Treacher Collins Prize Essay, 1979. Inflammatory disease of the outer eye.
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Biomedical subjects
Publications and source records attributed to D J Coster.
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A series of 41 cases of trichiasis was treated with cryosurgery using a standard retinal cryoprobe. The failure rate was approximately 50 per cent. The results should be improved by using properly designed equipment capable of cooling the lash follicles to -20 degrees C, and ensuring that this temperature is achieved by using a tissue thermocouple. A double freeze-thaw cycle should be used and a long-acting local anaesthetic containing adrenaline. The main complication is depigmentation which is a problem only with heavily pigmented patients. Cryosurgery does have potential for the treatment of trichiasis.
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Various theories of recurrence of herpetic disease are outlined to indicate the potential role that interferon, interferon-inducers, or a hypothetical perfect synthetic antiviral may have in preventing recurrences, and the possibilities of minimizing trigger effects are considered. Attention is drawn to certain aspects of the management of herpetic eye disease that have a direct bearing on the incidence of subsequent recurrence. There is a need to initiate a movement to mobibize ophthalmologists everywhere to educate general practitioners in order to restrain them from harmfully using steroids in undiagnosed red eyes.
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We define in this paper a rational approach to the management of the various stages of herpetic eye disease. We consider in more detail comparisons between idoxuridine (IDU), trifluorothymidine (F3T), and adenine arabinoside (Ara-a) (derived largely from clinical trials in herpetic ulcers). We discuss metaherpetic ulcers and certain aspects of keratoplasty.
55 patients with dendritic ulcer have been treated in a double-blind randomised manner by minimal wiping debridement of their ulcers followed by daily application of either partially purified human interferon (P.I.N.F.) or placebo. There were 6 recurrences of epithelial herpetic disease in 30 patients who received P.I.N.F. and 13 in 25 who received placebo. This provides the long-awaited data proving the antiviral effect of exogenous interferon in treatment of naturally occurring viral disease in man, and furnishes a sighting shot on the lower edge of the target of effective therapy.
An open trial suggested that monkey interferon had a therapeutic effect on ulcerative vaccinial keratitis in humans. A randomized, double-blind, placebo-controlled trial of either monkey interferon or drops of idoxuridine (given hourly by day and at 2-hr intervals by night for three days) suggested a therapeutic effect from idoxuridine but not from monkey interferon. Results of experiments with rabbits suggested that a daily application of human interferon (1.1 X 10(7) international units/ml) would be effective in the prevention of herpetic ulcers but might not affect established lesions. Preliminary results are encouraging in a placebo-controlled, randomized trial of human interferon given once daily for seven days for prevention of recrudescence of epithelial herpetic lesions after minimal wiping debridement with a cotton-tipped swab. The design of the trial is closely analogous to that of the experiments with rabbits and permits ethically acceptable, placebo-controlled trials of antiviral agents.
One hundred two unselected patients with ulceration of the cornea due to herpes simples virus were treated with either adenine arabinoside or trifluorothymide; the trial was double-blind, stratified, and radomized. The two drugs were given topically five times per day, and the rate of healing was observed and recorded. The series included 87 patients with dendritic ulcers and 15 with amoeboid ulcers. Dendritic ulcers of the cornea can be accurately measured, and the healing process can be easily followed. In this situation no statistically significant difference between the efficacy of adenine arabinoside and that of trifluorothymidine was demonstrated. Amoeboid ulcers are more difficult to evaluate than dendritic ulcers, and their responses to treatment vary considerably; however, data from this small group of patients suggest that trifluorothymodine may be more effective than adenine arabinoside for the treatment of amoeboid ulcers.
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The ultrastructural appearances of corneal crystalloidal deposits are described in two patients with an IgG-kappa paraproteinemia of uncertain pathogenesis. The crystalloids in one patient were overwhelmingly intracellular and were found mainly in stromal keratocytes, but also in basal corneal epithelial cells and the limbal vascular endothelium. Four types of crystalloid or immunoprotein-containing granules were recognizable in this case: 1) fibrillary crystalloids with a curvilinear filamentous substructure; 2) angulated geometric crystalloids that often had a linear filamentous substructure and transverse or oblique periodicity; 3) cordlike crystalloids; and 4) lysosomelike granules with amorphous contents. Immunoelectron microscopy demonstrated that all of these structures labeled for kappa-light chains, and rectangular type 2 crystalloids showed approximately a twofold greater concentration of the colloidal gold probe than the type 1 fibrillary crystalloids. The evidence suggested development of the crystalloids within lysosomes, with a progression from the granules containing amorphous material, through fibrillary crystalloids, to the geometric structures. The circumferential distribution of the corneal deposits, as well as the presence of vascular endothelial crystalloids and reduplication of external laminae around limbal blood vessels, suggests that the crystalloids originated predominantly or entirely from the blood, with transport of immunoprotein across damaged limbal microvasculature. The abnormal vasculature may also have contributed to corneal edema, which in turn may have exacerbated corneal opacification. The crystalloidal deposits in the other case were exclusively extracellular; they were located beneath and between corneal basal epithelial cells, and predominantly as a mantle around individual keratocytes. The crystalloids in this case consisted overwhelmingly of thick-walled tubules about 40 nm in diameter that labeled for both kappa-light chains and gamma chains with the colloidal gold immunoprobe. In addition, lucent vesicles within keratocytes were found only in sections labeled for kappa-light chains and were positive. The factors that might contribute to the formation of corneal crystalloidal deposits in immunoproliferative disorders are discussed, and include: 1) an inherent propensity for crystallization of some immunoglobulins or kappa-light chains, perhaps because of abnormal molecular structure; and 2) local factors in the cornea that might promote deposition and crystallization of immunoprotein, such as temperature, pH, the water content, and extracellular matrix components.
We report a case of acanthamoebic keratitis that occurred after minor ocular trauma in a healthy 31-year-old man. Multiple microbiological investigations failed to reveal the causative organism, which was identified as Acanthamoeba castellanii only after a corneal graft operation had been performed. A review of previously described cases reveals that this rare ocular infection tends to cause recalcitrant corneal ulcers after minor eye injuries in otherwise healthy individuals.