Browsing Doug Coster by Subject "Corneal Transplantation"
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ItemCorneal graft rejection occurs despite Fas ligand expression and apoptosis of infiltrating cells(BMJ Publishing Group - http://bjo.bmjjournals.com/, 2005-05) Williams, Keryn Anne; Standfield, Scott D; Smith, Justine R; Coster, Douglas JohnBACKGROUND/AIMS: Constitutive expression of Fas ligand (CD95L) protects the eye against cell mediated immune responses by inducing apoptosis in infiltrating Fas bearing T cells. This study was designed to examine Fas ligand expression on acutely rejecting rat corneal grafts and to investigate the kinetics of induction of apoptosis in infiltrating leucocytes. METHODS: Orthotopic penetrating corneal transplantation was performed between genetically disparate inbred rats. Fas ligand expression and the phenotype of infiltrating leucocytes were examined by immunohistochemistry. Apoptotic nuclei were visualised in sections of normal rat cornea, rejecting allografts, and time matched isografts by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling (TUNEL) and quantified by video image analysis. Staining with Hoechst dye 33258 was used to confirm the presence of apoptotic nuclei. RESULTS: Fas ligand was expressed on corneal endothelial and epithelial cells during acute corneal graft rejection. At all time points examined, including as early as the fifth postoperative day, the cells infiltrating both corneal isografts and allografts were TUNEL positive. By the 15th postoperative day, over 90% of all nuclei, many of which were T cells, were apoptotic. CONCLUSION: Expression of Fas ligand is not downregulated on the cornea during allograft rejection and infiltrating leucocytes in both isografts and allografts die rapidly in situ. Despite the death of the cells believed to be responsible for rejection, isografts survive indefinitely whereas allografts are irreparably damaged. ItemInfluence of advanced recipient and donor age on the outcome of corneal transplantation. Australian Corneal Graft Registry.(BMJ Publishing Group - http://bjo.bmjjournals.com/, 1997-10) Williams, Keryn Anne; Muehlberg, S M; Lewis, R F; Coster, Douglas JohnAIMS: The aims of this study were to examine the influence of advanced recipient and donor age on the long term outcome of corneal transplantation. METHODS: Records of 1036 penetrating corneal grafts in recipients aged > or = 80 years at surgery (defined as the elderly subset) and 8092 donor corneas used for transplantation were obtained from the Australian Corneal Graft Register database, Kaplan-Meier graft survival plots were compared using log rank statistics. RESULTS: Elderly recipients constituted 15% of the recipient pool. The major indication for corneal transplantation in the elderly was bullous keratopathy. Graft survival fell with increasing recipient age (p < 0.00001); the major cause of graft failure was rejection (33%). The desired outcome in 51% of cases was to improve vision and in 42% of cases to relieve pain; 23% of elderly recipients achieved a Snellen acuity of 6/18 or better in the grafted eye and 66% recorded improved acuity after transplantation. Elderly recipients suffered more complications and comorbidities in the grafted eye than did younger recipients. Donor age (stratified in 10 year intervals) did not influence corneal graft survival significantly (p = 0.10). CONCLUSIONS: Elderly graft recipients fared less well after corneal transplantation than did younger recipients, but outcomes in terms of long term graft survival and visual rehabilitation were still good. Donor age did not affect graft survival. ItemThe long term outcome of limbal allografts: the search for surviving cells(BMJ Publishing Group - http://bjo.bmjjournals.com/, 2001-05) Henderson, Timothy R; Coster, Douglas John; Williams, Keryn AnneBACKGROUND/AIMS: Limbal allotransplantation is increasingly being used for ocular surface repair in patients with limbal stem cell dysfunction. However, it is uncertain whether donor cells survive long term on the ocular surface and whether patients maintain the early benefits of the procedure. The aims of this study were to investigate the long term outcome of clinical limbal allografts and to correlate outcome with donor cell survival. METHODS: Five patients who had undergone allotransplantation-four keratolimbal allografts and one tarsoconjunctival allograft-from 3-5 years previously, and for whom residual frozen donor ocular tissue was available, were reviewed. Survival of donor cells lifted from the recipient ocular surface by impression cytology was investigated by DNA fingerprinting using primers detecting variable nucleotide tandem repeat sequences. Recipient buccal cells and scleral samples from the remnant donor eye were used to genotype recipients and donors, respectively. Polymerase chain reaction products were sized by Genescan analysis. RESULTS: An objective long term benefit from the procedure (improved Snellen acuity, reduced frequency of epithelial defects, reduced vascularisation, and scarring) was recorded for four patients. Some subjective benefit was also reported. However, in no instances were donor cells recovered from the ocular surface at 3-5 years post-graft. Initial experiments to examine sensitivity indicated that any surviving donor cells must have constituted less than 2.5% of cells sampled. CONCLUSION: Limbal stem cell allotransplantation can provide long term benefits, as measured by objective criteria. However, such benefits do not necessarily correlate with survival of measurable numbers of donor cells on the ocular surface.