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The eyes are one of the most important sensory organs in the human body. Currently, diseases such as limbal stem cell deficiency, cataract, retinitis pigmentosa and dry eye seriously threaten the quality of people's lives, and the treatment of advanced blinding eye disease and dry eye is ineffective and costly. Thus, new treatment modalities are urgently needed to improve patients' symptoms and suffering. In recent years, stem cell-derived three-dimensional structural organoids have been shown to mimic specific structures and functions similar to those of organs in the human body. Currently, 3D culture systems are used to construct organoids for different ocular growth and development models and ocular disease models to explore their physiological and pathological mechanisms. Eye organoids can also be used as a platform for drug screening. This paper reviews the latest research progress in regard to eye organoids (the cornea, lens, retina, lacrimal gland, and conjunctiva)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Encephalocraniocutaneous lipomatosis (ECCL) is a rare genetic condition with well-described skin, ocular, and central nervous system findings. Several case reports have been documented demonstrating the presence of low-grade gliomas in patients with ECCL and the association with certain FGFR1 mutations. We report on a case of diffuse low-grade glioma, mitogen activated protein kinase pathway altered in a patient with ECCL, who was found to have a distinct FGFR1 mutation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study investigated the effects of an eye care protocol (ECP) on patients in the intensive care unit (ICU)., Methods: This study utilized a randomized controlled design. Participants were patients who met the inclusion criteria and were admitted to the ICU (36 in the experimental group and 38 in the control group). The experimental group received an ECP, while the control group received standard eye care, starting the day after admission, for a duration of 10 days. The ECP classifies the degree of eyelid obstruction into three stages based on the degree of exposure to the lower eyelid conjunctiva and cornea. The protocol included cleansing with normal saline gauze, administering eye drops, applying silicone and polyurethane films, and recommending consultation with an ophthalmologist if necessary. The effectiveness of ECP was assessed by analyzing tear volume, hyperemia, chemosis, and eye discharge. Data analysis was conducted using SPSS 27.0, employing the Mann-Whitney U-test and generalized estimating equations., Results: On day 5, the experimental group demonstrated a significant increase in tear volume in both eyes compared with the control group. However, no statistically significant differences were observed in the incidence of hyperemia, chemosis, and eye discharge on days 5 and 10 of the intervention., Conclusion: The application of the ECP in this study increased tear volume in ICU patients, thereby reducing discomfort caused by dry eyes. It has the potential to prevent complications such as damage to the surface of the eyeball resulting from decreased tear volume., Competing Interests: The authors declared no conflict of interest., (© 2024 Korean Society of Nursing Science.)

Background: Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous mutations in the fibrillin-1 gene (FBN1). Other associated genes include LTBP2, MYH11, MYLK, and SLC2A10. There is significant clinical overlap between MFS and other Marfan-like disorders., Purpose: To expand the mutation spectrum of FBN1 gene and validate the pathogenicity of Marfan-related genes in patients with MFS and ocular manifestations., Methods: We recruited 318 participants (195 cases, 123 controls), including 59 sporadic cases and 88 families. All patients had comprehensive ophthalmic examinations showing ocular features of MFS and met Ghent criteria. Additionally, 754 cases with other eye diseases were recruited. Panel-based next-generation sequencing (NGS) screened mutations in 792 genes related to inherited eye diseases., Results: We detected 181 mutations with an 84.7% detection rate in sporadic cases and 87.5% in familial cases. The overall detection rate was 86.4%, with FBN1 accounting for 74.8%. In cases without FBN1 mutations, 23 mutations from seven Marfan-related genes were identified, including four pathogenic or likely pathogenic mutations in LTBP2. The 181 mutations included 165 missenses, 10 splicings, three frameshifts, and three nonsenses. FBN1 accounted for 53.0% of mutations. The most prevalent pathogenic mutation was FBN1 c.4096G>A. Additionally, 94 novel mutations were detected, with 13 de novo mutations in 14 families., Conclusion: We expanded the mutation spectrum of the FBN1 gene and provided evidence for the pathogenicity of other Marfan-related genes. Variants in LTBP2 may contribute to the ocular manifestations in MFS, underscoring its role in phenotypic diversity., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation and differs from programmed cell death, such as apoptosis, necrosis, and autophagy. Ferroptosis is associated with a variety of physiological and pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence and development of diseases by targeting metabolic pathways and signaling pathways in tumors, ischemic organ damage, and other degenerative diseases related to lipid peroxidation. Increasing evidence suggests that ferroptosis is closely linked to the onset and progression of various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, and retinoblastoma. Our review of the current research on ferroptosis in ophthalmic diseases reveals significant advancements in our understanding of the pathogenesis, aetiology, and treatment of these conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Lin, Han, Wang, Zheng and Wei.)

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000-3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl - ) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis.

Background: Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis., Methods: Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007., Results: tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-β1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007., Conclusions: Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy., (© 2024. The Author(s).)

Objectives: To identify canine breeds at risk for ocular melanosis and to compare the clinical and histologic features between affected Cairn Terriers (CTs) and non-Cairn Terriers (NCTs)., Design: Relative risk (RR) analysis and retrospective cohort study of dogs histologically diagnosed with ocular melanosis., Procedures: The COPLOW archive was searched for globe submissions diagnosed with ocular melanosis. Six hundred fifty globes were included, and RR analysis was performed to identify at-risk NCT breeds. A cohort of 360 CT and NCT globes diagnosed from 2013 to 2023 were included in the retrospective cohort study. Clinical data were collected from submission forms, medical records, and follow-up surveys. One hundred fifty-seven submissions underwent masked histologic review. Immunohistochemical staining for CD204 was performed to determine the predominance of melanophages in affected uvea from five NCTs., Results: At-risk NCT breeds included the Boxer, Labrador Retriever, and French Bulldog. Glaucoma was the reported reason for enucleation in 79.4% of submissions. At enucleation, clinical features less prevalent in NCTs than CTs included pigmentary abnormalities in the contralateral eye (33.7% vs. 63.1%, p = .0008) and abnormal episcleral/scleral pigmentation in the enucleated globe (25.4% vs. 53.6%, p = .0008). Histologic involvement of the episclera was also less frequent in NCTs than in CTs (39.7% vs. 76.9%, p = .008). Concurrent melanocytic neoplasms arising in melanosis were more common in NCTs (24.4%) than CTs (3.9%). Melanophages were not predominant in any samples evaluated immunohistochemically., Conclusions: Several popular NCT breeds carry risk for ocular melanosis, and some clinicopathologic disease features may differ from those described in CTs., (© 2024 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production.  (J Histochem Cytochem XX.XXX-XXX, XXXX) ., Competing Interests: Competing InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Vascular and neural structures of the retina can be visualized non-invasively and used to predict ocular and systemic pathologies. We set out to evaluate the association of hemoglobin (Hb) levels within the national reference interval with retinal vascular caliber, optical coherence tomography (OCT) and visual field (VF) parameters in the Northern Finland 1966 Birth Cohort (n = 2319, 42.1% male, average age 47 years). The studied parameters were evaluated in Hb quintiles and multivariable linear regression models. The lowest Hb quintile of both sexes presented the narrowest central retinal vein equivalent (CRVE) and the healthiest cardiometabolic profile compared to the other Hb quintiles. In the regression models, CRVE associated positively with Hb levels in both sexes, (B males  = 0.068 [0.001; 0.135], B females  = 0.087 [0.033; 0.140]), after being adjusted for key cardiometabolic and inflammatory parameters, smoking status, and fellow vessel caliber. No statistically significant associations of Hb levels with central retinal artery equivalent, OCT or VF parameters were detected. In conclusion, Hb levels were positively and specifically associated with CRVE, indicating that Hb levels are an independent factor affecting CRVE and the effect is in parallel with established risk factors for cardiometabolic diseases., (© 2024. The Author(s).)

The Hippo signalling pathway, an evolutionarily conserved kinase cascade, has been shown to be crucial for cell fate determination, homeostasis and tissue regeneration. Recent experimental and clinical studies have demonstrated that the Hippo signalling pathway is involved in the pathophysiology of ocular diseases. This article provides the first systematic review of studies on the regulatory and functional roles of mammalian Hippo signalling systems in eye diseases. More comprehensive studies on this pathway are required for a better understanding of the pathophysiology of eye diseases and the development of effective therapies., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The prevalence of visual impairments in human societies is worrying due to retinopathy complications of several chronic diseases such as diabetes, cardiovascular diseases, and many more that are on the rise worldwide. Since the proper function of this organ plays a pivotal role in people's quality of life, identifying factors affecting the development/exacerbation of ocular diseases is of particular interest among ophthalmology researchers. The extracellular matrix (ECM) is a reticular, three-dimensional (3D) structure that determines the shape and dimensions of tissues in the body. The ECM remodeling/hemostasis is a critical process in both physiological and pathological conditions. It consists of ECM deposition, degradation, and decrease/increase in the ECM components. However, disregulation of this process and an imbalance between the synthesis and degradation of ECM components are associated with many pathological situations, including ocular disorders. Despite the impact of ECM alterations on the development of ocular diseases, there is not much research conducted in this regard. Therefore, a better understanding in this regard, can pave the way toward discovering plausible strategies to either prevent or treat eye disorders. In this review, we will discuss the importance of ECM changes as a sentimental factor in various ocular diseases based on the research done up to now.

Lumican is a keratan sulfate proteoglycan that belongs to the small leucine-rich proteoglycan family. Research has lifted the veil on the versatile roles of lumican in the pathogenesis of eye diseases. Lumican has pivotal roles in the maintenance of physiological tissue homogenesis and is often upregulated in pathological conditions, e.g., fibrosis, scar tissue formation in injured tissues, persistent inflammatory responses and immune anomaly, etc. Herein, we will review literature regarding the role of lumican in pathogenesis of inherited congenital and acquired eye diseases, e.g., cornea dystrophy, cataract, glaucoma and chorioretinal diseases, etc., Competing Interests: Declaration of competing interest No conflicting relationship exits for any author., (Copyright © 2023. Published by Elsevier Inc.)

Aims: To determine the three-dimensional (3D) structure of the vitreous fluid including the posterior precortical vitreous pockets (PPVP), Cloquet's canal and cisterns in healthy subjects by AI-based segmentation of the vitreous of swept-source optical coherence tomography (OCT) images. In addition, to analyse the vitreous structures over a wide and deep area using ultrawidefield swept-source OCT (UWF-OCT)., Methods: Ten eyes of six patients with the mean age was 40.7±8.4 years and the mean refractive error (spherical equivalent) was -3.275±2.2 diopters were examined., Results: In the UWF OCT images, the structure of the vitreous was observed in detail over 23 mm wide and 5 mm area. AI-guided analyses showed the complex 3D vitreous structures from any angle. Cisterns were observed to overlie the PPVP from the anterior. The morphology and locations of the cisterns varied among the subjects but tended to be similar in the two eyes of one individual. Cisterns joined the PPVPs superior to the macula to form a large trunk. This joined trunk was clearly seen in 3D images even in eyes whose trunk was not detected in the B scan OCT images. In some eyes, the vitreous had a complex appearance resembling an ant nest without large fluid-filled spaces., Conclusions: A combination of UWF-OCT and 3D imaging is very helpful in visualising the complex structure of the vitreous. These technologies are powerful tools that can be used to clarify the normal evolution of the vitreous, pathological changes of vitreous and implications of vitreous changes in various vitreoretinal diseases., Competing Interests: Competing interests: ZM is an employee of Topcon., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Corneal opacification or scarring is one of the leading causes of blindness worldwide. Human limbus-derived stromal/mesenchymal stem cells (hLMSCs) have the potential of clearing corneal scarring. In the current preclinical studies, we aimed to determine their ability to heal the scarred corneas, in a murine model of corneal scar, and examined their ocular and systemic toxicity after topical administration to rabbit eyes. The hLMSCs were derived from human donor corneas and were cultivated in a clean room facility in compliance with the current good manufacturing practices (cGMP). Before the administration, the hLMSCs were analyzed for their characteristic properties including immunostaining, and were further subjected to sterility and stability analysis. The corneas (right eye) of C57BL/6 mice (n = 56) were stripped of their central epithelium and superficial anterior stroma using a rotary burr (Alger Brush ® II). Few mice were left untreated (n = 8), while few (n = 24) were treated immediately with hLMSCs after debridement (prophylaxis group). The rest (n = 24, scar group) were allowed to develop corneal scarring for 2 weeks and then treated with hLMSCs. In both groups, the treatment modalities included encapsulated (En+) and non-encapsulated (En-) hLMSCs and sham (vehicle) treatment. The follow-up (4 weeks) after the treatment or debridement included clinical photography, fluorescein staining, and optical coherence tomography at regular intervals. All the images and scans were analyzed using ImageJ software to assess the changes in corneal haze, scar area, and the reflectivity ratio of the epithelium to the stroma. The scar area and the scar intensity were found to be decreased in the groups that received hLMSCs. The reflectivity of the stroma was found to be normalized to the baseline levels before the debridement in the eyes that were treated with hLMSCs, relative to the untreated. In the safety study, the central corneas of the left eye of 18 New Zealand rabbits were scraped with a needle and then treated with En+ hLMSCs, En- hLMSCs, and the sham (n = 6 each). Rabbits were then followed up for 4 weeks, during which blood and tear samples were collected at regular intervals. These rabbits were then assessed for changes in the quantities of inflammatory markers (TNF-α, IL-6, and IgE) in the sera and tears, changes in the ocular surface observations such as intraocular pressure (IOP), and the hematological and clinical chemistry parameters. Four weeks later, the rabbits were euthanized and examined histopathologically. No significant changes in conjunctival congestion, corneal clarity, or IOP were noticed during the ophthalmic examination. The level of inflammatory molecules (TNF-α and IL-6 TNF-α) and the hematological parameters were similar in all groups without any significant changes. Histological examination of the internal organs and ocular tissues did not reveal any abnormalities. The results of these studies summarize that the En+ and En- hLMSCs are not harmful to the recipient and potentially restore the transparency of debrided or scarred corneas, indicating that hLMSCs can be assessed for clinical use in humans.

Objective: This study aims to compare a new prototype for a portable anterior eye segment imaging system with the standard method for ophthalmology examination., Methods: The new imaging system consisted of two IMX219 Arducam autofocus sensors (Arducam, China, Nanjing) for Raspberry Pi V2 camera module connected to a Raspberry Pi Zero W (Raspberry Pi Foundation, UK, Cambridge) that clips to a wearable headset. The 2D videos of the anterior eye segment were recorded with the new system and a 720p FaceTime HD camera (Apple, Cupertino, CA). Afterward, ophthalmologists evaluated the videos using a standard clinical eye examination form. These evaluations were compared with the standard slit-lamp clinical assessment performed during the patient's visit., Results: Thirty-five eyes were evaluated. The sensitivity and specificity percentages were statistically significant between the two imaging modalities (P ≤ 0.001). The evaluations performed from videos obtained with the new imaging system had better sensitivity and specificity percentages overall. However, statistically significant differences were only observed in cornea, anterior chamber, iris, and lens., Conclusions: Specificity percentages were higher than sensitivity percentages in both imaging modalities, indicating that video evaluations are less accurate for pathological screening. Nevertheless, the new system evaluations were significantly better than the webcam evaluations., Translational Relevance: This study presented an alternative system to assess eye conditions for telemedicine, one that provides more details than the current standard and uses new wearable headsets technologies.

3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with pleiotropic cytoprotective properties albeit without the bleeding risks. The anti-inflammatory activities of 3K3A-APC were demonstrated in multiple preclinical injury models, including various neurological disorders. We determined the ability of 3K3A-APC to inhibit ocular inflammation in a murine model of lipopolysaccharide (LPS)-induced uveitis. Leukocyte recruitment, microglia activation, NLRP3 inflammasome and IL-1β levels were assessed using flow cytometry, retinal cryosection histology, retinal flatmount immunohistochemistry and vascular imaging, with and without 3K3A-APC treatment. LPS triggered robust inflammatory cell recruitment in the posterior chamber. The 3K3A-APC treatment significantly decreased leukocyte numbers and inhibited leukocyte extravasation from blood vessels into the retinal parenchyma to a level similar to controls. Resident microglia, which underwent an inflammatory transition following LPS injection, remained quiescent in eyes treated with 3K3A-APC. An inflammation-associated increase in retinal thickness, observed in LPS-injected eyes, was diminished by 3K3A-APC treatment, suggesting its clinical relevancy. Finally, 3K3A-APC treatment inhibited inflammasome activation, determined by lower levels of NLRP3 and its downstream effector IL-1β. Our results highlight the anti-inflammatory properties of 3K3A-APC in ocular inflammation and suggest its potential use as a novel treatment for retinal diseases associated with inflammation.

Purpose: To evaluate the predictors of complete polypoidal lesion regression (CPREG) in polypoidal choroidal vasculopathy., Methods: Post hoc analysis of EVEREST II-a 24-month, multicenter, randomized, controlled clinical trial of 322 patients with polypoidal choroidal vasculopathy, randomized to receive ranibizumab with or without photodynamic therapy. Images of indocyanine green angiography (ICGA) were graded by a central reading center. Multiple logistic regression analysis with significant baseline predictors then was conducted to assess adjusted odds ratios for CPREG at month (M) 12., Results: Baseline ICGA characteristics were comparable between the treatment groups. Patients treated with combination therapy had higher odds of achieving CPREG at M12 (adjusted odds ratio = 4.64; 95% confidence interval, 2.85-7.55; P < 0.001) compared with those in the monotherapy group. Absence of polypoidal lesion pulsation on ICGA was also associated with CPREG at M12 (adjusted odds ratio = 2.62; 95% confidence interval, 1.32-5.21; P = 0.006). The presence of CPREG at M3 had higher odds of maintaining CPREG at M12 (adjusted odds ratio = 6.60; 95% confidence interval, 3.77-11.57; P < 0.001) compared with those with persistent polypoidal lesions., Conclusion: At M12, treatment with combination therapy was associated with higher probability of achieving CPREG than with ranibizumab monotherapy. The results contribute to the further understanding of the response of polypoidal lesions to treatment.

Background: The iridocorneal angle (ICA) is the major pathway of aqueous humour outflow from the anterior chamber of the eye. Ultrasound biomicroscopy (UBM) has been utilised to characterise the morphology of this drainage pathway in numerous species. UBM may allow for early recognition of aqueous humour outflow obstructions in horses, allowing for earlier recognition of risk for glaucoma, a vision-threatening and painful disease. UBM morphology of the normal equine ICA has yet to be described., Objectives: To determine the ultrasonographic morphology of the equine ICA by UBM in standing sedated horses., Study Design: In vivo experimental study., Methods: Thirty healthy adult horses underwent UBM of the ICA at four locations (superior, temporal, inferior, nasal) of each eye utilising standing sedation, topical anaesthesia and auriculopalpebral perineural anaesthesia. Anatomic structures were defined on ultrasound images through comparison to published histologic photomicrographs of the equine ICA., Results: Ultrasound imaging of the ICA at all four locations was easily performed in standing, sedated horses. High-resolution images of the ICA allowed for identification of the pectinate ligament, corneoscleral trabecular meshwork (TM), uveal TM and supraciliary TM., Main Limitations: Pupil size was midrange in all eyes, but was not strictly controlled. Lighting conditions not controlled. Various breeds included., Conclusion: In vivo UBM of the equine ICA is feasible and provides high-resolution images of the structures of the aqueous humour outflow pathway., (© 2022 EVJ Ltd.)

To better perform space missions and develop human spaceflights, the eye health of astronauts is receiving increasing attention from researchers. In this study, we used prolonged tail suspension to simulate microgravity cephalad fluid shift in space to observe intraocular pressure (IOP) changes, retinal structure, and optic nerve damage in rats. We observed significant choroidal thickening and optic nerve demyelination lesions in the rats in each experimental group. At the cellular level, retinal ganglion cells (RGCs) survival was significantly reduced, optic nerve oligodendrocytes were reduced, and apoptotic factors and microglia-mediated inflammation-related factors were detected in both the retina and optic nerve. The severity of these changes increased with increasing tails suspension time. In conclusion, simulated long-term microgravity can lead to slight intraocular pressure fluctuations, choroidal thickening, reduced RGCs survival, and optic nerve demyelination in rats., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To evaluate the choriocapillaris flow deficits (CCFD) on swept-source optical coherence tomography angiography (SS-OCTA) in eyes with unilateral polypoidal choroidal vasculopathy (PCV), fellow unaffected eyes, and to compare them with age-matched healthy controls., Methods: This study was a cross-sectional study which included treatment-naïve eyes with unilateral PCV (group 1), fellow unaffected eyes of patients with PCV (group 2), and normal eyes (group 3). Using the SS-OCTA, the Choriocapillaris (CC) slab was segmented from the structural optical coherence tomography (OCT) and the corresponding flow map was multiplied after signal compensation. The resultant image was evaluated for CCFD in equidistant squares measuring 1 × 1 mm, 1.5 × 1.5 mm, 2 × 2 mm, 2.5 × 2.5 mm, 3 × 3 mm, and 6 × 6 mm centered on the fovea., Results: The percentage of flow deficits were significantly increased (one-way ANOVA, P = 0.003 and P = 0.049) in the eyes with PCV as compared to the fellow eyes, and age-matched healthy controls. In the multiple pairwise comparison using post hoc Bonferroni, CCFD of 1 mm in group 1 and 2 (P = 0.019), group 1 and 3 (P = 0.003), and CCFD of 1.5 mm in group 1 and 3 (P = 0.044) were statistically significant. Correlation analysis showed no significant correlation between CCFD, age, Best corrected visual acuity (BCVA), foveal thickness (FT), and subfoveal choroidal thickness (SFCT) in our study. Linear regression analysis showed that the CCFD was negatively correlated with the distance from the foveal center in group 1 (β = -0.613, P = 0.046)., Conclusion: Eyes with PCV demonstrated a significant flow impairment in the choriocapillaris layer as compared to the fellow unaffected eyes and age-matched healthy eyes., Competing Interests: None

Twelve adult burrowing owls ( Athene cunicularia ) maintained in a managed environment underwent complete bilateral ophthalmic examinations to assess ocular parameters and, if present, describe lesions (n = 24 eyes). Tear production was measured with a Schirmer tear test (STT), and intraocular pressure (IOP) was measured with rebound tonometry using established calibration settings (D = dog/cat, P = other species). Retinography was performed for all birds after application of topical rocuronium bromide, and corneal diameter was measured. Menace response was absent bilaterally in 7 of 12 (58.3%) owls; however, this did not appear to be related to the presence of fundic lesions. Ocular lesions were visualized in 6 of 12 (50%) owls. The most common ophthalmic abnormality noted was mild multifocal fundic pigment clumping, suggestive of chorioretinal scarring. Other ocular lesions included 1 retinal tear and 1 incipient cataract. Mean tear production was 6.1 ± 3.0 mm/min. Mean IOPs were 11.6 ± 1.8 mm Hg and 7.1 ± 1.3 mm Hg for the D and P settings, respectively, and these were significantly different ( P < 0.001). The IOP results did not differ significantly based on patient age or between the right and left eyes, but a higher mean was obtained from males versus females using the D setting ( P < 0.039; male mean 12.1 ± 1.9 mm Hg; female mean 10.9 ± 1.2 mm Hg). Measurements obtained from the STT were not affected by either age or sex. Corneal height was 11 mm and width was 12 mm, regardless of age or sex. The rebound tonometer D setting is recommended for measuring IOP values in this species. Burrowing owls had inconsistent mydriasis following topical rocuronium bromide application to the eye; however, a complete fundic examination was possible with or without complete mydriasis.

Familial amyloid polyneuropathy (FAP) caused by a genetic mutation in transthyretin (TTR) is an autosomal dominant hereditary disease. The retrospective, observational case series study presents the ocular clinicopathological findings of five cases carrying the TTR mutation c.401A>G (p.Tyr134Cys). Multimodal retinal imaging and electrophysiological examination, Congo red staining and immunohistochemical analysis of specimens, and genetic analyses were performed. Cases 1 and 2 were symptomatic with vitreous and retinal amyloid deposition and poor visual recovery. Case 3 had a symptomatic vitreous haze in the left eye with good postoperative visual recovery. The right eye of case 3 and the eyes of cases 4 and 5 were asymptomatic. Thicker retinal nerve fiber layer, retinal venous tortuosity with prolonged arteriovenous passage time on fluorescein angiography and retinal dysfunction detected by multifocal electroretinogram occurred even in asymptomatic eyes. Moreover, the internal limiting membrane from patients with FAP was stained positive for Congo red and transforming growth factor-β1. The results highlight the amyloid deposition of mutant TTR in the optic disc and retina, even in the asymptomatic stage. The deposited amyloid leads to increased resistance to venous return and retinal functional abnormalities. Therefore, careful follow-up of structural and functional changes in the retina is needed, even in asymptomatic patients with FAP.

Objectives: Ocular amyloidoma is a rare disorder characterized by deposition of insoluble proteinaceous fibrils in the extracellular space of the ocular adnexa. This study details the clinicopathologic features and proteomic characteristics of periocular amyloid deposition., Methods: Specimens (1991-2020) were retrieved and reviewed. All available H&E slides and special stains were reviewed. Proteomic analysis was performed using immunohistochemistry (IHC) for IgG, IgG4, IgA, IgD, IgM, CD20, CD3, CD138, and κ/λ, as well as chromatography-electrospray tandem mass spectrometry on formalin-fixed, paraffin-embedded tissue., Results: There were 14 patients (7 men, 7 women). The depositions involved eyelid (n = 3), conjunctiva (n = 8), and orbit (n = 3). All patients were adults with a median age at diagnosis of 56 (range, 39-88) years. The deposits were predominantly λ light chain restricted (n = 6) and mixed light chains (n = 2), and one case was κ predominant. Two of the cases with a mixture of κ and λ light chains had an excess of transthyretin by mass spectrometry. Four of the cases did not have adequate material for proteomic subtyping., Conclusions: Amyloidomas involving ocular adnexa contain a variety of amyloid-related and immunoglobulin-associated peptides. The λ light chain predominates as in other body sites, but mixed patterns and rarely κ light chain restriction may be encountered., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics of an individual, differentiating man from woman, but also participate in the functioning of the various systems of the body. The evidence that many eye diseases differ in terms of prevalence between men and women has allowed us, in recent years, to carry out several studies that have investigated the association between sex hormones and the pathophysiology of eye tissues. Specific receptors for sex hormones have been found on the lacrimal and meibomian glands, conjunctiva, cornea, lens, retina, and choroid. This work summarizes the current knowledge on the role that sex hormones play in the pathogenesis of the most common ocular disorders and indicates our clinical experience in these situations. The aim is to stimulate an interdisciplinary approach between endocrinology, neurology, molecular biology, and ophthalmology to improve the management of these diseases and to lay the foundations for new therapeutic strategies.

Iron accumulates in the vital organs with aging. This is associated with oxidative stress, inflammation, and mitochondrial dysfunction leading to age-related disorders. Abnormal iron levels are linked to neurodegenerative diseases, liver injury, cancer, and ocular diseases. Canonical Wnt signaling is an evolutionarily conserved signaling pathway that regulates many cellular functions including cell proliferation, apoptosis, cell migration, and stem cell renewal. Recent evidences indicate that iron regulates Wnt signaling, and iron chelators like deferoxamine and deferasirox can inhibit Wnt signaling and cell growth. Canonical Wnt signaling is implicated in the pathogenesis of many diseases, and there are significant efforts ongoing to develop innovative therapies targeting the aberrant Wnt signaling. This review examines how intracellular iron accumulation regulates Wnt signaling in various tissues and their potential contribution in the progression of age-related diseases., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Austin Armstrong et al.)

Oxidative stress is an important pathomechanism found in numerous ocular degenerative diseases. To provide a better understanding of the mechanism and treatment of oxidant/antioxidant imbalance-induced ocular diseases, this article summarizes and provides updates on the relevant research. We review the oxidative damage (e.g., lipid peroxidation, DNA lesions, autophagy, and apoptosis) that occurs in different areas of the eye (e.g., cornea, anterior chamber, lens, retina, and optic nerve). We then introduce the antioxidant mechanisms present in the eye, as well as the ocular diseases that occur as a result of antioxidant imbalances (e.g., keratoconus, cataracts, age-related macular degeneration, and glaucoma), the relevant antioxidant biomarkers, and the potential of predictive diagnostics. Finally, we discuss natural antioxidant therapies for oxidative stress-related ocular diseases.

This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005-2007 and between 2008-2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances., Competing Interests: The authors have declared that no competing interests exist.

Although great potential hazards and threats still occur from sulfur mustard, there are no specific medicine or therapy for the intoxication of sulfur mustard. Herein, we have demonstrated a supramolecular approach for the detoxification of the sulfur mustard simulant CEES ( 4 ) in vitro and in vivo by carboxylatopillar[5]arene potassium salts (CP[5]AK 1 ) efficiently based on host-guest interactions. The encapsulation of CEES ( 4 ) by the cavity of the pillar[5]arene 2 is driven by C-H···π interactions between CEES ( 4 ) and the electron-rich cavity of pillar[5]arene 2 , which was investigated by 1 H NMR titration, density functional theory studies, and the independent gradient model studies. CEES ( 4 ) is degradated to the reactive sulfonium salts quickly in aqueous media, resulting in the alkylation of DNA and proteins. The sulfonium salts can be encapsulated by CP[5]AK 1 efficiently, which accelerates the degradation of the sulfonium salts about 14 times. The cell and animal experiments indicated that the bioactivities of the sulfonium salts are inhibited with the formation of stable host-guest complexes, and CP[5]AK 1 has a good therapeutic effect on the damages caused by CEES ( 4 ) at either pre- or post-treatments. Due to the low cytotoxicity and good therapeutic effect, the anionic pillar[5]arenes are expected to be developed as specific antidotes against sulfur mustard (HD).

Background: Prior ecologic studies suggest that UV exposure through sunlight to the retina might contribute to increased retinoblastoma incidence., Aims: Our study objectives were (1) to examine the relationship between exposure to sunlight during postnatal retinal development (prior to diagnosis of sporadic disease) and the risk of retinoblastoma, and (2) to examine the relationship between sun exposure during postnatal retinal development, and the extent of disease among children with unilateral and bilateral retinoblastoma., Methods and Results: We interviewed 511 mothers in the EpiRbMx case-control study about their child's exposure to sunlight during postnatal retinal cell division by examining three time periods prior to Rtb diagnosis coinciding with developmental stages in which outdoor activities vary. Weekly sun exposure was compared by age period, between unilateral (n = 259), bilateral (n = 120), and control (n = 132) children, accounting for two factors affecting UV exposure: residential elevation and reported use of coverings to shield eyes. For cases, association between sunlight exposure and clinical stage was examined by laterality at each age period. After adjusting for maternal education and elevation, sun exposure was lower in cases than controls in all three age periods especially during the first 6 months, and in children 12-23 months whose mothers did not cover their eyes when outdoors. In children diagnosed after 12 months of age, sun exposure during the second year of life (age 12-23 months) appeared inversely correlated (r = -0.25) with more advanced intraocular disease in bilateral Rtb children after adjusting for maternal education, residential elevation, and age of diagnosis (p < .09) consistent with effects of Vitamin D exposure on intraocular spread in earlier transgenic murine models of retinoblastoma, and suggesting potential chemopreventive strategies., Conclusion: Sun exposure in early childhood is protective for retinoblastoma and may decrease degree of intraocular spread in children with bilateral Rtb., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Purpose: This study was aimed at investigating the protective effect of antioxidant-rich fraction of Croton zambsicus (C-ZAMB) leaves on ocular-gastrointestinal dysfunction in rats exposed to environmental mixed-metal (EOMABRSL)., Materials and Methods: The rats were divided into five ( n  = 10) groups. Group I designates the control which received 0.5 mL of distilled water. Group II and III received 0.5 mL of EOMABRSL for 98 days (non-withdrawal) and 70 days (withdrawal for 28 days), respectively. Group IV received 0.5 mL EOMABRSL for 70 days and 400 mg/kg C-ZAMB fraction for 28 days. Group V received 400 mg/kg C-ZAMB only for 28 days via oral route., Results: Exposure of the animals to EOMARBSL for 98 days and 70 days significantly up-regulated the activities of ocular-gastrointestinal aldolase-reductase, α-amylase, α-glucosidase and eco-5 1 -nucleotidase with corresponding depletion of lactate dehydrogenase activity. Furthermore, exposure to EOMABRSL significantly altered the antioxidant proteins with up-production of MDA content. Apparently, management with 400 mg/kg C-ZAMB fraction significantly inhibited the key markers linked with ocular-gastrointestinal disorders., Conclusion: Hence, this study underscores the biochemical mechanisms for managing ocular-gastrointestinal lesions by 400 mg/kg C-ZAMB fraction on exposure to mixture of environmental metals.

Purpose: To compare phenotypic and genetic variations in polypoidal choroidal vasculopathy (PCV) between Caucasian and Asian patients., Methods: We analysed phenotypic and genotypic data from two sites, Association for Innovation and Biomedical Research on Light and Image, Portugal and Singapore National Eye Centre, Singapore. Baseline fundus photography, spectral domain-optical coherence tomography, indocyanine green and fluorescein angiography scans were analysed by respective reading centres using a standardised grading protocol. Single nucleotide polymorphisms across 8 PCV loci were compared between cases and controls selected from each population., Results: One hundred and forty treatment-naïve PCV participants (35 Portuguese and 105 Singaporean) were included. The Portuguese cohort were older (72.33±8.44 vs 68.71±9.40 years, p=0.043) and were comprised of a lower proportion of males (43% vs 71%, p=0.005) compared with the Singaporean cohort. Differences in imaging features include higher prevalence of soft drusen (66% vs 30%, p=0.004), lower prevalence of subretinal haemorrhage (14% vs 67%, p<0.001), smaller polypoidal lesion (PL) area (0.09±0.09 vs 0.76±0.93 mm 2 , p<0.001), lower ratio of PL to branching vascular network area (3% vs 38%, p<0.001) and lower central retinal thickness (346.48±93.74 vs 493.16±212.92 µm, p<0.001) in the Portuguese cohort. CETP rs3764261 (OR 2.467; 95% CI 1.282 to 4.745, p=0.006) in the Portuguese population was significantly associated with PCV and CFH rs800292 (OR 1.719; 95% CI 1.139 to 2.596, p=0.010) in the Singaporean population, respectively., Conclusion: Among Asian and Caucasian patients with PCV, there are significant differences in the expression of phenotype. We also identified different polymorphisms associated with PCV in the two populations., Competing Interests: Competing interests: RS reported receiving personal fees as member of the advisory board for Allergan, Alimera Sciences, Bayer, Novartis, Roche, Novo Nordisk and Thea Pharmaceuticals; JNM is a member of the scientific advisory board of Alcon; JF reported being a member of advisory boards for Alimera, Allergan, Bayer, Boehringer and Novartis; SV-P reported receiving personal fees as a consultant for Alimera Sciences, Bayer and Novartis. FC reported receiving personal fees as a consultant for Bayer, Allergan, Novartis, Brill-Alimera, Roche, Alcon and Dorc. AB reported receiving from Bayer consultation fees (advisory board), speaker fees, travel fees (for meetings) and reported receiving from Allergan consultation fees (advisory board), speaker fees, and travel fees (for meetings). The other authors declare that they have no conflict of interest., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

What Is Known and Objective: We performed a meta-analysis to evaluate the effects of glucagon-like peptide-1 receptor agonists compared to placebo on cardiovascular, kidney-related, and eye-related disease outcomes or on mortality in subjects with type 2 diabetes mellitus., Methods: A systematic literature search up to April 2021 was performed, and 8 studies included 61,661 subjects with type 2 diabetes mellitus at the start of the study, 29,034 of them were using glucagon-like peptide-1 receptor agonists and 32,627 were given a placebo. They reported on relationships between the effects of glucagon-like peptide-1 receptor agonists compared to placebo on mortality rates, cardiovascular, renal and ophthalmic outcomes in subjects with type 2 diabetes mellitus. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to assess the effects of glucagon-like peptide-1 receptor agonists compared to placebo on the listed outcomes on subjects with type 2 diabetes mellitus, using the dichotomous method with a random or fixed-effect model., Results: The use of glucagon-like peptide-1 receptor agonists was associated with significantly lowered all-cause mortality (OR, 0.76; 95% CI, 0.65-0.89, p < 0.001), cardiovascular deaths (OR, 0.87; 95% CI, 0.81-0.94, p < 0.001), myocardial infarctions (OR, 0.92; 95% CI, 0.85-0.98, p = 0.01), strokes (OR, 0.81; 95% CI, 0.74--0.90, p < 0.001), hospital admissions owing to heart failure (OR, 0.91; 95% CI, 0.83-1.00, p = 0.04) and renal events (OR, 0.83; 95% CI, 0.77-0.89, p < 0.001) compared to placebo in subjects with type 2 diabetes mellitus. However, glucagon-like peptide-1 receptor agonists had significantly higher ophthalmic events (OR, 1.15; 95% CI, 1.04-1.29, p = 0.009) compared to placebo in subjects with type 2 diabetes mellitus., What Is New and Conclusion: Glucagon-like peptide-1 receptor agonists may have a lower risk of all-cause mortality, cardiovascular death, myocardial infarction, stroke, hospital admission owing to heart failure and renal events compared to placebo in subjects with type 2 diabetes mellitus. However, they have significantly higher ophthalmic events compared to placebo in subjects with type 2 diabetes mellitus. Further studies are required to validate these findings., (© 2021 John Wiley & Sons Ltd.)

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. There is thus an urgent need to identify novel targets to prevent/treat scarring and postsurgical fibrosis in the eye. In this review, the latest progress in biological mechanisms underlying ocular fibrosis are discussed. We also summarize the current knowledge on preclinical studies based on viral and non-viral gene therapy, as well as chemical inhibitors, for targeting TGFβ or downstream effectors in fibrotic disorders of the eye. Moreover, the role of angiogenetic and biomechanical factors in ocular fibrosis is discussed, focusing on related preclinical treatment approaches. Moreover, we describe available evidence on clinical studies investigating the use of therapies targeting TGFβ-dependent pathways, angiogenetic factors, and biomechanical factors, alone or in combination with other strategies, in ocular tissue fibrosis. Finally, the recent progress in cell-based therapies for treating fibrotic eye disorders is discussed. The increasing knowledge of these disorders in the eye and the promising results from testing of novel targeted therapies could offer viable perspectives for translation into clinical use.

Cell transdifferentiation is the conversion of a cell type to another without requiring passage through a pluripotent cell state, and encompasses epithelial- and endothelial-mesenchymal transition (EMT and EndMT). EMT and EndMT are well defined processes characterized by a loss of epithelial/endothelial phenotype and gain in mesenchymal spindle shaped morphology, which results in increased cell migration and decreased apoptosis and cellular senescence. Such cells often develop invasive properties. Physiologically, these processes may occur during embryonic development and can resurface, for example, to promote wound healing in later life. However, they can also be a pathological process. In the eye, EMT, EndMT and cell transdifferentiation have all been implicated in development, homeostasis, and multiple diseases affecting different parts of the eye. Connexins, constituents of connexin hemichannels and intercellular gap junctions, have been implicated in many of these processes. In this review, we firstly provide an overview of the molecular mechanisms induced by transdifferentiation (including EMT and EndMT) and its involvement in eye diseases. We then review the literature for the role of connexins in transdifferentiation in the eye and eye diseases. The evidence presented in this review supports the need for more studies into the therapeutic potential for connexin modulators in prevention and treatment of transdifferentiation related eye diseases, but does indicate that connexin channel modulation may be an upstream and unifying approach for regulating these otherwise complex processes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.

The possible interconnection between the eye and central nervous system (CNS) has been a topic of discussion for several years just based on fact that the eye is properly considered an extension of the brain. Both organs consist of neurons and derived from a neural tube. The visual process involves photoreceptors that receive light stimulus from the external environment and send it to retinal ganglionic cells (RGC), one of the cell types of which the retina is composed. The retina, the internal visual membrane of the eye, processes the visual stimuli in electric stimuli to transfer it to the brain, through the optic nerve. Retinal chronic progressive neurodegeneration, which may occur among the elderly, can lead to different disorders of the eye such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Mainly in the elderly population, but also among younger people, such ocular pathologies are the cause of irreversible blindness or impaired, reduced vision. Typical neurodegenerative diseases of the CSN are a group of pathologies with common characteristics and etiology not fully understood; some risk factors have been identified, but they are not enough to justify all the cases observed. Furthermore, several studies have shown that also ocular disorders present characteristics of neurodegenerative diseases and, on the other hand, CNS pathologies, i.e., Alzheimer disease (AD) and Parkinson disease (PD), which are causes of morbidity and mortality worldwide, show peculiar alterations at the ocular level. The knowledge of possible correlations could help to understand the mechanisms of onset. Moreover, the underlying mechanisms of these heterogeneous disorders are still debated. This review discusses the characteristics of the ocular illnesses, focusing on the relationship between the eye and the brain. A better comprehension could help in future new therapies, thus reducing or avoiding loss of vision and improve quality of life.

In this study, it was aimed to present the results of microbiological, cytological, histopathological, and immunohistochemical analyses of ocular samples from an Antarctic (Ardley Island, King George Island) Gentoo penguin chick (Pygoscelis papua) with a pyogranulomatous lesion in the right eye. Samples were taken from both the healthy left eye and the lesion in the right eye. Conventional culture methods and phenotypic and molecular tests were used for bacterial isolation and identification, respectively. None of the isolates could be identified phenotypically. As a result, four of the five isolates obtained from the right eye were considered to belong to putative novel bacterial species and taxa as their similarity to GenBank data was below 98.75%. The isolates were considered to be Pasteurellaceae bacterium, Corynebacterium ciconiae, Cardiobacteriaceae bacterium, Actinomyces sp., and Dermabacteraceae bacterium. The only isolate from the left eye was identified as Psychrobacter pygoscelis. The cytological analysis demonstrated cell infiltrates composed mostly of degenerate heterophils, reactive macrophages, plasma cells, lymphocytes, and eosinophils. Based on histopathological findings, the lesion was defined as a typical pyogranulomatous lesion. Immunohistochemistry demonstrated that the granuloma was positive for TNF-α, IL-4, MMP-9, IL-1β, and IL-6. This is the first documented report of the unilateral pyogranulomatous ocular lesion in a Gentoo penguin chick, living in its natural habitat in Antarctica. This report also describes the isolation of four bacteria from the infected eye, which are considered to belong to novel Genus, species, or taxa. The primary bacterial pathogen that caused the ocular lesion was not able to be detected and remains unclear., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Graft-versus-host disease is a common complication of hematopoietic stem cell transplantation and the ocular surface is a main target of inflammatory reaction., (© 2021 Wiley Periodicals LLC.)

The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.

Purpose: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients., Materials and Methods: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987-2018). Descriptive and survival analyses were performed., Results and Limitations: Median age at VHL diagnosis was 34 years (IQR 25-43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up., Conclusions: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Vitiligo is characterized by the destruction of functional melanocytes in the skin. This destruction can target melanocytes anywhere in the body, in turn affecting the function of the organs in which the affected melanocytes reside. Melanocytes in the skin, uveal tract and ear are similar in their physiology and morphology, and share a common embryological origin., Aim: To study the association of vitiligo with ocular and auditory abnormalities., Methods: This case-control study was carried out on 40 patients with vitiligo and 20 healthy controls (HCs). All patients and HCs underwent auditory examination (otoscopic examination and immittance audiometry to assess middle ear pressure and exclude tympanic membrane perforation; pure tone audiometry to assess peripheral hearing sensitivity; and transient evoked otoacoustic emissions to assess central hearing ability) and standard ocular examination including visual acuity test, slit lamp biomicroscopy and optical coherence tomography., Results: Compared with controls, there was a significantly higher prevalence of hearing loss and ocular abnormalities in patients with vitiligo but no significant difference in visual acuity., Conclusion: Vitiligo is a systemic disease that can be associated with impairment of melanocyte function organs other than the skin, including the eyes and ears. The function of auditory melanocytes is related to the hearing process and thus their destruction could lead to hearing impairment. By contrast, ocular melanocytes do not play a direct role in detection or transfer of visual information, and thus should not affect vision. Vitiligo may be associated with ocular abnormalities and hearing loss., (© 2021 British Association of Dermatologists.)

The orbital phenomenon, cribra orbitalia, has long been a source of controversy, especially with regard to its nature, derivation, and relationship to anemia. Therefore, the external surfaces of orbital roofs were systematically examined microscopically in human skulls from historical collections. Superior orbital surfaces of 278 individual crania within the Hamann-Todd collection were assessed at various magnifications using epi-illumination microscopy to identify the presence of cribra orbitalia and characterize its nature. Also, 12 additional individuals with diagnosed anemia in the Hamann-Todd collection were evaluated. Orbital roof alterations, present in one-third of examined crania, had two discrete appearances: Vascular grooves (45%) and application of new bone in a vascular branching pattern on the orbit surface (55%). Porosity of the orbit was not observed. Evaluation of the orbits of 12 individuals with diagnosed anemia revealed one with a single deep defect, suggesting a space-occupying phenomenon, but no evidence of bone accretion, vascular grooves, or porosity. Cribra orbitalia has often been lumped indiscriminately as an indicator of organismal stress, rather than identified as a indicating a specific etiology. Neither that perspective nor porosity are supported by high resolution examination of orbital roof changes. Recognition of the blood vessel imprint pattern falsifies previous speculations and provides a new paradigm. The actual character of cribra orbitalia is documented and new hypotheses generated. While population prevalence of cribra orbitalia seems excessive for explanation on the basis of these hypotheses, the imprints are clearly vascular in origin., (© 2020 American Association for Anatomy.)

Exosomes have diverse functions and rich content and are involved in intercellular communication, immune regulation, viral infection, tissue regeneration, and the occurrence, development and metastasis of tumours. Notably, various stem cell-derived exosomes are expected to become new therapeutic approaches for inflammatory diseases and tumours and have good clinical application prospects. However, few studies have examined exosomes in ophthalmic diseases. Therefore, based on the functions of exosomes, this paper summarizes progress in the possible use of exosomes as treatment for specific ophthalmic diseases, aiming to determine the pathogenesis of exosomes to achieve more effective clinical diagnosis and treatment of these diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) S. aureus strains are well recognized as posing substantial problems in treating ocular infections. S. aureus has a vast array of virulence factors, including superantigens and enterotoxins. Their interactions and ability to signal antibiotics resistance have not been explored., Objectives: To predict the relationship between superantigens and methicillin and multidrug resistance among S. aureus ocular isolates., Methods: We used a DNA microarray to characterize the enterotoxin and superantigen gene profiles of 98 S. aureus isolates collected from common ocular sources. The outcomes contained phenotypic and genotypic expressions of MRSA. We also included the MDR status as an outcome, categorized as resistance to three or more drugs, including oxacillin, penicillin, erythromycin, clindamycin, moxifloxacin, tetracycline, trimethoprim-sulfamethoxazole and gentamicin. We identified gene profiles that predicted each outcome through a classification analysis utilizing Random Forest machine learning techniques., Findings: Our machine learning models predicted the outcomes accurately utilizing 67 enterotoxin and superantigen genes. Strong correlates predicting the genotypic expression of MRSA were enterotoxins A, D, J and R and superantigen-like proteins 1, 3, 7 and 10. Among these virulence factors, enterotoxin D and superantigen-like proteins 1, 5 and 10 were also significantly informative for predicting both MDR and MRSA in terms of phenotypic expression. Strong interactions were identified including enterotoxins A (entA) interacting with superantigen-like protein 1 (set6-var1&#95;11), and enterotoxin D (entD) interacting with superantigen-like protein 5 (ssl05/set3&#95;probe 1): MRSA and MDR S. aureus are associated with the presence of both entA and set6-var1&#95;11, or both entD and ssl05/set3&#95;probe 1, while the absence of these genes in pairs indicates non-multidrug-resistant and methicillin-susceptible S. aureus., Conclusions: MRSA and MDR S. aureus show a different spectrum of ocular pathology than their non-resistant counterparts. When assessing the role of enterotoxins in predicting antibiotics resistance, it is critical to consider both main effects and interactions., Competing Interests: The authors have declared that no competing interests exist.