds Alk5 and promotes the noncanonical Smad-independent TGFβ/TBRs signaling pathways during the healing of corneal epithelium debridement. [ABSTRACT FROM AUTHOR]

Communication between the different layers of the cornea (epithelium and stroma) is a complex, yet crucial element in the corneal healing process. Upon corneal injury, it has been reported that the bi-directional cross talk between the epithelium and stroma via the vesicular secretome, namely, extracellular vesicles (EVs), can lead to accelerated wound closure upon injury. However, the distinct protein markers of EVs derived from human corneal epithelial (HCE) cells, keratocytes (HCKs), fibroblasts (HCFs), and myofibroblasts (HCMs) remain poorly understood. All EVs were enriched for CD81 and showed increased expression levels of ITGAV and FN1 in HCM-EVs compared to HCE- and HCF-EVs. All EVs were negative for GM130 and showed minimal differences in biophysical properties (particle concentration, median particle size, and zeta potential). At the proteomic level, we show that HCM-EVs are enriched with proteins associated with fibrosis pathways, such as COL6A1, COL6A2, MMP1, MMP2, TIMP1, and TIMP2, compared to HCE-, HCK-, and HCF-EVs. Interestingly, HCE-EVs express proteins involved with the EIF-2 signaling pathway (stress-induced signals to regulate mRNA translation), such as RPS21, RALB, EIF3H, RALA, and others, compared to HCK-, HCF-, and HCM-EVs. In this study, we isolated EVs from cell-conditioned media from HCE, HCKs, HCFs, and HCMs and characterized their biophysical and protein composition by Western blot, nanoparticle tracking analysis, and proteomics. This study supports the view that EVs from the corneal epithelium and stroma have a distinct molecular composition and may provide novel protein markers to distinguish the difference between HCE-, HCK-, HCF-, and HCM-EVs. [ABSTRACT FROM AUTHOR]

Aim: To explore the molecular mechanism underlying the protective effect of hypothermic perfusion on the corneal endothelium during phacoemulsification. Methods: Phacoemulsification was performed on New Zealand white rabbits. Perfusate at different temperatures was used during the operation, and the aqueous humor was collected for proteomic sequencing after the operation. Corneal endothelial cell injury was simulated by a corneal endothelial cell oxygen–glucose deprivation/reoxygenation (OGD/R) model in vitro. Flow cytometry and evaluation of fluorescent LC3B puncta were used to detect apoptosis and autophagy, and western blotting was used to detect protein expression. Results: A total of 381 differentially expressed proteins were identified between the two groups. In vitro, 4 ℃ hypothermia significantly reduced apoptosis and promoted autophagy. Apoptosis increased after autophagy was inhibited by 3-Methyladenine (3-MA). Furthermore, adiponectin (ADIPOQ) knockdown inhibited phospho-AMPK and blocked the protective effect of hypothermia on corneal endothelial cells. Conclusions: We investigated the differential expression of proteins between the hypothermia group and normothermia group by proteomics. Moreover, hypothermia-induced ADIPOQ can reduce apoptosis by promoting AMPK-mediated autophagy. Key Messages: What is known • During phacoemulsification, the corneal endothelium may be damaged by ultrasonic energy. • The use of hypothermic perfusion during phacoemulsification can reduce postoperative inflammation. What is new • Hypothermia protects corneal endothelial cells from apoptosis by promoting autophagy. • Hypothermia induces adiponectin expression and protects corneal endothelial cells through AMPK-mediated autophagy. [ABSTRACT FROM AUTHOR]

To evaluate lenticular biomechanical and geometric parameters in Chinese adults with myopia and identify relevant factors using Brillouin microscopy (BM) and Pentacam. The biomechanical and geometric properties of the ocular lenses of Chinese adults with myopia were quantified using BM. Anterior segment images were acquired using a Pentacam. Correlated factors including age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), white-to-white ratio (WTW), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were analyzed. We studied 65 eyes from 65 participants (mean age, 25.23 ± 6.12 years). Width of Top Plateau (WTP), Width of Bottom Plateau (WBP), Slope of Anterior Cortex (SAC), Slope of Posterior Cortex (SPC), and Height of Plateau (Height) metrics obtained using BM showed mean values of 2.597 ± 0.393 mm, 4.310 ± 0.535 mm, 1.344 ± 0.549 GPa/mm, –1.343 ± 0.480 GPa/mm, and 3.373 ± 0.048 GPa, respectively. No significant correlation was found between these parameters and sex, SE, IOP, CCT, ACA, or Height. Interestingly, WBP (r = 0.467, P < 0.001), SAC (r = 0.412, P = 0.001), and SPC (r = –0.280, P = 0.024) were significantly associated with age, and an age-related increase of WBP (slope of 35.36 ± 10.08 μm per year) was identified. Both ACD and ACV showed significant correlations with SAC (r = 0.329 and 0.380, P = 0.008 and 0.002, respectively), but not with SPC. BM provided a novel perspective on lenticular biomechanical and geometric properties in Chinese adults with myopia, which correlated with age, AL, WTW, ACD, and ACV. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to compare choroidal thickness in juvenile open angle glaucoma (JOAG) and healthy controls using spectral domain optical coherence tomography (SD-OCT) and study its correlations. Methods: In this case–control study, 56 eyes of 28 JOAG patients and an equal number of controls were recruited. SD-OCT was used to measure the choroidal thickness (ChT), in the macular region at 5 locations: subfoveal, 1500 µm and 3000 µm nasal and temporal to the foveal center, and in the peripapillary region at 6 locations: up to 1500 µm, nasal and temporal to the disc, respectively. The ChT and its correlations with age, intraocular pressure, cup-to-disc ratio, central corneal thickness, mean deviation, and axial length were studied. Results: The average macular ChT in JOAG was 306.30 ± 56.49 µm vs. 277.12 ± 64.68 µm in controls. The average peripapillary ChT in JOAG was 197.79 ± 44.05 µm vs. 187.24 ± 38.89 µm in controls. The average total ChT (p = 0.042), the average macular ChT (p = 0.022), the subfoveal ChT (p = 0.022), the ChT 1500 µm (p < 0.001), and 3000 µm temporal to the fovea (p = 0.002) were significantly thicker in the JOAG group. In the JOAG group, the average macular ChT had a significant negative correlation with age, whereas axial length was positively correlated with the average peripapillary ChT. Conclusions: In this South Asian cohort of JOAG, the average total ChT, average macular ChT, subfoveal ChT, and ChT at 1500 µm, and 3000 µm temporal to the fovea were significantly thicker when compared to healthy controls. [ABSTRACT FROM AUTHOR]

Laser corneal reshaping is a safe and effective technique utilized to treat common vision disorders. An advanced laser delivery system equipped with a pulsed UV laser with specific parameters is used to ablate parts of the cornea surface to correct the existing refractive error. The argon fluoride (ArF) excimer pulsed gas laser at 193 nm is the most employed type in the commercial devices for such treatments. This laser is generated using a mixture of Argon, Fluorine, and a significant amount of Neon gases. However, due to the ongoing Russian‐Ukraine war, the availability of Neon gas is currently very limited, as this region is considered the primary supplier of pure Neon gas. Consequently we suggest replacing the common ArF laser source in the commercial devices with a solid‐state (forth harmonic neodymium‐doped yttrium aluminum garnet laser at 266 nm). This replacement uses the same operation parameters, optics, and scanning algorithm. Parameters from five commercial devices (Zeiss MEL 90, Technolas TENEO 317, Alcon Wave Light EX 500, Schwind Amaris 750 s, OptoSystems MICROSCAN VISUM) were compared with those of the i‐ablation device, a research device that uses a 266 nm laser source. Our goal is to reduce production costs through a simple modification that has a significant impact. Consequently, the present study aims to find an alternative laser source for the current ArF laser without exchanging the complete system's design. This recommendation is based on a numerical simulation study. The thermal effect on a human cornea model was numerically evaluated using finite‐element solutions of Pennes' bioheat equation on the COMSOL platform by applying two laser wavelengths. The results demonstrated that changing the laser source significantly impacts the thermal effect, even with the same laser settings. All studied devices showed a reduction in the thermal effect to below 40°C, compared with nearly 100°C under ordinary conditions. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To determine how corneoscleral geometry changes with axial length and to assess the usefulness of including the sagittal configuration of the anterior segment when predicting the axial length.An observational study was performed including 96 healthy subjects (96 eyes). Axial length was calculated from optical biometry (IOL Master 500). Corneal curvature and scleral sagittal height parameters at 13, 14 and 15 mm were obtained automatically using corneoscleral topography (eye surface profiler; ESP). In addition, corneal and scleral sagittal heights at numerous locations (21 radii: 0–10 mm from the corneal apex at 12 angles: 0–330°) were calculated using the raw height data extracted from the ESP. The relationships between axial length and the study parameters were analysed using Pearson correlation analysis. The equations for the prediction of axial length were obtained by fitting multiple linear regression models.The temporal‐nasal scleral asymmetry at 13‐, 14‐ and 15‐mm chord lengths was significantly correlated with axial length (r2 ≤ 0.26; p < 0.001). Significant inverse correlations were found between the temporal scleral sagittal height and axial length (r2 ≤ 0.28; p ≤ 0.02). The nasal scleral sagittal height was not associated with axial length. Three significant multiple linear regression models were fitted based on spherical equivalent, corneal radius and scleral asymmetry at 13 (r2 = 0.79; p < 0.001), 14 (r2 = 0.80; p < 0.001) and 15 (r2 = 0.80; p < 0.001) mm chord lengths.Larger ocular globes show reduced temporal‐nasal scleral asymmetry, mainly due to the lower sagittal height of the temporal sclera. Thus, the geometry of the temporal scleral may be a factor of interest during myopia progression. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusionBufalin (BU) is a bioactive ingredient extracted from the skin and parotid venom glands of Bufo raddei, which can effectively inhibit angiogenesis. The aim of this study was to investigate whether BU could affect corneal neovascularization (CoNV).A rat CoNV model (right eye) was constructed by administration of NaOH, and the left eye served as a control. Corneal damage scores of rats were detected. Hematoxylin & eosin, TUNEL, and Masson staining examined pathological changes, apoptosis, and fibrosis of corneal tissues. Immunohistochemistry and western blotting assessed the expression of proteins.BU intervention resulted in a significant reduction in corneal inflammatory cells, repair of corneal epithelial hyperplasia, significant reduction in stromal edema, and reduction in vascular proliferation. BU can inhibit corneal neovascularization.This study demonstrated that BU inhibits CoNV, fibrosis, and inflammation by modulating the STAT3 signaling pathway, elucidating the intrinsic mechanism of its protective effect. BU has great potential in the treatment of CoNV caused by corneal alkali burns. [ABSTRACT FROM AUTHOR]

Corneal reconstruction is a key part of veterinary ophthalmic practice and numerous reconstructive techniques have been described for use in small animals in the peer‐reviewed veterinary literature written in English. Despite the evidence accrued over the last six decades in over 40 clinical articles and numerous other publications on ocular surface health, several key areas require further study. The comparison between studies is difficult due to elements that go beyond common factors, such as the indication for surgery, the reconstructive technique preferred by the surgeon or the availability of reconstructive materials. However, the differences in reporting style adopted by different authors between similar studies and the lack of data found in retrospective studies add to this complexity. The present review is divided into three parts. One covers the use of autologous materials for reconstruction and corneal transplants, as well as corneal clarity. A second part focuses on biomaterials and keratoprosthetics, while the third part focuses on the use of corneal sutures and report of ocular discomfort/pain in the veterinary literature. The review focuses on the main findings of each reconstruction technique. It aims to identify areas where key information about common procedures is missing so that general guidelines may be provided for the planning of patient record keeping and future retrospective or prospective studies, while it also aims to highlight the presence of knowledge gaps that deserve further attention. [ABSTRACT FROM AUTHOR]

The surgical reconstruction of severe corneal disease is a common and crucial component of the clinical practice of veterinary ophthalmology. The first part of the present review described procedures that utilize autogenous ocular tissues, homologous donor tissues, and heterologous donor tissues in dogs, while the second part reviewed the use of biomaterials and keratoprosthetics in this species. This third part is dedicated to the review of the use of corneal sutures including suture type and suture pattern in corneal reconstruction of small animals including dogs and cats. The review also focused on the way studies report postoperative ocular discomfort/pain and how this is treated. Lastly, the author briefly presents the simple but effective techniques available to bury corneal knots for corneal reconstructive surgery in small animal patients, such as the “tugging” and “deep‐superficial‐superficial‐deep” methods for simple interrupted sutures, and the adaptation of the latter for simple continuous sutures. [ABSTRACT FROM AUTHOR]

Introduction: Objective markers describing corneal optical density (COD), thinnest corneal thickness (TCT), and anterior (ARC) and posterior (PRC) surface radii over the 3 mm thinnest region of the cornea were investigated to provide a model for estimating corrected distance visual acuity (CDVA) after corneal cross-linking (CXL) in keratoconus. Methods: CDVA, COD, TCT, ARC, and PRC were monitored (using Pentacam™) over 1 year in patients with (1) keratoconus treated with routine CXL (2) relatively stable untreated keratoconus, and (3) age/gender-matched controls. Results: In group 1 (n = 77), the median logMAR CDVA (mode, interquartile range) improved significantly (p < 0.01) from 0.26 (0.22, 0.12–0.65) to 0.07 (0.00, 0.02–0.21). The mean (± standard deviation, 95% confidence interval) COD (in 0–100 grey scale units) in the 0–2 mm central anterior corneal region (0–2 ant), TCT (µm), ARC (mm), and PRC (mm) changed significantly (p < 0.01), from 21.2 (± 3.70, 20.4–22.0), 454 (± 40.0, 446–462), 6.49 (± 0.71, 6.33–6.65), and 4.81 (± 0.65, 4.66–4.96) to 31.5 (± 9.19, 29.5–33.6), 423 (± 49.3, 412–434), 6.78 (± 0.80, 6.60–6.98), and 4.74 (± 0.64, 4.59–4.88), respectively, but remained stable in groups 2 (n = 23) and 3 (n = 24). Significant relationships (p < 0.01) were uncovered between postop CDVA and preop values of COD, TCT, ARC, and PRC. Multilinear regression revealed significant correlations between CDVA at 1 year and preop COD, TCT, ARC, and PRC (r2 = 0.533, r20-2ant = 0.126, r2TCT = 0.321, r2ARC = 0.506, r2PRC = 0.467). Including preop CDVA further enhanced this correlation (r2 = 0.637, r2LogMAR CDVApreop = 0.566). Conclusion: CXL improved CDVA, increased COD and ARC, and reduced TCT and PRC. The chance of correctly estimating the CDVA at 1 year after CXL using preoperative markers of COD, TCT, ARC, and PRC is 53%, improving to 64% with the inclusion of preoperative CDVA. Objective measurements taken at the preoperative screening stage may be useful to estimate the likely postoperative CDVA when preoperative CDVA measures are unreliable or unobtainable. Trial Registration: ClinicalTrials.gov identifier, NCT06522789. [ABSTRACT FROM AUTHOR]

• Prenatal ultrasound diagnosis of complete cryptophthalmos, aphakia, and corneal vascularization. • Fetal ocular malformations are often associated with malformations of other organs. • This case provides a new basis for prenatal diagnosis of this rare eye disease. Complete cryptophthalmos, congenital aphakia, and corneal vascularization are relatively uncommon congenital eye malformations during the fetal period. Herein, we report a case of a fetus with complete cryptophthalmos, congenital aphakia, and corneal vascularization in both eyes and review previous prenatal reports of related cases. The patient was a 27-year-old pregnant woman, gravida 2, para 1, who was referred to our hospital for consultation at 23 weeks of gestation due to a diagnosis of fetal right renal agenesis at an external hospital. The ultrasound system of our hospital diagnosed the fetus with complete cryptophthalmos, congenital aphakia, and corneal vascularization, which was verified under the postnatal water basin test, anatomical and pathological sections. Fetal ocular malformations are often associated with malformations of other organs, and if ultrasound findings are associated with such malformations, attention should be paid to the ocular examination to avoid missing the diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate curvature changes in different regions and their correlation with corneal epithelial remodeling in myopic patients undergoing femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and transepithelial refractive keratectomy (Trans-PRK) after surgery. Methods: One hundred and sixty-three patients (163 right eyes) undergoing Trans-PRK and LASIK were evaluated for up to 6 months using anterior segment optical coherence tomography (OCT) to measure the epithelial thickness and corneal topography to measure corneal curvature in different areas (2 mm, 5 mm, and 7 mm). We calculated the curvature ΔK (ΔK = preoperative - postoperative), ΔK5-2 (ΔK5-2 = K5mm - K2mm), ΔK7-5 (ΔK7-5 = K7mm - K5mm), and the epithelial thickness ΔET5-2 (ΔET5-2 = ET5mm - ET2mm) and ΔET7-5 (ΔET7-5= ET7mm - ET5mm). Results: Corneal curvature flattened in each region of the two groups (all p < 0.001) and gradually steepened during the follow-up period. The Trans-PRK group flattened more significantly within 2 mm and 5 mm, while the FS-LASIK group at 7 mm. Both groups of ΔK decreased over time. Both groups of ΔK5-2 and ΔK7-5 gradually decreased during the follow-up period (P5-2=0.025 and P7-5 < 0.001 for Trans-PRK, P5-2 = 0.011 and P7-5 < 0.001 for FS-LASIK). The corneal epithelium of the two groups gradually thickened during the follow-up period, with Trans-PRK significantly thickening in the central and peripheral regions and FS-LASIK in the central and paracentral regions. There is a significant correlation between the ΔK5-2 and ΔET5-2, ΔK7-5 and ΔET7-5 (all r > 0.37, p < 0.001). Conclusions: All groups showed significant curvature flattening after surgery and gradually steepening during the follow-up period. The corneal epithelium thickness in both groups of 17 regions became thicker,. In contrast, Trans-PRK group showed more significant thickening to the periphery and the central 5 mm area of the FS-LASIK. This study indicates a significant positive correlation between differences in epithelial thickening in different regions and differences in curvature changes in the corresponding areas PRK, FS-LASIK, curvature, corneal epithelial thickness [ABSTRACT FROM AUTHOR]

• The OphtalMimic device offers a precise simulation of human ocular conditions for improved ophthalmic drug product evaluation. • A novel hydrogel-based hybrid membrane closely replicates the human cornea's water content and morphology. • The device successfully differentiated between the drainage profiles of various ophthalmic formulations. • The system demonstrated its potential as a reliable platform for the high-throughput screening of ophthalmic drugs. • This advancement aligns with ethical mandates to reduce animal testing and accelerate the development of safer and more effective ophthalmic drugs. Envisaging to improve the evaluation of ophthalmic drug products while minimizing the need for animal testing, our group developed the OphthalMimic device, a 3D-printed device that incorporates an artificial lacrimal flow, a cul-de-sac area, a moving eyelid, and a surface that interacts effectively with ophthalmic formulations, thereby providing a close representation of human ocular conditions. An important application of such a device would be its use as a platform for dissolution/release tests that closely mimic in vivo conditions. However, the surface that artificially simulates the cornea should have a higher resistance (10 min) than the previously described polymeric films (5 min). For this key assay upgrade, we describe the process of obtaining and thoroughly characterizing a hydrogel-based hybrid membrane to be used as a platform base to simulate the cornea artificially. Also, the OphthalMimic device suffered design improvements to fit the new membrane and incorporate the moving eyelid. The results confirmed the successful synthesis of the hydrogel components. The membrane's water content (86.25 ± 0.35 %) closely mirrored the human cornea (72 to 85 %). Furthermore, morphological analysis supported the membrane's comparability to the natural cornea. Finally, the performance of different formulations was analysed, demonstrating that the device could differentiate their drainage profile through the viscosity of PLX 14 (79 ± 5 %), PLX 16 (72 ± 4 %), and PLX 20 (57 ± 14 %), and mucoadhesion of PLXCS0.5 (69 ± 1 %), PLX16CS1.0 (65 ± 3 %), PLX16CS1.25 (67 ± 3 %), and the solution (97 ± 8 %). In conclusion, using the hydrogel-based hybrid membrane in the OphthalMimic device represents a significant advancement in the field of ophthalmic drug evaluation, providing a valuable platform for dissolution/release tests. Such a platform aligns with the ethical mandate to reduce animal testing and promises to accelerate the development of safer and more effective ophthalmic drugs. [ABSTRACT FROM AUTHOR]

Introduction: Keratoconus (KC) is the most prevalent corneal ectasia in the world, and its pathogenesis is influenced by both ocular and systemic factors. This review explores the multifaceted associations between keratoconus and systemic health conditions, ocular characteristics, and various other environmental/exogenous factors, aiming to illuminate how these relationships influence the pathophysiology of the disease. Areas Covered: This review will summarize the fundamental attributes of KC, review and discuss the systemic and ocular association of KC including molecular biomarkers, and provide an organized overview of the parallel alterations occurring within various biological pathways in KC. Expert Opinion: Despite the substantial volume of research on keratoconus, the precise etiology of the disease remains elusive. Further studies are necessary to deepen our understanding of this intricate disorder and improve its management. [ABSTRACT FROM AUTHOR]

Dye-based angiography is the main imaging modality in evaluating the vasculature of the eye. Although most commonly used to assess retinal vasculature, it can also delineate normal and abnormal blood vessels in the anterior segment diseases—but is limited due to its invasive, time-consuming methods. Thus, anterior segment optical coherence tomography angiography (AS-OCTA) is a useful non-invasive modality capable of producing high-resolution images to evaluate the cornea and ocular surface vasculature. AS-OCTA has demonstrated the potential to detect and delineate blood vessels in the anterior segment with quality images comparable to dye-based angiography. AS-OCTA has a diverse range of applications for the cornea and ocular surface, such as objective assessment of corneal neovascularization and response to various treatments; diagnosis and evaluation of ocular surface squamous neoplasia; and evaluation of ocular surface disease including limbal stem cell deficiency and ischemia. Our review aims to summarize the new developments and clinical applications of AS-OCTA for the cornea and ocular surface. [ABSTRACT FROM AUTHOR]

Purpose: To report an unusual but important complication of routine cataract surgery, accidental intrastromal intraocular lens (IOL) implantation. Methods: During cataract surgery in a 66-year-old man, the IOL was delivered into the intrastromal space of the cornea accidentally. The lens was removed immediately and carefully by enlarging the corneal tunnel. Results: Anterior segment optical coherence topography (AS-OCT) was used for postoperative follow-up of the patient, which showed a viscoelastic substance in the stroma of the cornea that was washed out. Ther patient's final visual acuity was 20/20. Conclusions: A uniplanar corneal incision with wound-assisted IOL insertion can lead to intrastromal IOL injection. If a cataract surgeon encounters such a complication, AS-OCT could be a useful imaging technique for follow-up. [Journal of Refractive Surgery Case Reports. 2024;4(4):e36–e39.] [ABSTRACT FROM AUTHOR]