Orbital Compartment Syndrome in Severe Burns: Predictive Factors, Timing, and Complications of Intervention.

PURPOSE: Severe burn patients require high-volume fluid resuscitation, which increases risk for orbital compartment syndrome (OCS). We aimed to understand surgeons' practice patterns and to examine risk factors for OCS, timing of lateral canthotomy and cantholysis (LCC), and complications of intervention. METHODS: A survey of American Society of Ophthalmic Plastic and Reconstructive Surgery and North American Society of Academic Orbital Surgeons' practice patterns in burn patients was undertaken. In addition, a retrospective analysis was conducted of 107 patients with burns greater than 20% total body surface area at 1 institution from January 1, 2009, to June 1, 2018. Patients with Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, frostbite, or no ophthalmologic consultation were excluded. Risk factors for OCS, timing of LCC, and complications of the intervention were examined. RESULTS: In the survey, 37 of 54 respondents had treated burn patients, of which 29 followed no protocol. Threshold intraocular pressure for intervention varied widely, and nearly all reported having seen complications from LCC in burn patients. For the retrospective analysis, 107 patients met criteria, of which 22 (20.6%) required LCC. Renal failure, inhalation injury, eyelid burns, higher total body surface area, elevated lactate, increased number of escharotomies, and greater total fluid required were significantly associated with the clinical decision that the patient was at risk for OCS requiring LCC. Fluid resuscitation in excess of the Ivy Index (250 ml/kg) increased odds of LCC 8.6 times. Average time of LCC was 15.8 hours after burn. LCC patients experienced higher rates of complications including eyelid retraction, exposure keratopathy, and corneal ulceration. CONCLUSIONS: Severe burn patients should be monitored closely by an ophthalmologist during the first 48 hours for signs of OCS. Further studies should aim to recommend protocols guiding evaluation and intervention.

AIP1 suppresses neovascularization by inhibiting the NOX4-induced NLRP3/NLRP6 imbalance in a murine corneal alkali burn model.

BACKGROUND: Apoptosis signal-regulating kinase 1-interacting protein 1 (AIP1) participates in inflammatory neovascularization induction. NADPH oxidase 4 (NOX4) produces reactive oxygen species (ROS), leading to an imbalance in nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) and NLR family pyrin domain containing 6 (NLRP6) expression. The mechanisms of AIP1, NOX4, ROS and inflammasomes in corneal neovascularization were studied herein. METHODS: C57BL/6 and AIP1-knockout mice were used in this study. The alkali burn procedure was performed on the right eye. Adenovirus encoding AIP1 plus green fluorescence protein (GFP) (Ad-AIP1-GFP) or GFP alone was injected into the right anterior chamber, GLX351322 was applied as a NOX4 inhibitor, and then corneal neovascularization was scored. The expression of related genes was measured by quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining. 2',7'-Dichlorofluorescin diacetate staining was used to determine the ROS levels. RESULTS: The expression of AIP1 was decreased, while that of cleaved interleukin-1ß (clv-IL-1ß) and vascular endothelial growth factor A (VEGFa) was increased after alkali burn injury. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. NLRP3/NLRP6 expression was imbalanced after alkali burns. GLX351322 reversed the imbalance in NLRP3/NLRP6 by reducing the ROS levels. This treatment also reduced the expression of clv-IL-1ß and VEGFa, suppressing neovascularization. CONCLUSIONS: AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burn injury. Based on the pathogenesis of corneal neovascularization, these findings are expected to provide new therapeutic strategies for patients. Corneal alkali burn injury is a common type of ocular injury that is difficult to treat in the clinic. The cornea is a clear and avascular tissue. Corneal neovascularization after alkali burn injury is a serious complication; it not only seriously affects the patient's vision but also is the main reason for failed corneal transplantation. Corneal neovascularization affects approximately 1.4 million patients a year. We show for the first time that AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burns. The expression of AIP1 was decreased, while that of clv-IL-1ß and VEGFa was increased after alkali burns. We tried to elucidate the specific molecular mechanisms by which AIP1 regulates corneal neovascularization. NOX4 activation was due to decreased AIP1 expression in murine corneas with alkali burns. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. Additionally, NLRP3/NLRP6 expression was unbalanced, with NLRP3 activation and NLRP6 suppression in the corneal alkali burn murine model. Eye drops containing GLX351322, a NOX4 inhibitor, reversed the imbalance in NLRP3/NLRP6 by reducing ROS expression. This treatment also reduced the expression of clv-IL-1ß and VEGFa, reducing neovascularization. Therefore, we provide new gene therapeutic strategies for patients. With the development of neovascularization therapy, we believe that in addition to corneal transplantation, new drug or gene therapies can achieve better results. Video Abstract.

Corneal burn injury in picosecond laser treatment: A potential hazard in cosmetic therapy.

Key PointsWithout appropriate protection, cosmetic laser treatments can cause severe ocular side effects and permanent visual impairment. We present this case to emphasize the importance of ocular protection during the entire treatment period, especially treatments of lesions over the eyelids. According to our knowledge and database search, this is the first reported ocular injury caused by picolaser.

Effect of metronidazole ophthalmic solution on corneal neovascularization in a rat model.

PURPOSE: To evaluate the effect of metronidazole ophthalmic solutions on corneal neovascularization (CNV) in a rat model. METHODS: A chemical burn was created in the right central cornea of 40 rats. Animals were randomized and distributed into four study groups (n = 10 rats per group) designated Met_0.1%, Met_0.5%, sham, and untreated groups. Chemical-burned corneas in the Met_0.1% and Met_0.5% groups received ophthalmic solutions of 0.1 and 0.5% metronidazole, respectively. Corneas in the sham group received phosphate-buffered saline (metronidazole diluent). All treated eyes received ophthalmic solution at intervals of 6 h, for up to 30 days. Untreated corneas received no treatment. CNV was evaluated postinjury using corneal photographs at different evaluation time points. The main CNV outcome measures were: burn intensity, index of CNV, and percentage of vascularized corneal area. Five rats from each group were euthanized, on days 15 and 30; the samples were collected for histological analyses. Differences with P < 0.05 were considered significant. RESULTS: CNV was observed in the eyes from day 7 postinjury. However, the indices of CNV for the Met_0.1% and Met_0.5% groups were smaller than those for the sham and untreated groups (P < 0.05). Furthermore, corneas treated with 0.1 or 0.5% metronidazole had smaller vascularized areas compared to control corneas. On histological study, the presence of blood vessels confirmed clinical outcomes. CONCLUSIONS: Regular instillation of 0.1 or 0.5% metronidazole had a significant inhibitory effect for CNV on chemical burns induced in a rat model.

Predictive value of spectral-domain optical coherence tomography features in assessment of visual prognosis in eyes with acute welding arc maculopathy.

OBJECTIVE: To observe spectral-domain optical coherence tomography (SD-OCT) features and to determine whether baseline OCT features can be used as predictors of visual acuity outcome in eyes with acute welding arc maculopathy. METHODS: This retrospective study enrolled twenty-two eyes of eleven subjects with acute welding arc maculopathy. All subjects were evaluated by SD-OCT at baseline and final visit. The involved parameters included best-corrected visual acuity (BCVA), central macular thickness (CMT), the length of ellipsoid zone (EZ) defects, the greatest linear dimension (GLD) of outer retinal lesions, EZ reflectivity and relative EZ reflectivity (defined as the ratio of EZ reflectivity to retinal pigment epithelium reflectivity on OCT). RESULTS: Acute welding arc maculopathy was presented as abnormal hyperreflectivity, hyporeflectivity and defects of outer retinal layer in fovea on OCT. Compared with baseline, BCVA improved significantly accompanied by decreased GLD of outer retinal lesions and the length of EZ defects at final visit (P = 0.0004, P < 0.0001 and P < 0.0001, respectively). No significant changes were shown on CMT (P = 0.248). In multivariate regression analysis, final BCVA was associated with baseline BCVA and the length of EZ defects (P = 0.012 and P = 0.045, respectively). However, EZ reflectivity and relative EZ reflectivity were not associated with final BCVA (P > 0.05). CONCLUSION: In conclusion, SD-OCT images clearly reveal morphological changes in outer retinal layer in acute welding arc maculopathy. The baseline BCVA and length of EZ defects are the strongest predictors of final BCVA.

Investigation of scleral thermal injuries caused by ultrasonic pars plana phacoemulsification and aspiration using pig eyes.

PURPOSE: The purpose of this study was to investigate the thermal injuries caused by ultrasonic pars plana phacoemulsification and aspiration (PPPEA) using pig eyes. METHOD: Using a 20-gauge (G) vitrectomy system (Accurus®, Fragmatome; Alcon Laboratories) in both the 'open-tip' and 'closed-tip' techniques, PPPEA was performed in pig eyes and the subsequent thermal injuries generated around the scleral wound were measured by infrared thermal imaging (thermography). Post surgery, the state of the scleral wound was observed under a microscope, and a tissue slice containing the scleral wound was then prepared and observed under an optical microscope. RESULTS: Thermography measurements revealed a slight temperature rise around the scleral wound in the open-tip case, yet a marked temperature rise in the closed-tip case. The scleral wound incision produced by the open tip was linear, while that produced by the closed tip was expanded. Histological examination revealed mild degeneration of the sclera around the wound in the open-tip case, yet marked tissue degeneration by thermal injuries in the closed-tip case. CONCLUSION: Our findings showed that in PPPEA, the temperature of the tip of a 20G vitrectomy system rapidly increases due to the closed-tip technique, thus producing obvious thermal damage to the scleral wound. In order to prevent thermal injuries to the scleral wound during PPPEA, it is important to shorten the time of ultrasonic oscillation during surgery as much as possible while the tip is occluded with nuclear fragments.

Expression of peptidylarginine deiminase 4 in an alkali injury model of retinal gliosis.

Citrullination is an important posttranslational modification that occurs during retinal gliosis. We examined the expression of peptidyl arginine deiminases (PADs) to identify the PADs that mediate citrullination in a model of alkali-induced retinal gliosis. Mouse corneas were exposed to 1.0 N NaOH and posterior eye tissue from injured and control uninjured eyes was evaluated for transcript levels of various PADs by reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qPCR). Retinas were also subjected to immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP), citrullinated species, PAD2, and PAD4 and tissue levels of GFAP, citrullinated species, and PAD4 were measured by western blots. In other experiments, the PAD4 inhibitor streptonigrin was injected intravitreally into injured eyes ex vivo to test inhibitory activity in an organ culture system. We found that uninjured retina and choroid expressed Pad2 and Pad4 transcripts. Pad4 transcript levels increased by day 7 post-injury (p < 0.05), whereas Pad2 levels did not change significantly (p > 0.05) by qPCR. By IHC, PAD2 was expressed in uninjured eyes along ganglion cell astrocytes, but in injured retina PAD2 was downregulated at 7 days. On the other hand, PAD4 showed increased staining in the retina upon injury revealing a pattern that overlapped with filamentous GFAP staining in Müller glial processes by 7 days. Injury-induced citrullination and soluble GFAP protein levels were reduced by PAD4 inhibition in western blot experiments of organ cultures. Together, our findings for the first time identify PAD4 as a novel injury-inducible druggable target for retinal gliosis.

Damage to the macula associated with LED-derived blue laser exposure: A case report.

BACKGROUND: Light emitting diodes laser is emerging as an important source of light replacing conventional lights. It is widely used for illumination in the bar where young people love to go. But not everyone knows about the light damage to the eye especially to the macula. In this article, we report the case of a macular damage induced by LED-derived blue laser in a bar, studied with optical coherence tomography (OCT) to evaluate the retinal lesion and multifocal electroretinography (mfERG) to evaluate functional damage. CASE PRESENTATION: Four days after the photo injury to the right eye, the visual acuity was 0.5. Funduscopy revealed a round red lesion in the macula of the right eye. Fluorescein angiography (FA) revealed no leakage. OCT revealed a deficiency in the center of the fovea. MfERG revealed a reduction of the peak value in the right eye compared to the left eye. One month later, although the vision was 1.0 in the right eye, OCT revealed a hyporeflectivity of the ellipsoid zone. MfERG still showed a reduction of the peak value in the right eye compared to the left eye. CONCLUSION: We believe that general knowledge about laser injuries to the eye should be realized widely. We also think in cases of macular laser damage, the recovery of vision can not demonstrate the recovery of the function of photoreceptors.

Thermal Burn Scar-Related Squamous Cell Carcinoma in the Eyelid.

A 63-year-old woman presented with a large, ulcerokeratotic mass in her right lower eyelid that had grown over the last 2 months in a burn scar. She had experienced a thermal burn involving both inferior periorbital areas 35 years ago and received medical treatment. The lesion was excised with wide margins. The histologic diagnosis was squamous cell carcinoma. No recurrence was observed during a 22-month follow up. In the previous literature, a total of 10 cases of eyelid burn scar neoplasm, of which 9 were basal cell carcinoma, have been reported. To the authors' knowledge, this is the first reported case of thermal burn-related squamous cell carcinoma of the eyelid.

Histopathologic Clues in Diagnosing Oral Mucosal Grafts to the Conjunctiva.

Excised redundant, forniceal "conjunctival" tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.

MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions.

Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1ß and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 µl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP-8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP-8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL-6, CXCL1, and MMP-1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP-8KO mice. These results suggest that some of the anti-inflammatory effects of Dex are mediated through increased MMP-8 expression. J. Cell. Physiol. 231: 2506-2516, 2016. © 2016 Wiley Periodicals, Inc.

Stability of limbal stem cell deficiency after mechanical and thermal injuries in mice.

We studied the reproducibility and stability of limbal stem cell deficiency (LSCD) in mice following controlled injuries to the corneal and limbal epithelia. In one method, corneal and limbal epithelia were entirely removed with a 0.5 mm metal burr. In the other, limbus to limbus epithelial removal with the burr was followed by thermal injury to the limbus. These two methods were compared with a previously published one. Unwounded corneas were used as control. The corneas were examined monthly for three months by slit lamp with fluorescein staining. Immunofluorescence staining for cytokeratin 12 and 8 on corneal wholemount and cross sections were performed to determine the phenotype of the epithelium. Mechanical shaving of the epithelium, with or without thermal injury, resulted in a reproducible state of LSCD marked by superficial neovascularization, reduce of keratin 12 expression and presence of goblet cells on the cornea. The phenotype was stable in 100% of the eyes up to at least three months. Thermal injury produced a more severe phenotype with more significant stromal opacification. These corneal injury models may be useful for studying the mechanisms leading to limbal stem cell deficiency.

Efficacy of topical aflibercept versus topical bevacizumab for the prevention of corneal neovascularization in a rat model.

The aim of this experimental study was to compare the efficacy of topical aflibercept and topical bevacizumab in preventing corneal neovascularization. A chemical burn was created in the right central cornea of male Sprague-Dawley rats, followed immediately by instillation of one drop (25 mg/ml, 20 µl volume) of aflibercept (15 eyes), bevacizumab (14 eyes), or saline (15 eyes). Treatment was repeated twice daily for 7 days. Corneal neovascularization was determined using corneal photographs (ImageJ) on days 1, 4, 7, 10, and histological and immunofluorescence studies, on day 10. Stromal immunoreactivity was evaluated 2 days after injury in 6 rats treated singly with bevacizumab or aflibercept. Corneal neovascularization was observed clinically on day 4 in all groups. In the aflibercept group, the area of neovascularization increased from 7.38 ± 2.23% on day 4 to 21.73 ± 14.59% on day 7 and 31.0 ± 23.61% on day 10. Corresponding values in the bevacizumab group were 6.04% ± 1.81%, 51.27 ± 15.50%, and 54.4 ± 11.33%, and in the control group, 8.99 ± 1.93%, 42.6 ± 19.59%, and 55.15 ± 11.54%. The area of neovascularization was significantly smaller on days 7 and 10 in the aflibercept group than in the control and bevacizumab groups (P < 0.001, all analyses), with no significant differences between the latter two groups (day 7, P = 0.868; day 10, P = 0.213). Clinical findings were compatible with the histological data and supported by immunofluorescence and corneal flat-mount staining. Both drugs demonstrated variable penetration into the corneal stroma. Topical aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn. These findings may have important therapeutic implications for humans.

[Features of stress reactivity of the organism and clinical patterns of ocular burn].

Clinical patterns of ocular burn in patients with different types and variants of stress reactivity were studied. It is shown that patients with the maladaptive type of stress reactivity at any stage of the disease are at higher risk of complications. Rapid exhaustion of the sympathoadrenal system or a hyperactive stress response seen in cases of the labile and hyperergic individual adrenergic immune reactivity of the organism (IAIRO) can be considered as manifestations of a regulation disorder. The absence of complications along with mild changes in immune reactivity is characteristic of the normoergic variant of IAIRO.

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

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

An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model.

PURPOSE: We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. METHODS: After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. RESULTS: After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1ß (IL-1ß), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. CONCLUSIONS: The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing.

KH902, a recombinant human VEGF receptor fusion protein, reduced the level of placental growth factor in alkali burn induced-corneal neovascularization.

AIMS: To investigate the expression of placental growth factor (PIGF) in alkali burn-induced murine corneal neovascularization (NV); to evaluate the effects of KH902, a vascular endothelial growth factor receptor decoy, on prevention and regression of new vessels growths in the cornea; and to determine the influence of KH902 on the levels of vascular endothelial growth factor (VEGF) and PIGF in alkali burn-induced corneal NV. METHODS: Mouse corneal NV was induced by alkali burn. The expression of PIGF was detected by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). To evaluate the effects of KH902, corneal NV was observed and photographed every 3 days for a total of 28 days after the alkali burn. The percentage of NV area was measured and compared with that of the control group. The VEGF and PIGF levels in the cornea were evaluated by enzyme linked immunosorbent assay (ELISA). RESULTS: PIGF was expressed during the alkali burn-induced corneal neovascularization. On day 3 (D3), day 6 (D6) and day 9 (D9) after chemical cauterization, the length of the longest new vessel and the neovascularization areas in the KH902-treated groups were significantly smaller than those of the PBS-treated group (p < 0.05). The areas of established corneal NV of the KH902-treated groups regressed with time, but the control groups showed no natural regression. The VEGF and PIGF levels of the cornea in the treated groups were significantly decreased compared to those of the control group (p < 0.05). CONCLUSIONS: PIGF may be involved in alkali burn-induced corneal NV. KH902 significantly inhibited new vessel growth and promoted the regression of established vessels in a mouse model of corneal NV, and it also reduced the levels of VEGF and PIGF in the cornea.

Use of Ethylenediaminetetraacetic Acid in Chronic Calcium-Based Chemical Injury.

PURPOSE: This study presents the successful management of a patient with chronic chemical-based injury using ethylenediaminetetraacetic acid (EDTA) chelation. METHODS: This is a case report of a 59-year-old man who presented to us 2 months after a bilateral, accidental, ocular injury with lime particles at his workplace. RESULTS: The patient was initially managed with extensive debridement and amniotic membrane grafting for both eyes. At 4-month follow-up, the left eye appeared to have extensive calcium-based plaques. 0.02N EDTA chelation was performed for his left eye. Postchelation, the visual acuity improved to 20/800. At 1-week follow-up, a repeat EDTA chelation was performed. The corneal clarity improved further, and the patient recovered a visual acuity of 20/200. CONCLUSIONS: EDTA chelation in the setting of calcium deposition in the chronic phase of chemical injuries can be reasonably effective.