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Abstract Purpose Ocular emergencies require immediate intervention to prevent rapid vision loss or functional impairment. The aim of this study was to determine the proportion of true ocular emergencies among patients who presented to the general emergency department with ocular complaints and were referred to the Eye Clinic. Methods In a retrospective cross-sectional study in a tertiary hospital in Istanbul, patients aged 0–100 years who presented to the general emergency department with ocular complaints between January and December 2022 were included. Inconclusive diagnoses and incomplete records were excluded. Patients were divided into three groups: top eye emergencies (TE), relative eye emergencies (REE), and non-emergency eyes (NEE). Results Among the 652,224 individuals seeking care, 9,982 (1.5%) were referred to the Eye Emergency Clinic. Of these, 2,788 (27.9%) were female, and 7,194 (72.1%) were male, with ages ranging from 0 to 98 years. TopEye Emergencies (TEE), Relative Eye Emergencies (REE), and Non-Eye Emergencies (NEE) accounted for 13%, 60%, and 27% of the cases, respectively. Common top-eye emergencies (TEE) include chemical injuries, orbital-preseptal cellulitis, and orbital fractures. Relative eye emergencies (REEs) commonly feature corneal foreign bodies, corneal erosion, and conjunctivitis. Nonemulsion eye (NEE) methods involve simple eye redness, trauma without eye involvement, and subconjunctival haemorrhage. Conclusions Consistent with the literature, 1.5% of patients presenting to the general emergency department had eye complaints.However, 27% of those referred to the ophthalmological clinic did not have an urgent eye condition. This is partly due to the high proportion of patients presenting to the emergency department with ocular complaints and the lack of knowledge of ophthalmological diseases by emergency physicians, leading to unnecessary referrals to the ophthalmology clinic, resulting in a loss of the workforce and reduced time allocated to patients with true ocular emergencies.

Purpose: Ocular emergencies require immediate intervention to prevent rapid vision loss or functional impairment. The aim of this study was to determine the proportion of true ocular emergencies among patients who presented to the general emergency department with ocular complaints and were referred to the Eye Clinic. Methods: In a retrospective cross-sectional study in a tertiary hospital in Istanbul, patients aged 0–100 years who presented to the general emergency department with ocular complaints between January and December 2022 were included. Inconclusive diagnoses and incomplete records were excluded. Patients were divided into three groups: top eye emergencies (TE), relative eye emergencies (REE), and non-emergency eyes (NEE). Results: Among the 652,224 individuals seeking care, 9,982 (1.5%) were referred to the Eye Emergency Clinic. Of these, 2,788 (27.9%) were female, and 7,194 (72.1%) were male, with ages ranging from 0 to 98 years. TopEye Emergencies (TEE), Relative Eye Emergencies (REE), and Non-Eye Emergencies (NEE) accounted for 13%, 60%, and 27% of the cases, respectively. Common top-eye emergencies (TEE) include chemical injuries, orbital-preseptal cellulitis, and orbital fractures. Relative eye emergencies (REEs) commonly feature corneal foreign bodies, corneal erosion, and conjunctivitis. Nonemulsion eye (NEE) methods involve simple eye redness, trauma without eye involvement, and subconjunctival haemorrhage. Conclusions: Consistent with the literature, 1.5% of patients presenting to the general emergency department had eye complaints.However, 27% of those referred to the ophthalmological clinic did not have an urgent eye condition. This is partly due to the high proportion of patients presenting to the emergency department with ocular complaints and the lack of knowledge of ophthalmological diseases by emergency physicians, leading to unnecessary referrals to the ophthalmology clinic, resulting in a loss of the workforce and reduced time allocated to patients with true ocular emergencies. [ABSTRACT FROM AUTHOR]

Corneal wound healing is a complex biological process that integrates a host of different signals to coordinate cell behavior. Upon wounding, there is the generation of an endogenous wound electric field that serves as a powerful cue to guide cell migration. Concurrently, the corneal epithelium reduces sialylated glycoforms, suggesting that sialylation plays an important role during electrotaxis. Here, we show that pretreating human telomerase-immortalized corneal epithelial (hTCEpi) cells with a sialyltransferase inhibitor, P-3FAX-Neu5Ac (3F-Neu5Ac), improves electrotaxis by enhancing directionality, but not speed. This was recapitulated using Kifunensine, which inhibits cleavage of mannoses and therefore precludes sialylation on N-glycans. We also identified that 3F-Neu5Ac enhanced the responsiveness of the hTCEpi cell population to the electric field and that pretreated hTCEpi cells showed increased directionality even at low voltages. Furthermore, when we increased sialylation using N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz), hTCEpi cells showed a decrease in both speed and directionality. Importantly, pretreating enucleated eyes with 3F-Neu5Ac significantly improved re-epithelialization in an ex vivo model of a corneal injury. Finally, we show that in hTCEpi cells, sialylation is increased by growth factor deprivation and reduced by PDGF-BB. Taken together, our results suggest that during corneal wound healing, reduced sialylated glycoforms enhance electrotaxis and re-epithelialization, potentially opening new avenues to promote corneal wound healing.

Perioperative visual loss (POVL) is a rare but severe complication following non-ophthalmological surgery under general anesthesia. A POVL can be caused by lesions in any part of the optical system. The predominant causes include corneal injuries and particularly ischemic damage. The symptoms of POVL substantially vary ranging from reduced vision to complete blindness. The risks involve factors related to the surgery as well as patient-specific factors. In general, the prognosis in cases of mechanical damage is better than for ischemic lesions. The treatment measures depend on the underlying pathomechanism and due to the limited evidence only a few treatment options are available. Therefore, preventive measures and meticulous documentation play a crucial role. [ABSTRACT FROM AUTHOR]

A 54-year-old man with noncontributory medical history presented to an ophthalmologist in January 2022 after 10 days of irritation in his right eye. The patient recounts having felt something get into his eye and under his contact lens (CL) while he was climbing into his car, but he was unsure what the foreign body may have been. Initial examination by the clinician found uncorrected distance visual acuity of 20/100-2 with a corneal abrasion, 4+ corneal edema, and 3+ conjunctival injection, for which he was placed on topical antibiotics (ocuflox and tobradex) with a bandage CL. 1 week later, visual acuity was 20/80, corneal edema had improved, and he was noted to have corneal scarring and an epithelial defect. Tobradex was continued while prednisolone drops and preservative-free artificial tears were started. 1 week later, the patient had worsening visual acuity to 20/250 and was referred to our tertiary center. On initial consultation, the patient had an uncorrected distance visual acuity of 20/500 and an uncorrected near visual acuity of >J10 in the right eye. Slitlamp examination of the right eye was significant for vortex keratopathy and mild corneal pannus with 360-degree subtle conjunctivalization of the limbus ( Figure 1JOURNAL/jcrs/04.03/02158034-202210000-00022/figure1/v/2022-10-03T121249Z/r/image-tiff ). The corneal topograph was obtained showing significant surface irregularity on the Placido image ( Figure 2JOURNAL/jcrs/04.03/02158034-202210000-00022/figure2/v/2022-10-03T121249Z/r/image-tiff ). Examination of the left eye was unremarkable. The ocular history is significant for myopia of -4.0 diopters and CL use for 20 years. The patient admits to regularly wearing soft CLs for several days straight and only removing them for a few hours. Antibiotics were discontinued, corticosteroid drops were reduced in frequency, and the patient was continued on preservative-free artificial tears. What imaging might you consider? What is your differential diagnosis at this point? What would be the most appropriate surgical and/or medical interventions? What would you counsel in prognosis for this patient?

Background: Corneal degeneration is a form of progressive cell death caused by multiple factors, such as diabetic retinopathy. It is the most well-known neural degenerative disease caused by macular degeneration in the aged and those with retinitis pigmentosa. Myocardial infarction is becoming a more common burden, causing cardiomyocyte degeneration, ischemia, and heart tissue death. This study examined the preventive effects of rutin on isoproterenol (ISO)-induced oxidative damage (that is, inflammation) on rabbit corneal epithelial cells and mouse heart injuries. Methods: These investigations involved a cytotoxicity test, biochemical analysis, qRT-PCR, Western blotting, and mouse cardiac histopathology. Results: The results showed that rutin enhanced ADH7 and ALDH1A1, retinoic acid signaling components in SIRC1 rabbit corneal cell lines. The production of NO by ocular epithelial cells was significantly reduced. It reduced cTnT and cTnI, CK-MB, and LDH contents in mouse cardiac tissue. The nuclear expressions of Nrf2, Sirt, and HO-1 were all increased by rutin. Docking studies revealed a good interaction between rutin and the Keap protein, enhancing Nrf2 nuclear activity. Conclusions: This showed that rutin can potentially enhance ADH7 and ALDH1A1 corneal signaling components, preventing corneal degeneration and mitigating ISO-induced myocardial infarction (MI) via Keap/Nrf2 expressions.

Aims: To identify the incidence, prevalence and risk factors of exposure keratopathy (EK) among critically ill patients. Design: Systematic review and meta‐analysis, in accordance with the PRISMA 2020 Statement. Methods: The Cochrane Library, PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China Knowledge Resource Integrated Database (CNKI), Chinese Biomedical Database (CBM), Weipu Database (VIP) and WanFang Database were systematically searched from inception to June 2022. Observational studies that reported EK among paediatric and adult critically ill patients were screened and included original articles based on the inclusion criteria. Two reviewers independently completed data extraction and quality assessments. Subgroup analysis investigated potential causes of heterogeneity. Results: Of the 4508 studies identified, 23 studies involving 3519 subjects were included. The pooled prevalence of EK was 34.0%, and the pooled incidence rate of EK was 23.0%. Risk factors associated with EK in critically ill patients included lagophthalmos, chemosis, eye blinks <5 times per minute, mechanical ventilation, sedation, lower Glasgow Coma Scale (GCS) score and higher Acute Physiology and Chronic Health Evaluation (APACHE) II score. Conclusion: This review shows that EK rates are high in critically ill patients and are influenced by multiple factors. Medical staff should pay more attention to EK in critically ill patients, conduct professional evaluations and implement targeted eye care protocols to reduce its occurrence. Implications for Practice: This study shows the frequency of and multiple risk factors for EK in critically ill patients, which provides evidence‐based guidance for nurses to evaluate the risk of EK in critically ill patients and take appropriate precautions to reduce the risk. Protocol Registration: The protocol was registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022346964). Patient or Public Contribution: No patient or public contribution. [ABSTRACT FROM AUTHOR]

PurposeTo determine whether a community health worker (CHW) program increases referrals to local eye care providers and ultimately reduces the incidence of corneal ulcers.DesignCluster-randomized trial performed from 2014 to 2017 in rural South India.MethodsThis was a community-based study that included all inhabitants of 42 rural South Indian communities. CHWs were trained to diagnose corneal abrasions and assist participants in seeking care at a local vision center. Given the nature of the intervention, the trial was not masked. The main outcome measure was incident corneal ulcer, defined as an active infiltrate or evidence of a new opacity, as assessed by means of penlight examination during an annual door-to-door census.ResultsTwenty-one study clusters were randomized to the CHW intervention and 21 to no intervention. Vision centers diagnosed 195 corneal abrasions from the intervention clusters during the 2-year study (rate, 223 per 100,000 person-years; 95% CI, 28-1743) and 62 from the control clusters (rate, 62 per 100,000 person-years; 95% CI, 8-496; incidence rate ratio, 3.57; 95% CI, 2.01-6.35; P < .001). The estimated incidence of corneal ulceration during the study period was 60 per 100,000 person-years (95% CI, 25-141) in the intervention group and 32 per 100,000 person-years (95% CI, 13-80) in the control group (incidence rate ratio, 1.86; 95% CI, 0.5-6.4; P = .32).ConclusionsA CHW program resulted in 3.5 times more referrals to local eye care providers for corneal abrasions, but no difference could be detected in the incidence of corneal ulceration. CHW programs provide a mechanism for increasing referrals to eye hospitals.Trial registrationClinicalTrials.gov ID: NCT02284698.

BackgroundCorneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.MethodsA cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.FindingsWe assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.InterpretationWe did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.FundingNational Eye Institute.

PurposeCorneal chemical injuries (CCI) obscure vision by opacifying the cornea; however, current treatments may not fully restore clarity. Here, we investigated potential-driven electrochemical treatment (P-ECT) to restore clarity after alkaline-based CCI in ex vivo rabbit corneas and examined collagen fiber orientation changes using second harmonic generation (SHG).MethodsNaOH was applied to the corneas of intact New Zealand white rabbit globes. P-ECT was performed on the opacified cornea while optical coherence tomography (OCT) imaging (∼35 frames per second) was simultaneously performed. SHG imaging evaluated collagen fiber structure before NaOH application and after P-ECT. Irrigation with water served as a control.ResultsP-ECT restored local optical clarity after NaOH exposure. OCT imaging shows both progression of NaOH injury and the restoration of clarity in real time. Analysis of SHG z-stack images show that collagen fibril orientation is similar between control, NaOH-damaged, and post-P-ECT corneas. NaOH-injured corneas flushed with water (15 minutes) show no restoration of clarity.ConclusionsP-ECT may be a means to correct alkaline CCI. Collagen fibril orientation does not change after NaOH exposure or P-ECT, suggesting that no irreversible matrix level fiber changes occur. Further studies are required to determine the mechanism for corneal clearing and to ascertain the optimal electrical dosimetry parameters and electrode designs.Translational relevanceOur findings suggest that P-ECT is a potentially effective, low-cost treatment for alkaline CCI.

Mononuclear phagocytes (MP) have central importance in innate immunity, inflammation, and fibrosis. Recruited MPs, such as macrophages, are plastic cells and can switch from an inflammatory to a restorative phenotype during the healing process. However, the role of the MPs in corneal wound healing is not completely understood. The purpose of this study is to characterize the kinetics of recruited MPs and evaluate the role of macrophage metalloelastase (MMP12) in the healing process, using an in vivo corneal chemical injury model. Unwounded and wounded corneas of wild-type (WT) and Mmp12-/- mice were collected at 1, 3, and 6 days after chemical injury and processed for flow cytometry analysis. Corneal MP phenotype significantly changed over time with recruited Ly6Chigh (proinflammatory) cells being most abundant at 1 day post-injury. Ly6Cint cells were highly expressed at 3 days post-injury and Ly6Cneg (patrolling) cells became the predominant cell type at 6 days post-injury. CD11c+ dendritic cells were abundant in corneas from Mmp12-/- mice at 6 days post-injury. These findings show the temporal phenotypic plasticity of recruited MPs and provide valuable insight into the role of the MPs in the corneal repair response, which may help guide the future development of MP-targeted therapies.

Introduction: Corneal Abrasion (CA) is the most common ophthalmic complication that occurs after General Anaesthesia (GA) in non ocular surgeries. GA results in reduced basal tear volume, loss of light reflex, and lack of pain perception, resulting in corneal drying. This makes the cornea susceptible to abrasion and keratitis. Research suggests that preventing corneal mechanical exposure and providing artificial tears can help mitigate these risks. Aim: The aim of this study was to assess the efficacy of eye taping with and without Hydroxypropyl Methylcellulose (HPMC) drops in preventing perioperative CA. Materials and Methods: This prospective comparative interventional study was conducted in the Department of Anaesthesia, Justice Hegde KS Charitable Hospital in Mangaluru, India, from June 2021 to November 2021. A total of 122 patients who underwent GA for non ocular surgeries lasting more than 45 minutes were grouped into group T or group D, depending on whether their eyes were only taped during GA (T) using hypoallergenic adhesive tape or had HPMC drops instilled in their eyes along with tape (D). Participants were evaluated 2 and 12 hours after the end of GA in the postanaesthesia care unit using a questionnaire to assess eye symptoms. Conjunctival hyperaemia and chemosis were evaluated using scoring systems. Other parameters noted included age, gender distribution, type, and duration of surgery. Statistical analysis using the chi-square test/likelihood ratio was performed to assess the association between the eye protection method used and postsurgical outcomes. Results: Out of the 122 patients who received either of the two eye protection methods under GA, 68 (55.7%) were females and 54 (44.3%) were males. A total of 85 (69.6%) were between the ages of 20-60 years, while 29 (23.8%) were above the age of 60 years. There was no statistically significant association found between the age or gender of the patients and the eye protection method used. No statistically significant difference was noted between the duration, type of surgeries, and the eye protection method used in this study. There was no statistical significance (p-value>0.05) noted with respect to the conjunctival hyperaemia and chemosis scoring in the two groups. However, 15 (24.6%) patients in group D were found to have adhesive lids two hours postsurgery. There was an association (p-value

Abstract Aims To identify the incidence, prevalence and risk factors of exposure keratopathy (EK) among critically ill patients. Design Systematic review and meta‐analysis, in accordance with the PRISMA 2020 Statement. Methods The Cochrane Library, PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China Knowledge Resource Integrated Database (CNKI), Chinese Biomedical Database (CBM), Weipu Database (VIP) and WanFang Database were systematically searched from inception to June 2022. Observational studies that reported EK among paediatric and adult critically ill patients were screened and included original articles based on the inclusion criteria. Two reviewers independently completed data extraction and quality assessments. Subgroup analysis investigated potential causes of heterogeneity. Results Of the 4508 studies identified, 23 studies involving 3519 subjects were included. The pooled prevalence of EK was 34.0%, and the pooled incidence rate of EK was 23.0%. Risk factors associated with EK in critically ill patients included lagophthalmos, chemosis, eye blinks

PurposeMesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow-derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits.MethodsHuman bone marrow-derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes.ResultsThe viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1% ± 2.1% and 94.9% ± 1.3%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5% ± 12.1% in epithelial cells co-cultured with MSCs compared with 40.8% ± 23.1% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100% corneal wound closure compared with 79.9% ± 5.5% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection.ConclusionsSubconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models.Translational relevanceThese results provide preclinical data to support a phase I clinical study.

With 1.5-2.0 million new cases annually worldwide, corneal injury represents a common cause of vision loss, often from irreversible scarring due to surface corneal defects. In this study, we assessed the use of hepatocyte growth factor (HGF) loaded into an in situ photopolymerizable transparent gelatin-based hydrogel for the management of corneal defects. In vitro release kinetics showed that, in regard to the total amount of HGF released over a month, 55 ± 11% was released during the first 24 h, followed by a slow release profile for up to one month. The effect of HGF was assessed using an ex vivo model of pig corneal defect. After three days of organ culture, epithelial defects were found to be completely healed for 89% of the corneas treated with HGF, compared to only 11% of the corneas that had fully re-epithelialized when treated with the hydrogel without HGF. The thickness of the epithelial layer was found to be significantly higher for the HGF-treated group compared to the group treated with hydrogel without HGF (p = 0.0012). Finally, histological and immunostaining assessments demonstrated a better stratification and adhesion of the epithelial layer in the presence of HGF. These results suggest that the HGF-loaded hydrogel system represents a promising solution for the treatment of persistent corneal defects at risk of scarring.

The transformation of quiescent keratocytes to activated fibroblasts and myofibroblasts (KFM transformation) largely depends on transforming growth factor beta (TGFβ) signaling. Initiation of the TGFβ signaling cascade results from binding of TGFβ to the labile type I TGFβ receptor (TGFβRI), which is stabilized by the 90 kDa heat shock protein (Hsp90). Since myofibroblast persistence within the corneal stroma can result in stromal haze and corneal fibrosis in patients undergoing keratorefractive therapy, modulation of TGFβ signaling through Hsp90 inhibition would represent a novel approach to prevent myofibroblast persistence. In vitro, rabbit corneal fibroblasts (RCFs) or stratified immortalized human corneal epithelial cells (hTCEpi) were treated with a Hsp90 inhibitor (17AAG) in the presence/absence of TGFβ1. RCFs were cultured either on tissue culture plastic, anisotropically patterned substrates, and hydrogels of varying stiffness. Cellular responses to both cytoactive and variable substrates were assessed by morphologic changes to the cells, and alterations in expression patterns of key keratocyte and myofibroblast proteins using PCR, Western blotting and immunocytochemistry. Transepithelial electrical resistance (TEER) measurements were performed to establish epithelial barrier integrity. In vivo, the corneas of New Zealand White rabbits were wounded by phototherapeutic keratectomy (PTK) and treated with 17AAG (3× or 6× daily) either immediately or 7 days after wounding for 28 days. Rabbits underwent clinical ophthalmic examinations, SPOTS scoring and advanced imaging on days 0, 1, 3, 7, 10, 14, 21 and 28. On day 28, rabbits were euthanized and histopathology/immunohistochemistry was performed. In vitro data demonstrated that 17AAG inhibited KFM transformation with the de-differentiation of spindle shaped myofibroblasts to dendritic keratocyte-like cells accompanied by significant upregulation of corneal crystallins and suppression of myofibroblast markers regardless of TGFβ1 treatment. RCFs cultured on soft hydrogels or patterned substrates exhibited elevated expression of α-smooth muscle actin (αSMA) in the presence of 17AAG. Treatment of hTCEpi cells disrupted zonula occludens 1 (ZO-1) adherens junction formation. In vivo, there were no differences detected in nearly all clinical parameters assessed between treatment groups. However, rabbits treated with 17AAG developed greater stromal haze formation compared with controls, irrespective of frequency of administration. Lastly, there was increased αSMA positive myofibroblasts in the stroma of 17AAG treated animals when compared with controls. Hsp90 inhibition promoted reversion of the myofibroblast to keratocyte phenotype, although this only occurred on rigid substrates. By contrast, in vivo Hsp90 inhibition was detrimental to corneal wound healing likely due to impairment in corneal epithelial closure and barrier function restoration. Collectively, our data demonstrated a strong interplay in vitro between biophysical cues and soluble signaling molecules in determining corneal stromal cell phenotype.

Introduction: Corneal Abrasion (CA) is the most common ophthalmic complication that occurs after General Anaesthesia (GA) in non ocular surgeries. GA results in reduced basal tear volume, loss of light reflex, and lack of pain perception, resulting in corneal drying. This makes the cornea susceptible to abrasion and keratitis. Research suggests that preventing corneal mechanical exposure and providing artificial tears can help mitigate these risks. Aim: The aim of this study was to assess the efficacy of eye taping with and without Hydroxypropyl Methylcellulose (HPMC) drops in preventing perioperative CA. Materials and Methods: This prospective comparative interventional study was conducted in the Department of Anaesthesia, Justice Hegde KS Charitable Hospital in Mangaluru, India, from June 2021 to November 2021. A total of 122 patients who underwent GA for non ocular surgeries lasting more than 45 minutes were grouped into group T or group D, depending on whether their eyes were only taped during GA (T) using hypoallergenic adhesive tape or had HPMC drops instilled in their eyes along with tape (D). Participants were evaluated 2 and 12 hours after the end of GA in the postanaesthesia care unit using a questionnaire to assess eye symptoms. Conjunctival hyperaemia and chemosis were evaluated using scoring systems. Other parameters noted included age, gender distribution, type, and duration of surgery. Statistical analysis using the chi-square test/likelihood ratio was performed to assess the association between the eye protection method used and postsurgical outcomes. Results: Out of the 122 patients who received either of the two eye protection methods under GA, 68 (55.7%) were females and 54 (44.3%) were males. A total of 85 (69.6%) were between the ages of 20-60 years, while 29 (23.8%) were above the age of 60 years. There was no statistically significant association found between the age or gender of the patients and the eye protection method used. No statistically significant difference was noted between the duration, type of surgeries, and the eye protection method used in this study. There was no statistical significance (p-value >0.05) noted with respect to the conjunctival hyperaemia and chemosis scoring in the two groups. However, 15 (24.6%) patients in group D were found to have adhesive lids two hours postsurgery. There was an association (p-value <0.05) between the occurrence of adhesive lids at two hours postsurgery and the eye protection method used. Conclusion: Eye protection is mandatory in all non ophthalmic cases under GA. Both eyelid taping alone and eyelid taping with HPMC drops are equally effective in preventing perioperative ocular injury. [ABSTRACT FROM AUTHOR]

Recently, stable gastric pentadecapeptide BPC 157 therapy by activation of collateral pathways counteracted various occlusion/occlusion-like syndromes, vascular, and multiorgan failure, and blood pressure disturbances in rats with permanent major vessel occlusion and similar procedures disabling endothelium function. Thereby, we revealed BPC 157 cytoprotective therapy with strong vascular rescuing capabilities in glaucoma therapy. With these capabilities, BPC 157 therapy can recover glaucomatous rats, normalize intraocular pressure, maintain retinal integrity, recover pupil function, recover retinal ischemia, and corneal injuries (i.e., maintained transparency after complete corneal abrasion, corneal ulceration, and counteracted dry eye after lacrimal gland removal or corneal insensitivity). The most important point is that in glaucomatous rats (three of four episcleral veins cauterized) with high intraocular pressure, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, nor- mal retinal and choroidal blood vessel presentation, and normal optic nerve presentation. The one episcleral vein rapidly upgraded to accomplish all functions in glaucomatous rats may correspond with occlusion/occlusion-like syndromes of the activated rescuing collateral pathway (azygos vein direct blood flow delivery). Normalized intraocular pressure in glaucomatous rats corresponded to the counteracted intra-cranial (superior sagittal sinus), portal, and caval hypertension, and aortal hypotension in occlusion/occlusion-like syndromes, were all attenuated/eliminated by BPC 157 therapy. Furthermore, given in other eye disturbances (i.e., retinal ischemia), BPC 157 instantly breaks a noxious chain of events, both at an early stage and an already advanced stage. Thus, we further advocate BPC 157 as a therapeutic agent in ocular disease. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Medical shops in Nepal are a main point of treatment for many diseases including ophthalmic conditions. We sought to evaluate pharmaceutical shop worker knowledge of corneal ulcers and abrasions. A pharmaceutical shop worker from each of 117 different pharmacies surrounding Bharatpur, Nepal, was presented four different eye photographs (i.e., corneal ulcer, corneal abrasion, conjunctivitis, and a normal eye) and asked about diagnosis and management. Of 117 participants, 86 (74%) identified conjunctivitis correctly but few were able to identify corneal abrasion (50/117; 43%) or corneal infection (47/117; 40%). When presented with an illustrated diagram of potential medications to dispense, 15 (13%) participants chose a topical medication containing a corticosteroid for the corneal abrasion and 25 (21%) did so for the corneal ulcer. The appropriate use of corticosteroids for external eye infections is an important topic for additional training, given the potential for these medications to worsen corneal abrasions and ulcers.

Purpose: Dry eye disorders are a major health care burden. We previously reported the identification of N-methyl-N-phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine [cystic fibrosis transmembrane conductance regulator (CFTR)act-K267], which activated human wild-type CFTR chloride conductance with EC50 ∼ 30 nM. Here, we report in vivo evidence for CFTRact-K267 efficacy in an experimental mouse model of dry eye using a human compatible ophthalmic vehicle. Methods: CFTR activation in mice in vivo was demonstrated by ocular surface potential difference (OSPD) measurements. Ocular surface pharmacodynamics was measured in tear fluid samples obtained at different times after topical administration of CFTRact-K267. Dry eye was produced by lacrimal duct cautery (LDC) and corneal epithelial injury and was assessed by Lissamine green (LG) staining. Results: OSPD measurements demonstrated a hyperpolarization of -8.6 ± 3 mV (standard error of the mean, 5 mice) in response to CFTRact-K267 exposure in low chloride solution that was reversed by a CFTR inhibitor. Following single-dose topical administration of 2 nmol CFTRact-K267, tear fluid CFTRact-K267 concentration was >500 nM for more than 6 h. Following LDC, corneal surface epithelial injury, as assessed by LG staining, was substantially reversed in 10 of 12 eyes receiving 2 nmol CFTRact-K267 3 times daily starting on day 2, when marked epithelial injury had already occurred. Improvement was seen in 3 of 12 vehicle-treated eyes. Conclusion: These studies provide in vivo evidence in mice for the efficacy of a topical, human use compatible CFTRact-K267 formulation in stimulating chloride secretion and reversing corneal epithelial injury in dry eye.

Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.

PurposeCorneal endothelial cell regeneration varies by species, with nonhuman primates (NHPs) and rabbits displaying low and high proliferative capacities, respectively. Recent studies report that topical application of rho-associated kinase (ROCK) inhibitors accelerates corneal endothelial wound healing in animal models and human patients with endothelial dysfunction. This study determines the regenerative capacity of canine corneal endothelial cells in vivo and their response to a topical ROCK inhibitor, Y27632, after transcorneal freezing.MethodsRight eyes of 6 beagles underwent transcorneal freezing; 10 mM ROCK inhibitor Y27632 or vehicle control was applied topically to both eyes at least 4 times daily for 56 days. Endothelial cell density was evaluated by in vivo confocal microscopy, and corneal thickness was measured by Fourier-domain optical coherence tomography (FD-OCT) and ultrasound pachymetry.ResultsTranscorneal freezing induced severe central corneal edema in dogs, with restoration of transparency occurring within 4 weeks. Y27632 significantly decreased corneal thickness by FD-OCT and ultrasound pachymetry in the acute phase and significantly increased endothelial cell density at days 28 and 42 post-cryoinjury, suggesting faster restoration of endothelial cell recovery.ConclusionsCanine corneal endothelial function recovers at a similar rate as NHPs but more slowly than rabbits after cryoinjury. Faster corneal endothelial wound healing was observed by in vivo confocal microscopy and FD-OCT in dogs treated with Y27632 versus vehicle controls. Thus, a canine cryoinjury model may be a useful alternative to NHPs in detecting a response to therapies directed at endothelial regeneration.

Research with animal models of Pseudomonas aeruginosa keratitis has shown that use of a topical corticosteroid alone against an established infection can significantly increase the number of colonizing bacteria or worsen clinical disease. Moreover, retrospective analysis has suggested that corticosteroid use in humans is associated with an increased risk of keratitis in eyes with pre-existing disease. Thus, while corticosteroids are often used to reduce ocular inflammation in the absence of infection, the risk of opportunistic infection remains a concern. However, the effect of corticosteroids on the intrinsic barrier function of uninfected corneas is unknown. Here, we tested if short-term topical corticosteroid treatment of an uninfected murine cornea would increase susceptibility to P. aeruginosa colonization or infection after epithelial injury. Topical prednisolone acetate (1%) was administered to one eye of C57BL/6 mice three times a day for 3 days; control eyes were treated with sterile PBS. Prior to inoculation with a cytotoxic P. aeruginosa corneal isolate strain 6206, corneas were subject to superficial-injury by tissue paper blotting, or scratch-injured followed by 12 h of healing. Previously we have shown that blotting renders mouse corneas susceptible to P. aeruginosa adhesion, but not infection, while 12 h healing reduces susceptibility to infection after scratching. Corneas were evaluated at 48 h for bacterial colonization and microbial keratitis (MK). To monitor impact on wound healing, corneal integrity was examined by fluorescein staining immediately after scarification and after 12 h healing. For both the tissue paper blotting and scratch-injury models, there was no significant difference in P. aeruginosa colonization at 48 h between corticosteroid-pretreated eyes and controls. With the blotting model, one case of MK was observed in a control (PBS-pretreated) cornea; none in corticosteroid-pretreated corneas. With the 12 h healing model, MK occurred in 6 of 17 corticosteroid-pretreated eyes versus 2 of 17 controls, a difference not statistically significant. Corticosteroid-pretreated eyes showed greater fluorescein staining 12 h after scarification injury, but this did not coincide with increased colonization or MK. Together, these data show that short-term topical corticosteroid therapy on an uninfected murine cornea does not necessarily enhance its susceptibility to P. aeruginosa colonization or infection after injury, even when it induces fluorescein staining.

Objective: To identify the incidence of corneal injury in patients hospitalized in the Intensive Care Unit and associate the main risk factors with the occurrence of corneal injury in patients hospitalized in the Intensive Care Unit. Methods: This is a prospective cohort study, in which 40 patients admitted to the Intensive Care Unit were included, from December 2019 to February 2020. Data analysis was descriptive and inferential, using statistical tests and effect measures. Results: The sample consisted of 40 patients. Corneal injury developed in 20% (n=8) of participants and is significantly associated with the following factors: length of stay from two to seven days (70%; n=28), Glasgow < 13 (50%; n= 7), use of sedatives (33.3%; n=8), use of bronchodilators (36.8%; n=7), use of tracheostomy (TCT) (50%; n=6) and invasive mechanical ventilation (IMV) (58.3%; n=7), blinking less than five times (61.5%; n=8), partial eyelid closure (38.9%; n=7), hyperemia (34.8%; n=8), eyelid edema (41.2%; n=7), conjunctival edema (50%; n=7) and dryness (50%; n=5). Conclusion: Patients admitted to the Intensive Care Unit are exposed to several risk factors for developing corneal injury, with emphasis on mechanical ventilation and Glasgow less than 13, requiring the implementation of prophylactic measures for corneal injury, through the control and mitigation of risk factors and patient exposure. [ABSTRACT FROM AUTHOR]

This case series reviewed medical records of eight patients who underwent autologous simple limbal epithelial transplantation (SLET) for total limbal stem cell deficiency (LSCD) secondary to chemical injury (n=5), thermal injury (n=2), or autoimmune disorder (n=1) between 2016 and 2019 at the Caritas Medical Centre. The mean time from injury to SLET was 67 months (range, 3 weeks to 30 years). The mean time to re-epithelialization was 20 (range, 13-42) days. The follow-up duration ranged from 1 to 6 years. At the 1-year follow-up, the success rate of SLET was 37.5%, and visual gain among the three successful cases ranged from <1 line to >6 lines. Patients with Dua grade V or VI chemical injury and patients with systemic causes of LSCD had poorer prognosis, as did those with cicatricial lid changes, anterior segment necrosis, glaucoma, sterile cornea ulceration, superimposed infections, or tobacco usage. SLET should be a reconstructive procedure for chronic LSCD rather than for acute injury or inflammation. [ABSTRACT FROM AUTHOR]

Background: Patients in Intensive Care Units (ICUs) are at risk of eye disorders such as Exposure keratopathy (EK) due to impaired blinking and incomplete eye closure. The aim of this study was to assess the effects of passive blinking exercise (PBE) on EK among patients in ICUs. Materials and Methods: This single-blind, randomized, clinical trial was conducted in 2017. The study participants included 51 patients purposively recruited from the three ICUs of Valiasr Teaching Hospital, Arak, Iran. Through coin tossing, one eye of each participant was randomly allocated to the intervention group and the other to the control group. The eye in the control group received routine eye care, whereas the eye in the intervention group received routine eye care and PBE for a week. EK prevalence and severity were assessed daily for 7 consecutive days using fluorescein eye staining papers and an ophthalmoscope with a cobalt blue filter. Results: The study groups did not significantly differ from each other in terms of the baseline prevalence and severity of EK. After the intervention, the prevalence of EK (χ2 = 13.44, df = 1, p < 0.001) and the prevalence of grade II EK (χ2 = 8.33, df = 1, p = 0.003) in the intervention group were significantly lower than the control group. Conclusions: PBE is effective in significantly reducing EK prevalence and severity among patients in ICUs. Therefore, critical care nurses are recommended to use PBE for EK prevention and management.

IntroductionCorneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.Methods and analysisThe Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.Ethics and disseminationThe University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberNCT01969786; Pre-results.

The outermost layer of the eye, the cornea, is renewed continuously throughout life. Stem cells of the corneal epithelium reside in the limbus at the corneal periphery and ensure homeostasis of the central epithelium. However, in young mice, homeostasis relies on cells located in the basal layer of the central corneal epithelium. Here, we first studied corneal growth during the transition from newborn to adult and assessed Keratin 19 (Krt19) expression as a hallmark of corneal maturation. Next, we set out to identify a novel marker of murine corneal epithelial progenitor cells before, during and after maturation, and we found that Bmi1 is expressed in the basal epithelium of the central cornea and limbus. Furthermore, we demonstrated that Bmi1+ cells participated in tissue replenishment in the central cornea. These Bmi1+ cells did not maintain homeostasis of the cornea for more than 3 months, reflecting their status as progenitor rather than stem cells. Finally, after injury, Bmi1+ cells fueled homeostatic maintenance, whereas wound closure occurred via epithelial reorganization. Stem Cells 2018;36:562-573.

Hepatocyte growth factor (HGF) is a glycoprotein produced by mesenchymal cells and operates as a key molecule for tissue generation and renewal. During corneal injury, HGF is primarily secreted by stromal fibroblasts and promotes epithelial wound healing in a paracrine manner. While this mesenchymal-epithelial interaction is well characterized in various organs and the cornea, the role of HGF in corneal stromal and endothelial wound healing is understudied. In addition, HGF has been shown to play an anti-fibrotic role by inhibiting myofibroblast generation and subsequent production of a disorganized extracellular matrix and tissue fibrosis. Therefore, HGF represents a potential therapeutic tool in numerous organs in which myofibroblasts are responsible for tissue scarring. Corneal fibrosis can be a devastating sequela of injury and can result in corneal opacification and retrocorneal membrane formation leading to severe vision loss. In this article, we concisely review the available literature regarding the role of HGF in corneal wound healing. We highlight the influence of HGF on cellular behaviors in each corneal layer. Additionally, we suggest the possibility that HGF may represent a therapeutic tool for interrupting dysregulated corneal repair processes to improve patient outcomes.

PurposeNitrogen mustard (NM), which simulates the effects of sulfur mustard (SM), is a potent vesicant known to cause irreversible corneal damage. This study investigates the mechanisms by which NM induces corneal damage by examining the impact of NM exposure on the morphology and lipidome of the cornea.MethodsIntact ex vivo rabbit eyes were placed in serum-free DMEM organ culture. NM (0, 1, 2.5, 5 or 10 mg/ml) was applied to the central cornea for 5, 10 or 15 min using a 5 mm filter disk and subsequently rinsed with DMEM. Corneas were then cultured for 3, 24, or 48 h before being fixed for morphological analysis or for 24 h before being snap frozen for lipidomic analysis.ResultsNo morphological changes were detected 3 h after NM exposure. Twenty-four h after exposure, 1 mg/ml NM caused erosion of the corneal epithelium, but no damage to the underlying stroma. Damage caused by 2.5 mg/ml NM extended almost two thirds through the corneal stroma, while 5 mg/ml completely penetrated the corneal stroma. An altered lipid profile occurred 24 h after corneas were exposed to NM. Specific sphingomyelins, ceramides, and diacylglycerols were increased up to 9-, 60- and 10-fold, respectively.ConclusionsNM induces concentration- and exposure time-dependent damage to the cornea that increases in severity over time. Alterations in the sphingomyelin-ceramide pathway may contribute to the damaging effects of NM exposure.

Introduction: Corneal foreign bodies account for nearly one-third of all eye injuries and are a common emergency in ophthalmology. While many cases are straightforward, involving clear diagnosis and treatment, some present significant challenges due to the complexity of the foreign body involved., Observation: A 20-year-old male presented with discomfort in his right eye following an accident while cutting a tree without wearing protective eyewear. Examination using slit-lamp biomicroscopy revealed a reed foreign body embedded in the cornea. Anterior Segment Optical Coherence Tomography (AS-OCT) provided detailed images, showing the foreign body embedded 300 µm beneath the corneal epithelium but not affecting deeper layers. The foreign body was surgically removed under topical anesthesia, followed by thorough cleansing and suturing of the wound., Conclusion: AS-OCT is invaluable in the diagnosis and management of complex corneal foreign bodies, enabling precise treatment planning and successful outcomes, as demonstrated in this case.