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J V Forrester

Publications and source records attributed to J V Forrester.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of sight-threatening uveitis in Scotland.

AIM: To identify and quantify the prevalence of patients with uveitis receiving systemic immunosuppression in Scotland. METHODS: Anonymised data were prospectively collected on all patients with uveitis requiring systemic immunosuppression. Seven health boards participated over a 4-month period between 1 August 2005 and 30 November 2005. RESULTS: 373 patients were identified, of whom 205 (55%) were female. The mean age was 46.4 (range 7-97 years). Using the data from the seven participating health boards, an estimated Scottish prevalence of 9 per 100 000 was calculated. Prevalence varied between 2 and 59 per 100 000. In National Health Service Grampian, all patients with uveitis, whether sight-threatening or not, are followed up at a specialist clinic. Extrapolating this figure to Scotland gives a prevalence of 25 per 100 000. DISCUSSION: The data from National Health Service Grampian suggest that there is a significant shortfall in the number of patients identified by survey. If the "missing population" exists, then where are they? Some might be receiving appropriate treatment at non-specialist clinics, although simple under-reporting may play a part. Greater concern is for those patients receiving inappropriate treatment for their uveitis, or for those within the community who are either oblivious to or in self denial of their condition.

Adolescent↗
PubMed2006

Properties of porcine and recombinant human collagen matrices for optically clear tissue engineering applications.

Porcine and recombinant human atelocollagen I solutions were cross-linked with a water soluble carbodiimide at various stoichiometries and collagen concentrations (5-20 w/w %). The resulting hydrogels were clear and, when used as cell growth matrices, allowed cell and nerve visualization in vitro and in vivo. We have previously reported that, after six months of implantation in pigs' and rabbits' corneas, these robust hydrogels allowed regeneration of host cells and nerves to give optically clear corneas with no detected loss in thickness, indicating stable engraftment. Here, the biocompatible hydrogel formulations leading to this novel in vivo performance were characterized for amine consumption, gel hydration, thermal properties, optical clarity, refractive index, nutrient diffusion, biodegradation, tensile measurements, and average pore diameters. Gels with excellent in vitro (epithelial overgrowth, neurite penetration) and in vivo performance (clarity, touch sensitivity regeneration) had 4-11 nm pores, yet had glucose and albumin diffusive coefficients similar to mammalian corneas and allowed neurite extension through the gels.

Amines↗
PubMed2005

Photodynamic therapy for inflammatory choroidal neovascularisation unresponsive to immunosuppression.

AIM: To report on visual and angiographic outcomes of a consecutive series of patients with inflammatory choroidal neovascular membranes (CNV) unresponsive to systemic immunosuppression treated with photodynamic therapy (PDT). METHODS: The medical records of six consecutive patients with inflammatory CNVs that failed to respond to systemic immunosuppression and that later underwent PDT were retrospectively reviewed. Patient demographics, visual acuity, and fluorescein angiographic findings were evaluated. RESULTS: There were five females and one male with a mean age of 40.8 years (range 35-58 years). Four patients had clinical features consistent with punctate inner choroidopathy and two with presumed ocular histoplasmosis. In all cases clinical signs of CNV activity, including subretinal fluid, subretinal blood, hard exudates, and/or recent decrease in visual acuity were present prior to PDT. All patients had been treated with high dose systemic immunosuppressants, which failed to induce regression of the CNV and/or to improve vision. The CNVs were subfoveal in five patients and juxtafoveal in one; all were classified as predominantly classic. Following PDT an improvement in vision occurred in all cases (median improvement of 18 letters, range 3-42 letters). At last follow up, signs of decreased activity in the CNV were detected in all cases. Patients were followed for a median of 10 months (range 9-20 months). CONCLUSION: PDT appears to be a useful option in the management of patients with inflammatory CNVs unresponsive to immunosuppressive therapies.

Adult↗
PubMed2005

Choroidal dendritic cells require activation to present antigen and resident choroidal macrophages potentiate this response.

BACKGROUND/AIM: The uveal compartment of the eye contains extensive networks of resident macrophages and dendritic cells. These cells are now recognised to have a role in many ocular pathologies. The aim of this study was to isolate, characterise, and compare the function of ciliary body/choroid dendritic cells and macrophages from the normal eye. METHODS: Explants of rat and human ciliary body/choroid were cultured in vitro for various periods of time and cells harvested either from the supernatant fluid or from enzyme digested and washed explants. The cells were then phenotyped by microscopy and flow cytometry, examined by video time lapse photomicroscopy, and analysed functionally in a series of immunoassays. RESULTS: Two main types of dendritic cell were identified: large veil-like MHC class II(mid) motile but relatively non-translocatory cells and small MHC class II(hi) motile and rapidly translocating cells. Tissue macrophages mainly remained associated with the explants in culture but gradually lost their resident tissue marker (ED2) and detached from the explants as clusters of low density, large, CR3 (ED7)(+) cells, some of which underwent apoptosis. Video time lapse studies showed dendritic cells constantly interacting with large single cells and cell clusters by traversing the interstices of the cell clusters. In functional studies, freshly isolated dendritic cells were poor presenters of antigen and required activation by short term culture for acquisition of antigen presenting function. In contrast, dendritic cell depleted choroidal cell preparations containing macrophages and other cells failed to present antigen even after short term culture but augmented the antigen presenting function of dendritic cells when tested in co-culture. CONCLUSION: At least two types of dendritic cells are present in the normal ciliary body/choroid layer of the eye. It is likely that these cells have different functions based on their motility and potential to migrate to secondary lymphoid tissue either during normal physiological homeostatic processes or during an inflammatory response. The behaviour of resident tissue myeloid cells may decide the outcome of the organism's response to stress, foreign antigen, and ageing processes such as age related macular degeneration.

Animals↗
PubMed2004

The scanning laser ophthalmoscope--a review of its role in bioscience and medicine.

The scanning laser ophthalmoscope (SLO) offers the potential for retinal imaging that is complementary both to that of the fundus camera and also the newly developing technique of optical coherence tomography (OCT). It has the ability to produce rapid images at low light levels using light of specific wavelengths. This permits temporal studies of fluorescent-labelled cells which offer a unique insight into inflammatory processes in the eye. The facility to image with several different wavelengths simultaneously offers the potential for spectral imaging of retinal tissue with the aim of revealing those early changes in tissue perfusion that indicate the onset of retinal disease, so increasing the probability of successful therapy.

Animals↗
PubMed2004

Systemic CD4(+) T cell phenotype and activation status in intermediate uveitis.

AIM: To investigate peripheral blood lymphocyte phenotype in patients with intermediate uveitis using CD69, chemokine receptor, and cytokine expression. METHODS: Peripheral blood lymphocytes of 18 patients with idiopathic intermediate uveitis and 6 patients with presumed sarcoid intermediate uveitis were evaluated for CD4(+) T cell expression of CD69, CCR4, CCR5, CXCR3 and the intracellular cytokines IFNgamma, TNFalpha, and interleukin (IL)-10 by flow cytometry, and for IL-2, IL-4, IL-5, IL-10, IFNgamma, and TNFalpha production following unstimulated and activated culture using cytokine bead array and compared with healthy control subjects. RESULTS: The expression of CD69 and TNFalpha by peripheral blood CD4(+) lymphocytes of patients with idiopathic intermediate uveitis and presumed sarcoid intermediate uveitis was significantly higher than control subjects (p = 0.002 and p<0.05, respectively). The ratios of the concentrations of IL-2:IL-5 and IFNgamma:IL-5 in supernatants of activated peripheral blood lymphocyte cultures were significantly higher in patients with presumed sarcoid intermediate uveitis than control subjects. CONCLUSIONS: This study implicates TNFalpha in the pathogenesis of intermediate uveitis, highlighting the potential role of anti-TNF treatments for this disease. Studies of Th1:Th2 cytokine ratios suggested polarisation of the immune response towards Th1 in presumed sarcoid intermediate uveitis despite clinically quiescent systemic disease.

Adolescent↗
PubMed2004

Quantitative evaluation of the corneal endothelium in the mouse after grafting.

BACKGROUND/AIM: Corneal graft survival depends critically on the quality of the endothelium. In this study the authors aimed to evaluate corneal endothelium in mice at different times after transplantation and to correlate endothelial integrity with corneal graft survival. METHODS: Syngeneic and allogeneic corneal grafts at various times (days 0-60) after engraftment were examined in flat mount preparation by confocal microscopy, by evaluating the hexagonal pattern of the endothelial monolayer using actin staining of the cell cortex. Corneas from untreated mice and from mice, who were grafted after removal of draining lymph nodes served as controls. RESULTS: In control corneas, more than 90% of the posterior surface was covered by endothelium. Syngeneic grafts were always covered by 54-99% of endothelium. In contrast, the posterior surface of corneal allografts showed great variation in the degree of endothelial cell coverage (0-98%). In addition, clinical opacity grading measure was not a reliable predictor of endothelial coverage. CONCLUSION: In corneal allografts there is progressive loss of endothelium over time, unlike with syngeneic grafts. However, in the early stages of allograft rejection, the grade of graft opacity does not accurately reflect the degree of endothelial cell coverage. Although corneal opacity grade is considered the main determinant of graft rejection, the data suggest that both the grade of corneal opacity plus a sufficient post-graft time duration (>8 weeks in the mouse) are required for the diagnosis of irreversible graft rejection.

Animals↗
PubMed2004

Altered L-selectin expression in lymphocytes and increased adhesion to endothelium in patients with diabetic retinopathy.

AIM: To investigate L-selectin expression and shedding in patients with and without retinopathy and to determine if any observed changes are reflected by a functional change in the adhesion of leucocytes to an endothelial monolayer. METHODS: Age matched diabetic patients (26 with retinopathy, 19 without retinopathy) were compared to 24 non-diabetic controls to determine L-selectin surface protein expression, L-selectin mRNA production, and serum L-selectin levels by flow cytometry, RT-PCR, and ELISA, respectively. An adhesion assay was used to determine the binding of lymphocytes from the respective test groups to a monolayer of human endothelial cells. RESULTS: Significantly reduced (p = 0.004) L-selectin expression was demonstrated on lymphocytes (CD3+) from patients with diabetes compared to controls, the lowest levels being found in those with diabetic retinopathy (p = 0.004). L-selectin mRNA levels (p = 0.007) were significantly higher in the retinopathy group than in the no retinopathy group. Serum L-selectin levels were significantly higher (p = 0.04) in those with retinopathy compared to controls. Lymphocyte adhesion relative to control (100%) was essentially unchanged (84.0% (SD 27.7%), p = 0.15) for diabetic patients with no retinopathy and was markedly increased (192% (37.6%)) for those with retinopathy (p = 0.0001). CONCLUSION: Lymphocyte activation, reduced surface L-selectin, increased circulating L-selectin, and a corresponding increase in adhesion of patients' cells using an in vitro assay, is evident in people with diabetic retinopathy. This suggests a role for lymphocyte activation in the pathogenesis of diabetic retinopathy.

CD3 Complex↗
PubMed2003

A comparative evaluation of digital imaging, retinal photography and optometrist examination in screening for diabetic retinopathy.

AIMS: To compare the respective performances of digital retinal imaging, fundus photography and slit-lamp biomicroscopy performed by trained optometrists, in screening for diabetic retinopathy. To assess the potential contribution of automated digital image analysis to a screening programme. METHODS: A group of 586 patients recruited from a diabetic clinic underwent three or four mydriatic screening methods for retinal examination. The respective performances of digital imaging (n=586; graded manually), colour slides (n=586; graded manually), and slit-lamp examination by specially trained optometrists (n=485), were evaluated against a reference standard of slit-lamp biomicroscopy by ophthalmologists with a special interest in medical retina. The performance of automated grading of the digital images by computer was also assessed. RESULTS: Slit-lamp examination by optometrists for referable diabetic retinopathy achieved a sensitivity of 73% (52-88) and a specificity of 90% (87-93). Using two-field imaging, manual grading of red-free digital images achieved a sensitivity of 93% (82-98) and a specificity of 87% (84-90), and for colour slides, a sensitivity of 96% (87-100) and a specificity of 89% (86-91). Almost identical results were achieved for both methods with single macular field imaging. Digital imaging had a lower technical failure rate (4.4% of patients) than colour slide photography (11.9%). Applying an automated grading protocol to the digital images detected any retinopathy, with a sensitivity of 83% (77-89) and a specificity of 71% (66-75) and diabetic macular oedema with a sensitivity of 76% (53-92) and a specificity of 85% (82-88). CONCLUSIONS: Both manual grading methods produced similar results whether using a one- or two-field protocol. Technical failures rates, and hence need for recall, were lower with digital imaging. One-field grading of fundus photographs appeared to be as effective as two-field. The optometrists achieved the lowest sensitivities but reported no technical failures. Automated grading of retinal images can improve efficiency of resource utilization in diabetic retinopathy screening.

Adolescent↗
PubMed2003

High glucose concentration decreases insulin-like growth factor type 1-mediated mitogen-activated protein kinase activation in bovine retinal endothelial cells.

Clinical trials have incontrovertibly demonstrated that the onset and progression of diabetic retinopathy (DR) is influenced by the control of glucose levels in patients. In the present study, we examined the effect of glucose concentration on the responsiveness of bovine retinal endothelial cells (BREC) to insulin-like growth factor type 1 (IGF-1). Retinal endothelial cells were isolated from bovine retina and cultured in 5 or 20 mmol/L glucose with or without 100 ng/mL IGF-1. The level of cell growth and p42/44 and p38 mitogen-activated protein kinase (MAPK) activation was determined using the alamarBlue (Serotech) assay and Western blotting, respectively. IGF-1 significantly enhanced cell growth in BREC exposed to 5 mmol/L glucose but not in cells exposed to high glucose concentrations (20 mmol/L). IGF-1 induced a transient activation of p42/44 MAPK, with peak activation at 15 minutes in cells exposed to 5 mmol/L glucose; however, no increase in p42/44 MAPK was evident at the higher glucose concentration of 20 mmol/L. There was no significant change in the level of p38 MAPK during the time period examined when IGF-1 was also present. However, high glucose concentrations alone increased the level of p38 MAPK after 60 minutes and the level of p42/44 MAPK after only 15 minutes exposure in 20 mmol/L glucose. Thus, BREC exposed to high glucose concentrations are not sensitive to IGF-1 and this is due, at least in part, to a reduced activation of the p42/44 MAPK pathway. Furthermore, the presence of IGF-1 appears to exert a protective effect on the cells in high glucose concentration by preventing progression through the cell cycle.

Animals↗
PubMed2003

Genetic polymorphism of HLA DR in a Scottish population of patients with pars planitis.

PURPOSE: Human leucocyte antigen (HLA) class II influences the immunological susceptibility for a variety of diseases including many types of non-infectious intraocular inflammation. Previous studies on North American patients with pars planitis, a subtype of intermediate uveitis, reported an increased prevalence of HLA DR15 in this population. In contrast, two European studies could not find an association between HLA DR2 or its allelic subtype DR15 and various forms of intermediate uveitis. We therefore investigated the genotype frequency of HLA DR alleles in a Scottish population of patients with typical pars planitis. METHODS: Twenty patients with pars planitis were identified from the uveitis database of Grampian University Hospitals. Only patients with bilateral vitritis and snowbanks in at least one eye in the absence of systemic disease were included in the study. Fifteen patients and 34 healthy controls underwent HLA DR genotyping for all DRB genes using PCR sequence specific primers. RESULTS: HLA DR15 was found in 13% of patients with pars planitis and in 24% of controls. There was no statistically significant difference between these two groups. Furthermore, the frequencies of HLA DR 1, 3-14, and 16 did not differ significantly between patients and controls. CONCLUSIONS: There appears to be no association between the occurrence of pars planitis and the HLA DR15 or other known HLA DR genotypes in Scottish patients. However, the small sample size limits the power of this study.

Alleles↗
PubMed2003

The value of digital imaging in diabetic retinopathy.

OBJECTIVES: To assess the performance of digital imaging, compared with other modalities, in screening for and monitoring the development of diabetic retinopathy. DESIGN: All imaging was acquired at a hospital assessment clinic. Subsequently, study optometrists examined the patients in their own premises. A subset of patients also had fluorescein angiography performed every 6 months. SETTING: Research clinic at the hospital eye clinic and optometrists' own premises. PARTICIPANTS: Study comprised 103 patients who had type 1 diabetes mellitus, 481 had type 2 diabetes mellitus and two had secondary diabetes mellitus; 157 (26.8%) had some form of retinopathy ('any') and 58 (9.9%) had referable retinopathy. INTERVENTIONS: A repeat assessment was carried out of all patients 1 year after their initial assessment. Patients who had more severe forms of retinopathy were monitored more frequently for evidence of progression. MAIN OUTCOME MEASURES: Detection of retinopathy, progression of retinopathy and determination of when treatment is required. RESULTS: Manual grading of 35-mm colour slides produced the highest sensitivity and specificity figures, with optometrist examination recording most false negatives. Manual and automated analysis of digital images had intermediate sensitivity. Both manual grading of 35-mm colour slides and digital images gave sensitivities of over 90% with few false positives. Digital imaging produced 50% fewer ungradable images than colour slides. This part of the study was limited as patients with the more severe levels of retinopathy opted for treatment. There was an increase in the number of microaneurysms in those patients who developed from mild to moderate. There was no difference between the turnover rate of either new or regressed microaneurysms for patients with mild or with sight-threatening retinopathy. It was not possible in this study to ascertain whether digital imaging systems determine when treatment is warranted. CONCLUSIONS: In the context of a national screening programme for referable retinopathy, digital imaging is an effective method. In addition, technical failure rates are lower with digital imaging than conventional photography. Digital imaging is also a more sensitive technique than slit-lamp examination by optometrists. Automated grading can improve efficiency by correctly identifying just under half the population as having no retinopathy. Recommendations for future research include: investigating whether the nasal field is required for grading; a large screening programme is required to ascertain if automated grading can safely perform as a first-level grader; if colour improves the performance of grading digital images; investigating methods to ensure effective uptake in a diabetic retinopathy screening programme.

Diabetes Mellitus, Type 1↗
PubMed2002

[Efficiency of mycophenolate mofetil in the treatment of intermediate and posterior uveitis].

BACKGROUND: The severity of disease and the side-effects of long-term corticosteroid treatment support the rationale for other immunosuppressive drugs in the management of uveitis. Mycophenolate mofetil (MMF) is a selective inhibitor of ionosine monophosphate dehydrogenase and exerts its major effects by modulation of the function of T and B lymphocytes. This study was undertaken to evaluate the clinical effect of MMF in the control of intermediate and posterior uveitis. METHODS: A retrospective study of 18 consecutive patients with intermediate or posterior uveitis treated with MMF was performed. Activity of intraocular inflammation was graded according to the guidelines of the international uveitis study group before and during treatment with MMF. Furthermore, the ability of MMF treatment to reduce the steroid dosage and/or substitute other immunosuppressive agents with unacceptable side-effects (cyclosporin A, tacrolimus, azathioprine) was evaluated. RESULTS: The indication for treatment with MMF in all 18 patients (age range: 11-73 years) was either poor control of ocular inflammation by the previous immunosuppressive therapy or unacceptable side-effects of this therapy. The daily MMF dose was 2 g and therapy was combined with cyclosporin A and/or prednisolone. One patient received MMF monotherapy. Corticosteroids were discontinued in 4 patients and the steroid dose could be reduced in 14 patients following MMF therapy. Marked resolution of ocular inflammatory activity occurred in 13 patients. The most frequently observed side-effects of MMF were myalgia, fatigue, headache and gastrointestinal problems. CONCLUSION: MMF was effective in disease control in the majority of patients with intermediate and posterior uveitis and proved to be a useful second line immunosuppressant for refractory intraocular inflammatory disease with an acceptable profile of side-effects.

Adolescent↗