Effect of topical bovine colostrum in wound healing of corneal surface after acute ocular alkali burn in mice.

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.

PLGA nanoparticles containing Lingzhi extracts rescue corneal epithelial cells from oxidative damage.

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.

Topical cell-free conditioned media harvested from adipose tissue-derived stem cells promote recovery from corneal epithelial defects caused by chemical burns.

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)-1ß, 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.

Treatment of acute ocular chemical burns.

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.

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.

Short-term effects of extremely low-frequency pulsed electromagnetic field and pulsed low-level laser therapy on rabbit model of corneal alkali burn.

This study was conducted to investigate the effect of combining extremely low frequency-pulsed electromagnetic field (ELF-PEMF) and low-level laser therapy (LLLT) on alkali-burned rabbit corneas. Fifty alkali-burned corneas of 50 rabbits were categorized into five groups: ELF-PEMF therapy with 2 mT intensity (ELF 2) for 2 h daily; LLLT for 30 min twice daily; combined ELF-PEMF and LLLT (ELF + LLLT); medical therapy (MT); and control (i.e., no treatment). Clinical examination and digital photography of the corneas were performed on days 0, 2, 7, and 14. After euthanizing the rabbits, the affected eyes were evaluated by histopathology. The clinical and histopathologic results were compared between the groups. On days 7 and 14, no significant difference in the corneal defect area was evident between the ELF, LLLT, ELF + LLLT, and MT groups. Excluding the controls, none of the study groups demonstrated a significant corneal neovascularization in both routine histopathology and immunohistochemistry for CD31. Keratocyte loss was significantly higher in the MT group than in the ELF, LLLT, and ELF + LLLT groups. Moderate to severe stromal inflammation in the LLLT group was comparable with that in the MT group and was significantly lower than that in the other groups. In conclusion, combining LLLT and ELF was not superior to ELF alone or LLLT alone in healing corneal alkali burns. However, given the lower intensity of corneal inflammation and the lower rate of keratocytes loss with LLLT, this treatment may be superior to other proposed treatment modalities for healing alkali-burned corneas.

Conjunctival proliferation after a mild pepper spray injury in a young child.

PURPOSE: To report a case of conjunctival proliferation in a 2.5-year-old boy after initial evidence of a mild chemical injury after ocular exposure to pepper spray (oleoresin capsicum). METHODS: Case report with ophthalmologic and histologic findings. RESULTS: A child presented with mild conjunctival injection and chemosis without any corneal erosion after direct exposure to pepper spray. Three weeks later, a significant conjunctival proliferation was found at the limbus, which was refractory to treatment with topical corticosteroids. Finally, proliferative tissue was surgically excised without clinical recurrence during 2 months of follow-up. CONCLUSIONS: We hypothesize that the young age of the patient may have been an important factor for the severe conjunctival proliferation in comparison to a mainly uncomplicated course of pepper spray injuries in most adults. We recommend the use of topical antiinflammatory treatment even in apparently mild pepper spray injuries, especially in young children.

Ocular burn: rinsing and healing with ionic marine solutions and vegetable oils.

PURPOSE: We investigated the effects of various rinsing and healing protocols on corneal wound repair and inflammation following alkali burn in rabbits. METHODS: We conducted in vitro, in vivo and ex vivo studies. First, different rinse solutions were tested in vitro after incubation of ocular cells with methanol or NaOH. Cell viability was then assessed using the neutral red test (cytofluorometry). Second, NaOH was applied to rabbit corneas and associations of rinse solutions (NaCl 0.9% or controlled ionization marine solutions) with N-acetylcysteine or vegetable oils (from Calophyllum inophyllum and Aleurites moluccana) were tested in vivo. The regeneration of the corneal epithelium and the infiltration of inflammatory cells were evaluated using in vivo confocal microscopy and ex vivo histological cuts. RESULTS: The association of a controlled ionization marine solution with 10% C. inophyllum oil and 90% A. moluccana oil induced regeneration of the corneal epithelium and a decrease in inflammatory cells. CONCLUSIONS: Irrigation with marine solution followed by treatment with a mixture of C. inophyllum and A. moluccana oils is a promising treatment for ocular burns.

[Significance of immediate affixation of a hard contact lens in the emergency treatment of severe alkali burns of the cornea (case report)]. / Die Bedeutung der frühzeitigen Aufklebung harter Kontaktlinsen in der Notfallbehandlung schwerer Alkaliverätzungen der Hornhaut (Fallbericht).

BACKGROUND: Severe alkali burns lead to massive limbal stem cell damage resulting in persistent epithelial defects, infiltration and stromal melting early in the disease process. A glued-on hard contact lens may serve as an "artificial epithelium" and protect the cornea from these complications. CASE REPORT: A 39-year-old male presented with severe lime burns in both eyes one week after injury. The right eye showed a totally denuded cornea and conjunctiva with circular paralimbic ischemia. In the left eye "only" two thirds of the cornea and adjacent conjunctiva and limbus were affected with less ischemia. Amniotic membrane transplantation was performed in both eyes but failed after four days already in the right eye. A hard contact lens was therefore glued on the right eye and allowed for visual acuity of 0.4 without correction in this primarily most heavily afflicted eye for 12 months duration. After removal of the contact lens, reepithelisation was quick, and function remained stable with addition of autologous serum eye drops. The primarily far less injured left eye, however, for which the amniotic membrane surgery was primarily judged to be adequate, could not be stabilised. The cornea perforated 4 weeks later necessitating a mini-keratoplasty plus a glued-on contact lens, and correctable vision never became better than 1/35. CONCLUSION: The clinical course confirms former observations that a glued-on hard contact lens is an effective treatment early after alkali burn and prevents the cornea from infiltration and melting. Moreover, two aspects merit consideration: first, with proper technique and timing of the gluing-on a patient may retain useful vision throughout the period of wearing the contact lens; second, for the long period during which the cornea was sealed by the contact lens, improper repopulation by conjunctival epithelium was inhibited, and proper corneal epithelium was given a chance for repopulation after recovery of the limbal area resulting in a stable surface and useful vision without additional keratoplasty measures.

Modern concepts of treatment and prevention of chemical injuries.

Chemical injuries are commonly encountered following exposure to acids and alkali, including hydrofluoric acid, formic acid, anhydrous ammonia, cement, and phenol. Other specific agents that cause chemical burns include white phosphorus, elemental metals, nitrates, hydrocarbons, and tar. Even though there are more than 65,000 chemicals available on the market, and an estimated 60,000 new chemicals produced each year, the potential deleterious effects of these chemicals on humans are still unknown. The Superfund Amendments and Reauthorization Act contains extensive provisions for emergency planning and the rights of communities to know about toxic chemical releases. Since 1990, the Agency for Toxic Substances and Disease Registry (ATSDR) has maintained an active, state-based Hazardous Substances Emergency Events Surveillance (HSEES) system to describe the public health consequences risked by access to hazardous chemicals. Most chemical agents damage the skin by producing a chemical reaction rather than hyperthermic injury. Although some chemicals produce considerable heat as a result of an exothermic reaction when they come in contact with water, their ability to produce direct chemical changes on the skin accounts for the most skin injury. Specific chemical changes depend on the agent, including acids, alkalis, corrosives, oxidizing and reducing agents, desiccants, vesicants, and protoplasmic poisons. The concentration of toxic agent and duration of its contact primarily determine degree of skin destruction. Hazardous materials (hazmats) are substances that may injure life and damage the environment if improperly handled. HAZMAT accidents are particularly dangerous for responding personnel, who are in danger from the moment of arrival on the scene until containment of the accident. Consequently, the Superfund Amendment and Reauthorization Act mandates community preparedness for dealing with hazmat accidents. Paramedics and members of the hazmat response team (usually firefighters) must work together to identify toxic chemicals and assess hazardous environments. The contingency plan for hazmat management can be divided into two parts: initiation of the site plan and evacuation. In coping with hazmat incidents, two distinct goals must be achieved concomitantly. First, hazmats must be contained, fire and explosions must be extinguished, and the site eventually must be cleaned. Second, those exposed to hazmats must be treated at the scene of contamination as well as in the hospital and rehabilitation setting.

Ocular irrigant alternatives in pediatric emergency medicine.

Minimizing pain and discomfort is an important consideration in pediatric ocular decontamination. The pH of an irrigant solution plays a significant role in its tolerability, because a solution with a pH that is too low or too high may cause edema and discomfort to the conjunctiva. We reviewed several available ocular irrigation solutions with respect to their chemical composition, pH, and cost efficiency. Currently, the irrigation solution of first choice for most ocular decontaminations in the pediatric emergency department (ED) is 0.9 % saline solution or normal saline (NS), which has a pH range between 4.5 and 6.0. Alternative ocular irrigant solutions available include Lactated Ringers solution (LR), which has a pH range between 6.2 and 7.5, buffered NS with pH adjusted to 7.4 with sodium bicarbonate, and Balanced Salt Solution Plus (BSS Plus), which has a pH of 7.4. Of these alternative solutions, all except BSS Plus are comparable in cost efficiency to NS. The use of more pH neutral solutions such as LR, NS with bicarbonate buffer, or BSS Plus may decrease ocular pain and irritation associated with copious irrigation, and may improve tolerance of ocular decontamination by a child.

Ocular injuries caused by mustard gas: diagnosis, treatment, and medical defense.

Sulfur mustard has been used as a vesicant chemical warfare agent. To investigate the ocular damage it causes, we studied the effects on chemical casualties in the Iran-Iraq War. The patient population consisted of more than 5,000 chemical casualties, both military and civilian. The range of ocular damage was wide. The most common ocular effects were conjunctivitis and photophobia. Patients with significant corneal involvement are at risk for corneal ulceration and rarely for anterior chamber scarring and neovascularization, any of which would result in prolonged disability. In conclusion, the eye is the organ most sensitive to sulfur mustard vapor. Ocular injuries generally heal completely. In severe cases, blindness may occur. The need for corneal transplantation is rare.

Personal defense sprays: effects and management of exposure.

BACKGROUND: Most personal defense sprays contain o-chlorobenzylidene malononitrile (CS), w-chloroacetophenone (CN), oleoresin capsicum (OC), or a combination of these ingredients as the active agent. They are designed to incapacitate by causing acute ocular irritation, lacrimation, conjunctivitis, blepharospasm, and mild to moderate respiratory distress. METHODS: To assess the ocular effects of sprays containing OC as the active agent. Snellen visual acuities and anterior segment appearances of 22 police officers were determined before and after spray exposure. To assess the effects of OC spray contamination on soft contact lenses, four brands of lenses were sprayed and cleaned twice with an alcohol-based cleaner. Gas chromatography was used to search for residual OC in the lenses. RESULTS: All officers experienced intense blepharospasm, lacrimation, conjunctivitis, and incapacitation as the result of spray exposure. Acute effects lasted about 5 to 10 min, with relatively complete recovery occurring in about 30 to 60 min. All had significant conjunctivitis, and some had water-drop-shaped corneal defects that stained with fluorescein. These defects resolved within 24 hours without treatment. OC residue was found to be present in the soft lenses that had been sprayed and cleaned twice. CONCLUSIONS: Optometrists can manage uncomplicated spray exposure patients by directing at-home irrigation with water, and following up with an in-office examination. Soft lenses contaminated by OC spray should be discarded.

[Late results of the treatment of eye burns]. / Odlegla ocena wyników leczenia oparzen oczu.

An analysis of patients treated in the Ophthalmic Department in Bydgoszcz for eye burns in the 10 years period from 1980 till 1990. Taken into account were the causes of burns, the treatment installed in the early period and in cases of late complications. All the patients were asked to call in for a control examination in order to compare the condition of the eyes at the date of discharge and in the long-lasting time. Among 118 eyes in 91 the visual acuity amounted 0.5-1.0, in the remaining 25 it was only hand movements--0.4. The main causes of low visual acuity were: corneal leucoma, secondary glaucoma, complicated cataract. The eye was enucleated in 2 patients because a painful ocular atrophy developed in the course of the pathological process. These were the cases of thermal burns combined with a mechanical injury. The obtained results were evaluated as sufficiently favourable and comparable to the data of other authors.

[Subconjunctival autohemotherapy of eye burns in our cases]. / Podspojówkowa autohemoterapia oparzen oczu w obserwacji wlasnej.

The authors present the results of subconjunctival autohemotherapy of thermal and chemical burns in 940 eyes which concerned 734 patients; simultaneously they discuss the causes of these burns. The obtained results confirm the very well known opinion that subconjunctival autohemotherapy applied together with the vasodilating drugs is still a very valuable method in the treatment of ocular burns.

[The antiphlogistic effect of the ginkgolide BN 52 021 in the chemically burned rabbit eye]. / Zur antiphlogistischen Wirksamkeit des Ginkgolids BN 52 021 bei der Verätzung des Kaninchenauges.

BN 52 021, a specific antagonist of PAF receptors, was tested in the early-phase treatment of chemically burned eyes in 30 rabbits. The local application of BN 52 021 eyedrops-1% (water-soluble preparation, 5 times daily, in comparison with the other eye as a control) led to a visible anti-inflammatory effect (microscopically and macroscopically) of the chemically burned anterior eye segment. There was only a moderate increase of the concentration of PGF2 alpha after the chemical burn. The use of specific PAF antagonists seems to have a real chance for treatment of inflammatory reactions of the anterior eye segment. A combination with other mediator antagonists should be tested in further experiments.

Chemical burns.

In chemical skin injuries, reduction of the time of exposure to the causative agent and recognition of systemic toxicity are necessary to lessen the severity of the insult, reduce morbidity, and maximize survival. During a 17-year period (1969 through 1985), 87 (2.1%) of the 4,212 burned patients admitted to the U.S. Army Institute of Surgical Research sustained chemical burns. Twelve of 87 patients died (13.8%). White phosphorous, the most common causative agent, produced cutaneous injury in 49 patients. Acids (13 patients), alkalies (ten patients), and organic solvents (five patients) were the other common causes of injury. Initial treatment consisted of water lavage. Later wound management was carried out with topical antibiotic therapy and excision and grafting as necessary. Systemic toxicity due to phenol, nitrate, and formate absorption occurred, as did acute tubular necrosis following copper sulfate treatment of white phosphorus burns. Inhalation injury occurred in five patients. A decrease in hospital stay for chemically injured patients was observed. To minimize chemical injury, clothing should be removed promptly and water lavage begun. Systemic toxicity and inhalation injury are rare but often severe and increase mortality.

Role of the emergency physician in treatment of the poisoned patient.

Toxicology is part of the core knowledge necessary for the practice of emergency medicine. The basic principles outlined in this article include initial emergency department treatment; prehospital management; the special problems of ocular and cutaneous exposures and inhaled toxins; the definitive treatment of ingested toxins; and the indications for discharge from the emergency department.