Effect of Topical Losartan in the Treatment of Established Corneal Fibrosis in Rabbits.

Purpose: The purpose of this study was to evaluate the safety and efficacy of topical losartan in the therapeutic treatment of established corneal scaring fibrosis at 1 month after alkali burn in rabbits. Methods: Standardized alkali burns were performed in 1 eye of 24 rabbits with 0.75N NaOH for 15 seconds. Corneas were allowed to heal and develop scaring of the cornea for 1 month. Twelve eyes per group were treated with 50 µL of topical 0.8 mg/mL losartan in balanced salt solution (BSS), pH 7.0, and 12 eyes were treated with vehicle BSS 6 times per day. Six corneas were analyzed at 1 week or 1 month in each group. Standardized slit lamp photographs were obtained at the end point for each cornea and opacity was quantitated using ImageJ. Corneoscleral rims were cryofixed in optimum cutting temperature (OCT) solution and combined duplex immunohistochemistry for myofibroblast marker alpha-smooth muscle actin (α-SMA), mesenchymal cell marker vimentin, and TUNEL assay for apoptosis was performed on all corneas. Results: Topical losartan was effective in the treatment of established stromal fibrosis following alkali burn injury to the rabbit cornea. Stromal myofibroblast density was decreased and stromal cell apoptosis was increased (included both α-SMA-positive myofibroblasts and α-SMA-negative, vimentin-positive cells) at both 1 week and 1 month in the topical losartan-treated compared with vehicle-treated groups. Conclusions: Topical losartan is effective in the treatment of established stromal fibrosis in rabbits. Most myofibroblasts disappear from the stroma within the first month of losartan treatment. Longer treatment with topical losartan is needed to allow time for corneal fibroblast regeneration of the epithelial basement membrane (in coordination with epithelial cells) and the removal of disordered extracellular matrix produced by myofibroblasts.

Limbal graft transplantation: a rare implementation in pediatric limbal stem cell deficiency.

PURPOSE: To evaluate limbal graft transplantation success in pediatric patients with chemical injury-induced limbal stem cell deficiency (LSCD) using the 'LSCD Working Group' staging system. METHODS: Medical records of 11 eyes of 11 children who underwent limbal graft transplantation (limbal autograft/limbal allograft) were included. Surgical success was defined as improvement in the post-operative 1st year LSCD stage. RESULTS: The mean age was 12 ± 5 (4-17) years. Causative agent was alkaline in 4(36.4%) and acid in 3(27.2%) patients. Limbal autograft was performed in 9 (81.8%) eyes with unilateral LSCD, and allograft transplantation was performed in 2 (18.2%) eyes with bilateral LSCD. The mean follow-up time was 33.89 ± 30.73 (12-102.33) months. The overall limbal graft transplantation success rate was 72.7%. Among 9 patients who receive limbal autograft, 8 had improvement in post-operative LSCD stage, 1 had stable LSCD stage. Of the 2 patients who receive limbal allograft, post-operative LSCD stage remained the same in 1 and worsened in 1 patient. The mean time between injury and the surgery was 30.47 ± 30.08 (7-108.47) months. Penetrating keratoplasty was performed in 3 (27.2%) of 11 patients following limbal graft transplantation. CONCLUSION: Management of LSCD in children is challenging and appears to be somewhat different from that of adults. Limited data in the literature indicate that cultivated or simple limbal epithelial transplantations (CLET/SLET) are primarily preferred in children. Although the tendency to take small tissue from the healthy eye is noteworthy, conventional limbal allograft and autograft transplantations also show promising results without any further complications in at least 1 year follow-up period.

Visual restoration with KPro after face allotransplantation with a grade III phthisical eye.

The Boston Keratoprosthesis type I (KPro-I) has been shown to be successful in restoring vision after severe ocular burns; however, its long-term outcomes in phthisical eyes have rarely been reported. A monocular woman with a history of severe alkali chemical injury necessitating facial transplantation presented with a light perception left eye after a complicated course, including failed KPro-I, therapeutic penetrating keratoplasty, endophthalmitis, hypotony, total retinal detachment, and structural changes, including a shrunken 18 mm axial length and eye wall thickening. The patient underwent a combined vitrectomy with silicone oil and KPro-I implantation, resulting in her regaining ambulatory visual acuity (20/250) at 3 years' follow-up.

The effect of lactoferin on the free radical and cytokine status of cornea in the experimental thermal burn.

The free radical and cytokine statuses of the cornea during its thermal burn and the possibility of its correction by lactoferrin have been studied in Soviet Chinchilla rabbits. The development of a corneal thermal burn was accompanied by the development of oxidative stress (increased levels of TBA-reactive substances and carbonyl derivatives of proteins, decreased activity of SOD and GPx enzymes) and a pronounced inflammatory reaction with increased levels of TNF-1α, IL-10, TGF-1ß. The use of lactoferrin had a pronounced therapeutic effect, which was manifested by accelerated healing, prevention of the development of complications (corneal perforations), a decrease in the severity of oxidative stress, an increase in the concentrations of TNF-1α (in the early stages), IL-10 (in the later stages), TGF-1ß (throughout the experiment). At the same time, by the end of regeneration more severe corneal opacification was recognized compared to the control group. This may be associated with an increased level of anti-inflammatory cytokines, especially TGF-1ß.

Development of an injectable oxidized dextran/gelatin hydrogel capable of promoting the healing of alkali burn-associated corneal wounds.

The cornea serves as an essential shield that protects the underlying eye from external conditions, yet it remains highly vulnerable to injuries that could lead to blindness and scarring if not promptly and effectively treated. Excessive inflammatory response constitute the primary cause of pathological corneal injury. This study aimed to develop effective approaches for enabling the functional repair of corneal injuries by combining nanoparticles loaded with anti-inflammatory agents and an injectable oxidized dextran/gelatin/borax hydrogel. The injectability and self-healing properties of developed hydrogels based on borate ester bonds and dynamic Schiff base bonds were excellent, improving the retention of administered drugs on the ocular surface. In vitro cellular assays and in vivo animal studies collectively substantiated the proficiency of probucol nanoparticle-loaded hydrogels to readily suppress proinflammatory marker expression and to induce the upregulation of anti-inflammatory mediators, thereby supporting rapid repair of rat corneal tissue following alkali burn-induced injury. As such, probucol nanoparticle-loaded hydrogels represent a prospective avenue to developing long-acting and efficacious therapies for ophthalmic diseases.

An antifouling supramolecular polymer ophthalmic ointment alleviates symblepharon in rat alkali burn eyes.

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.

[Ocular burns: epidemiological, clinical, therapeutic and evolutionary aspects at the Cocody University Hospital, Côte d'Ivoire]. / Les brûlures oculaires : aspects épidémiologiques, cliniques, thérapeutiques et évolutifs au Centre hospitalier universitaire de Cocody, Côte d'Ivoire.

Justification: This study describes the socio-demographic characteristics, clinical, therapeutic, and evolutionary aspects of ocular burns to contribute to the improvement of their management. Method: A retrospective study was conducted in the Ophthalmology Department of the Cocody University Hospital (CHU) in Abidjan, Côte d'Ivoire, from January 1, 2020, to January 31, 2021. It focused on 49 patient records with ocular trauma, including 12 bilateral cases, totaling 61 eyes. For each patient, socio-demographic data, the nature of the traumatic agent, burn etiologies, ocular burn stage, initial and final uncorrected visual acuity of the affected eye, and treatment were collected. Results: The proportion of ocular burns was 11% out of 436 cases of ocular trauma that consulted in the department. The average age of patients was 27.9 years ± 14.2, ranging from 3 to 60 years, with a male predominance (70%). Students were the most frequent socio-professional category (39%). Work-related accidents were the predominant circumstances, in a third of cases. Chemical agents were the main traumatic agents, in 54% of cases. The average consultation time was 3.5 days ± 7.9, ranging from 1 to 60 days. Stage 1 of the Roper-Hall classification was the most observed stage (51% of cases). Initial visual acuity of the affected eye was less than 1/20 in 28% of cases. Treatment was mainly medical, and a third of treated eyes had a final acuity less than 1/20. Conclusion: Visual prognosis is influenced by burn stages, etiologies, and consultation time, varying according to social and geographical origins.

Mitochondria Transplantation Promotes Corneal Epithelial Wound Healing.

Purpose: The integrity of the corneal epithelium is essential in maintaining normal corneal function. Conditions disrupting the corneal epithelial layer range from chemical burns to dry eye disease and may result in impairment of both corneal transparency and sensation. Identifying factors that regulate corneal wound healing is key for the development of new treatment strategies. Here, we investigated a direct role of mitochondria in corneal wound healing via mitochondria transplantation. Methods: Human corneal epithelial cells (hCECs) were isolated from human corneas and incubated with mitochondria which were isolated from human ARPE-19 cells. We determined the effect of mitochondria transplantation on wound healing and proliferation of hCECs. In vivo, we used a mouse model of corneal chemical injury. Mitochondria were isolated from mouse livers and topically applied to the ocular surface following injury. We evaluated the time of wound repair, corneal re-epithelization, and stromal abnormalities. Results: Mitochondria transplantation induced the proliferation and wound healing of primary hCECs. Further, mitochondria transplantation promoted wound healing in vivo. Specifically, mice receiving mitochondria recovered twice as fast as control mice following corneal injury, presenting both enhanced and improved repair. Corneas treated with mitochondria demonstrated the re-epithelization of the wound area to a multi-layer appearance, compared to thinning and complete loss of the epithelium in control mice. Mitochondria transplantation also prevented the thickening and disorganization of the corneal stromal lamella, restoring normal corneal dehydration. Conclusions: Mitochondria promote corneal re-epithelization and wound healing. Augmentation of mitochondria levels via mitochondria transplantation may serve as an effective treatment for inducing the rapid repair of corneal epithelial defects.

Trimebutine prevents corneal inflammation in a rat alkali burn model.

Alkaline burns to the cornea lead to loss of corneal transparency, which is essential for normal vision. We used a rat corneal alkaline burn model to investigate the effect of ophthalmic trimebutine solution on healing wounds caused by alkaline burns. Trimebutine, an inhibitor of the high-mobility group box 1-receptor for advanced glycation end products, when topically applied to the burned cornea, suppressed macrophage infiltration in the early phase and neutrophil infiltration in the late phase at the wound site. It also inhibited neovascularization and myofibroblast development in the late phase. Furthermore, trimebutine effectively inhibited interleukin-1ß expression in the injured cornea. It reduced scar formation by decreasing the expression of type III collagen. These findings suggest that trimebutine may represent a novel therapeutic strategy for corneal wounds, not only through its anti-inflammatory effects but also by preventing neovascularization.

Multiple conjunctival autografts from the contralateral eye for management of recurrent symblepharon in eyes with unilateral chemical burn.

We present two cases which underwent complex ocular surface reconstruction to achieve a stable ocular surface. Conjunctival autograft (CAG) procedure was required more than once, in addition to simple limbal epithelial transplantation to address extensive symblepharon in the eyes with total unilateral limbal stem cell deficiency secondary to acid ocular burns. These cases demonstrate that multiple CAGs may be harvested from the contralateral unaffected eye to correct recurrent symblepharon without any donor site complications if the correct surgical technique is adopted.

Bilateral Thermal Keratopathy Due to Plasma Skin Regeneration.

A 40-year-old woman underwent periocular plasma skin regeneration, a cosmetic treatment for periorbital rejuvenation. She subsequently developed bilateral thermal keratitis, manifesting as blurred vision, irritation, and redness, with a vision decrease to 20/60 and 20/50 in her OD and OS, respectively. Examination demonstrated bilateral large, irregular corneal epithelial defects and edema, necessitating treatment with amniotic membrane grafts, bandage contact lenses, and hypertonic saline. One year posttreatment, her visual acuity improved to 20/20 and 20/25, albeit with ongoing symptomatic dryness and bilateral anterior stromal haze. This case, as only the second reported instance of ocular damage from periocular plasma skin regeneration, underscores the need for heightened awareness of potential ocular complications following plasma skin regeneration and reinforces the importance of protective measures during periocular procedures.

Causes of Corneal Melt After the Boston Keratoprosthesis Type I: The Chinese People's Liberation Army General Hospital Experience.

PURPOSE: The purpose of this study was to evaluate the long-term incidence, risk factors, and the management of corneal melt following Boston type I keratoprosthesis (B-KPro I) implantation. METHODS: This is a retrospective observational case series. Data were collected regarding demographics, preoperative characteristics, incidence, and outcomes of corneal melt in 102 patients who underwent B-KPro I in the Chinese PLA General Hospital between 2011 and 2018, with a follow-up period ranging from 4 to 11 years. RESULTS: Chemical burn was the most common indication for B-KPro I (n = 56; 53.8%), followed by ocular trauma (n = 26; 25.0%). During the follow-up period (107 ± 25.7 months), corneal melt occurred in 60 cases among 37 eyes (35.6%), with an incidence of 20.2% at 1 year after surgery. Fourteen cases presented with recurrent corneal melt. Patients with multiple corneal allograft failures had a higher risk of corneal melt. Thermal burns, compared with alkali burns, significantly elevated the odds ratio (OR) of corneal melt (OR, 5.11; 95% confidence interval, 1.05-24.86; P = 0.043). CONCLUSIONS: Corneal melt significantly reduced the retention time of KPro ( P < 0.01), and its coexistence with other complications further shortened the retention time. A specific pattern of corneal melt occurrence was identified, with a peak incidence at 1 year postoperatively. Our findings suggest variations in the risk of corneal melt among different indications, with thermal burns carrying the highest OR. Moreover, each previous failed keratoplasty doubled the risk of corneal melt after B-KPro I.

Combining the Tunnel Orbicularis Oculi Muscle Flap Technique With Skin Grafting for Enhanced Adhesion in Burn-Induced Ectropion Repair.

PURPOSE: Scar contracture of the eyelid following facial burns often has adverse consequences. Total cicatricial contracture often makes adjustment flap translation challenging to implement. Previously used upper and lower eyelid adhesion methods are ineffective for patients with severe cicatricial contracture, and ectropion can easily recur. This study aimed to retrospectively examine upper and lower eyelid adhesions using an orbicularis oculi muscle flap and verify its stability. METHODS: In patients with ectropion caused by severe scar contracture following head and face burns, we employed a tunnel orbicularis oculi muscle flap technique, which involved creating a tunnel between the skin and the tarsal plate of the eyelid, mobilizing the orbicularis oculi muscle, and rotating it into this tunnel to provide stable adhesion of the upper and lower eyelids. Full-thickness skin grafting was then performed. The eyelids were examined postoperatively to determine whether reoperation was necessary and to monitor for any potential complications. RESULTS: This study included 26 patients and 46 eyes. No accidental disconnection occurred after eyelid adhesion, which lasted for an average of 21.87 ± 10.08 months before the eyelid adhesion was cut open. No complications or adverse reactions occurred, and the adhesions did not break unexpectedly. CONCLUSIONS: Repairing eyelid ectropion with the tunnel orbicularis oculi muscle flap is a simple procedure that immediately creates tension against upper and lower eyelid contractures, providing long-term stable adhesion. This method avoids structural disorders, such as eyelid margin scarring, minimally influences surrounding tissues, and has few postoperative complications. It holds great value for repairing eyelid tissue defects and warrants further study.

Tamarind seed polysaccharide-metformin insert: Higher ocular retention, slow-release, and efficacy against corneal burn.

Metformin (MET) can be an alternative therapeutic strategy for managing ocular burn primarily because of its pleiotropic mechanism. Longer retention on the ocular surface and sustained release are necessary to ensure the efficacy of MET for ocular application. Although the high aqueous solubility of MET is good for formulation and biocompatibility, it makes MET prone to high nasolacrimal drainage. This limits ocular residence and may be a challenge in its application. To address this, polymers approved for ophthalmic application with natural origin were analyzed through in silico methods to determine their ability to bind to mucin and interact with MET. An ocular insert of MET (3 mg/6 mm) was developed using a scalable solvent casting method without using preservatives. The relative composition of the insert was 58 ± 2.06 %w/w MET with approximately 14 %w/w tamarind seed polysaccharide (TSP), and 28 %w/w propylene glycol (PG). Its stability was demonstrated as per the ICH Q1A (R2) guidelines. Compatibility, ocular retention, drug release, and other functional parameters were evaluated. In rabbits, efficacy was demonstrated in the 'corneal alkali burn preclinical model'. TSP showed potential for mucoadhesion and interaction with MET. With adequate stability and sterility, the insert contributed to adequate retention of MET (10-12 h) in vivo and slow release (30 h) in vitro. This resulted in significant efficacy in vivo.

Clinical and pathologic characterization of a mouse model of graded limbal stem cell deficiency.

Limbal stem cell deficiency (LSCD) is a clinically challenging eye disease caused by damage to limbal stem cells (LSCs). Currently, the international consensus classifies LSCD into three clinical stages based on the disease severity. However, no existing animal models attempt to replicate the varying degrees of LSCD observed in clinical cases. The present study demonstrates an easy-to-create, reproducible, and reliable mouse model of graded LSCD. To achieve mild, moderate, or severe LSCD, filter paper rings with a variety of central angles (90°, 180°, or 270°) are utilized to deliver alkali burns to different sizes of the limbal area (1, 2, or 3 quarters). The animal model has successfully resulted in the development of clinical signs and pathological manifestations in escalating severity that are similarly observed in the three clinical stages of LSCD. Our study thus provides new insights into distinct pathological features underlying different grades of LSCD and serves as a new tool for further exploring the disease mechanisms and developing new effective therapeutics for repairing damaged LSCs.

Adaptor protein 14-3-3zeta promotes corneal wound healing via regulating cell homeostasis, a potential novel therapy for corneal injury.

Severe corneal injury can lead to blindness even after prompt treatment. 14-3-3zeta, a member of an adaptor protein family, contributes to tissue repair by enhancing cellular viability and inhibiting fibrosis and inflammation in renal disease or arthritis. However, its role in corneal regeneration is less studied. In this study, filter disc of 2-mm diameter soaked in sodium hydroxide with a concentration of 0.5 N was placed at the center of the cornea for 30 s to establish a mouse model of corneal alkali injury. We found that 14-3-3zeta, which is mainly expressed in the epithelial layer, was upregulated following injury. Overexpression of 14-3-3zeta in ocular tissues via adeno-associated virus-mediated subconjunctival delivery promoted corneal wound healing, showing improved corneal structure and transparency. In vitro studies on human corneal epithelial cells showed that 14-3-3zeta was critical for cell proliferation and migration. mRNA-sequencing in conjunction with KEGG analysis and validation experiments revealed that 14-3-3zeta regulated the mRNA levels of ITGB1, PIK3R1, FGF5, PRKAA1 and the phosphorylation level of Akt, suggesting the involvement of the PI3K-Akt pathway in 14-3-3zeta-mediated tissue repair. 14-3-3zeta is a potential novel therapeutic candidate for treating severe corneal injury.

Chemical eye injuries: a 10 year retrospective review of acute presentations and clinical outcomes in Auckland, New Zealand.

To assess the aetiologies, clinical characteristics, treatment regimens, and outcomes of acute chemical injuries treated at an emergency eye clinic. Retrospective, observational study of all cases of chemical eye injury that presented acutely to the Greenlane Clinical Centre in Auckland, New Zealand from 1 January 2012 through 31 December 2021. Patient demographics, activity at the time of injury, causative chemical, clinical characteristics of injury at presentation, severity (Dua) classification, admission and discharge best corrected visual acuity (BCVA), treatment regimen, time to epithelisation and number of follow-up appointments were recorded. In total, 1522 cases involving 1919 eyes were studied. The mean age was 40.6 ± 18.8 years and 65% were male. The majority of cases occurred at home (62%) and cleaning was the most common activity (38%). There were 1490 Grade I (98%), 22 Grade II (1.5%), 5 Grade III (0.3%), 1 Grade IV (0.07%), 0 Grade V, and 4 Grade VI (0.3%) cases. An epithelial defect was noted in 409 cases (26.9%), of which re-epithelialisation occurred within one week for 378 cases (92%) and within 30 days for 384 cases (94%). Moderate vision loss (BCVA ≤ 6/12) attributed to the injury occurred in 152 (10%), while severe vision loss (BCVA ≤ 6/60) occurred in 30 (2%). Lack of irrigation at the scene was associated with an increased risk of severe injury and longstanding visual impairment (p = 0.0001). Most acute chemical injuries are mild with good clinical outcomes. Although rare, severe injuries are associated with a lack of irrigation at the scene and worse visual outcomes.

Scleral Contact Lens to Preserve a Corneal Graft in Chronic Lagophthalmos.

Facial burns involving the periorbital region may lead to cicatricial ectropion and lagophthalmos, causing severe exposure keratopathy and eventually blindness if uncorrected. In these patients, it is critical to provide aesthetic and functional surgical correction to protect the ocular surface from chronic desiccation in addition to visual rehabilitation. Conventional methods may not be sufficient to provide visual rehabilitation in complex cases. Scleral lenses can be a multipurpose alternative for these patients. Herein, we present the challenging case of a patient who developed cicatricial lagophthalmos and exposure keratopathy after facial transplantation due to gasoline burns and received a scleral contact lens for visual rehabilitation.

Dexamethasone sodium phosphate loaded nanoparticles for prevention of nitrogen mustard induced corneal injury.

Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that is primarily absorbed through skin, inhalation, or ocular surface. Ocular exposure of NM can cause acute to chronic keratopathy which can eventually lead to blindness. There is a current lack of effective countermeasures against ocular exposure of NM despite their imperative need. Herein, we aim to explore the sustained effect of Dexamethasone sodium phosphate (DSP)-loaded polymeric nanoparticles (PLGA-DSP-NP) following a single subconjunctival injection in the management and prevention of corneal injury progression upon exposure to NM. DSP is an FDA approved corticosteroid with proven anti-inflammatory properties. We formulated PLGA-DSP-NP with zinc chelation ion bridging method using PLGA polymer, with particles of approximately 250 nm and a drug loading of 6.5 wt%. Under in vitro sink conditions, PLGA-DSP-NP exhibited a sustained drug release for two weeks. Notably, in NM injured cornea, a single subconjunctival (SCT) injection of PLGA-DSP-NP outperformed DSP eyedrops (0.1%), DSP solution, placebo NP, and saline, significantly mitigating corneal neovascularization, ulceration, and opacity for the two weeks study period. Through PLGA-DSP-NP injection, sustained DSP release hindered inflammatory cytokine recruitment, angiogenic factors, and endothelial cell proliferation in the cornea. This strategy presents a promising localized corticosteroid delivery system to effectively combat NM-induced corneal injury, offering insights into managing vesicant exposure.