Tear and serum interleukin-8 and serum CX3CL1, CCL2 and CCL5 in sulfur mustard eye-exposed patients.

BACKGROUND: The serum and tear levels of four inflammatory chemokines were evaluated in sulfur mustard (SM)-exposed with serious ocular problems. MATERIALS AND METHODS: In this study, 128 SM-exposed patients and 31 healthy control participants participated. Tear and serum levels of chemokines were assessed by ELISA method. RESULTS: There was no significant difference in the serum level of IL-8/CXCL8, CX3CL1/fractalkine, CCL2/MCP-1, and CCL5/RANTES between all SM-exposed subjects and control groups. The tear level of IL-8 in the SM-exposed group was lower than the control group, but the difference was not significant. In the SM-exposed group with the abnormalities in tear breakup time (TBUT) test, fundus and pannus formation were significantly higher than SM-exposed patients without these problems. CX3CL1 levels have significantly increased in SM-exposed group with blepharitis, pterygium, and conjunctival pigmentation as compared with the control group. Besides, significantly higher levels of CX3CL1 were observed in SM-exposed group with or without bulbar conjunctival hyperemia and abnormal vessels a well as with fundus abnormality compared to the control group. Only, SM-exposed group with subconjunctival fibrosis had significantly lower levels of CCL5 than SM-exposed group without this problem. CONCLUSION: The higher level of CX3CL1 and consistent levels of IL-8/CXCL8, MCP-1/CCL2, and RANTES/CCL5 in SM-exposed individuals may indicate an anti-inflammatory response against the destructive effects of SM gas. High tear level of IL-8/CXCL8 reflects the severity of ocular surface abnormalities, yet significantly low tear level found in mild SM-exposed subgroup compared with the control group. The lower levels of CX3CL1 and RANTES/CCL5 may represent the different pathophysiology which requires further studies.

Tear and serum MMP-9 and serum TIMPs levels in the severe sulfur mustard eye injured exposed patients.

INTRODUCTION: Sulfur mustard (SM) intoxication produces local and systemic changes in the human body. In this study, the relationship between tear and serum matrix metalloproteinase (MMP)-9 and serum tissue inhibitors of metalloproteinases (TIMPs) are assessed in serious eye-injured SM-exposed casualties. METHODS: A group of 128 SM-exposed patients with serious ocular injuries in three subgroups (19 mild, 31 moderate, and 78 severe cases) is compared with 31 healthy controls. Tear and ocular status and serum MMPs and MMP-9/TIMPs complex levels were evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum level of MMP-9 was significantly higher in the SM-exposed group compared to the control group (P = 0.009). Mean serum MMP-9 level in the SM-exposed group with ocular abnormalities was significantly higher than that in the SM-exposed group without ocular abnormalities. SM-exposed people with corneal calcification had significantly higher serum MMP-9/TIMP-1 level compared to the SM-exposed ones without this problem (P = 0.045). The SM-exposed group with severe ocular injuries had significantly higher MMP-9/TIMP-1 than the controls (P = 0.046). The SM-exposed group had significantly lower levels of MMP-9/TIMP-4 complex than the controls (P < 0.001). The SM-exposed group with tear meniscus and fundus abnormality had significantly higher MMP-9/TIMP-4 levels than the SM-exposed group without these problems (P = 0.009 and P = 0.020). CONCLUSION: Serum MMP-9 level had increased in SM-exposed groups with ocular problems, while TIMP-1 and TIMP-2 levels had remained unchanged. Serum TIMP-4 drastically decreased in SM-exposed group, which clearly explains the severity of the systemic and ocular damages.

Ocular Parasitosis Caused by Protozoan Infection during Travel: Focus on Prevention and Treatment.

International travel is rising quickly worldwide. Many people travel to tropical and subtropical areas, where there has been increasing exposure of travelers to infectious pathogens. Ocular parasitic infections are more prevalent in these geographical areas and they can lead to morbidity and mortality, often due to late or misdiagnosis due to the unfamiliarity of health staff with these diseases. This is an up-to-date comprehensive review article that familiarizes physicians with ocular signs and symptoms, treatment, prevention, and geographic distribution of some parasites associated with travel.

Clinical Practice Guidelines for Prevention, Diagnosis and Management of Early and Delayed-onset Ocular Injuries Due to Mustard Gas Exposure.

PURPOSE: To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas. METHODS: The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores. RESULTS: The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries. CONCLUSION: Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals.

Possible long term effects of chemical warfare using visual evoked potentials.

Some studies have already addressed the effects of occupational organic solvent exposure on the visually evoked potentials (VEPs). Visual system is an important target for Sulphur Mustard (SM) toxicity. A number of Iranian victims of Sulphur Mustard (SM) agent were apprehensive about the delay effect of SM on their vision and a possible delay effect of SM on their visual cortex. This investigation was performed on 34 individuals with a history of chemical exposure and a control group of 15 normal people. The Toennies electro-diagnosis device was used and its signals were saved as the latencies. The mean of N75, N140 and P100 of victims of chemical warfare (VCWs) and control group indicated no significant results (P>0.05). The VCWs did not show any visual symptoms and there was no clear deficit in their VEPs.

Association of serum immunoglobulins levels and eye injuries in sulfur mustard exposed: Sardasht-Iran Cohort Study.

In this study the associations between ocular problems and serum levels of immunoglobulins in sulfur mustard (SM) exposed population 20 years after exposure in context of Sardasht-Iran Cohort Study was explored. Serum immunoglobulins (Ig) levels including IgM, IgA, IgE, IgG, and subclasses of IgG (IgG1, IgG2, IgG3 and IgG4) in 372 SM-exposed patients were titrated and compared with 128 unexposed controls considering their ocular problems. In exposed patients with tearing and blurring of vision, serum IgM levels were significantly lower than matched controls (P=0.026 and 0.027, respectively). Serum IgM levels in exposed patients with normal ocular conditions were significantly lower (P<0.050) than that of matched controls. Serum levels of IgA, IgE and IgG and IgG3 levels were not significantly different between the two groups with abnormal and normal ocular conditions. Mean serum IgG1 levels in exposed patients with normal ocular conditions were significantly higher than the matched controls (P<0.05) except for tearing and photophobia. Mean serum IgG2 levels in exposed with blurring of vision and without tearing, ocular pain, photophobia, lids and bulbar conjuctival abnormalities were significantly higher than that of matched controls (P<0.050). Mean serum levels of IgG4 in exposed patients with normal ocular conditions and most of the abnormal ocular conditions were significantly lower than the matched controls (P<0.05). The results of the current study showed that even 20 years after SM exposure serum immunoglobulins are different from matched normal controls and the levels of IgM and IgG4 are associated with some aspects of ocular surface problems.

Association of ophthalmic complications in patients with sulfur mustard induced mild ocular complications and serum soluble adhesion molecules: Sardasht-Iran Cohort Study.

The aim of this study was to evaluate possible association between ophthalmic complications in sulfur mustard (SM) exposed patients with mild ocular injuries and serum soluble adhesion molecules. Serum levels of sICAM-1, sL-selectin, sP-selectin and sE-selectin in 367 SM-exposed individuals with or without eye injuries were checked and compared with 128 unexposed controls. All participants underwent ocular examinations. Serum sICAM-1 level in SM exposed with blurred vision, was significantly (p=0.021) higher than in SM exposed with no blurred vision. Serum sL-selectin level was significantly (p=0.024) higher in SM exposed with photophobia than SM exposed with no photophobia. Serum P-selectin level in exposed without any slit lamp findings was significantly (p=0.003) lower than the matched control groups. Similar finding was seen in exposed group without ocular problem compared with the control groups. Serum sE-selectin level in exposed with normal ocular condition except for photophobia and blurred vision was significantly (p<0.05) higher than the matched controls. Serum E-selectin level in exposed with photophobia condition was significantly (p=0.047) higher than the control group with photophobia. In conclusion it seems that the changes in the E- and P-selectins is a regulatory mechanism for inhibition of SM induced ocular problems, although the local levels are more important and further investigations required in more severe ocular problems in SM exposed patients.

Systemic complications of trinitrotoluene (TNT) in exposed workers.

INTRODUCTION: 2,4,6-trinitrotoluene (TNT) has been widely used as an explosive. TNT can induce some well-recognized toxic impacts comprising toxic hepatitis, aplastic anemia and cataract. The aim of study was evaluation of TNT exposed workers for systemic complication. METHODS: In a cross-sectional study, we carried out Liver Function Test (LFT), complete blood count (CBC) and slit lamp biomicroscopy to compare the prevalence and severity of these 3 complications between 47 male TNT exposed workers (with at least one year continuous experience of TNT exposure) and 43 unexposed male hospital worker who hadn't had any previous contacts with TNT. We also performed Pulmonary Function Test (PFT) to assess the probable obstructive/restrictive abnormalities, caused by TNT. RESULTS: Mean alkaline phosphatase (ALP) level of TNT exposed group was significantly higher than the unexposed group (p = 0.023) Forced Expiratory Volume in one second to Forced Vital Capacity (FEV1/FVC) ratios of both groups were in the range of restrictive pattern (82.03% and 81.42% for the exposed and unexposed group, respectively) with no meaningful difference. We didn't find out any specific TNT induced cataract and general cortical cataract (CC) and nuclear sclerotic cataract (NSC) prevalence was not significantly different. DISCUSSION: we haven't found TNT as a chemical, causing toxic hepatitis or aplastic anemia; neither did we find it as a compound, responsible for a meaningful increase in cataract prevalence. However, due to the increased ALP serum levels and FEV1/FVC ratios among TNT workers, safety precautions are advised.

Tear total protein analysis in patients with late sulfur mustard-induced ocular complications: a cross-sectional study.

BACKGROUND: Eyes are the most sensitive organs to sulfur mustard (SM). Late ocular complications have been reported even 15-20 years post-exposure. To date, no study has investigated the composition of tear proteins in tear samples of SM-intoxicated patients. METHODS: Total protein content as well as concentrations of vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and substance P were measured in unstimulated tears of chemically-injured patients who suffer from late ocular complications of SM. These levels were compared to corresponding values obtained from tears of healthy control subjects. The concentration of total proteins was measured using the Bradford method and those of VEGF, CGRP and substance P by ELISA. RESULTS: Total protein concentration was significantly lower in tears of the SM compared to control group (p<0.01). In contrast, tear samples of the SM group had significantly higher VEGF and VEGF/total protein compared to control group (p<0.01). Tear CGRP concentration was found to be lower in the SM vs. control group (p<0.05) but no significant difference in CGRP/total protein was observed (p>0.05). Finally, tear substance P concentrations were not found to be significantly different between the two groups (p>0.05). CONCLUSION: The results of this investigation indicated decreased total protein and CGRP, and elevated VEGF concentration in tears of SM-intoxicated patients who suffer from chronic ocular complications.

Evaluation of the tear and serum levels of IL-8 in sulfur mustard intoxicated patients 20 years after exposure.

PURPOSE: Delayed keratitis is the most dangerous ocular complication of sulfur mustard (SM) exposure. This study aimed to evaluate the role of tear and serum levels of interleukin-8 (IL-8) in SM exposed subjects. DESIGN AND METHODS: In this historical cohort study, the experimental group included 370 participants who had been exposed to SM 20 years prior. Data were compared with those of 128 unexposed participants as the control group. After completing a thorough systemic and ocular examination, serum IL-8 levels in all exposed and controls were compared. According to the statistical calculation, tear IL-8 levels, were compared in randomly selected 48 exposed and 37 controls. Based on the ocular findings, the selected subjects were divided into two subgroups, normal subjects include those participants who had no ocular signs and abnormal subjects, were those who had at least one or more ocular signs. RESULTS: Bulbar conjunctiva and limbal tissues evaluation in all participants showed a significantly higher number of abnormalities in exposed group than in the control group (P=0.004 and P=0.048 respectively). Serum IL-8 levels in all exposed were significantly lower than the matched controls (P=0.002). Tear IL-8 levels in the selected exposed were significantly lower than in the selected controls (P=0.030). In exposed group with normal conditions of the lids, bulbar conjunctiva, cornea, tear status, limbus, slit lamp findings and final ophthalmic assessment, tear IL-8 levels were significantly lower than in the matched controls (P=0.022, 0.037, 0.027, 0.050, 0.039, 0.029, 0.045 respectively). With respect to the global ophthalmic assessment, tear fluid IL-8 levels in the abnormal controls were significantly lower than in the normal controls (P=0.049), but this decrease in secretion of tear IL-8 were not encountered in abnormal exposed (P=0.415). CONCLUSION: Tear IL-8 secretion was significantly inhibited in the unexposed controls with ocular surface abnormalities, while these inhibitory responses were not encountered in SM-exposed cases with ocular surface abnormalities.

Long-term ocular consequences of sulfur mustard in lung-injured war veterans.

PURPOSE: Ocular and pulmonary involvement are the most important complications of sulfur mustard (SM) that may happen many years after exposure. This study aims to evaluate the severity of ocular involvement and the correlation between late ocular and lung complications in patients exposed to SM. METHODS: This descriptive cross-sectional study was conducted on SM lung-injured war veterans. Status of pulmonary involvement was categorized into normal, mild, moderate, and severe based on the "Forced Expiratory Volume in first second (FEV1)".Status of ocular involvement was also categorized into normal, mild, moderate, and severe, based on the slit lamp findings. Correlation between pulmonary and ocular involvements was evaluated by Spearman rank correlation test. RESULTS: Totally, 292 war veterans with clinical pulmonary involvement were included in the study. Status of pulmonary involvement was 3.8% normal, 11.2% mild, 16.1% moderate, and 68.9% severe. Status of the ocular involvement was 68.2% normal, 13.8% mild, 5.4% moderate, and 12.6% severe. Among all patients, 96.3% had pulmonary involvement and 32.5% had ocular involvement. There was a positive correlation between the severity of ocular and pulmonary involvements (p = 0.049 and r = 0.122). CONCLUSION: The results of this study showed that although there was a positive correlation between the severity of pulmonary and ocular involvement, this correlation was weak. This might be due to the nature of the studied population or differences in the tissue susceptibilities, gas types, or exposure patterns.

Evaluation of relationship between the serum levels of inflammatory mediators and ocular injuries induced by sulfur mustard: Sardasht-Iran Cohort Study.

Ocular damages induced by sulfur mustard (SM) are the important problems in exposed patients. The damaging mechanisms are not clearly understood. In the present study the relationship between the serum levels of inflammatory mediators and ocular injuries induced by SM was evaluated. Bulbar conjunctiva and limbal tissue abnormalities were significantly more frequent in the expose versus control group (P=0.004 and 0.048 respectively). The serum levels of IL-1alpha and TNF-alpha in the exposed group with and without Slit lamp findings were significantly lower than their counterpart in the control group. The serum levels of IL-1beta in the exposed group with Slit lamp findings were significantly lower than their counterpart in the control group. The serum levels of IL-1beta in the controls with Slit lamp findings were significantly higher than the controls without Slit lamp findings. The serum levels of IL-1Ra and MMP-9 in the exposed group with and without Slit lamp findings do not display any significant differences as compared to the similar controls. The serum levels of IL-6 in the exposed group with or without Slit lamp findings were significantly lower than their counterpart in the control group (P=0.048 and 0.008 respectively). The serum titers of the CRP and RF in the exposed group without Slit lamp findings were significantly elevated versus their counterpart in the control group (P=0.004 and 0.011 respectively). The serum levels of these inflammatory cytokines except for IL-1Ra and MMP-9, decreased in SM exposed subject independent of ocular problems. More local studies on the eyes are needed to clarify the exact role of this cytokines in ocular problems of chemical.

Long-term ocular consequences of sulfur mustard in seriously eye-injured war veterans.

INTRODUCTION: Sulfur mustard (SM) has been used as a dangerous chemical warfare agent since the early 20th century. Although many descriptive studies about SM-induced ocular injuries are present in the medical literature, few of them have been conducted over a large group with serious ocular involvement. MATERIALS AND METHODS: This descriptive study was conducted on 149 severe SM-intoxicated war veterans. Ocular history, anterior and posterior segment findings using a slit lamp, and direct and indirect ophthalmoscopic findings were recorded. Severity of the disease was also recorded based on a chart of the Foundation of Martyrs and Veterans Affairs. RESULTS: Ocular complains included photophobia (73.2%), sense of decreased vision (72.5%), dry eye sensation (66.4%), foreign body sensation (61.1%), tearing (46.3%), and pain (43.0%). Slit lamp findings were meibomian gland dysfunction (MGD; 96%), blepharitis, punctal closure, trichiasis, tear break-up time, and tear meniscus layer abnormality (80% to 90%). Conjunctival disturbances included vascular abnormality, ischemia, hyperemia, subconjunctival fibrosis, and pterygium. Limbal changes were abnormal vessels, limbal tissue loss and pigment loss, and pannus formation. Corneal problems included epithelial and stromal disturbances, calcium deposition, and melting. The most frequent previous surgeries were punctal closure, lamellar keratoplasty (LK), and stem cell allograft. Severity of intoxication included mild (17%), moderate (25%), and severe (57%). CONCLUSION: Chronic blepharitis and decreased tear secretion are the 2 most important and influencing factors in progression of ocular problems in SM injuries. The more severe the initial exposure, percentage of disability, and duration of ocular involvement, the higher the likelihood of mustard gas keratopathy.

Long-term ocular complications of sulfur mustard in the civilian victims of Sardasht, Iran.

Eyes are very sensitive to sulfur mustard (SM) gas because they have wet surfaces. The severity of ocular damage is related to the dose and duration of exposure to SM, and recovery may take up to several years after the exposure. We conducted a large cohort study to evaluate the ocular signs and symptoms of 367 chemical war victims in Sardasht City, Iran, 20 years after their exposure to mustard gas. The results of these chemical war victims (i.e., the cases) were compared with the results for 128 unaffected civilians (i.e., the controls). Photophobia was the most significant symptom in the cases (36.8%) (compared with 20.3% in the controls) (p < or = .001). Ocular surface discomfort (burning, itching, and redness) was the second most significant symptom in the cases (29.2%) (compared with 19.5% in the controls) (p = .034). Other symptoms such as foreign-body sensation, tearing, pain, blurring of vision, and dry eye sensation were not significantly different between the 2 groups. In the slit-lamp findings, bulbar conjunctival abnormality was the most significant sign in the cases (9.3%) (compared with 1.6% in the controls) (p = .004). Limbal tissue changes were the second most significant sign in the cases (3.0%) (compared with 0.0% in the controls) (p = .048). Other slit-lamp findings related to tearing and abnormalities in the lids and cornea were not significantly different between the 2 groups. Our findings in the present study showed that photophobia and ocular surface discomfort (burning, itching, and redness) were the most significant symptoms. In addition, bulbar conjunctival abnormalities and limbal tissue changes were the most significant signs among the sulfur mustard chemical war victims.