Chronic and Delayed-Onset Mustard Gas KeratitisReport of 48 patients and review of literature

Javadi, Mohammad-Ali; Yazdani, Shahin; Sajjadi, Hamid; Jadidi, Khosrow; Karimian, Farid; Einollahi, Bahram; Jafarinasab, M R; Zare, Mohammad

doi:10.1016/j.ophtha.2004.09.027

Cited by 120 publications

(169 citation statements)

References 14 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…However, the Iraqi use of SM in the 1985-1988 Iran-Iraq war prompted Iranian ophthalmologists to record the range of ocular injuries incurred by their exposed troops. [4][5][6][7][8][9][10][11][12] This has highlighted the global need for ocular therapies against SM exposure. Even after 100 years of study, there are still no U.S. Food and Drug Administration (FDA)-approved countermeasures against vesicant exposures, whether to the eye, skin, or lung.…”

mentioning

confidence: 99%

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Gordon

Desantis

Deshmukh

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Purpose: The goals of this study were (1) to compare the injury at the basement membrane zone (BMZ) of rabbit corneal organ cultures exposed to half mustard (2 chloroethyl ethyl sulfide, CEES) and nitrogen mustard with that of in vivo rabbit eyes exposed to sulfur mustard (SM); (2) to test the efficacy of 4 tetracycline derivatives in attenuating vesicant-induced BMZ disruption in the 24-h period postexposure; and (3) to use the most effective tetracycline derivative to compare the improvement of injury when the drug is delivered as drops or hydrogels to eyes exposed in vivo to SM. Methods: Histological analysis of hematoxylin and eosin-stained sections was performed; the ultrastructure of the corneal BMZ was evaluated by transmission electron microscopy; matrix metalloproteinase-9 was assessed by immunofluorescence; doxycycline as drops or a hydrogel was applied daily for 28 days to eyes exposed in vivo to SM. Corneal edema was assessed by pachymetry and the extent of neovascularization was graded by length of longest vessel in each quadrant. Results: Injury to the BMZ was highly similar with all vesicants, but varied in degree of severity. The effectiveness of the 4 drugs in retaining BMZ integrity did not correlate with their ability to attenuate matrix metalloproteinase-9 expression at the epithelial-stromal border. Doxycycline was most effective on organ cultures; therefore, it was applied as drops or a hydrogel to rabbit corneas exposed in vivo to SM. Eyes were examined at 1, 3, 7, and 28 days after exposure. At 7 and 28 days after SM exposure, eyes treated with doxycycline were greatly improved over those that received no therapy. Corneal thickness decreased somewhat faster using doxycycline drops, whereas the hydrogel formulation decreased the incidence of neovascularization. Conclusions: Corneal cultures exposed to 2-chloroethyl ethyl sulfide and nitrogen mustard were effective models to simulate in vivo SM exposures. Doxycycline as drops and hydrogels ameliorated vesicant injury. With in vivo exposed animals, the drops reduced edema faster than the hydrogels, but use of the hydrogels significantly reduced neovascularization. The data provide proof of principle that a hydrogel formulation of doxycycline as a daily therapy for ocular vesicant injury should be further investigated.

show abstract

mentioning

confidence: 99%

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Gordon

Desantis

Deshmukh

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

show abstract

“…The 17-year latency period for delayed symptoms is slightly longer than the 1 -15 yr period reported in a review of 17 cases of delayed-form mustard gas keratitis in victims of the Iran -Iraq war 3 , but is typical for delayed mustard gas complications seen in a group of patients gassed during World War I. 7 The clinical abnormalities observed in our case included stromal scarring, a mild vascular tortuosity in the conjunctiva, corneal thinning, and a reduced tear break up timefindings which have been previously reported in other delayed-form cases.…”

Section: Discussionmentioning

confidence: 65%

“…This patient exhibited typical symptoms of delayed-form mustard gas keratitis, including excessive burning, tearing, pain, photophobia, and moderate to severe dry eye 3,6 . The 17-year latency period for delayed symptoms is slightly longer than the 1 -15 yr period reported in a review of 17 cases of delayed-form mustard gas keratitis in victims of the Iran -Iraq war 3 , but is typical for delayed mustard gas complications seen in a group of patients gassed during World War I.…”

Section: Discussionmentioning

confidence: 92%

“…Severe cases of exposure may resolve or can lead to either chronic inflammation or a delayed-onset keratitis, the latter occurring after a latent asymptomatic period ranging from 1 to 40 years. 1,[3][4][5] While the delayed course occurs in less than 1% of all cases, it can be particularly distressing, with degenerative changes, recurrent and worsening pain and inflammation, ulceration, and progressive loss of vision. 1,3 The pathophysiologic processes underlying this delayed form of keratitis are not well understood.…”

Section: Introductionmentioning

confidence: 99%

“…Histopathologic examination of affected corneas after penetrating keratoplasty has revealed abnormal cellular and morphologic features 3,4 , however, their origins are unclear. In-vivo confocal microscopy provides a method for gathering detailed structural and morphologic information in the living cornea, and may provide further insights into the mechanisms responsible for the long-term toxicity of mustard gas, particularly in patients where keratoplasty is not indicated.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Delayed Mustard Gas Keratitis: Clinical Course and In Vivo Confocal Microscopy Findings

Lagali

2009

Cornea

View full text Add to dashboard Cite

Purpose:To report the detailed clinical and in-vivo confocal microscopic findings in a patient with delayed-onset mustard gas keratitis observed 20 years after initial exposure. Methods:Case report. A 38-year-old man who was exposed to mustard gas in Iraq at the age of 19 was examined after presenting with ocular symptoms 17 years after initial recovery from the exposure. Slit-lamp biomicroscopy, corneal topography and in-vivo confocal microscopy was performed on both corneas. Results:The clinical symptoms were consistent with a delayed-form of mustard gas keratitis, although the patient had clear central corneas and good visual acuity. Confocal microscopic findings included evidence of epithelial abnormalities, necrotic changes in the anterior stroma, subbasal and anterior stromal nerve proliferation, and deep stromal keratocyte activation. Conclusions:In-vivo confocal microscopy revealed persistent morphologic abnormalities in the anterior stroma of both corneas 20 years after initial exposure to mustard gas. The detection of a population of dendritic cell bodies in the central epithelium and evidence of keratocyte activation and migration in the deep stroma indicated the presence of ongoing sub-clinical processes.

show abstract

Ophthalmology From Ancient Persia to the Modern Era

Khodadoust¹

2006

Arch Ophthalmol

View full text Add to dashboard Cite

Chronic and Delayed-Onset Mustard Gas KeratitisReport of 48 patients and review of literature

Cited by 120 publications

References 14 publications

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Delayed Mustard Gas Keratitis: Clinical Course and In Vivo Confocal Microscopy Findings

Ophthalmology From Ancient Persia to the Modern Era

Contact Info

Product

Resources

About