Search

Corneal alkali burns persist as a significant challenge in our field, often leading to a prolonged treatment course with various sight-threatening problems. This work, of utmost importance, aimed to apply the photo-tissue bonding technique (PTB) to weld the amniotic membrane (AM) to the corneal surface versus an amniotic membrane graft (AMG) and explore its safety in saving corneal protein against alkali burn.Methods Twenty-seven rabbits with an induced corneal ulcer using 1 mol/L NaOH solution. Nine rabbits were used as an ulcer group without treatment, and the rest (n = 18) were subjected to two treatment protocols with AM. The first was attaching the AM to the corneal ulcer through photo-tissue bonding using 532 nm and rose Bengal stain as a photosynthesizing agent. The second was using cyanoacrylate glue as a tissue adhesive. The corneal total protein (TP), refractive index (RI), DNA fragmentation, and oxidative stress index (OSI) were evaluated. Results: The cornea's TP showed a significant decrease (p˂0.001) immediately, 1 week, and 2 weeks after ulcer induction (-58.9%, -64.4%, and - 72.6%, respectively). The treatment with AM PTB showed improvement immediately (-45.2%, p˂0.001), after one week (-27.4%, p˂0.01), and after two weeks (-14.38%, p˂0.05). Moreover, the treatment with AMG showed improvement after the same periods with percentage changes of -52.05%, (p˂0.001), -41.8% (p˂0.001), and - 32.2%, (p˂0.01) with respect to the control. Moreover, RI of corneal protein showed improvement after two weeks of treatment with AM PTB (3%, p˃0.05) and AMG (7%, p˃0.05), respectively. The corneal protein DNA base pairs improved 88.49% for AM PTB and 82.35% for the AMG group. The oxidative stress was shifted towards an antioxidative state in AM PTB (-3.9%, P > 0.05) and the AMG group (15.9%, P < 0.05). Conclusion: The AM PTB technique used in corneal ulcers showed promising improvement in total corneal proteins, refractive index, DNA fragmentation, and OSI than AMG using cyanoacrylate glue. These results strongly support the use of AM PTB for ophthalmic purposes, suggesting its potential to enhance clinical research and practice for patients with corneal ulcers and ocular surface diseases., Competing Interests: Competing interests: The authors declare no competing interests. Ethical statement: The Institutional Animal Care and Use Committee, Cairo University (CU-IACUC) approved the study with approval no. 1/F/30/19. All experiments were performed in accordance with the relevant guidelines and regulations. All methods were conducted in compliance with the ARRIVE guidelines. We ensured animal welfare and minimalized animal suffering during the experiment., (© 2024. The Author(s).)

Background: Chemical eye injuries are potentially sight-threatening injuries, representing 10-22% of all ocular trauma presentations. Prompt assessment and management of chemical eye injuries in general practice and urgent care clinic settings can prevent patients from losing vision., Objective: This article presents a clinically useful guide for general practitioners to support the primary management of chemical-related eye injuries, particularly in rural and regional settings. This article will first discuss the variety of chemical eye irritants found in domestic and commercial settings. It will then describe the steps for assessment of chemical-related eye injuries, methods for irrigation and post-irrigation management., Discussion: Among chemical eye injuries occurring in rural areas, cleaning agents are the most common cause, followed by injuries from personal products, industrial agents, pesticides and herbicides, and petroleum-based products. General practitioners should conduct an initial assessment and instigate immediate management of chemical eye injuries. Advice about the pH level of substances can be obtained from the Poisons Information Centre. Chemical eye injuries coinciding with an epithelial defect or decreased vision should be reviewed by an ophthalmologist within 24 hours of the initial injury.

Purpose: To evaluate the efficacy of topical erythropoietin for chemical burn induced scleral necrosis., Methods: This study included 18 eyes of 16 patients with chemical burn induced scleral necrosis who presented within 6 weeks of the injury. In the prospective arm, 11 eyes received topical erythropoietin, 3000 IU/mL every 6 h, along with standard medical treatment. Retrospectively, we included 7 consecutive eyes of 7 patients who were managed with conventional treatment as historical control group. The main outcome measure was healing of avascular scleral lesions. The secondary outcome measure was complete re-epithelization of cornea., Results: Mean patient age was 39.8 ± 16.2 years in the erythropoietin group, and they presented 16.6 ± 15.2 days after acute chemical injury. Scleral necrosis improved in all eyes after 30.7 ± 23.2 days of treatment with topical erythropoietin. Corneal epithelial defects were completely healed in 10 eyes 61.9 ± 50.7 days after the start of the medication. In comparison, standard medical treatment alone did not improve scleral necrosis in the historical control group, necessitating ocular surface reconstruction including conjunctival advancement (1 eye) and tenonplasty (6 eyes)., Conclusion: The results of our study showed that topical erythropoietin was effective in the management of chemical burn induced scleral necrosis. This treatment could avoid ocular surface reconstruction procedures in inflamed eyes., Competing Interests: Declaration of Competing Interest The authors do not have competing interests to declare., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

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.

Chemical burns of the ocular surface (CBOS) are emergencies of highest urgency. Therefore, an adequate emergency care is mandatory. Following a precise analysis of the initial damage, a staged therapeutic approach is used to prevent persistent impairment of the ocular surface. In the acute stage, the prevention of complications is targeted (symblepharon, conjunctival scarring, lacrimal stenosis, corneal ulceration, intraocular inflammation, elevated intraocular pressure, etc.). In later stages, if complications have developed, a secondary restoration of the ocular surface is focussed. Sometimes this requires several surgical interventions. Based on a review of international literature, this review highlights the pathophysiology according to different chemical agents, CBOS stages as well as main therapy strategies in early and advanced stages of CBOS. Acute treatment aims to lower inflammation, oxidative stress and tries to promote reepithelialisation. Besides conjunctival scarring, loss of goblet cells and corneal opacification a limbal stem cell insufficiency is the most harming complication. Several new techniques have been developed to recover the ocular surface with a sufficient and clear epithelial layer in order to avoid neovascularization of the cornea. The knowledge concerning the high risk potential for persistent visual impairment in CBOS patients and the ability for appropriate emergency care should be kept in every physician's mind dealing with CBOS., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

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., (Copyright © 2024 SFMTSI.)

Pediatric ocular burns carry a risk of permanent vision impairment. This study identifies risk factors that place these patients at high risk of permanent visual complications. A retrospective review was conducted in our academic urban pediatric burn center. All 300 patients under 18 years of age admitted from January 2010 to December 2020 with periorbital or ocular thermal injuries were included. Variables analyzed included patient demographics, burn characteristics, ophthalmology consultation, ocular exam findings, follow up time period, and early and late ocular complications. Etiologies of burn injuries were as follows: 112 (37.5%) scald, 80 (26.8%) flame, 35 (11.7%) contact, 31 (10.4%) chemical, 28 (9.4%) grease, and 13 (4.3%) friction. Overall, 207 (70.9%) patients with ocular burns received an ophthalmology consult. Of these patients, 61.5% had periorbital cutaneous burns and 39.8% had corneal injuries, and only 61 (29.5%) presented for a follow-up visit. Ultimately, six had serious ocular sequelae, including ectropion, entropion, symblepharon, and corneal decompensation. While thermal burns involving the ocular surface and eyelid margins are relatively infrequent overall, they carry a small risk of serious to long-term sequelae. Recognizing those at greatest risk, and initiating appropriate early intervention is critical., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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 ınjury of intraocular structures were found to have a great influence on the outcome of their visual acuity., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to evaluate the effect of bovine colostrum (BC) in the regeneration of corneal epithelial cells on an ocular alkali burn model. Twenty-four C57BL/6 mice were categorized into two gender/age-matched groups for treatment. Two days after inducing a corneal alkali burn in all left eyes with 4 μl of sodium hydroxide 0.15 mol/l, both eyes of group 1 were treated with BC 4 times per day, and both eyes of group 2 were treated with isotonic saline solution (SS). The epithelial defect was photographed and measured by fluorescein staining on days two, four, seven, and ten. Ocular burn damage was assessed with a pre-established classification in clock hours from the limbus. After 10 days both eyes were processed, half of the group's corneas were assessed histopathologically, and the other half was used for pro/anti-inflammatory cytokine quantification using ELISA. BC treated (Group 1) corneas revealed significantly improved fluorescein staining score for limbal involvement when compared to SS treated (Group 2) corneas at days 4 (p = 0.013), 7 (p < 0.001), and 10 (p < 0.001), respectively. No differences were noted in limbal involvement at day 2 between the two groups (p > 0.99). The overall change (difference in slope) in fluorescein staining for limbal involvement between days 2 and 10 was -0.1669 (p = 0.006). Histologic examinations and cytokine measurements of group 2 demonstrated a strong inflammatory component compared to group 1. Our data indicates that topical application of BC facilitates corneal re-epithelialization and wound healing by suppressing the inflammatory process in an ocular alkali burn model., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Contact Lens Association of Ophthalmologists.)

We aimed to evaluate the characteristics and colonization by pathogenic microorganisms of the ocular surface in patients in a burn center and to determine their association with sedation, mechanical ventilation, and periocular burn. We prospectively evaluated 40 patients during an 8-mo period. Five evaluations where performed, at baseline and weekly on four more occasions or until hospital discharge or death. On each visit, we assessed periocular burn, lid position, Bell's phenomenon, Schirmer's test, presence of chemosis, conjunctival hyperemia, and exposure keratopathy; conjunctival fornix swabs were taken for microbiology culture. Also, we documented the level of sedation, mechanical ventilation status, and systemic and ocular treatment. Absent Bell's phenomenon and chemosis were significantly different at baseline in patients under mechanical ventilation, sedation, and in those with a periocular burn. The cumulative incidence of exposure keratopathy was 22.5% and the cumulative incidence of ocular surface colonization by pathogenic microorganisms was 32.5%. Both outcomes were associated with mechanical ventilation and periocular burn. The most frequent pathogenic microorganisms on the ocular surface were Candida parapsilosis, Acinetobacter baumanii, and Pseudomonas aeuroginosa. We did not observe any case of a persistent epithelial defect, infectious keratitis, corneal perforation or corneal opacity in this cohort. Results from our study may benefit future patients by allowing better risk stratification and treatment strategies for the ocular surface care in burn units., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To describe the management and outcome of an ocular surface alkali burn in the setting of previous laser in situ keratomileusis (LASIK)., Methods: This is a case report and review of relevant literature., Results: A 25-year-old man with a history of LASIK presented 4 weeks after a sodium hydroxide splash to his left eye with visual acuity of 20/60 and a nonhealing epithelial defect adjacent to sectoral inferior limbal ischemia in the setting of trichiasis from upper eyelid cicatricial entropion. After topical corticosteroids were discontinued following the repair of the entropion, the patient returned 3 days later with worsening vision and severe diffuse lamellar keratitis with the melting of the LASIK flap. After promptly lifting the flap and debriding the interface, inflammation was managed with oral, instead of topical, corticosteroids. Over several weeks, the epithelium healed, and inflammation and interface edema resolved. At 10 years of follow-up, the patient had developed a localized pseudopterygium with mild corneal neovascularization but maintained 20/20 uncorrected visual acuity., Conclusions: A chemical burn over a LASIK flap poses a challenge for managing corticosteroids, which are required to prevent diffuse lamellar keratitis but can also contribute to keratolysis beyond the first week after an alkali injury. Oral corticosteroid therapy may be beneficial in this situation, with a low threshold to lift the LASIK flap and debride the interface if inflammation occurs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Oxidative stress-related ocular surface epithelial damage can be initiated by ambient oxygen, UV radiation, and chemical burns. The oxidative damage to cornea can lead to inflammation and even vision loss. Lingzhi (Ganoderma lucidum) is a Chinese herbal drug and has been shown to prevent chronic diseases in clinical practices and has been proven to possess anti-oxidative and anti-inflammatory properties. In the study, we prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as a sustained drug release system of Lingzhi (LZH) to improve bioavailability. The particle size of developed NPs containing LZH (LZH-NPs) was ~184 nm with narrow size distribution. The results of cellular uptake revealed that using NPs as a drug delivery system could significantly increases the intracellular retention time. The results of the cell viability and chemiluminescence assay revealed that 5 μg/ml of LZH-NPs might be the threshold concentration for cultivation of corneal epithelial cells. After treating LZH-NPs in oxidative damaged cells, the results showed that the inflammation-related gene expression and DNA fragmentation level were both significantly decreased. Post-treatment of LZH-NPs in damaged corneal epithelial cells could increase the cell survival rate. In the rabbit corneal alkali burn model, topical instillation of LZH-NPs could promote corneal wound healing and decrease the inflammation. These results suggest that LZH-NPs may have the potential to treat ocular surface diseases caused by oxidative stress., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Eye burns, which are usually caused by chemicals such as acidic, alkaline and heat-related substances, are true medical emergencies. These substances can lead to potential permanent damage to the eyelids, cornea, ocular surface and intraocular tissues. In severe cases, eye burns may result in blindness. Currently, there is a lack of uniform and standardized guidelines for the diagnosis and treatment of eye burns. As a result, a considerable number of patients have a poor prognosis. Therefore, the Cornea Group of Chinese Ophthalmological Society has developed this consensus statement after thorough discussions, hoping to provide guiding opinions on the clinical diagnosis and treatment of eye burns. (Chin J Ophthalmol, 2021, 57:254-260) .

Purpose: This study aimed to investigate the therapeutic effects and underlying mechanisms of locally delivered regulatory T cells (Tregs) on acute corneal wound healing after alkali burn., Methods: After corneal alkali burn, the mice were injected subconjunctivally with regulatory T cells (Tregs) isolated from syngeneic mice. The wound healing process was monitored by clinical manifestation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). As amphiregulin (Areg) was significantly upregulated, its reparative function in injured corneas was suggested. The hypothesis was further verified via loss- and gain-of-function experiments by administrating the antibody of Areg (anti-Areg) and recombinant Areg (rmAreg)., Results: Subconjunctivally injected Tregs rapidly migrated to injured corneas. The mice treated with Tregs showed prominently reduced corneal opacity, alleviated edema, and faster re-epithelialization compared with the control group. Mechanistically, Treg treatment led to suppressed infiltration of inflammatory cells, along with improved proliferation and inhibited apoptosis of corneal epithelial cells. Tregs expressed upregulated functional markers, including Areg. Expectantly, the levels of Areg in corneas were dramatically higher in the Treg injection group, in line with better corneal restoration. Additional experiments showed that the administration of anti-Areg blunted the reparative effect of Tregs, while exogenous Areg enhanced it. Treg-treated corneas also exhibited less neovascularization and fibrosis at a later reconstruction stage of corneal repair., Conclusions: The findings showed that the subconjunctival injection of Tregs effectively promoted corneal wound healing by inhibiting excessive inflammation and enhancing epithelial regeneration, with an indispensable reparative role of Areg. Subsequent complications of corneal vascularization and fibrosis were therefore reduced.

Competing Interests: Competing interests: None declared.

Eye burns due to the accidental application of pharmacological or nonpharmacological substances packaged in plastic dropper bottles have been described for more than three decades and continue to occur. These burns can cause potentially serious corneal injuries. We report the case of a patient who mistakenly applied salicylic acid to the right eye after confusing it with an eye lubricant, which caused him a severe corneal burn. Fortunately, after aggressive medical and surgical management (including oxygen therapy and amniotic membrane grafting), the visual results were good. We suggest conducting educational campaigns and taking legislative measures in our country to avoid packaging corrosive substances in this type of dropper bottle to reduce the risk of accidental burns.

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., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Corneal chemical burns can lead to blindness following serious complications. As most of these complications are caused by failure of reepithelization during the acute phase, treatment at this stage is critical. Although there have been some studies on corneal injury recovery using adipose tissue-derived stem cells (ADSCs), none has reported the effect of topical cell-free conditioned culture media (CM) derived from ADSCs on corneal epithelial regeneration. Here, the best conditions for CM were selected and used for in vitro and in vivo experiments. Corneal burn in rats was induced using 100% alcohol. The chosen CM was administered to corneal burn rats (CM-treated [CT] group) four times a day for three days and this group was compared with the normal control and corneal burn (CB) groups. Biomicroscopic fluorescence images and the actual physical corneas were taken over time and used for analysis. mRNA levels of hepatocyte growth factor and epidermal growth factor (EGF) were significantly increased, whereas those of vascular endothelial growth factor, interleukin (IL)-1β, IL-6, IL-10, and matrix metalloproteinase-9 were significantly decreased in the CT group compared with those in the CB group. The numbers of proliferating cell nuclear antigen- and zonular occludens-1-positive cells in the CT group were significantly higher than those in the CB group. The macrophage-infiltrating corneas in the CT group expressed significantly more of the M2 marker arginase than corneas in the CB group. Optimal CM (× 0.5 concentration) treatment significantly accelerated the migration of corneal epithelial cells and induced upregulation of the expression of IL-6, EGF, and C-X-C chemokine receptor type 4 mRNAs. Overall, in this study, topical administration of cell-free CM promoted regeneration of the corneal epithelium after induction of 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.

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., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

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 Ca 2+ /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., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

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., (© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Competing Interests: Competing interests: None declared.

Purpose: There is currently uncertainty about the most efficacious decontamination solution for corrosive chemical eye burns. This 30-year longitudinal study evaluated the relative efficacy of two different decontamination methods. Passive decontamination consists of rinsing with tap water, 0.9% normal saline, isotonic buffered phosphate solution, or Ringer's lactate. Active decontamination adds an amphoteric, polyvalent, and chelating component with Previn® (Diphoterine®) solution (Laboratoire Prevor, Valmondois, France)., Methods: A prospective evaluation of patients treated in two specialized eye clinics for eye burns was begun in 1988. Recorded data included exposure circumstances, type of corrosive, different types of first therapy, and clinical treatment and outcome. Patients were treated from clinic admission and up to 24 h after the corrosive chemical burn with rinsing for 15 min using two different protocols. From 1988 to 2005, sterile 0.9% normal saline or Ringer's lactate was used. Since 2006, sterile, hypertonic, amphoteric Previn® solution was used. Comparative statistical analysis was done with the Fisher contingency tables and Wilcoxon tests., Results: There were a total of 1495 patients with 2194 chemically burned eyes. In 1988-2005, the annual incidence was 66.1/year; in 2006-2017, it was 65.5/year. Similar incidences were noted when initial rinsing was with tap water or isotonic buffered phosphate solutions. There was a significantly more severe outcome of corrosive chemical eye burns with any first aid rinsing solutions other than Previn® solution or tap water was used (p < 0.001). Previn® solution or tap water rinsing in the pre-hospital setting and secondary rinsing with Previn® solution in the hospital decreased lesion severity in comparison with all other rinsing solutions (p < 0.001)., Conclusion: The frequency of corrosive chemical eye burns was comparatively high despite tightening of occupational health and safety regulations over the past 30 years. The severity of corrosive chemical eye burns has been dramatically decreased since the introduction of Previn® solution for initial and secondary rinsing. A new protocol for immediate Previn® solution use by the Cologne Fire Brigade and secondary Previn® solution rinsing in hospital has reduced the frequency of severe corrosive chemical eye burns to less than 60% as compared to the period of 1988-2005 when other rinsing solutions were utilized.

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.

Purpose: To compare the outcomes of conventional medical treatment vs combined medical treatment and amniotic membrane transplantation (AMT) in the management of patients with Roper-Hall grade IV ocular chemical injury., Design: Randomized, parallel-controlled clinical trial., Methods: Setting: Single tertiary referral hospital., Patients: Sixty eyes of 60 patients with Roper-Hall grade IV ocular chemical injury with a minimum follow-up of 12 months were enrolled in the study., Intervention: Patients were randomly assigned to 2 groups: Group 1 (30 eyes) received topical preservative-free lubricating gel and drops, chloramphenicol, betamethasone, homatropine, oral vitamin C, and doxycycline; Group 2 (30 eyes) received amniotic membrane transplant (AMT) on the entire ocular surface in addition to the medical treatment provided in Group 1., Outcome Measures: The main outcome measure was time to complete corneal epithelialization. Secondary outcome measures were best-corrected visual acuity (BCVA) and neovascularization in the central 5 mm of the cornea., Results: Mean follow-up time was 20.3 ± 2.5 months (range 13-24 months). Corneal epithelial defects healed within 72.6 ± 30.4 (21-180) days in Group 1 vs 75.8 ± 29.8 (46-170) days in Group 2 (P = .610). Mean BCVA was 2.06 ± 0.67 (0.4-2.6) logMAR vs 2.06 ± 0.57 (1-2.9) logMAR in Groups 1 and 2, respectively (P = .85). Group 1 developed more central corneal neovascularization (22 eyes; 73.3%) compared to Group 2 (16 eyes; 53.3%); however, it was not statistically significant (P = .108)., Conclusions: In comparison to conventional medical therapy, combined amniotic membrane transplantation and medical therapy does not accelerate corneal epithelialization or affect final visual acuity in severe chemical injuries., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

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 Sprague‑Dawley female rats were divided into a normal group (Control), a normal MSC treatment group (Normal MSCs), an miR146a knockout MSC treatment group (miR146a‑low MSCs) and an miR146a high‑expression MSC treatment group (miR146a‑high 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)‑γ and interleukin (IL)‑10 by ELISA. The miR146a‑high MSCs improved cell viability of MSCs and inhibited apoptosis of MSCs following alkali burn. miR146a‑high MSCs decreased the expression levels of p65NF‑κB and PCNA, and enhanced the expression level of Fas. Furthermore, miR146a‑high MSCs improved the cornea opacity and enhanced the inhibition of neovascularization in the rats following alkali burn. miR146a‑high MSCs inhibit the expression of VEGF, CD45, IFN‑γ, while enhanced the expression of IL‑10. Therefore, miR146a promotes the repair of corneal alkali burn in rats treated with MSCs.

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., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Ocular chemical burns are an ophthalmic emergency and are responsible for 11.5%-22.1% of ocular injuries. Immediate copious irrigation is universally recommended in acute ocular burns to remove the offending agent and minimize damage. Conventional medical therapy consists of the use of agents that promote epithelialization, minimize inflammation, and prevent cicatricial complications. Biological fluids such as autologous serum, umbilical cord blood serum, platelet-rich plasma, and amniotic membrane suspension are a rich source of growth factors and promote healing when used as adjuncts to conventional therapy. Surgical treatment of acute ocular burns includes the debridement of the necrotic tissue, application of tissue adhesives, tenoplasty, and tectonic keratoplasty. Amniotic membrane transplantation is a novel surgical treatment that is increasingly being used as an adjunct to conventional treatment to promote epithelial healing, minimize pain, and restore visual acuity. Various experimental treatments that aim to promote wound healing and minimize inflammation are being evaluated such as human mesenchymal and adipose stem cells, beta-1,3 glucan, angiotensin-converting enzyme inhibitors, cultivated fibroblasts, zinc desferrioxamine, antifibrinolytic agents, antioxidants, collagen cross-linking, and inhibitors of corneal neovascularization., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Purpose: To evaluate the results of cultivated limbal epithelial and oral mucosal epithelial transplantation (CLET and COMET) in limbal stem cell deficiency (LSCD)-induced rabbit model., Materials and Methods: Six New Zealand white rabbits were divided into two groups of three rabbits each. Limbal tissue was harvested from the first group, and oral mucosal biopsy was obtained from the second group. The tissues were cultured using an explant technique with amniotic membrane as a substrate and co-culture with the 3T3 fibroblast and air-lifting method. The right eye of each rabbit was induced to have LSCD using alkali burns. After three weeks, the LSCD-induced rabbit eyes were transplanted with the cultivated limbal and oral mucosal epithelial sheet in the first and second group, respectively. The transplanted eye was evaluated weekly post-operation. After 2 months, all transplanted eyes were enucleated and the epithelial morphology and phenotype of ocular surfaces were studied and compared with normal corneal and oral mucosal tissue., Results: At 2-month post-transplantation, the eyes of four animals recovered with corneal transparency, one partially recovered, and one failed. The histology of the majority of transplanted eyes was stratified layers of corneal epithelia similar to normal rabbit cornea with some different findings such as goblet cells in the limbal region. Corneal epithelial thickening and stromal vascularization in two animals were observed. Phenotypic characterization of transplanted eyes showed a similar pattern of marker expression with the absence of p63 expression in the limbal or corneal epithelium in the COMET group., Conclusions: The histology and phenotype of transplanted eyes after CLET and COMET were most likely to have similar characteristics as a normal healthy rabbit eye even though the COMET eyes have some inferior characteristics to the CLET eyes.

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.

Purpose: To evaluate the efficacy of mannitol solution as a decontamination agent on the chemical burn of the human corneas., Methods: Eight donor corneas from an eye bank were exposed to 25μl of 2.5% hydrofluoric acid (HF) solution on a filter paper for 20s. Three eyes were rinsed with 1000ml of mannitol 20% for 15min immediately after removal of the filter paper, 3 other were rinsed with sodium chloride (NaCl) 0.9% (1000ml for 15min) and two eyes were not rinsed. Microstructural changes were monitored in the time domain by optical coherence tomography (OCT) imaging for 75min., Results: NaCl reduced the penetration depth to approximately half the thickness of the cornea at 15min; scattering within the anterior cornea was higher than that for the unrinsed eye. With mannitol, no increased scattering was observed in the posterior part of the corneal stroma within a time period of 1h after rinsing. OCT images revealed low-scattering intensity within the anterior stroma at the end of the rinsing period., Conclusion: In eye bank human corneas, mannitol proved to be an efficient agent to decontaminate HF burn., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Reports of laser-induced ocular injuries have become more frequent in recent years, especially due to high-energy laser pointers. The article presents for the first time in the German literature a case of self-inflicted laser-induced maculopathy in an adolescent. In addition to the clinical findings, the results of funduscopy and spectral domain optical coherence tomography (SD-OCT) follow-up are presented.