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Biomedical subjects

Douglas J Coster

Publications and source records attributed to Douglas J Coster.

At least 19 recordsLinked to original sources

How effective is penetrating corneal transplantation? Factors influencing long-term outcome in multivariate analysis.

BACKGROUND: In a large patient cohort, we investigated long-term corneal graft outcome, risk factors for graft failure, and whether corneal graft survival had improved over time. METHODS: Records of 10,952 full-thickness corneal grafts with associated archival follow-up were examined within a prospectively-maintained, national database of 13,831 records, with follow-up extending for up to 18 years. Kaplan-Meier survival analysis was used to indicate variables of interest for Cox proportional hazards regression analysis. A model clustered by individual patient to control for inter-eye or inter-graft dependence was constructed to identify variables best predicting penetrating corneal graft failure. RESULTS: Probability of corneal graft survival was 0.86 at 1 year, 0.73 at 5 years, 0.62 at 10 years, and 0.55 at 15 years. Graft survival did not improve over a 15-year timeframe. Variables predicting graft failure in multivariate analysis included transplant centre, donor age, preoperative diagnosis, number of previous ipsilateral grafts, lens status, history of corneal neovascularisation, ocular inflammation or raised intraocular pressure in the grafted eye, requirement for anterior vitrectomy, graft size, early suture removal, postoperative events including graft neovascularisation, rise in intraocular pressure, and rejection episodes, type of treatment for raised intraocular pressure, and arrangements for recipient follow-up. A further 11 variables showing a significant influence on graft survival in univariate analysis were not included in the final Cox model. CONCLUSION: The long-term results of corneal transplantation are no better than for other forms of transplantation and have shown no measurable improvement over the past 15 years.

Corneal Transplantation↗

The efficacy of a nurse-led preoperative cataract assessment and postoperative care clinic.

OBJECTIVE: To describe the implementation of a nurse-led preoperative cataract assessment and postoperative care clinic and to assess the safety, efficacy and outcomes. DESIGN, SETTING AND PARTICIPANTS: A prospective study involving 185 public patients (221 eyes) referred to the Department of Ophthalmology at Flinders Medical Centre for cataract surgery. The study was conducted between February 2003 and August 2004. INTERVENTIONS: Patients were assessed in the nurse-led preoperative assessment clinic. Those deemed suitable for cataract surgery were also assessed by an ophthalmologist and underwent cataract surgery if appropriate. The nurse managed postoperative care. MAIN OUTCOME MEASURES: Concordance between nurse practitioner and ophthalmologist assessments; waiting times for first clinic appointment and surgery; visual acuity and degree of visual disability; patient satisfaction. RESULTS: 114 patients (61.6%) were assigned to see the ophthalmologist for cataract surgery. Median waiting times fell from 115 days (range, 23-268 days) to 21 days (range, 9-43 days) for initial clinic appointment, and from 44 days (range, 5-148 days) to 29 days (range, 14-154 days) for surgery. All 114 patients were listed for cataract surgery, and surgery had been performed on 121 eyes by the end of the study. After surgery, visual acuity improved by a mean of 0.45 logMAR (logarithm of the minimal angle of resolution) (SD, 0.24; range, 0.08-1.32). All patients had improved visual ability and high levels of satisfaction. Three quality assurance evaluations demonstrated full concordance between nurse and ophthalmologist assessments. CONCLUSIONS: Implementing a nurse-led cataract assessment clinic improved access to care for public patients with cataracts. The safety and efficacy of the program and its excellent visual and patient-centred outcomes commend its adaptation and implementation to other ophthalmology departments.

Aged↗

A review of randomized controlled trials of penetrating keratoplasty techniques.

PURPOSE: To assess the effects of variations in operative technique on the outcomes of penetrating keratoplasty (PK). METHOD: Systematic literature review of published randomized controlled trials of operative techniques in PK. MAIN OUTCOME MEASURES: Visual acuity, refractive error, endothelial cell density, graft rejection, intraocular pressure (IOP), and other surgical complications. RESULTS: Twenty-seven trials were identified. Many involved small numbers, some of which were probably compromised by inadequate statistical power. There was some limited evidence from a small number of studies (usually 1 or 2) for preoperative cauterization of the cone in keratoconus, excimer laser trephination, taking into account the effect of trephine sizing on postoperative IOP, taking into account the effect of trephine sizing on postoperative spherical equivalent, using sodium hyaluronate, avoiding vitrectomy if possible, using an iris-fixated posterior chamber lens implant in the absence of capsular support, and adjusting a single continuous suture intraoperatively if used. However, there was little convincing evidence for choosing interrupted suturing versus continuous suturing or for an effect of suturing on final sutures-out astigmatism. Likewise, there was no convincing evidence for the superiority of any lamellar alternative to PK for deep stromal disease. Overall, most of the effects of changing technique were small, and there was no evidence for the superiority of any specific technique in terms of improved quality of life or cost-effectiveness. CONCLUSIONS: There is a need for further studies with which to refine decision-making as regards the choice of operative techniques in PK.

Cell Count↗

Delayed surface opacification of a hydroview intraocular lens.

The insertion of an intraocular lens during cataract surgery is routine but delayed opacification of hydrophilic foldable intraocular lenses (IOLs) has been increasingly noticed as a late post-operative complication. Such opacification may present with reduced visual acuity and can be diagnosed with slitlamp biomicroscopy. Lens explantation may be required. We report an 89-year-old female presenting with opacification of a Hydroview IOL and correlate the clinical findings of the lens in situ with the light microscopy of the explanted lens, as well as transmission electron microscopy (TEM), scanning electron microscopy (SEM) and elemental analysis. Pathological analysis of an explanted IOL may assist in a better understanding of the condition and may become relevant in medico-legal proceedings.

Aged, 80 and over↗

Penetrating keratoplasty for keratoconus: the nexus between corneal wavefront aberrations and visual performance.

PURPOSE: To compare the visual and optical performance after penetrating keratoplasty (PK) for keratoconus to normal patients and to examine the relationship between corneal wavefront aberrations and visual performance in patients with PK. METHODS: Visual performance testing, with optimal refractive correction, included low contrast visual acuity (LCVA) and Pelli-Robson contrast sensitivity with and without glare, and high contrast visual acuity. Corneal first surface wavefront aberrations were calculated from EyeSys topography data using VOL-Pro software v7.00 for a 4.0-mm pupil as a 10th order Zernike expansion and converted into single value metrics. Normal patients were compared to patients with PK using analysis of variance, and linear regression was used to compare wavefront aberration metrics to visual performance. RESULTS: Patients with PK (n=14, age 41.6 +/- 7.0 years) and normal patients (n=14, age 36.7-9.0 years) were of similar age (F(1, 26) = 2.54, P = .12). Normal patients saw significantly better on all visual performance measures and had better optical performance for total higher order root-mean-square corneal wavefront aberration (mean-SD): PK, 0.67 +/- 0.41 microm; normal, 0.09 +/- 0.02 microm (F(1,26) = 28.41, P < .001) and across all Zernike orders and modes. Wavefront aberrations in PK eyes were dominated by trefoil 0.35 +/- 0.27 microm, coma 0.47 +/- 0.37 microm, spherical aberration 0.17 +/- 0.10 microm, and tetrafoil 0.12 +/- 0.07 microm. The relationships between corneal wavefront aberration and visual performance metrics were strongest for LCVA = 0.30-0.98 Pupil fraction for wavefront (tessellation) -0.04 Half width at half height, R2=0.75. CONCLUSIONS: In this series, patients with PK had poorer visual performance compared to normal patients, which is due to increased corneal wavefront aberrations. Outcomes research in corneal transplantation should include measurement of wavefront aberrations and visual performance in the contrast domain.

Adult↗

Recall from informed consent counselling for cataract surgery.

The authors investigated the effect of giving written material on information recall from informed consent counselling for cataract surgery. Fifty English-speaking patients who underwent non-urgent cataract extraction at Flinders Medical Centre, South Australia, were prospectively enrolled. Systematic counselling for cataract surgery was provided, with a written copy of the content given to a randomly selected group of patients (n = 24). All subjects completed a questionnaire after counselling and again at two weeks after surgery to test their satisfaction with, and recall of, information provided. Patients were found to be satisfied with the amount of information they received and most were able to recall details about the cataract surgery procedure. However, many could not recall success rates or complication rates and only a minority could list any complication. The provision of written information did not significantly alter recall (p>0.05). Recall was significantly better immediately after counselling than two weeks after surgery (p<0.05). Younger patients also had significantly better recall (p<0.05). Patients were happy with the information they had been given but did not remember enough from the informed consent process to satisfy legal requirements.

Aged↗

Prolongation of sheep corneal allograft survival by transfer of the gene encoding ovine IL-12-p40 but not IL-4 to donor corneal endothelium.

Immunological rejection is the major cause of human corneal allograft failure. We hypothesized that local production of IL-4 or the p40 subunit of IL-12 (p40 IL-12) by the grafted cornea might prolong allograft survival. Replication-deficient adenoviral vectors encoding ovine IL-4 or p40 IL-12 and GFP were generated and used to infect ovine corneas ex vivo. mRNA for each cytokine was detected in infected corneas, and the presence of secreted protein in corneal supernatants was confirmed by bioassay (for IL-4) or immunoprecipitation (for p40 IL-12). Sheep received uninfected or gene-modified orthotopic corneal allografts. Postoperatively, untreated corneas (n = 13) and corneas expressing GFP (n = 6) were rejected at a median of 21 and 20 days, respectively. Corneas expressing IL-4 (n = 6) underwent rejection at 18.5 days (p > 0.05 compared with controls) and histology demonstrated the presence of eosinophils. In contrast, corneas expressing p40 IL-12 (n = 9) showed prolonged allograft survival (median day to rejection = 45 days, p = 0.003). Local intraocular production of p40 IL-12 thus prolonged corneal graft survival significantly, but local production of the prototypic immunomodulatory cytokine IL-4 induced eosinophilia, inflammation, and rejection. These findings have important implications for the development of novel strategies to improve human corneal graft survival.

Adenoviridae↗

The impact of corneal allograft rejection on the long-term outcome of corneal transplantation.

PURPOSE: To examine the influence of corneal allograft rejection on the survival of penetrating corneal transplantation, to review the status of conventional therapies to improve graft survival, and to consider prospects for alternative approaches to reduce the impact of rejection. DESIGN: Perspective, including prospective, observational cohort study. METHODS: An examination of the literature on human corneal graft rejection and data from the Australian Corneal Graft Registry, reviewed in the context of clinical experience. RESULTS: Corneal graft outcome is not improving with era. The sequelae of inflammation, whether occurring before corneal transplantation or subsequently, exert a profound influence by predisposing the graft to rejection. Of the developments that have been instrumental in reducing rejection in vascularized organ transplantation, living-related donation is not an option for corneal transplantation. However, HLA matching may be beneficial and requires reassessment. The evidence base to support the use of systemic immunosuppressive agents in corneal transplantation is thin, and topical glucocorticosteroids remain the drugs of choice to prevent or reverse rejection episodes. Experimental approaches to local allospecific immunosuppression, including the use of antibody-based reagents and gene therapy, are being developed but may be difficult to translate from the laboratory bench to the clinic. CONCLUSIONS: Corneal allograft rejection remains a major cause of graft failure. High-level evidence to vindicate the use of a particular approach or treatment to prevent or treat corneal graft rejection is lacking. In the absence of extensive data from randomized, controlled clinical trials, corneal graft registers and extrapolation from experimental models provide some clinically useful information.

Cornea↗

Antigens of selected Acanthamoeba species detected with monoclonal antibodies.

Acanthamoeba species are ubiquitous soil and freshwater protozoa that have been associated with infections of the human brain, skin, lungs and eyes. Our aim was to develop specific antibodies to aid in rapid and specific diagnosis of clinically important isolates. Mice were variously immunised with live mixtures of Acanthamoeba castellanii strain 112 (AC112) trophozoites and cysts, or with sonicated, formalin-fixed or heat-treated trophozoites, or with a trophozoite membrane preparation. Eight hybridoma cell lines secreting monoclonal antibodies reactive with A. castellanii epitopes were generated. Seven of the new antibodies (designated AMEC1-3 and MTAC1-4) were isotyped as IgMkappa and one (MTAC5) as IgG1kappa. All of the novel antibodies bound to AC112 cysts, and MTAC4 and MTAC5 also bound to trophozoites as measured by flow cytometry on unfixed cells. Single chain antibody fragments that retained parental antibody binding characteristics were engineered from three of the hybridomas (AMEC1, MTAC3 and MTAC4). Four monoclonal antibodies (AMEC1, AMEC3, MTAC1, MTAC3) bound reliably to unfixed cysts of clinical isolates of A. castellanii (two strains) and Acanthamoeba polyphaga (two strains), belonging to Pussard-Pons morphological group II, and to Acanthamoeba lenticulata and Acanthamoeba culbertsoni, belonging to Pussard-Pons morphological group III. None of the antibodies bound to cysts or trophozoites of the environmental group I species, Acanthamoeba tubiashi. Antibodies AMEC1, MTAC3, MTAC4 and MTAC5 reacted with buffered formalin-fixed AC112 by immunohistochemistry, and also stained Acanthamoeba in sections of infected rat cornea and buffered formalin-fixed, paraffin-embedded infected human cornea. These antibodies may be useful in diagnosing pathogenic Acanthamoeba species in clinical specimens, provided that cysts are present.

Acanthamoeba↗

Pathways of corneal and ocular surface inflammation: a perspective from the cullen symposium.

The goal of this symposium was to coalesce information presented by 22 investigators in the field of corneal and ocular surface inflammation into common pathways of inflammation. The perspective elucidated in this article defines the components of the normal ocular surface immune architecture and describes the consensus reached on the mechanisms/pathways involved in 1) acute inflammation; 2) late-stage (chronic) response; and 3) allergic disease. Seven diagrams didactically illustrate mechanisms. This paper is the introductory article in a supplement containing 18 articles by the symposium participants.

Journal Article↗

Mechanisms of corneal allograft rejection.

More effective therapies are required to improve clinical corneal allograft outcomes. The strategies that have led to improvements in vascularized organ graft survival are not always applicable to the cornea. New treatments that modulate the afferent arm of the immune response to a corneal allograft are more likely to prove effective than are treatments that target the effector arm of the immune response. We briefly discuss two such options: the use of engineered antibody fragments to block antigen presentation, and the use of gene therapy approaches to abrogate antigen presenting-cell function.

Journal Article↗

Local or short-term systemic costimulatory molecule blockade prolongs rat corneal allograft survival.

BACKGROUND: Costimulatory molecule blockade with antibody-based immunosuppressive agents has been shown to prolong the survival of many types of allograft. The effects were evaluated of local costimulatory molecule blockade with different CTLA4-Ig constructs and of systemic, short-term treatment with an anti-CD28 monoclonal antibody on orthotopic corneal allograft survival in the rat. METHODS: Adult Fischer-344 rats underwent Wistar-Furth orthotopic corneal grafts. The rats were treated with two different CTLA4-fusion proteins administered intraocularly in the perioperative period, or systemically with anti-CD28 monoclonal antibody JJ319. Corneal graft survival was determined by daily slit-lamp examination. The day of rejection was defined as the first postoperative day on which the iris margin was no longer clearly visible through the corneal graft. RESULTS: Local administration of CTLA4-fusion protein with mutated immunoglobulin constant region domains via a single perioperative intraocular injection prolonged corneal graft survival modestly but significantly (P < 0.05), in contrast to a CTLA4-fusion protein with wild-type immunoglobulin domains, which had no effect on graft survival (P > 0.5). Systemic short-term administration of 400 microg total of an anti-CD28 monoclonal antibody also prolonged corneal graft survival significantly (P < 0.05) and was more effective than systemic administration of 2 mg total of CTLA4-fusion protein (P < 0.05). CONCLUSIONS: Local administration of CTLA4-fusion protein with mutated (non-functional) immunoglobulin domains or systemic administration of anti-CD28 monoclonal antibody can prolong corneal allograft survival in the rat.

Abatacept↗

Implementation and evaluation of an ophthalmic nurse practitioner emergency eye clinic.

BACKGROUND: To describe the implementation and assess the efficacy of an ophthalmic nurse practitioner (ONP) emergency eye clinic. METHODS: In a 13-month period, patients were assessed in an ONP emergency eye clinic in a teaching hospital setting. The ONP clinic was run on a defined scope of practice. Risk assessment was carried out in two audit sessions, 4 weeks duration each, at months 1 and 7. Patient outcomes were monitored for reattendance to the department following discharge. RESULTS: A total of 259 patients were assessed, 143 (55.2%) were within the scope of practice. In the two audit periods, concordance with the ophthalmologist was high, diagnosis 100% and management 95.2%. Many patients assessed (111, 42.9% of total) had minor external eye conditions--chiefly corneal foreign body or abrasion (n = 50), conjunctivitis (n = 14) and minor (non-alkali) chemical injuries (n = 11). No reattendance was noted in these patients when monitored for a mean of 12 months (range 7-19 months). CONCLUSIONS: This study demonstrates the safety and effectiveness of an ONP emergency eye clinic when practising within a defined scope of practice. An ONP-led emergency eye clinic is a viable addition to acute ophthalmic eye care in Australia.

Adolescent↗

Strain-dependent differences in oxygen-induced retinopathy in the inbred rat.

PURPOSE: To examine the susceptibilities of different rat strains to oxygen-induced retinopathy, a model of human retinopathy of prematurity. METHODS: Litters of newborn rats of five inbred strains (Fischer 344 [F344], Dark Agouti [DA], Sprague-Dawley [SD], Wistar-Furth [WF], Lewis [LEW]) and one outbred strain (Hooded Wistar [HW]) were maintained in room air or were exposed to alternating 24-hour cycles of hyperoxia (80% oxygen in air) and normoxia (21% oxygen in air) for 14 days and were killed for analysis, either immediately (postnatal day 14, [P14]) or after 4 days in room air (P18). The fluorophore-conjugated isolectin GS-IB4 was used to label the endothelial cells of wholemounted retinas, and digital images were analyzed for avascular area and for morphologic abnormalities. RESULTS: Exposure to cyclic hyperoxia inhibited retinal vascularization in all strains relative to age-matched room air control animals. Total retinal avascular area at P14 after cyclic hyperoxia varied significantly among strains (P < 0.001). Avascular areas were smallest for the albino F344, WF, and LEW strains; larger for the albino SD strain; and largest for the pigmented DA and HW strains. Susceptibility to hyperoxic vascular attenuation was associated with ocular pigmentation, but neither with body mass nor with natural variation in litter size. Room air exposure for 4 days after cyclic hyperoxia was also associated with strain-related differences in retinal vascularization and with abnormalities in vascular morphology (P < 0.05). For all strains, the size of the avascular retinal area at P14 was predictive of the severity of morphologic abnormality at P18. CONCLUSIONS: Marked and consistent variations in the response of different inbred rat strains to cyclic hyperoxia were observed, suggestive of a genetic component to oxygen-induced retinopathy.

Animals↗

Local gene transfer to modulate rat corneal allograft rejection.

PURPOSE: Allograft rejection is the leading cause of corneal graft failure. CD4(+) T cells control the allograft response and represent targets for antirejection therapy. The purpose of this study was to transfer cDNA encoding a monomeric anti-CD4 antibody fragment to donor corneal endothelium, to attempt to modulate orthotopic corneal allograft rejection in the rat. METHODS: A replication-deficient adenoviral vector (AdV) encoding anti-CD4 single-chain, variable-domain antibody fragment (scFv) and enhanced green fluorescent protein (eGFP) was constructed (AdCD4GFP). AdV encoding eGFP alone (AdGFP) was used as a control. Transgenic product was detected by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, flow cytometry, and fluorescence microscopy. The alloinhibitory capacity of anti-rat CD4 scFv was measured in the one-way mixed lymphocyte reaction (MLR). The survival of Wistar-Furth corneas transduced with AdV either immediately or 3 days before orthotopic transplantation in Fischer 344 recipients was examined. RESULTS: ScFv and eGFP mRNAs were detected in rat corneas transduced in vitro, and active scFv secreted in corneal supernatants peaked at days 4 to 5 after transduction at 23 +/- 4 ng of protein per cornea per day. Antibody and scFv against rat CD4 blocked alloproliferation in MLR. However, transduction of corneas with AdCD4GFP ex vivo, immediately before transplantation, or in vivo, 3 days before transplantation, did not significantly prolong corneal allograft survival (P > 0.05). CONCLUSIONS: Anti-CD4 scFvs were capable of blocking allostimulation, but their local expression within the eye did not prolong corneal allograft survival, suggesting that sensitization may still occur.

Adenoviridae↗