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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.

This case series reports eight eyes with keratoconus treated with laser implantation of one or two segments of progressive thickness corneal intrastromal ring (PT-ICRS). In this case series, it was evident that the insertion of PT-ICRS induces more pronounced corneal flattening at the thickest point, causing a reduction in distortion (coma) and lower astigmatism, resulting in a remarkable improvement in vision. Compared to the implementation of traditional intrastromal rings, the PT-ICRS variant showed superior results despite the small sample size. However, the same degree of asymmetry enhancement was not observed in cases in which a 330° PT-ICRS was implanted, despite the improvement in visual results when replacing a 320° traditional ring with a 330° PT-ICRS. These conclusions are limited as this is a case series with few cases.

The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes ZNF469 and PRDM5 each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated ZNF469 and PRDM5 on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes' development of aneurysmal and dissection diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: To verify whether there are pathological dysfunctions in the cornea of patients with endometriosis. Methods: Case-control research with a quantitative approach that compared topographic and tomographic examinations of the cornea of patients with a laparoscopic diagnosis of endometriosis, without the use of hormonal medications, to the control group. Results: We analyzed 78 eyes, 34 from the endometriosis group and 44 from the control group. The loss of orthogonality between the axes of the corneal curvatures was more frequent in the group with endometriosis (p = 0.0744). The difference between the mean keratometric measurements of the two eyes was significantly greater in the control group (p = 0.0204). In the tomographic findings, the group with endometriosis presented higher means of posterior elevation compared to the control group (p = 0.0060). Conclusion: The results do not allow us to conclude that women with endometriosis have a higher risk of developing corneal ectasia, although the posterior elevation map demonstrated a greater posterior curvature of the cornea in this group, with a statistically significant difference. However, an isolated increase in the posterior elevation map does not have good diagnostic accuracy.

AimsTo evaluate the clinical and visual outcomes of fluid-filled scleral lens devices (SL) wear in patients with limbal stem cell deficiency (LSCD).DesignRetrospective consecutive case series.Methods27 eyes with LSCD confirmed by in vivo confocal microscopy at the Stein Eye Institute and fitted with SL were included. Correlations between corrected distance visual acuity (CDVA) and LSCD stage determined by clinical grading were performed between baseline (after the SL fit) and the last follow-up (the time of discontinuation of SL wear or the last visit in eyes in which SL were continued). In a subset of patients that had worsened LSCD while using SL, anterior segment optical coherence tomography (AS-OCT) and anterior segment fluorescein angiogram (AS-FA) were performed.ResultsBaseline LSCD grading was stage I in 12 eyes (44.4%), stage 2 in 12 eyes (44.4%), and stage III in 3 eyes (11.1%). At the last follow-up, CDVA was improved in 7 eyes (25.9%), remained stable in 13 eyes (48.1%) and decreased in 7 eyes (25.9%, P = 0.16). The LSCD stage was improved in 7 eyes (25.9%), remained stable in 8 eyes (29.6%) and worsened in 12 eyes (44.4%, P = 0.10). AS-OCT and AS-FA, performed in 5 eyes, showed limbal compression and delayed fluorescein filling.ConclusionSL can improve visual acuity and maintain the ocular surface in the majority of eyes. Worsening of the ocular surface might be a result of limbal hypoxia. Close monitoring of SL fit is necessary in these compromised eyes.

Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity of ExoS. Genetic and pharmacologic approaches using MCC950 reveal that NLRP3 is also essential for bacterial killing and disease severity in a murine model of P. aeruginosa corneal infection (keratitis). Overall, these findings reveal a function for ExoS ADPRT in regulating inflammasome subtype usage in neutrophils versus macrophages and an unexpected role for NLRP3 in P. aeruginosa keratitis.

PURPOSE: The aim of this study was to investigate basal epithelial cell morphology (CM) in the central cornea and limbal areas of eyes with limbal stem cell deficiency (LSCD). METHODS: This was a prospective, cross-sectional comparative study. We developed a CM scoring system based on basal epithelial cell phenotypes graded from 0 (normal) to 3 (severe morphologic alterations); this system was evaluated by 2 independent masked observers. The CM score was compared with the LSCD clinical score, mean best-corrected visual acuity, and in vivo laser scanning confocal microscopy parameters used to stage LSCD (ie, basal epithelial cell density, basal epithelial thickness, and subbasal corneal nerve fiber length density). RESULTS: One hundred sixty-eight eyes with LSCD and 63 normal eyes were included. Compared with the control group, the LSCD group had significantly higher mean (±SD) CM scores in the central cornea (1.8 ± 0.7 vs. 0.5 ± 0.4, respectively; P = 0.01) and limbal areas (1.6 ± 0.2 vs. 1.3 ± 0.0, respectively; P < 0.05). The mean CM score in the central cornea was positively correlated with the clinical score ( P < 0.01, r = 0.66) and negatively correlated with the best-corrected visual acuity ( P < 0.01, r = 0.42). The CM scores were positively correlated with all other in vivo laser scanning confocal microscopy parameters in the central cornea and limbal areas (all P < 0.001). CONCLUSIONS: Basal epithelial CM is altered in the central cornea and limbus of eyes with LSCD and thus can be used to stage the clinical severity of the disease.

Stefan Futterknecht,1,2 Eleftherios Chatzimichail,1 Konstantin Gugleta,1,3 Georgios D Panos,4,5,&ast; Zisis Gatzioufas1,3,&ast; 1Department of Ophthalmology, University Hospital of Basel, Basel, Switzerland; 2Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland; 3Department of Ophthalmology, School of Medicine, University of Basel, Basel, Switzerland; 4Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 5Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UK&ast;These authors contributed equally to this workCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.comAbstract: The cornea, as the outermost layer of the eye, plays a crucial role in vision by focusing light onto the retina. Various diseases and injuries can compromise its clarity, leading to impaired vision. This review aims to provide a thorough overview of the pharmacological properties, therapeutic potential and associated risks of Rho-associated protein kinase (ROCK) inhibitors in the management of corneal diseases. The article focuses on four key ROCK inhibitors: Y-27632, fasudil, ripasudil, and netarsudil, providing a comparative examination. Studies supporting the use of ROCK inhibitors highlight their efficacy across diverse corneal conditions. In Fuchs’ endothelial corneal dystrophy, studies on the application of Y-27632, ripasudil, and netarsudil demonstrated noteworthy enhancements in corneal clarity, endothelial cell density, and visual acuity. In pseudophakic bullous keratopathy, the injection of Y-27632 together with cultured corneal endothelial cells into the anterior chamber lead to enhanced corneal endothelial cell density and improved visual acuity. Animal models simulating chemical injury to the cornea showed a reduction of neovascularization and epithelial defects after application of fasudil and in a case of iridocorneal endothelial syndrome netarsudil improved corneal edema. Addressing safety considerations, netarsudil and ripasudil, both clinically approved, exhibit adverse events such as conjunctival hyperemia, conjunctival hemorrhage, cornea verticillata, conjunctivitis, and blepharitis. Monitoring patients during treatment becomes crucial to balancing the potential therapeutic benefits with these associated risks. In conclusion, ROCK inhibitors, particularly netarsudil and ripasudil, offer promise in managing corneal diseases. The comparative analysis of their pharmacological properties and studies supporting their efficacy underscore their potential therapeutic significance. However, ongoing research is paramount to comprehensively understand their safety profiles and long-term outcomes in diverse corneal conditions, guiding their optimal application in clinical practice.Keywords: rho kinase inhibitors, cornea, corneal diseases, corneal dystrophies, Fuchs’ endothelial corneal dystrophy, corneal transplantation

ObjectiveTo describe the clinical findings, multimodal corneal imaging features and treatment in canine patients diagnosed with endotheliitis.Animals studiedFour canine patients met inclusion criteria for bilateral corneal disease with endothelial inflammation and secondary corneal edema that responded to topical anti-inflammatory treatment.MethodsThe patients selected underwent a complete ophthalmic examination with emphasis on the cornea including ultrasound pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), in vivo confocal microscopy (IVCM), and digital slit lamp photography.ResultsAll patients in this study demonstrated thickened corneas due to edema with USP and FD-OCT. With IVCM, mild to severe polymegathism and pleomorphism of corneal endothelial cells, reduced endothelial cell density, hyperreflective keratic precipitates (KPs), and extracellular debris as well as hyporeflective pseudoguttata were observed. With FD-OCT, hyperreflective KPs were commonly observed on the inferior cornea. Clinical examination and advanced imaging results were consistent with a diagnosis of endotheliitis. All patients initially responded to topical anti-inflammatory treatment and required continued therapy; two patients also received topical netarsudil, a rho-associated coiled-coil kinase inhibitor.ConclusionEndotheliitis should be considered for canine patients with bilateral edema that is most severe in the inferior cornea. Careful inspection of Descemet's membrane-endothelial complex should be performed for KPs or inflammatory debris. Chronic administration of topical anti-inflammatories may be necessary to prevent flare-ups of endotheliitis.

Neutrophil extracellular traps (NETs) play an essential role in antimicrobial defense. However, NETs have also been shown to promote and mediate a wide spectrum of diseases, including cancer, diabetes mellitus, cardiovascular diseases, and ocular diseases. Data regarding NETs in ocular diseases remain limited. In physiological conditions, NETs protect the eye from debris and cleave proinflammatory cytokines, including several interleukins. On the other hand, NETs play a role in corneal diseases, such as dry eye disease and ocular graft-versus-host disease, where they promote acinar atrophy and delayed wound healing. Additionally, NET levels positively correlate with increased severity of uveitis. NETs have also been described in the context of diabetic retinopathy. Although increased NET biomarkers are associated with an increased risk of the disease, NETs also assist in the elimination of pathological blood vessels and the regeneration of normal vessels. Targeting NET pathways for the treatment of ocular diseases has shown promising outcomes; however, more studies are still needed in this regard. In this article, we summarize the literature on the protective roles of NETs in the eye. Then, we describe their pathogenetic effects in ocular diseases, including those of the cornea, uvea, and retinal blood vessels. Finally, we describe the therapeutic implications of targeting NETs in such conditions. [ABSTRACT FROM AUTHOR]

The eye is a complex sensory organ that enables visual perception of the world. The dysfunction of any of these tissues can impair vision. Conduction studies on laboratory animals are essential to ensure the safety of therapeutic products directly applied or injected into the eye to treat ocular diseases before eventually proceeding to clinical trials. Among these tissues, the cornea has unique homeostatic and regenerative mechanisms for maintaining transparency and refraction of external light, which are essential for vision. However, being the outermost tissue of the eye and directly exposed to the external environment, the cornea is particularly susceptible to injury and diseases. This review highlights the evidence for selecting appropriate animals to better understand and treat corneal diseases, which rank as the fifth leading cause of blindness worldwide. The development of reliable and human-relevant animal models is, therefore, a valuable research tool for understanding and translating fundamental mechanistic findings, as well as for assessing therapeutic potential in humans. First, this review emphasizes the unique characteristics of animal models used in ocular research. Subsequently, it discusses current animal models associated with human corneal pathologies, their utility in understanding ocular disease mechanisms, and their role as translational models for patients. [ABSTRACT FROM AUTHOR]