Mustard Gas-Induced Ocular Surface Disorders: An Update on the Pathogenesis, Clinical Manifestations, and Management.
Journal
Cornea
ISSN: 1536-4798
Titre abrégé: Cornea
Pays: United States
ID NLM: 8216186
Informations de publication
Date de publication:
01 Jun 2023
01 Jun 2023
Historique:
received:
24
05
2022
accepted:
12
09
2022
pmc-release:
01
06
2024
medline:
8
5
2023
pubmed:
3
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries. Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye." Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging. MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.
Identifiants
pubmed: 36729713
doi: 10.1097/ICO.0000000000003182
pii: 00003226-202306000-00020
pmc: PMC10164045
mid: NIHMS1836270
doi:
Substances chimiques
Mustard Gas
T8KEC9FH9P
Chemical Warfare Agents
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
776-786Subventions
Organisme : NEI NIH HHS
ID : P30 EY001792
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024349
Pays : United States
Organisme : NEI NIH HHS
ID : UG3 EY031809
Pays : United States
Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors have no funding or conflicts of interest to disclose.
Références
Graham JS, Schoneboom BA. Historical perspective on effects and treatment of sulfur mustard injuries. Chemico-Biological Interactions. 2013;206:512–522.
Ghasemi H, Ghazanfari T, Yaraee R, et al. Systemic and ocular complications of sulfur mustard: A panoramic review. Toxin Reviews. 2009;28:14–23.
Panahi Y, Gholami N, Ghojazadeh M, et al. Complications and carcinogenic effects of mustard gas-a systematic review and meta-analysis in Iran. Asian Pac J Cancer Prev. 2015;16:7567–7573.
McNutt PM, Hamilton TA, Lyman ME, et al. Ocular toxicity of chemical warfare agents. In: Handbook of Toxicology of Chemical Warfare Agents. San Diego, CA: Elsevier. 2020. p. 567–588.
Ghassemi-Broumand M, Aslani J, Emadi S-N. Delayed ocular, pulmonary, and cutaneous complications of mustards in patients in the city of Sardasht, Iran. Cutan Ocul Toxicol. 2008;27:295–305.
Ghabili K, Agutter PS, Ghanei M, et al. Mustard gas toxicity: the acute and chronic pathological effects. J Appl Toxicol. 2010;30:627–643.
Baradaran-Rafii A, Eslani M, Tseng SCG. Sulfur mustard-induced ocular surface disorders. Ocul Surf. 2011;9:163–178.
Panahi Y, Abdolghaffari AH, Sahebkar A. A review on symptoms, treatments protocols, and proteomic profile in sulfur mustard‐exposed victims. J Cell Biochem. 2018;119:197–206.
Kadar T, Turetz J, Fishbine E, et al. Characterization of acute and delayed ocular lesions induced by sulfur mustard in rabbits. Curr Eye Res. 2001;22:42–53.
Ghasemi H, Javadi MA, Ardestani SK, et al. Alteration in inflammatory mediators in seriously eye-injured war veterans, long-term after sulfur mustard exposure. Int Immunopharmacol. 2020;80:105897.
Ghasemi H, Ghazanfari T, Yaraee R, et al. Evaluation of relationship between the serum levels of inflammatory mediators and ocular injuries induced by sulfur mustard: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9:1494–1498.
Ghazanfari T, Mostafaie A, Talebi F, et al. Alteration in serum levels of immunoglobulins in seriously eye-injured long-term following sulfur-mustard exposure. Int Immunopharmacol. 2020;80:105895.
Ghazanfari T, Ghasemi H, Yaraee R, et al. Tear and serum interleukin-8 and serum CX3CL1, CCL2 and CCL5 in sulfur mustard eye-exposed patients. Int Immunopharmacol. 2019;77:105844.
Heidary F, Ardestani SK, Ghasemi H, et al. Alteration in serum levels of ICAM-1 and P-E-and L-selectins in seriously eye-injured long-term following sulfur-mustard exposure. Int Immunopharmacol. 2019;76:105820.
Ghasemi H, Yaraee R, Hassan ZM, et al. Association of ophthalmic complications in patients with sulfur mustard induced mild ocular complications and serum soluble adhesion molecules: Sardasht–Iran Cohort Study. Int Immunopharmacol. 2013;17:980–985.
Yaraee R, Ghazanfari T, Faghihzadeh S, et al. Alterations in the serum levels of soluble L, P and E-selectin 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9:1477–1481.
Ghasemi H, Yaraee R, Faghihzadeh S, et al. Tear and serum MMP-9 and serum TIMPs levels in the severe sulfur mustard eye injured exposed patients. Int Immunopharmacol. 2019;77:105812.
Uhde GI. Mustard-gas burns of human eyes in World War II. Am J Ophthalmol. 1946;29:929–938.
Panahi Y, Rajaee SM, Sahebkar A. Ocular effects of sulfur mustard and therapeutic approaches. J Cell Biochem. 2017;118:3549–3560.
Fuchs A, Giuliano EA, Sinha NR, et al. Ocular toxicity of mustard gas: A concise review. Toxicol Lett. 2021;343:21–27.
Shohrati M, Peyman M, Peyman A, et al. Cutaneous and ocular late complications of sulfur mustard in Iranian veterans. Cutan Ocul Toxicol. 2007;26:73–81.
Javadi M-A, Yazdani S, Sajjadi H, et al. Chronic and delayed-onset mustard gas keratitis: report of 48 patients and review of literature. Ophthalmology. 2005;112:617–625.
Safarinejad MR, Moosavi SA, Montazeri B. Ocular injuries caused by mustard gas: diagnosis, treatment, and medical defense. Mil Med. 2001;166:67–70.
McNutt PM, Tuznik KM, Glotfelty EJ, et al. Contributions of tissue‐specific pathologies to corneal injuries following exposure to SM vapor. Ann N Y Acad Sci. 2016;1374:132–143.
McNutt PM, Nguyen DL, Nelson MR, et al. Corneal endothelial cell toxicity determines long-term outcome after ocular exposure to sulfur mustard vapor. Cornea. 2020;39:640–648.
McNutt P, Tuznik K, Nelson M, et al. Structural, morphological, and functional correlates of corneal endothelial toxicity following corneal exposure to sulfur mustard vapor. Invest Ophthalmol Vis Sci. 2013;54:6735–6744.
Kanavi MR, Javadi A, Javadi MA. Chronic and delayed mustard gas keratopathy: a histopathologic and immunohistochemical study. Eur J Ophthalmol. 2010;20:839–843.
Saladi RN, Smith E, Persaud AN. Mustard: a potential agent of chemical warfare and terrorism. Clin Exp Dermatol. 2006;31:1–5.
Baradaran-Rafii A, Javadi M-A, Rezaei Kanavi M, et al. Limbal stem cell deficiency in chronic and delayed-onset mustard gas keratopathy. Ophthalmology. 2010;117:246–252.
Rajavi Z, Safi S, Javadi MA, et al. Clinical practice guidelines for prevention, diagnosis and management of early and delayed-onset ocular injuries due to mustard gas exposure. J Ophthalmic Vis Res. 2017;12:65–80.
Ghasemi H, Ghazanfari T, Ghassemi-Broumand M, et al. Long-term ocular consequences of sulfur mustard in seriously eye-injured war veterans. Cutan Ocul Toxicol. 2009;28:71–77.
Ghasemi H, Owlia P, Jalali-Nadoushan MR, et al. A clinicopathological approach to sulfur mustard-induced organ complications: a major review. Cutan Ocul Toxicol. 2013;32:304–324.
Ghasemi H, Ghazanfari T, Babaei M, et al. Long-term ocular complications of sulfur mustard in the civilian victims of Sardasht, Iran. Cutan Ocul Toxicol. 2008;27:317–326.
Karimian F, Zarei-Ghanavati S, Baradaran-Rafii A, et al. Microbiological evaluation of chronic blepharitis among Iranian veterans exposed to mustard gas: a case-controlled study. Cornea. 2011;30:620–623.
Ghasemi H, Owlia P, Ghazanfari T, et al. Conjunctival microbial florae in patients with seriously sulfur mustard induced eye injuries. Cutan Ocul Toxicol. 2013;32:13–17.
Panahi Y, Naderi M, Zare MA, et al. Ocular effects of sulfur mustard. J Curr Ophthalmol. 2013;25:90.
Kadar T, Dachir S, Cohen M, et al. Prolonged impairment of corneal innervation after exposure to sulfur mustard and its relation to the development of delayed limbal stem cell deficiency. Cornea. 2013;32:e44–e50.
McNutt P, Lyman M, Swartz A, et al. Architectural and biochemical expressions of mustard gas keratopathy: preclinical indicators and pathogenic mechanisms. PLoS One. 2012;7:e42837.
Balali‐Mood M, Hefazi M. The pharmacology, toxicology, and medical treatment of sulphur mustard poisoning. Fundam Clin Pharmacol. 2005;19:297–315.
English F, Bennett Y. The challenge of mustard-gas keratopathy. Med J Aust. 1990;152:55–56.
Pleyer U, Sherif Z, Baatz H, et al. Delayed mustard gas keratopathy: clinical findings and confocal microscopy. Am J Ophthalmol. 1999;128:506–507.
Jadidi K, Mohazzab-Torabi S, Pirhadi S, et al. A study of corneal biomechanics in delayed-onset mustard gas keratopathy compared to cases with corneal scarring and normal corneas. Eye Contact Lens. 2019;45:112–116.
Safaei A, Saluti R, Kumar PV. Conjunctival dysplasia in soldiers exposed to mustard gas during the Iraq-Iran war: scrape cytology. Acta Cytol. 2001;45:909–913.
Kadar T, Cohen M, Cohen L, et al. Endothelial cell damage following sulfur mustard exposure in rabbits and its association with the delayed-onset ocular lesions. Cutan Ocul Toxicol. 2013;32:115–123.
López-García JS, Rivas L, García-Lozano I. Corneal epithelium squamous metaplasia determination as diagnostic factor in limbal deficiency. Arch Soc Esp Oftalmol. 2006;81:281–288.
Jafarinasab MR, Zarei-Ghanavati S, Kanavi MR, et al. Confocal microscopy in chronic and delayed mustard gas keratopathy. Cornea. 2010;29:889–894.
Lagali N, Fagerholm P. Delayed mustard gas keratitis: clinical course and in vivo confocal microscopy findings. Cornea. 2009;28:458–462.
Tripathi R, Balne PK, Sinha NR, et al. A novel topical ophthalmic formulation to mitigate acute mustard gas keratopathy in vivo: a pilot study. Translational Vis Sci Technol. 2020;9:6.
Gordon MK, DeSantis A, Deshmukh M, et al. Doxycycline hydrogels as a potential therapy for ocular vesicant injury. J Ocul Pharmacol Ther. 2010;26:407–419.
Amir A, Turetz J, Chapman S, et al. Beneficial effects of topical anti‐inflammatory drugs against sulfur mustard‐induced ocular lesions in rabbits. J Appl Toxicol. 2000;20:S109–S114.
Kadar T, Dachir S, Cohen L, et al. Ocular injuries following sulfur mustard exposure—pathological mechanism and potential therapy. Toxicology. 2009;263:59–69.
Phulke S, Kaushik S, Kaur S, et al. Steroid-induced glaucoma: an avoidable irreversible blindness. J Curr Glaucoma Pract. 2017;11:67–72.
Murray VS, Volans GN. Management of injuries due to chemical weapons. Br Med J. 1991;302:129–130.
Sun M, Yang Y, Meng W, et al. Advanced biotherapy for the treatment of sulfur mustard poisoning. Chemico-Biological Interactions. 2018;286:111–118.
Joseph A, Dua HS, King AJ. Failure of amniotic membrane transplantation in the treatment of acute ocular burns. Br J Ophthalmol. 2001;85:1065–1069.
Tsai RJF, Li LM, Chen JK. Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. New Engl J Med. 2000;343:86–93.
Javadi M-A, Baradaran-Rafii A. Living-related conjunctival-limbal allograft for chronic or delayed-onset mustard gas keratopathy. Cornea. 2009;28:51–57.
Figueiredo FC, Glanville JM, Arber M, et al. A systematic review of cellular therapies for the treatment of limbal stem cell deficiency affecting one or both eyes. Ocul Surf. 2021;20:48–61.
Javadi MA, Jafarinasab MR, Feizi S, et al. Management of mustard gas-induced limbal stem cell deficiency and keratitis. Ophthalmology. 2011;118:1272–1281.
Wolffsohn JS, Travé Huarte S, Jones L, et al.; TFOS ambassadors. Clinical practice patterns in the management of dry eye disease: A TFOS international survey. Ocul Surf. 2021;21:78–86.
Jadidi K, Panahi Y, Ebrahimi A, et al. Topical cyclosporine a for treatment of dry eye due to chronic mustard gas injury. J Ophthalmic Vis Res. 2014;9:417–422.
Jadidi K, Ebrahimi A, Panahi Y, et al. Topical cyclosporine a for mustard gas induced ocular surface disorders. J Ophthalmic Vis Res. 2015;10:21–25.
Tewari-Singh N, Jain AK, Inturi S, et al. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries. Toxicol Appl Pharmacol. 2012;264:23–31.
Horwitz V, Dachir S, Cohen M, et al. The beneficial effects of doxycycline, an inhibitor of matrix metalloproteinases, on sulfur mustard-induced ocular pathologies depend on the injury stage. Curr Eye Res. 2014;39:803–812.
Kadar T, Amir A, Cohen L, et al. Anti-VEGF therapy (bevacizumab) for sulfur mustard-induced corneal neovascularization associated with delayed limbal stem cell deficiency in rabbits. Curr Eye Res. 2014;39:439–450.
Gore A, Horwitz V, Cohen M, et al. Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model. Exp Eye Res. 2018;171:183–191.
Panahi Y, Roshandel D, Sadoughi MM, et al. Sulfur mustard-induced ocular injuries: update on mechanisms and management. Curr Pharm Des. 2017;23:1589–1597.
Shtein RM, Shen JF, Kuo AN, et al. Autologous serum-based eye drops for treatment of ocular surface disease: a report by the American Academy of Ophthalmology. Ophthalmology. 2020;127:128–133.
Giannaccare G, Versura P, Buzzi M, et al. Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus Apher Sci. 2017;56:595–604.
Gu S, Xing C, Han J, et al. Differentiation of rabbit bone marrow mesenchymal stem cells into corneal epithelial cells in vivo and ex vivo. Mol Vis. 2009;15:99–107.
Lin K-J, Loi M-X, Lien G-S, et al. Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration. Stem Cel Res Ther. 2013;4:72.
Beigi Harchegani A, Khor A, Tahmasbpour E, et al. Role of oxidative stress and antioxidant therapy in acute and chronic phases of sulfur mustard injuries: a review. Cutan Ocul Toxicol. 2019;38:9–17.
Batal M, Rebelo-Moreira S, Hamon N, et al. A guanine-ethylthioethyl-glutathione adduct as a major DNA lesion in the skin and in organs of mice exposed to sulfur mustard. Toxicol Lett. 2015;233:1–7.
Jafarinasab MR, Feizi S, Javadi MA, et al. Lamellar keratoplasty and keratolimbal allograft for mustard gas keratitis. Am J Ophthalmol. 2011;152:925–932.
Rall DP, Pechura CM. Veterans at Risk: The Health Effects of Mustard Gas and Lewisite. Washington, DC: National Academies Press. 1993.
Javadi MA, Yazdani S, Kanavi MR, et al. Long-term outcomes of penetrating keratoplasty in chronic and delayed mustard gas keratitis. Cornea. 2007;26:1074–1078.
Daya SM, Ilari FA. Living related conjunctival limbal allograft for the treatment of stem cell deficiency. Ophthalmology. 2001;108:126–133.
Tsubota K, Shimmura S, Shinozaki N, et al. Clinical application of living-related conjunctival-limbal allograft. Am J Ophthalmol. 2002;133:134–135.
Solomon A, Ellies P, Anderson DF, et al. Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency. Ophthalmology. 2002;109:1159–1166.
Richter MN, Wachtlin J, Bechrakis NE, et al. Keratoplasty after mustard gas injury: clinical outcome and histology. Cornea. 2006;25:467–469.
Alio JL, Rodriguez AE, WróbelDudzinska D. Eye platelet-rich plasma in the treatment of ocular surface disorders. Curr Opin Ophthalmol. 2015;26:325–332.
Nair AP, D'Souza S, Shetty R, et al. Altered ocular surface immune cell profile in patients with dry eye disease. Ocul Surf. 2021;21:96–106.
Ma B, Zhou Y, Liu R, et al. Pigment epithelium-derived factor (PEDF) plays anti-inflammatory roles in the pathogenesis of dry eye disease. Ocul Surf. 2021;20:70–85.
Gonzalez GG, Gallar J, Belmonte C. Influence of diltiazem on the ocular irritative response to nitrogen mustard. Exp Eye Res. 1995;61:205–212.
Banin E, Morad Y, Berenshtein E, et al. Injury induced by chemical warfare agents: characterization and treatment of ocular tissues exposed to nitrogen mustard. Invest Ophthalmol Vis Sci. 2003;44:2966–2972.
Morad Y, Banin E, Averbukh E, et al. Treatment of ocular tissues exposed to nitrogen mustard: beneficial effect of zinc desferrioxamine combined with steroids. Invest Ophthalmol Vis Sci. 2005;46:1640–1646.
Jiping C, Jie Z, WeiGuo H, et al. Therapeutic effects of combination of three drugs on healing of rabbit corneal wound caused by mustard gas. Bull Acad Mil Med Sci. 2001:126–129.
Jiping C, Weiguo H, Mingxue Z. Effect of basic fibroblast growth factor on healing of rabbit corneal wound caused by mustard gas. Acad J Second Mil Med Coll. 2002;23:67–68.
Fagerholm P, Lagali NS, Carlsson DJ, et al. Corneal regeneration following implantation of a biomimetic tissue‐engineered substitute. Clin Translational Sci. 2009;2:162–164.
Horwitz V, Cohen-Gihon I, Egoz I, et al. A comprehensive analysis of corneal mRNA levels during sulfur mustard induced ocular late pathology in the rabbit model using RNA sequencing. Exp Eye Res. 2019;184:201–212.
Panahi Y, Shahbazi A, Naderi M, et al. Sulfur mustard-related ocular complications: a review of proteomic alterations and pathways involved. Curr Pharm Des. 2018;24:2849–2854.
Gore A, Kadar T, Dachir S, et al. Therapeutic measures for sulfur mustard-induced ocular injury. Toxicol Lett. 2021;340:58–66.
Shojaati G, Khandaker I, Funderburgh ML, et al. Mesenchymal stem cells reduce corneal fibrosis and inflammation via extracellular vesicle-mediated delivery of miRNA. Stem Cells Translational Med. 2019;8:1192–1201.