Oriented cellulose hydrogel: Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers.

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-ß and PDGF-ß inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

An Antibiotic Nanobomb Constructed from pH-Responsive Chemical Bonds in Metal-Phenolic Network Nanoparticles for Biofilm Eradication and Corneal Ulcer Healing.

In the treatment of refractory corneal ulcers caused by Pseudomonas aeruginosa, antibacterial drugs delivery faces the drawbacks of low permeability and short ocular surface retention time. Hence, novel positively-charged modular nanoparticles (NPs) are developed to load tobramycin (TOB) through a one-step self-assembly method based on metal-phenolic network and Schiff base reaction using 3,4,5-trihydroxybenzaldehyde (THBA), ε-poly-ʟ-lysine (EPL), and Cu2+ as matrix components. In vitro antibacterial test demonstrates that THBA-Cu-TOB NPs exhibit efficient instantaneous sterilization owing to the rapid pH responsiveness to bacterial infections. Notably, only 2.6 µg mL-1 TOP is needed to eradicate P. aeruginosa biofilm in the nano-formed THBA-Cu-TOB owing to the greatly enhanced penetration, which is only 1.6% the concentration of free TOB (160 µg mL-1). In animal experiments, THBA-Cu-TOB NPs show significant advantages in ocular surface retention, corneal permeability, rapid sterilization, and inflammation elimination. Based on molecular biology analysis, the toll-like receptor 4 and nuclear factor kappa B signaling pathways are greatly downregulated as well as the reduction of inflammatory cytokines secretions. Such a simple and modular strategy in constructing nano-drug delivery platform offers a new idea for toxicity reduction, physiological barrier penetration, and intelligent drug delivery.

A comparison of antimicrobial regimen outcomes and antibiogram development in microbial keratitis: a prospective cohort study in Alexandria, Egypt.

INTRODUCTION: Antimicrobial resistance in microbial keratitis has not been previously explored in Alexandria. We aim to recommend effective therapies through identification of etiological agents, determination of antimicrobial susceptibilities, and comparing outcomes of empiric topical antimicrobials. METHODS: In this 2022 prospective cohort conducted in Alexandria Main University Hospital cornea clinic, antimicrobial susceptibilities of isolated microorganisms from corneal scrapings were detected and antibiograms were developed. Bacterial (BK), fungal (FK), or mixed fungal/bacterial keratitis (MFBK) patients on empiric regimens were compared for ulcer healing, time-to-epithelialization, best-corrected visual acuity, interventions, and complications. RESULTS: The prevalent microorganisms in 93 positive-cultures were coagulase-negative staphylococci (CoNS, 30.1%), Pseudomonas aeruginosa (14%), and Aspergillus spp. (12.9%). CoNS were susceptible to vancomycin (VAN, 100%) and moxifloxacin (MOX, 90.9%). Gram-negative bacteria showed more susceptibility to gatifloxacin (90.9%) than MOX (57.1%), and to gentamicin (GEN, 44.4%) than ceftazidime (CAZ, 11.8%). Methicillin-resistance reached 23.9% among Gram-positive bacteria. Fungi exhibited 10% resistance to voriconazole (VRC). Percentages of healed ulcers in 49 BK patients using GEN + VAN, CAZ + VAN and MOX were 85.7%, 44.4%, and 64.5%, respectively (p = 0.259). Their median time-to-epithelialization reached 21, 30, and 30 days, respectively (log-rank p = 0.020). In 51 FK patients, more ulcers (88.9%) healed with natamycin (NT) + VRC combination compared to VRC (39.1%) or NT (52.6%) (p = 0.036). Their median time-to-epithelialization was 65, 60, and 22 days, respectively (log-rank p < 0.001). The VRC group required more interventions (60.9%) than NT + VRC-treated group (11.1%) (p = 0.018). In 23 MFBK patients, none healed using NT + CAZ + VAN, while 50% healed using VRC + CAZ + VAN (p = 0.052). Regimens had comparable visual outcomes and complications. CONCLUSION: Based on the higher detected susceptibility, we recommend empiric MOX in suspected Gram-positive BK, gatifloxacin in Gram-negative BK, and GEN + VAN in severe BK. Due to better outcomes, we recommend NT + VRC in severe FK. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05655689. Registered December 19, 2022- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05655689?cond=NCT05655689.&draw=2&rank=1.

Decreased levels of interleukin-6 level in tears and clinical changes in subjects with moderate-to-severe infection corneal ulcers treated with platelet-rich fibrin lysate eye drops.

PURPOSE: To assess the change of interleukin-6 (IL-6) levels in tears and ocular clinical parameters in corneal ulcer patients with moderate-to-severe infection after adjunctive therapy with platelet-rich fibrin (PRF) lysate-eyedrops compared with autologous serum eyedrops. MATERIALS AND METHODS: This study was a randomized double-blind controlled trial, which compared two groups of patients at Dr. Sardjito Hospital, Yogyakarta. A total of 42 patients (42 eyes) were divided into the control group (21 patients) and the intervention group (21 patients). All patients received antibacterial/antifungal therapy based on the etiology, and an adjunctive eyedrop therapy: autologous serum eyedrops for the control group and PRF lysate eyedrops for the intervention group. The IL-6 levels and clinical changes in patients, such as the area of corneal defects, pericorneal injection, and the level of blepharospasm were measured at the baseline, day 6, and day 13 after starting the treatment. RESULTS: Compared to baseline, the mean IL-6 level in day 13 decreased by 426.6 ± 665.4 pg/ml (P = 0.005) and 1283.7 ± 1569.1 pg/ml (P = 0.079) in the intervention and control groups, respectively. However, the difference between the two groups was not statistically significant (P = 0.164). In term of corneal defect area, there was a significant decrease at day 6 and day 13 in both groups but there was no statistically significant difference between the two groups in all time points. Similarly, the proportion of blepharospasm and pericorneal injection severity appeared to improve especially on day 13 in both groups but were not statistically different between the two. CONCLUSION: There was a statistically significant decrease in IL-6 levels in the tears in patient using PRF lysate, but there was no significant difference when compared to those using autologous serum. The difference in defect area, degree of blepharospasm, and pericorneal injection was not statistically significant between the two treatment options.

The effect of social determinants of health on severity of microbial keratitis presentation at a tertiary eye care hospital in Southern India.

Purpose: Understanding the association between social determinants of health (SDoHs) and microbial keratitis (MK) can inform underlying risk for patients and identify risk factors associated with worse disease, such as presenting visual acuity (VA) and time to initial presentation. Methods: This was a cross-sectional study was conducted with patients presenting with MK to the cornea clinic at a tertiary care hospital in Madurai, India. Patient demographics, SDoH survey responses, geographic pollution, and clinical features at presentation were collected. Descriptive statistics, univariate analysis, multi-variable linear regression models, and Poisson regression models were utilized. Results: There were 51 patients evaluated. The mean age was 51.2 years (SD = 13.3); 33.3% were female and 55% did not visit a vision center (VC) prior to presenting to the clinic. The median presenting logarithm of the minimum angle of resolution (logMAR) VA was 1.1 [Snellen 20/240, inter-quartile range (IQR) = 20/80 to 20/4000]. The median time to presentation was 7 days (IQR = 4.5 to 10). The average particulate matter 2.5 (PM2.5) concentration, a measure of air pollution, for the districts from which the patients traveled was 24.3 µg/m3 (SD = 1.6). Age- and sex-adjusted linear regression and Poisson regression results showed that higher levels of PM2.5 were associated with 0.28 worse presenting logMAR VA (Snellen 2.8 lines, P = 0.002). Patients who did not visit a VC had a 100% longer time to presentation compared to those who did (incidence rate ratio = 2.0, 95% confidence interval = 1.3-3.0, P = 0.001). Conclusion: Patient SDoH and environmental exposures can impact MK presentation. Understanding SDoH is important for public health and policy implications to mitigate eye health disparities in India.

Effects of platelet-rich plasma on corneal re-epithelization and metalloproteinase expression in the cornea of sheep with experimentally-induced infectious keratoconjunctivitis.

Background and Aim: Infectious bovine keratoconjunctivitis is the most crucial ophthalmic disease among ruminants worldwide. Moraxella is the bacteria generally associated with this disease and leads to keratitis, conjunctivitis, corneal ulcers, or blindness. Platelet-rich plasma (PRP) effects in corneal ulcers and different ocular superficial diseases in animals and humans are beneficial and enhance rapid healing and improvement, but the effects in infectious keratoconjunctivitis in ruminants are uncertain. This study aimed to examine the effect of PRP on re-epithelization, corneal tissue, clinical signs, and matrix metalloproteinase (MMP) expression in sheep with infectious keratoconjunctivitis. Materials and Methods: Eighteen sheep were divided into three groups and subjected to a disease-induction experiment. Group 1 (G1) was administered 1.0 mL PRP subconjunctivally, Group 2 (G2) was administered 1.0 mL PRP subconjunctivally and 50 µL gentamicin drops, and the control group (CG) was administered 50 µL saline solution topically every 12 h. Clinical ophthalmologic examination, fluorescein staining, and photography were carried out. Ulcerated areas were measured employing J-Image software. Five and eleven days following the procedure, half of the animals from each group were euthanized, and their corneas were evaluated by histopathology and zymography. Results: Control Group and G2 epithelialized more rapidly. The CG exhibited fewer clinical signs of ocular disease. In histopathological analysis, in G2, alterations were observed only in the epithelium. The CG and G1 exhibited alterations in the epithelium, stroma, and Descemet's membrane. In zymography, a decline in MMP-2 expression in the animals treated with PRP was detected. Matrix metalloproteinase-9 was significantly expressed in the animals treated with PRP monotherapy, whereas PRP + gentamicin and CG caused a decrease. Conclusion: Platelet-rich plasma alone did not demonstrate any beneficial effect on re-epithelialization, a decline in clinical signs, tissue alterations, and expression of metalloproteinases. Platelet-rich plasma combined with gentamicin was capable of suppressing MMPs, primarily MMP-9, but do not display positive effects in re-epithelization, reduction of clinical signs, or tissue effects. These outcomes are similar to those discovered in untreated animals, so the use of PRP in patients with infectious keratoconjunctivitis does not offer greater benefits in sheep. Additional research is required to validate the results of PRP use in natural disease presentation.

A scoping review of patients' barriers to eye care for glaucoma and keratitis.

In this scoping review, we examine underlying causes of loss to follow-up for chronic (glaucoma) and acute (corneal ulcers) eye conditions using the Penchansky and Thomas access to care framework. We explore barriers by World Health Organization income levels and by studying geographical location. We identified 6,363 abstracts, with 75 articles retrieved and 16 meeting inclusion criteria. One article discussed barriers to follow-up care for people with corneal ulcers, and the other 15 were for people with glaucoma. The most frequent barriers to care were affordability, awareness, and accessibility. The international studies had a greater percentage of studies report acceptability as a barrier to loss to follow-up. Countries with universal healthcare included affordability as a loss to follow-up barrier, emphasizing that cost goes beyond the ability to pay for direct treatment costs. Understanding and addressing barriers to follow-up care can aid the goal of continued care and decrease the risk of poor outcomes and vision loss.

Resultados de los pacientes operados de queratoplastia terapéutica en la provincia de Matanzas

Introducción: la queratoplastia terapéutica se define como un procedimiento cuyo propósito es contribuir a erradicar o reducir la infección cuando la terapia médica máxima no es eficaz para lograr este fin. Objetivo: evaluar la evolución y resultados de los pacientes operados de queratoplastia terapéutica. Materiales y métodos: se realizó un estudio descriptivo transversal en un universo de 15 pacientes con diagnóstico de úlcera grave corneal. Dichos pacientes fueron operados de queratoplastia terapéutica en el Servicio de Córnea del Hospital Universitario Comandante Faustino Pérez Hernández, de la provincia de Matanzas, entre abril de 2017 y febrero de 2020, y dieron su consentimiento informado para participar en la investigación. Resultados: predominó el sexo masculino, con un 53,3 % y una media de edad de 58,8 años. Como factores predisponentes, prevaleció el antecedente de trauma en el 33,3 %, seguido del uso de lentes de contacto y la diabetes mellitus como enfermedad sistémica asociada. Las úlceras de etiología micótica predominaron en el 26,6 % de los casos; la perforación corneal y el descemetocele se presentaron en el 40 % y 26,6 % de los pacientes respectivamente. Durante el primer mes, las complicaciones postoperatorias más frecuentes fueron la recidiva de la sepsis y la necrosis del injerto. Por su parte, la opacidad y vascularización corneal fueron las secuelas más frecuentes. Conclusiones: la demora en iniciar el protocolo de tratamiento adecuado provoca cuadros severos de la enfermedad, realizando queratoplastia "en caliente" en córneas perforadas o con necrosis, que devienen complicaciones postoperatorias y secuelas no alentadoras para los pacientes.

Introduction: therapeutic keratoplasty is defined as a procedure whose purpose is to help eradicate or reduce the infection when maximum medical therapy is not efficacious to achieve this end. Objective: to evaluate the evolution and results of the patients operated on therapeutic keratoplasty. Materials and methods: a cross-sectional, descriptive study was carried out in a universe of 15 patients with a diagnosis of severe corneal ulcer. The patients underwent therapeutic keratoplasty surgeries in the Cornea Service of the Clinical Surgical University Hospital Comandante Faustino Perez Hernandez, in the province of Matanzas, between April 2017 and May 2020, and gave their informed consent to participate in the research. Results: male gender predominated, with 53.3% and a mean age of 58.8 years. As predisposing factors, trauma antecedent predominated in 33.3%, followed by the use of contact lenses and diabetes mellitus as associated systemic disease. Ulcers of mycotic etiology predominated in 26.6% of the cases; corneal perforation and descemetoceles occurred in 40% and 26.6% of the cases respectively. During the first month, the most frequent postsurgery complications were recidival sepsis and graft necrosis. On the other hand, corneal opacity and vascularization were the most frequent sequels. Conclusions: the delay in initiating the adequated protocol treatment causes severe symptoms of the disease that lead to "in hot" keratoplasty in perforated or necrosed corneas, causing postsurgery complications and non-encouraging sequels for patients.

Advances and prospects of platelet-rich plasma therapy in veterinary ophthalmology.

In the recent decades, there has been a significant uptick on the use of platelet-rich plasma (PRP) as a better alternative for ophthalmologic therapies in pathologies, primarily of the ocular surface. PRP is a class of liquid platelet concentrate containing a supra-physiological concentration of platelets in a relatively small amount of plasma. Its potential to heal various tissues has piqued interest in its therapeutic application as a biomaterial in regenerative medicine. It is currently a popular therapeutic agent in plastic surgery, cardiothoracic surgery, reconstructive surgery, and even oral and maxillofacial surgery. Based on the data from in vitro and in vivo studies, it can be concluded that PRP possesses adequate therapeutic potential in ocular pathologies, especially those involving cornea. In addition, the high concentrations of growth factors (TGF-ß, VEGF, EGF) present in the PRP accelerate the healing of the corneal epithelium. PRP has great therapeutic prospects in veterinary ophthalmology as a regenerative therapeutic modality. However, several variables are yet to be defined and standardized that can directly affect the efficacy of PRP application in different ophthalmic conditions. There is a shortage of research on the use of PRP in ocular surface defects compared to the number of studies and reports on the use of autologous and allogeneic serum eye drops. Therefore, a data-driven approach is required to generate consensus/guidelines for the preparation, characterization, and therapeutic use of PRP in veterinary ophthalmology. This review aims to inform readers of the latest research on PRP, including its preparation methods, physiological and biochemical properties, clinical applications in veterinary ophthalmology, and their safety and efficacy.

Urgent unmet needs in the care of bacterial keratitis: An evidence-based synthesis.

Bacterial corneal infections, or bacterial keratitis (BK), are ophthalmic emergencies that frequently lead to irreversible visual impairment. Though increasingly recognized as a major cause of global blindness, modern paradigms of evidence-based care in BK have remained at a diagnostic and therapeutic impasse for over half a century. Current standards of management - based on the collection of corneal cultures and the application of broad-spectrum topical antibiotics - are beset by important yet widely underrecognized limitations, including approximately 30% of all patients who will develop moderate to severe vision loss in the affected eye. Though recent advances have involved a more clearly defined role for adjunctive topical corticosteroids, and novel therapies such as corneal crosslinking, overall progress to improve patient and population-based outcomes remains incommensurate to the chronic morbidity caused by this disease. Recognizing that the care of BK is guided by the clinical axiom, "time equals vision", this chapter offers an evidence-based synthesis for the clinical management of these infections, underscoring critical unmet needs in disease prevention, diagnosis, and treatment.