Management of Mustard Gas-Induced Limbal Stem Cell Deficiency and Keratitis

Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Ophthalmology (Impact Factor: 6.14). 03/2011; 118(7):1272-81. DOI: 10.1016/j.ophtha.2010.11.012
Source: PubMed


To report the clinical findings and compare outcomes of different surgical techniques evolved over time in a large series of patients with delayed-onset mustard gas keratitis (MGK).
Retrospective, comparative, interventional case series.
Ninety Iranian male survivors (175 eyes) of Iraqi chemical warfare with chronic or delayed-onset MGK.
The symptoms and clinical findings of patients are presented, and medical and surgical interventions to address dry eye, limbal ischemia and limbal stem cell deficiency (LSCD), and corneal involvements are explained. The results of limbal stem cell transplantation techniques (living-related conjunctival-limbal allograft [lrCLAL] versus keratolimbal allograft [KLAL]) as well as corneal transplantation techniques (penetrating keratoplasty [PK] versus lamellar keratoplasty [LK]) are compared in terms of clinical outcomes and graft survival rates.
Ocular findings and appropriate surgical approach for LSCD and corneal involvements.
A total of 175 eyes of 90 cases (all male) between 34 and 68 years of age were followed up for 101±30.3 months (range, 36-198 months). The most common ocular involvements were chronic blepharitis and dry eye. Conjunctival vascular abnormalities and limbal ischemia were observed in 27.4% and 29.7% of eyes, respectively. Limbal stem cell deficiency necessitating stem cell transplantation developed in 41.1% of eyes. The most common corneal sign was central and peripheral anterior stromal opacity (58.9%), followed by corneal stromal thinning (36.0%) and neovascularization (27.4%). Living-related conjunctival-limbal allograft was performed in 32 eyes, and KLAL was performed in 40 eyes. The rejection-free graft survival rate was 39.1% in the lrCLAL group and 80.7% in the KLAL group at month 40, with a mean length of 24.9 and 68.8 months, respectively (P = 0.02). Thirty eyes underwent PK and 51 underwent LK. Corneal graft failure was observed in 9 PK eyes and in 6 LK eyes. The rejection-free graft survival rate was 39.0% in the PK group and 90.3% in the LK group at month 28, with a mean length of 29.6 and 85.0 months, respectively (P<0.001).
Chemical warfare victims who initially have mild symptoms ultimately may experience significant ocular involvements requiring surgical intervention. Limbal and corneal abnormalities can be managed best by KLAL and LK, respectively.

Download full-text


Available from: Mohammad Reza Jafarinasab,
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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). 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.
    Cutaneous and Ocular Toxicology 09/2011; 31(2):104-10. DOI:10.3109/15569527.2011.615359 · 1.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ocular injuries following exposure to the chemical agent sulfur mustard (SM) are characterized by acute corneal erosions and inflammation of the anterior segment that may be followed by delayed Partial Limbal Stem Cell Deficiency (LSCD), expressed clinically by corneal neovascularization and epithelial defects. LSCD may derive from direct destruction of limbal stem cells or indirectly from altered limbal stromal niche. The aim of this study was to investigate the mechanism underlying LSCD in SM injuries, focusing on the effects of the chemical on limbal epithelium. Rabbit eyes were exposed to SM vapor and were observed by slit lamp examinations and pachymetry. Eyes were taken for histological and molecular biology evaluations at different time points (4 h-4 weeks), to include acute and delayed injuries. Epithelial stem cells were identified by ABCG2, p63 and by in vivo BrdU labeling for slow cycling cells. Limbal stem cells were not damaged during the acute phase following SM exposure, in contrast to the severe injury of the central corneal epithelium. On the contrary, limbal epithelium became activated, responding to corneal insult with a wound healing process, as shown by histology and by transient elevation of the stem cells markers. Simultaneously, inflammation was taking place in the limbal stroma lasting for weeks. A gradual loss of stem cells was observed later-on (2-4 weeks), associated with typical symptoms of LSCD. LSCD associated with SM ocular toxicity was not derived from a direct cytotoxic effect on the epithelial stem cells, but apparently from pathological events at the limbal stroma, that produced an abnormal microenvironment for the stem cells, triggering their gradual death. The results, and in particular the absence of a primary damage to the epithelial stem cells, indicate the presence of a therapeutic window for intervention to avoid the development of the delayed LSCD.
    Current eye research 12/2011; 36(12):1098-107. DOI:10.3109/02713683.2011.609305 · 1.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study explored the efficacy of optical coherence tomography (OCT) as a high-resolution, noncontact method for imaging the palisades of Vogt by correlating OCT and confocal microscopy images. Human limbal rims were acquired and imaged with OCT and confocal microscopy. The area of the epithelial basement membrane in each of these sets was digitally reconstructed, and the models were compared. OCT identified the palisades within the limbus and exhibited excellent structural correlation with immunostained tissue imaged by confocal microscopy. OCT successfully identified the limbal palisades of Vogt that constitute the corneal epithelial stem cell niche. These findings offer the exciting potential to characterize the architecture of the palisades in vivo, to harvest stem cells for transplantation more accurately, to track palisade structure for better diagnosis, follow-up and staging of treatment, and to assess and intervene in the progression of stem cell depletion by monitoring changes in the structure of the palisades.
    Investigative ophthalmology & visual science 01/2012; 53(3):1381-7. DOI:10.1167/iovs.11-8524 · 3.40 Impact Factor
Show more