Evaluation of the Treatment Effects of Conditioned Medium from Human Orbital Adipose-Derived Stem Cells in a Corneal Alkali Burn Rabbit Model.

Purpose: This study aimed to evaluate the effects of a new treatment-conditioned medium from human orbital adipose-derived stem cells (OASC-CM)-on corneal recovery after alkali burns in a rabbit model. Methods: The corneal alkali burn rabbit model was established and treated with OASC-CM, conditioned medium from human abdominal subcutaneous adipose-derived stem cells (ABASC-CM), and fresh control culture medium (con-CM) three times a day for 7 days, respectively. Subsequently, the treatment effects were evaluated and compared through clinical, histological, immunohistochemical, and cytokine evaluations. Results: Clinically, OASC-CM alleviated corneal opacity and edema and promoted recovery of corneal epithelium defect. Histologically and immunohistochemically, OASC-CM inhibited neovascularization, conjunctivalization, and immuno-inflammatory reaction, while promoting corneal regeneration and rearrangement. Increased secretion of interleukin-10 and inhibited protein levels of cluster of differentiation 45, interferon-γ, and tumor necrosis factor-α were observed in the alkali-burned cornea after OASC-CM treatment, which might be the relevant molecular mechanism. Conclusions: OASC-CM showed significant effects on the recovery of rabbit corneal alkali burns and eliminated immunological and ethical limitations, representing a new option for corneal wound treatment.

Ocular-periocular burns in a tertiary hospital: Epidemiologic characteristics.

PURPOSE: Ocular burns are ophthalmic emergencies that can cause devastating injuries. This study aimed to analyze the epidemiology, complications, and management of ocular-periocular burns. METHODS: A total of 193 patients with ocular-periocular burns were admitted to our tertiary hospital from January 2018 to December 2020. The demographic characteristics of the patients, injury variables, complications, and treatments were evaluated. RESULTS: There were 142 male (73.6%) and 51 female (26.4%) patients with a mean age of 32.53±17.75 years. The average total body surface area was 12% (range, 1-80%). Injuries were most common at work (52.3%) and home (36.3%). Thermal burns were the most common injuries (74.6%), followed by chemical (14.5%) and electrical burns (10.9%). Alkaline agents (75.0%), mainly sodium hydroxide and lime, were common in chemical burns. Superficial lid burns were significantly higher in the thermal group (p < 0.001), and grade III-IV corneal burns were significantly higher in the chemical group (p < 0.001). Various complications were developed in 50 (13%) eyes. Medical treatment only was performed in 318 (82.4%) eyes, and additional surgical treatment was performed in 64 (17.6%) eyes; however, 54 (14.0%) underwent more than one surgery. The most common complications were corneal scars (7.3%), limbal deficiency (4.1%), and ectropion (3.9%). The most frequent procedures performed were amniotic membrane transplantation (AMT) (11.9%) and tarsorrhaphy (6.7%). CONCLUSION: Chemical burns, limbal and conjunctival ischemia, and full-thickness eyelid defects had a poor prognosis. The degree of limbal deficiency and injury of intraocular structures were found to have a great influence on the outcome of their visual acuity.

Carbide Gun-Related Ocular Injuries: A Case Series.

PURPOSE: The purpose of this study was to report a case series of sight-threatening ocular injuries caused by calcium carbide guns used as fire crackers. METHODS: Medical records of 15 eyes of 14 patients with ocular injuries caused while using carbide guns, visiting the Institute, from January 2021 to January 2022, were retrospectively reviewed. The collected data included patients' demography (age, sex), presenting ophthalmic features, management, and outcome. Grade I and II ocular injuries were managed medically. All grade III-V injuries were managed using Amniotic Membrane Transplantation. RESULTS: All patients were male. The mean age of the patients was 23.57 ± 11.76 years. According to the Dua classification, 5 eyes (33.3%) had Grade I-II ocular surface burns, 3 eyes (20%) had grade III burns, and 7 eyes (46.6%) had grade IV-VI burns. Presenting visual acuity ranged between hand movements to 20/50, and in 6 eyes (40%), the visual acuity was ≤20/200. Five eyes were managed medically alone, and 10 (66.6%) eyes needed surgical intervention (Amniotic Membrane Transplantation). After a mean follow-up of 14.23 ± 11.92 weeks, complete epithelization was seen in 10 eyes (66.6%). Partial limbal stem cell deficiency and its sequelae such as conjunctivalization of the cornea were noted in 7 eyes (46.6%). CONCLUSIONS: Calcium carbide-related ocular injuries can result in corneal blindness secondary to limbal stem cell deficiency in young individuals. Loss of vision in this age group can lead to loss of economic productivity and cosmetic disfigurement. More advocacy efforts are thus needed to prevent these injuries.

Hypoxia-induced mesenchymal stem cells inhibit corneal fibroblast proliferation by regulating the WWP2/Notch1 axis.

Aim: This study aimed to explore the role of hypoxic mesenchymal stem cells (MSCs) in corneal alkali burns and the underlying mechanism. Materials & methods: Rat corneal fibroblasts were incubated with IL-6, followed by treatment with hypoxic MSC supernatant. A rat corneal alkali burn model was implemented and processed with hypoxic MSCs. The associated factors were detected by corresponding methods. Results: Hypoxic MSCs reduced the Notch1 level and the proliferation of rat corneal fibroblasts. Hypoxic MSCs or WWP2 overexpression in MSCs enhanced ubiquitination of Notch1. WWP2 interacted with Notch1, and WWP2 silencing reversed the effects of the hypoxic MSCs. Hypoxic MSC treatment in vivo decreased the corneal neovascularization scores and opacity scores. Conclusion: Hypoxic MSCs inhibited inflammation and alleviated corneal injury in alkali burns via the WWP2/Notch1 axis.

Acute ocular chemical burns are ophthalmic emergencies which require immediate diagnosis and treatment. Quiescent corneal cells differentiate into active fibroblast and myofibroblast phenotypes after corneal injury. Mesenchymal stem cells (MSCs) under hypoxia treatment are applied for the treatment of acute ocular chemical burns. We aimed to explore the role of hypoxic MSCs in corneal alkali burns and the underlying mechanism. The result showed that hypoxic MSCs reduced the proliferation of rat corneal fibroblasts, implying an anti-inflammatory effect. In vivo, treatment with hypoxic MSCs decreased the corneal neovascularization scores and opacity scores, indicating a protective effect on corneal alkali burns. We concluded that hypoxic MSCs could alleviate corneal injury in alkali burns and may be a promising therapeutic option for corneal alkali burns.

Ten Years of Pediatric Ocular Chemical Burn Experience in a Tertiary Eye Care Center in Turkey.

OBJECTIVES: To report 10 years of pediatric ocular chemical burn experience in a tertiary eye care center in Turkey. METHODS: Thirty-three patients aged 18 years and younger who presented with ocular chemical burn between 2011 and 2021 were enrolled. Demographic data and clinical characteristics of patients were reviewed. Limbal stem cell deficiency (LSCD) stage was assessed according to LSCD working group's staging system. The initial and final best-corrected visual acuities were recorded. RESULTS: The mean age was 10.4±5.5 (0.25-18) years with an F/M ratio of 12/21. Eleven (33.3%) of the patients were injured with acid and 5 (15.1%) with alkaline. The most common causative agent was nail polish remover (n=7, 21.2%), followed by cologne (n=5, 15.1%) and hand sanitizer (n=4, 12.1%). The severity of burn was ≥grade 4 in 20 patients (60.6%). Chemical injury resulted in LSCD in 18 patients (54.5%). Surgery was performed (LSCD ≥Stage 2 B) in 13 patients (39.3%); limbal stem cell transplantation (LSCT) (n=11), staged amniotic membrane transplantation, and symblepharon release (n=2). Penetrating keratoplasty after LSCT was performed in three of 11 patients. The mean follow-up time was 31.9±28.6 months (6-102.33) after the surgery. CONCLUSIONS: In pediatric population, accurate diagnosis and management of ocular chemical burns are challenging. Although the severity of burn and consequently LSCD rate seems to be high in children, comparative studies in a larger population are still needed.

Safety and feasibility of subconjunctival injection of mesenchymal stem cells for acute severe ocular burns: A single-arm study.

PURPOSE: To investigate the safety and feasibility of topical injection of bone marrow derived mesenchymal stem cells (BM-MSCs) in acute severe ocular burns. METHODS: In this open-label，single-arm study, subconjunctival injection of allogenic BM-MSCs combined with standard treatment was given to 16 patients with acute severe ocular burns (Dua's grade IV to VI) within 2 weeks after injury. The primary outcome was efficacy rate which referred to the proportion of complete corneal epithelialization patients without perforation. The secondary outcome was safety, visual acuity, the number of symblephara, and elevated intraocular pressure. RESULTS: One patient was lost to follow-up. During the follow-up period, no corneal perforation was developed. Complete corneal epithelialization was noted 8 (ranged 4-10 weeks) weeks after treatment in 13 eyes (81.3%). The efficacy rate was 87.5% (95% confidence interval, CI: 61.7-98.4). Hypopyon was detected and later well controlled in 1 eye. Partial or total limbal stem cell deficiency (LSCD) was noted in all eyes. Improvement of visual acuity was achieved in 5 out of 16 eyes (31.3%). Seven eyes' visual acuity was reached 0.1. Symblepharon with varied severity was noted in 5 eyes. Two eyes had elevated intraocular pressure. CONCLUSIONS: This study confirms the safety of subconjunctival injection of BM-MSCs as an innovative and convenient procedure in ocular burns. The overall result is promising considering the absence of perforation, the low severity of symblepharon and visual acuity improvement.

Fibrin-Plasma Rich in Growth Factors Membrane for the Treatment of a Rabbit Alkali-Burn Lesion.

The purpose of this work is to describe the use of Fibrin-Plasma Rich in Growth Factors (PRGF) membranes for the treatment of a rabbit alkali-burn lesion. For this purpose, an alkali-burn lesion was induced in 15 rabbits. A week later, clinical events were evaluated and rabbits were divided into five treatment groups: rabbits treated with medical treatment, with a fibrin-PRGF membrane cultured with autologous or heterologous rabbit Limbal Epithelial Progenitor Cells (LEPCs), with a fibrin-PRGF membrane in a Simple Limbal Epithelial Transplantation and with a fibrin-PRGF membrane without cultured LEPCs. After 40 days of follow-up, corneas were subjected to histochemical examination and immunostaining against corneal or conjunctival markers. Seven days after alkali-burn lesion, it was observed that rabbits showed opaque cornea, new blood vessels across the limbus penetrating the cornea and epithelial defects. At the end of the follow-up period, an improvement of the clinical parameters analyzed was observed in transplanted rabbits. However, only rabbits transplanted with cultured LEPCs were positive for corneal markers. Otherwise, rabbits in the other three groups showed positive staining against conjunctival markers. In conclusion, fibrin-PRGF membrane improved the chemically induced lesions. Nonetheless, only fibrin-PRGF membranes cultured with rabbit LEPCs were able to restore the corneal surface.

Craniofacial and neck burns in the pediatric population.

INTRODUCTION: Burn injuries can present with catastrophic physical and psychiatric harm with extensive, long-term sequelae. The pediatric population may especially be at-risk given this population's early neurocognitive and behavioral state of development. Innovations in treatment modalities and the development of evidence-based guidelines have helped mitigate burn morbidity and mortality in the pediatric population. Unfortunately, a surprising dearth of literature identifies risk-factors, epidemiological data, injury mechanisms, and prognostic factors within the pediatric population in the setting of craniofacial burns. METHODS: An analysis of emergency department visits under the National Electronic Injury Surveillance System was conducted for the most recent 5-year period available (2014-2018). Available information includes demographical data, such as age and sex, mechanism of injury, visit circumstances, as well as visit disposition. Additionally, details surrounding the injury, including type of burn and anatomical location of injury, were compared. RESULTS: After a review of results, a total of 2599 patients were included for analysis. Our study shows that infants and young children are at increased risk for grave injury 27.3% and 13% of infants and toddlers transferred or admitted, respectively, p < 0.05). 59.8% of infant burns in particular were caused by liquid or kitchen products, while 44.5% of burns in toddlers were caused by chemical products (p < 0.05 for both). Conversely, adolescents are at greater risk of burns in the setting of occupational and hobby-based activities (20.4% of adolescent burns). CONCLUSIONS: Craniofacial burns in the pediatric population may present with complex pathology and sometimes necessitate advanced care. Presentations and prognoses are different dependent upon age and injury mechanism. These findings may serve as important framework in the establishment of guidelines for medical and legislative reform.

Early Application of Bevacizumab After Sclerocorneal Grafting for Patients With Severe Late-Stage Ocular Chemical Burns.

PURPOSE: To investigate whether subconjunctival bevacizumab help prevent corneal graft neovascularization and prolong the graft survival of patients with chemical burns. METHODS: We performed a prospective nonrandomized comparative case series study. Twenty-six eyes received subconjunctival bevacizumab (10 mg/0.4 mL) once and topical immunosuppressive agents after sclerocorneal lamellar keratoplasty as the treatment, and 13 eyes received a topical immunosuppressant alone and served as the control group. The main outcomes were a cumulative probability of graft survival, development of corneal neovascularization, and complications. RESULTS: The postoperative follow-up time was 14.3 months (range, 2-62 mo). The cumulative graft survival time was significantly longer in the treatment group than that in the control group (42.9 ± 5.9 vs. 4.8 ± 0.7 mo; log rank < 0.001). In the treatment group, 19 of the 26 grafts (73.1%) survived as transparent with a mean follow-up of 18.7 ± 3.0 months. At the end of the follow-up, 4 grafts remained free of neovascularization, 2 developed edema without neovascularization, and 15 remained transparent with a stable ocular surface and some neovascular vessels in the peripheral transplant interface. The other 5 grafts became opaque and neovascularized. In the control group, all grafts became opaque and neovascularized within the follow-up period (5.5 ± 0.7 mo). During the follow-up, a corneal epithelial defect developed in 9 eyes in the treatment group and 7 in the control group. CONCLUSIONS: Early application of subconjunctival bevacizumab after sclerocorneal lamellar keratoplasty can significantly prevent corneal neovascularization and promote graft survival for severe late-stage ocular chemical burns.

Choking agents and chlorine gas - History, pathophysiology, clinical effects and treatment.

INTRODUCTION: Choking agent exposure, among them chlorine gas, occurs in household or industrial accidents, chemical warfare and terrorist attacks. AIMS: Review of published animal and human data regarding the history, pathophysiology, clinical effects and management of chlorine exposure. PATHOPHYSIOLOGY: Highly soluble agents cause quick upper respiratory tract symptoms. Chlorine gas has a medium solubility, also causing delayed lower airway symptoms, mainly due to its oxidizing potential by releasing hypochlorous and hydrochloric acid, but also by interacting with Transient Receptor Potential channels. SYMPTOMS: Eyes may show conjunctival injection, abrasions and corrosions. Burns of the oronasal mucosa and trachea can occur. Dyspnea, bronchospasm and possible retrosternal pain occur frequently. Glottis edema or laryngospasm are acute life-threatening emergencies. Chlorine gas can cause toxic pneumonitis, lung edema and acute respiratory distress syndrome (ARDS). MANAGEMENT: General management includes physical examination, pulse oximetry and arterial blood gases. Eyes should be irrigated, humidified oxygen and inhalative bronchodilators administered. An EKG, cardiac enzymes and complete-blood-count should be obtained if there is retrosternal pain. Routine chest x-ray is not recommended - except if pulmonary edema is suspected. Laryngoscopy should be performed if glottis edema is suspected. Sodium bicarbonate inhalation after chlorine gas inhalation is discussed controversially. Mechanical ventilation with continuous-positive-airway-pressure or intubation/tracheotomy with high positive-end-expiratory-pressure may be necessary. Glucocorticoids for prevention of pulmonary edema should be applied restrictively. Prophylactic antibiotics are not recommended. In severe ARDS, extracorporeal membrane oxygenation (ECMO) can be considered. CONCLUSION: Treatment is mainly symptom oriented. New and promising therapies are in development.

Ophthalmological evaluation of facial burns in a regional burns centre.

Ocular burns are ophthalmological emergencies, owing to their potentially serious visual complications. Prompt recognition, irrigation and comprehensive examination including fluorescein staining is recommended to optimise outcomes. Burns standards recommend ophthalmological services be available in a 'timely' manner. This paper is a retrospective review of facial burn admissions between November 2017 and November 2018 at the Queen Elizabeth Hospital Birmingham (QEHB), a regional burns centre in the United Kingdom. This study aims to assess referral rates to ophthalmology, timeliness of review and the proportion of patients reviewed within a 24h window. From the data available we also aim to determine the frequency of fluorescein examination. Of 88 patients admitted with facial burns, data was available for 80 patients. The majority (n=77, 87.6%) suffered thermal burns. Twenty-two (27.5%) patients were referred to ophthalmology, and 18 (22.5%) had a documented review. Mean time from admission to review was 45.0h, with 10 (52.6%) patients being seen within 24h. Of 80 patients, 50 (62.5%) patients had no documented fluorescein examination. Further prospective studies are necessary to inform clinical guidelines and optimise management of facial burns.

Irrigation with phosphate-buffered saline causes corneal calcification during treatment of ocular burns.

Corneal calcification is a vision-threatening manifestation of calcium containing agents in ocular burn. As we previously reported, our interest was sparked by a particular discrepancy of a case: A patient treated for a non-calcium containing agent in eye burn from exposure to an alkaline mixture of NaOH and KOH, who unexpectedly developed corneal calcification. This current study aims to elucidate whether the 2min lasting irrigation with a phosphate-buffered saline itself, regardless of rinsing regimen, triggers corneal calcification. The Ex Vivo Eye Irritation Test (EVEIT) system was used on rabbit corneas to replicate the very same phosphate-buffered saline solution the patient was treated with. The rabbit corneas were first burned with 1 M NaOH, rinsed with 4.9% phosphate-buffered saline for 2 min, and were then moisturized with an artificial tear solution for 48 h. All corneas were fluorescein-stained for photo documentation, snap-frozen, lyophilizated, and the electrolyte content was analyzed by Energy-Dispersive X-ray spectroscopy (EDX). The EDX analysis revealed pathological phosphorous in corneal stroma after a single rinsing with phosphate-buffered saline. Ongoing application of artificial tears containing physiological 14.581 mmol Ca2+ /l led to macroscopically visible calcification, but only in areas of induced corneal erosion. Regardless of the rinsing protocol neither 2 or 15 min of eye rinsing with phosphate containing rinsing solutions, we have given proof that corneal calcification is a foreseeable effect of the phosphate-buffered saline rinsing of mechanically epithelial damaged and chemically burnt eyes. Thus, it is crucial to legally restrict the formulations of phosphate-buffered salines in the medical treatment of eye burns, corneal erosions or chemical splashes of the eye.

Long-Term Results of Cultured Limbal Stem Cell Versus Limbal Tissue Transplantation in Stage III Limbal Deficiency.

We aimed to evaluate efficiency and safety of transplantation of limbal stem cells (LSC) cultured on human amniotic membrane with no feeders and to compare cultured LSC with limbal tissue transplantation. Thirty eyes with stage III LSC deficiency were treated with autologous (autoLSC) or allogeneic (alloLSC) cultured LSC transplantation (prospective phase II clinical trial; average follow-up time, 72 months) or autologous (autoLT) or allogeneic (alloLT) limbal tissue transplantation (retrospective control group; average follow-up time, 132 months) between 1993 and 2014. The 5-year graft survival defined by absence of recurrence of the clinical signs of limbal deficiency was 71% for autoLSC, 0% for alloLSC, 75% for autoLT, and 33% for alloLT. Visual acuity improved by 9.2 lines for autoLSC and 3.3 lines for autoLT. It decreased by 0.7 lines for alloLSC and 1.9 lines for alloLT. Adverse events were recorded in 1/7 autoLSC, 7/7 alloLSC, 6/8 autoLT, and 8/8 alloLT patients. Corneal epithelial defect was the only adverse event recorded after autoLSC, whereas severe sight-threatening adverse events were recorded in the remaining three groups. Compared with failed grafts, successful grafts featured greater decrease in fluorescein staining, greater superficial vascularization-free corneal area, lower variability of the corneal epithelial thickness, and higher corneal epithelial basal cell density. Autologous cultured LSC transplantation was associated with high long-term survival and dramatic improvement in vision and was very safe. Autologous limbal tissue transplantation resulted in similar efficiency but was less safe. Cadaver allogeneic grafts resulted in low long-term success rate and high prevalence of serious adverse events. Stem Cells Translational Medicine 2019;8:1230&1241.

Ocular Chemical burns in the dermatology office: a practical approach to managing safety precautions.

Chemical burns to the eyes are one of the few ocular emergencies that dermatologists may encounter in their everyday clinic. As such, dermatologists should be confident in their ability to urgently manage ocular chemical injuries should accidental exposure occur during a procedure. We report a case of accidental ocular exposure to aluminum chloride hexahydrate during skin biopsy of the cheek and subsequent transient ocular injury that resolved with early appropriate management. This article provides background information on acute chemical ocular injuries, offers practical step-by-step guidance for the dermatologist, and highlights immediate copious irrigation as perhaps the most critical step in determining the clinical course of the injury.

Therapeutic effects of three human-derived materials in a mouse corneal alkali burn model.

Purpose: To compare the therapeutic effects of human derivatives in a mouse alkali burn model. Methods: The right eyes of mice were injured using NaOH. After alkali injury, one of the following agents was topically administered for 7 d: human amniotic membrane (hAM) suspension, human umbilical cord serum (hUCS), and human peripheral blood serum (hPBS), or saline. The epithelial defect areas on days 1, 2, and 3 degrees of opacity on days 2, 3, and 7, and corneal neovascularization (NV) areas on day 7 were evaluated. Histologic examination and mRNA expression levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-8, and MMP-9 were also evaluated on day 7. Results: The epithelial defect areas in the hUCS group were smaller than those in the control and hPBS groups on day 3 (p < .05, respectively). The epithelial defect areas in the hAM suspension group showed smaller than those in the control and hPBS groups on days 1 and 2 (p < .05, respectively). The degrees of opacity were lower in all treatment groups than that of the saline control group on day 7 (p < .05, respectively). Corneal NV areas were not different among groups on day 7 (p = 0.20). The expression levels of TNF-α, IL-6, MMP-8, and MMP-9 mRNA and the infiltration of the inflammatory cells in all treatment groups were lesser than those in the control group on day 7 (p< .05, respectively). Conclusions: All treatments reduced inflammatory reactions and corneal opacity development. Corneal reepithelialization was faster in the hUCS group.

[Emergency management of chemical eye burns]. / Kemiska ögonfrätskador ­ akut diagnostik och behandling - Omedelbar spolning är avgörande för att begränsa skadan.

Chemical burn injury of the eye is a medical emergency that requires immediate intervention and structured ophthalmic assessment without unnecessary delay. Chemicals, alkali in particular but also acids, cause profound damage to the anatomy of the ocular surface or even deeper eye structures. The injury is potentially sight-threatening and can, in the worst cases, lead to loss of the eye. Reconstructive surgery is complex and often involves multiple surgeries but can give very good results in carefully selected cases. This article summarizes present evidence-based guidelines relevant for Swedish conditions and in use at St. Erik Eye Hospital in Stockholm.

Role of microRNA 146a on the healing of cornea alkali burn treated with mesenchymal stem cells.

The aim of the present study was to investigate the effect of microRNA 146a (miR146a) on promoting the repair of corneal alkali burn with bone marrow mesenchymal stem cells (MSCs). A total of 24 Sprague­Dawley female rats were divided into a normal group (Control), a normal MSC treatment group (Normal MSCs), an miR146a knockout MSC treatment group (miR146a­low MSCs) and an miR146a high­expression MSC treatment group (miR146a­high MSCs) according to the random number table. Quantitative polymerase chain reaction was used to evaluate the expression levels of miR146a. MTT assay was performed to measure the cell viability of mesenchymal stem cells (MSCs) and apoptosis was measured by flow cytometry. The expression levels of p65 nuclear factor (NF)­κB, proliferating cell nuclear antigen (PCNA) and Fas proteins were analyzed by western blotting. MSCs were tested for the secretion levels of vascular endothelial growth factor (VEGF), CD45, interferon (IFN)­Î³ and interleukin (IL)­10 by ELISA. The miR146a­high MSCs improved cell viability of MSCs and inhibited apoptosis of MSCs following alkali burn. miR146a­high MSCs decreased the expression levels of p65NF­κB and PCNA, and enhanced the expression level of Fas. Furthermore, miR146a­high MSCs improved the cornea opacity and enhanced the inhibition of neovascularization in the rats following alkali burn. miR146a­high MSCs inhibit the expression of VEGF, CD45, IFN­Î³, while enhanced the expression of IL­10. Therefore, miR146a promotes the repair of corneal alkali burn in rats treated with MSCs.

Type, severity, management and outcome of ocular and adnexal firework-related injuries: the Rotterdam experience.

PURPOSE: To study the type, severity, management and outcome of firework-related adnexal and ocular injuries during New Year's Eve festivities. METHODS: A retrospective analysis of 123 injured patients (143 eyes) treated at the Rotterdam Eye Hospital between 2009 and 2013. All ages were included and analysed according to age, gender, active participant or bystander, laterality, location, dimension and severity of injury. Outcome parameter was the final best-corrected visual acuity. RESULTS: The mean age was 22 ± 13 years with 87% males and 53% bystanders. 52% were ≤18 years. There was a higher number of female than male bystanders (63% versus 51%, p = 0.30). 50% of the eyes sustained mild, 13% moderate and 37% severe trauma. Adults suffered more from severe injuries compared to children (42% versus 31%). The most frequent intervention was gunpowder removal (20%), followed by traumatic cataract surgery (12%) and amniotic membrane grafting (8%). 76% of patients were followed over 1 year. At the end of follow-up, 88 (61.5%) eyes had recovered fully, while 55 (38.5%) eyes suffered from persistent complications with reduced vision ≤0.8 in 30% of injured eyes. 15 patients (12%, 10 adults, five children) were considered legally blind (vision ≤0.1). Three (2%) eyes were subject to evisceration. CONCLUSION: Every year, around New Year's Eve 30-45 victims were referred to the Rotterdam Eye Hospital; 50% sustained moderate-to-severe trauma. In severe firework injuries, patients required multiple treatments that may not prevent permanent blindness and/or functional/cosmetic disfigurement. The majority was bystander and younger than 18 years.

Navigating Market Authorization: The Path Holoclar Took to Become the First Stem Cell Product Approved in the European Union.

Gene therapy, cell therapy, and tissue engineering have the potential to revolutionize the treatment of disease and injury. Attaining marketing authorization for such advanced therapy medicinal products (ATMPs) requires a rigorous scientific evaluation by the European Medicines Agency-authorization is only granted if the product can fulfil stringent requirements for quality, safety, and efficacy. However, many ATMPs are being provided to patients under alternative means, such as "hospital exemption" schemes. Holoclar (ex vivo expanded autologous human corneal epithelial cells containing stem cells), a novel treatment for eye burns, is one of the few ATMPs to have been granted marketing authorization and is the first containing stem cells. This review highlights the differences in standards between an authorized and unauthorized medicinal product, and specifically discusses how the manufacture of Holoclar had to be updated to achieve authorization. The result is that patients will have access to a therapy that is manufactured to high commercial standards, and is supported by robust clinical safety and efficacy data. Stem Cells Translational Medicine 2018;7:146-154.

Comparison of Collagen Cross-Linking and Amniotic Membrane Transplantation in an Experimental Alkali Burn Rabbit Model.

PURPOSE: To compare the effects of collagen cross-linking (CXL) and amniotic membrane transplantation (AMT) on acute corneal alkali burns. METHODS: After establishment of an alkali burn model, 32 rabbits were divided into 4 groups: control group, AMT group, CXL group, and AMT + CXL (combined) group. Clinical parameters, including epithelial wound, opacity, ulceration, and neovascularization, were evaluated on postinjury days 1, 7, 14, and 18. Histological parameters were examined in hematoxylin/eosin (H&E) and Masson trichrome-stained corneal sections. Immunohistochemical analyses, including a terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling assay and cluster of differentiation 68 (CD68) labeling, were performed to determine the apoptotic index and macrophage activation. RESULTS: On postinjury day 18, the epithelial wound of AMT {4.08% [interquartile range (IQR), 0.68%-5.22%]}, CXL [1.84% (IQR, 0.01%-3.89%)], and combined [3.44% (IQR, 0.01%-4.36%)] groups were significantly lower than the control [15.23% (IQR, 9.86%-23.06%)] group (P = 0.003). No significant difference was detected between the groups in terms of opacity (P = 0.303). Neovascularization was the least severe in the CXL group [16.18% (IQR, 8.39%-21.28%)] and the most severe in the AMT [34.47% (IQR, 17.71%-62.77%)] and combined [35.12% (IQR, 31.96%-59.98%)] groups on day 18 (P = 0.033). Significant increases in the apoptotic index and CD68 labeling were detected in the CXL and combined groups compared with those in the control group (P = 0.047 and P = 0.001, respectively). CONCLUSIONS: CXL treatment is an effective adjuvant treatment for promoting reepithelialization, reducing inflammation and neovascularization, and preventing ulceration in acute alkali burns. Providing AMT after suppressing inflammation may be a more effective treatment.