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Biomedical subjects

D J Coster

Publications and source records attributed to D J Coster.

At least 19 recordsLinked to original sources

Corneal virulence, cytopathic effect on human keratocytes and genetic characterization of Acanthamoeba.

Acanthamoeba keratitis is a sight-threatening complication of corneal trauma or contact lens wear. Although the majority of corneal isolates of Acanthamoeba belong to Group II in the Pussard-Pons classification based on cyst morphology, they have been placed in at least six species and their genetic relatedness is uncertain. The aim of this study was to determine the virulence of, and the relationship among, strains derived from the cornea, the nasal mucosa, and other environmental sources. To assess virulence, 10(4) trophozoites of each strain were incubated with monolayers of human corneal fibroblasts. By day 7, 12 of 29 strains tested had induced significant cytopathic changes. In addition, inocula of 10(4) cysts or trophozoites with 10(6) Corynebacterium xerosis were injected into the corneas of Porton rats; 11 amoebic strains induced infection within 7 days. The correlation between the virulence of trophozoites in vitro and in vivo was 86%. Using allozyme electrophoresis, 23 Acanthamoeba strains clustered into 5 major phylogenic divisions. Three divisions contained one or more strains that were virulent in the rat cornea. Virulent Pussard-Pons Group II strains clustered tightly to a fixed allelic difference of 13.6%. The eight corneal isolates clustered to 33%, dividing into three lineages. Five avirulent nasal isolates were strongly differentiated from other Group II strains. The results were not in accord with species designations based primarily on morphological criteria. These data suggest that particular subsets of Acanthamoeba strains are virulent in the human cornea.

Acanthamoeba

Use of DNA polymorphisms and the polymerase chain reaction to examine the survival of a human limbal stem cell allograft.

PURPOSE: The extent to which limbal epithelial stem cell allografts will repopulate the human corneal ocular surface, and the time frame over which such cells survive, are uncertain. We investigated the survival of donor-derived epithelial cells after limbal stem cell allotransplantation in a patient with bilateral limbal stem cell failure by using short tandem-repeat DNA polymorphisms to distinguish donor and recipient cells. METHODS: Epithelial cells were harvested by impression cytology from the grafted eye before and at various times after transplantation. DNA was extracted and amplified by the polymerase chain reaction at an informative locus, D8S264. RESULTS: Cells of donor genotype were present over the grafted areas at the time of surgery but were not detected in the central cornea until 12 weeks postoperatively, indicating that repopulation of the epithelial surface from transplanted limbal stem cells took considerable time. However, by the 20th postoperative week, only recipient-type cells were detected in the grafted eye, despite systemic immunosuppression of the recipient with azathioprine and cyclosporine. CONCLUSIONS: Discrimination between donor and recipient cells on the ocular surface after limbal allotransplantation was possible using genotypic variation at DNA polymorphic sites (microsatellites). Long-term survival of donor cells after limbal transplantation did not occur in this patient. Detection of DNA polymorphisms amplified by the polymerase chain reaction is a simple, rapid, and noninvasive method of following the course of transplanted cells at the ocular surface.

Adult

How successful is corneal transplantation? A report from the Australian Corneal Graft Register.

Corneal graft outcome was assessed within a large, prospectively collected database of 4499 records. Penetrating corneal graft survival was 91% at 1 year, 72% at 5 years and 69% at 7 years. The three most common indications for graft were keratoconus (30%), bullous keratopathy (25%) and failed previous graft (18%); the three most common causes of graft failure were rejection (34%), infection (18%) and glaucoma (9%). The vast majority of grafts were performed for improved visual acuity. About four-fifths of recipients achieved at least one line of better acuity on the Snellen chart post-operatively; of the remainder with unchanged or worse acuity, only 21% had failed grafts. Overall, 43% of recipients achieved a best corrected Snellen acuity of 6/12 or better, 52% achieved 6/18 or better, and 20% had acuitities of less than 6/60. Reasons for poor post-operative acuity (recorded as less than 6/60) included graft failure (41%) and comorbidities in the grafted eye (43%). A number of risk factors for graft failure were examined: in most instances, there was little room for decision-making or expert intervention.

Astigmatism

Transplantation of the cornea.

Corneal transplantation is the most widely practised form of allografting in clinical practice. The operation is used to correct developmental abnormalities of corneal shape such as keratoconus, to overcome opacities of the cornea, to relieve pain and to mend perforations. Corneal transplantation is generally successful but contrary to popular belief, corneal grafts can be rejected. This is a particular problem for patients treated for the sequelae of inflammatory disease. The relative importance of measures such as systemic immunosuppression and tissue typing is less in corneal transplantation than in other forms of clinical allografting. Overcoming rejection, achieving the best optical configuration in a graft, and increasing the number of donor corneas available for transplantation represent the main avenues for achieving improvements in corneal transplantation.

Cornea

Effect of heparin surface modification of polymethylmethacrylate intraocular lenses on signs of postoperative inflammation after extracapsular cataract extraction. One-year results of a double-masked multicenter study.

PURPOSE: A heparin surface modified posterior chamber intraocular lens (IOL) was compared with a conventional polymethylmethacrylate (PMMA) IOL regarding postoperative complications caused by inflammation. METHODS: Five hundred twenty-four patients from 10 different centers were included in a parallel group, double-masked, multicenter study. RESULTS: The cumulative number of patients with inflammatory cellular deposits on their IOLs during the first postoperative year differed significantly in favor of the heparin surface modified group, with 29.8% of the patients having cellular deposits compared with 48.8% of patients in the control group. Cellular deposits were observed most frequently at 3 months after surgery, and the difference between the groups was most pronounced and statistically significant at this time. The same results were seen at 1 year, but the difference was not significant. The number of cellular deposits per patient, however, was significantly lower in the heparin surface modified group at 1 year. Cumulatively, there were significantly more patients with posterior synechiae in the PMMA group than in the heparin surface modified group during the 1-year follow-up. Complications were few and comparable between the groups. CONCLUSION: The results of this study indicate that heparin surface modification reduces the inflammatory response to PMMA IOLs.

Adult

Factors predictive of corneal graft survival. Report from the Australian Corneal Graft Registry.

Risk factors for graft failure after penetrating keratoplasty were investigated in 961 patients from records collected prospectively by the Australian Corneal Graft Registry. The most common cause of graft failure was irreversible rejection. A multivariate proportional hazards regression analysis indicated that the key predictors of graft failure were: an indication for graft other than keratoconus or corneal dystrophy; a failed previous graft (ipsilateral eye); aphakia; inflammation at the time of graft; presence of an anterior chamber or iris-clip intraocular lens; graft size outside the range of 7.0 to 7.9 mm diameter; and corneal vascularization occurring in the postoperative period.

Adolescent

Patterns of corneal graft rejection in the rabbit and reversal of rejection with monoclonal antibodies.

The purpose of this study was to determine whether the local administration of monoclonal antibodies could reverse rabbit corneal graft rejection. To provide a rational basis for the choice of monoclonal antibodies as potential immunosuppressive agents, the phenotypes of cells infiltrating rejecting rabbit corneal allografts were examined by immunohistochemistry. About half the leukocytes accumulating in these grafts bore an immunodominant T cell marker, over two-thirds carried MHC class II antigens, and about one-fifth carried myeloid cell markers. A kinetic study of the cell population appearing in rabbit aqueous during corneal graft rejection was performed by examination of repetitive anterior chamber taps taken over a ten-day period; again, the major components were T cells, MHC class II antigen-positive cells and myeloid cells. Monoclonal antibodies L11/135 (directed against a peripheral T cell determinant), 2C4 (directed against a monomorphic MHC class II antigen), and LION 2 (directed against a myeloid antigen) were chosen for intracameral injection into rabbits with rejecting corneal grafts. Each animal received a total of 50-100 micrograms of antibody in two injections at 3-4-day intervals. L11/135 and LION 2 reversed rejection in 5/9 and 8/12 animals, respectively, in the absence of any other immunosuppression; 2C4 was without effect. We suggest that monoclonal antibody therapy in corneal transplantation deserves further attention.

Animals

Cryopreservation of rabbit and cat corneas at -18 to -24 degrees C.

A simple method of corneal cryopreservation, in which corneas were frozen at -18 to -24 degrees C, was examined. Rabbit and cat corneas were placed successively in solutions of 50% fetal calf serum in McCarey-Kaufman medium with an increasing glycerol and glucose content. They were then frozen and stored in a -20 degrees C domestic freezer. Rabbit corneas stored in this way were examined in vitro by light and scanning electron microscopy, and both rabbit and cat corneas were also assessed after orthotopic allotransplantation into adult recipient animals. Functional corneal grafts were obtained with rabbit and cat tissue that had been cryopreserved for 3-4 weeks and 1 week, respectively. Endpoint analysis (by light and scanning electron microscopy) of grafts that had survived for 50 days indicated the presence of an intact corneal endothelial monolayer. The corneal endothelium slowly degenerated as the storage time was increased. Importantly, however, the endothelium appeared to withstand the freezing and thawing processes and we conclude that it may be possible to store corneas at temperatures above -196 degrees C, without the need for complex, low-temperature cryopreservation systems.

Animals

Long-term outcome after corneal transplantation. Visual result and patient perception of success.

Snellen acuity, reading line, and keratometry were measured in a cohort of 60 patients at 2 or more years after penetrating keratoplasty was performed. Patients were asked to complete a questionnaire to elicit information on their perceptions of visual function and the success of the procedure. Using preferred correction, a Snellen acuity of 6/18 or better was achieved by 65%, and a reading line of N8 or better was achieved by 57% of index grafts. Thirty-eight percent had more than 5 diopters (D) of astigmatism in the graft. Approximately 75% of patients reported satisfaction with their graft (satisfaction being associated with better acuity in the grafted eye than the other eye), graft clarity, and a perceived improvement in lifestyle. Dissatisfaction appeared to be associated with graft failure and problems with contact lens wear. The findings have implications for patient selection for corneal transplantation and for the measurement of outcome.

Adolescent

The Montgomery Lecture. Some factors which affect the visual outcome of corneal transplantation.

Corneal transplantation, which began in Dublin early in the nineteenth century, is now widely practised. Most grafts are done for visual reasons, some to manage corneal destructive disease. The factors associated with allograft rejection are well known, but a clear graft does not mean that the transplantation procedure has been successful. Successful corneal grafts enable patients to improve their life-style. To achieve this, the graft must be transparent and free of optical aberrations, the eye must be capable of achieving good vision, and the patient must have a life-style which would benefit from a successful functioning graft. A study of patients who have had corneal grafts identified the presence of a functioning graft, the lack of need for a contact lens, and the achievement of visual acuity in the operated eye which exceeds that of the contralateral eye, as requirements for patient satisfaction.

Algorithms

Ophthalmic surgery.

Ophthalmic surgery has changed considerably in recent years. Eye surgery is safer, more reliable, and more effective. The author reviews the major changes in the surgical treatment of cataract and refractive disorders, and discusses laser therapy, which continues to advance in a spectacular fashion.

Cataract Extraction

Ocular injury induced by methyl ethyl ketone peroxide.

Methyl ethyl ketone peroxide is a commonly used catalyst in various industries. We studied 19 eyes with a single exposure to methyl ethyl ketone peroxide that developed clinical patterns of mild injury, moderate injury, severe injury, or delayed keratitis. Delayed methyl ethyl ketone peroxide keratitis may cause exacerbations and remissions of corneal and limbal disease lasting more than 20 years with palpebral and bulbar hyperemia equal to the initial chemical exposure. With repeat exacerbation, further pannus may occur, which can be associated with a poorer outcome. Based on the capability of methyl ethyl ketone peroxide to change DNA to a new weak antigen, we suggest possible methods of therapy to prevent or limit delayed methyl ethyl ketone peroxide keratitis. This proposed type of injury has important implications in studying various limbal and corneal diseases. A major factor in the severity of ocular injury was the length of time from exposure to methyl ethyl ketone peroxide to obtaining a topical ocular local anesthetic to perform adequate lavage.

Adult

Pathogenicity of Acanthamoeba and a Corynebacterium in the rat cornea.

Acanthamoeba keratitis is a sight-threatening disease that is difficult to treat. The development of an animal model is necessary for many of the studies required to improve visual outcome in human patients. A rat model is proposed that is dependent on coinoculation of amebae and corynebacteria into the corneal stroma. The infective dose was determined for a virulent Acanthamoeba isolate and was used to screen 17 other isolates, including 7 from the human cornea. A total of 6 were infective in the rat cornea. The model should be useful for controlled in vivo studies of this intractable condition.

Acanthamoeba

The corneal endothelium.

The endothelium is a monolayer of cells on the posterior corneal surface that transports water from the stroma into the anterior chamber. This movement of water counters a natural tendency for the stroma to swell and is necessary to maintain a transparent cornea. Embryologic studies, in particular the demonstration of the derivation of the endothelium from the neural crest, have provided insight into the factors that govern the response of this tissue to disease. In some species the endothelium can regenerate after injury, but in man cellular enlargement is the main mechanism of repair after cell loss. A clinical estimate of endothelial cell density and function is provided by specular microscopy, fluorophotometry and pachymetry. In this paper we review the development, structure and function of the corneal endothelium, and then consider the pathological processes that can affect this tissue.

Animals

Donor cornea procurement: six-year review of the role of the eye bank in South Australia.

The Lions Eye Bank of South Australia was established six years ago and has collected corneas from 790 donors. The consent rate is currently 82% of requests made. Two-thirds of donors have been male, with mean donor age/year varying from 54 to 64 years (range two to 93 years). Cardiovascular and respiratory diseases, trauma and haemorrhage account for 80% of all donor deaths. Mean death to enucleation time is five hours. Corneas assessed as being of excellent or very good quality are released preferentially from the bank; those with central endothelial cell counts of less than 1500 cells/mm2 are discarded. Fewer than 1% of donors have returned a positive result for HIV or hepatitis B. Of the 1580 corneas collected by the bank, 863 (55%) have been used for transplantation with a primary non-function rate of 0.46%. The evolving policies, logistics of operation and methodologies employed by the bank are described in detail.

Adolescent