Browsing Doug Coster by Subject "Cornea"
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ItemInfluence of format on in vitro penetration of antibody fragments through porcine cornea(BMJ Publishing Group - http://bjo.bmjjournals.com/, 2005-09) Brereton, Helen Mary; Taylor, Susan D; Farrall, Alexandra L; Hocking, Dianna M; Thiel, Michael A; Tea, Melinda Nay; Coster, Douglas John; Williams, Keryn AnneAIM: Antibody fragments, appropriately formulated, can penetrate through the ocular surface and thus have potential as therapeutic agents. The aim was to investigate the influence of protein fragment format on the kinetics and extent of ocular penetration in vitro. METHODS: Immunoglobulin single chain variable domain fragments of a murine monoclonal antibody with specificity for rat CD4 were engineered with a 20 or 11 amino acid linker by assembly polymerase chain reaction, expressed in Escherichia coli and purified by chromatography. Fab fragments of the parental antibody were prepared by papain digestion. Antibody fragments were formulated with a penetration and a viscosity enhancer and were applied to the surface of perfused pig corneas for up to 10 hours in vitro. Penetration was quantified by flow cytometry on rat thymocytes. RESULTS: 20-mer antibody fragments formed natural monomers and dimers following purification that could be separately isolated, while 11-mer fragments were dimeric. All formats of fragment (20-mer monomers and dimers, 11-mer dimers, Fab) showed penetration through the pig cornea after 6 hours of intermittent topical administration. CONCLUSION: Antibody fragments of different shapes and sizes can penetrate the cornea after topical administration, thereby increasing the potential of this class of proteins for topical ophthalmic use. ItemLate onset post-keratoplasty astigmatism in patients with keratoconus(BMJ Publishing Group - http://bjo.bmjjournals.com/, 2004-03) Lim, L; Pesudovs, Konrad; Goggin, M; Coster, Douglas JohnAIM: 10 eyes of 10 patients are reported where progression of keratoconus in the host cornea occurred more than 10 years after penetrating keratoplasty with resultant increase in astigmatism. The technique and results of graft refractive surgery in seven eyes are presented. METHODS: The clinical features and management of these patients were retrospectively analysed. Graft refractive surgery involved an incision at the graft-host junction adjacent to the host thinning with compressive resuturing. Astigmatic changes were calculated using vector analysis. RESULTS: There were seven men and three women with a mean age of 41.2 years. The average age when undergoing penetrating keratoplasty in the affected eye was 28.4 years and the average time after penetrating keratoplasty until keratoconus appeared in the host cornea defined by host thinning was 13.5 years. The mean cylinder power before host thinning was noted was 5.07 D (SD 2.19) and the mean after host thinning was 11.0 D (2.53). The mean vector calculated disease induced astigmatism magnitude was 7.59 D (3.09). Graft refractive surgery was performed in seven eyes. The mean cylinder power before and after graft refractive surgery was 11.28 D (2.15) and 7.09 D (5.53) respectively. The surgically induced astigmatism vector magnitude was 7.36 D (4.88). CONCLUSION: Progression of keratoconus in the host cornea late after penetrating keratoplasty is characterised by a large astigmatic change where the flat axis of astigmatism passes through an area of host thinning visible on slit lamp examination. Compressive resuturing performed in the area of host thinning resulted in satisfactory reduction of astigmatism.