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Biomedical subjects

Susan Lightman

Publications and source records attributed to Susan Lightman.

At least 19 recordsLinked to original sources
PubMed2006

Ocular complications in heart, lung and heart-lung recipients.

AIM: To prospectively assess ocular morbidity and the need for ocular screening in patients on long term, high dose immunosuppression for the maintenance of solid organ transplants. METHODS: Dilated ocular examinations were performed on patients receiving immunosuppression for the maintenance of heart, lung and heart-lung transplants. Patients were examined repeatedly in the post transplant period. RESULTS: Of the 115 transplant recipients examined 62 (54%) had ocular findings. The most common findings were cataracts (17% of those examined) followed by hypertensive change (8%), chorioretinal scarring (5%) and diabetic retinopathy (3%). One patient developed ocular infective complications following surgery due to Aspergillus spp. endophthalmitis. 18 patients (16%) were symptomatic at examination with the most common symptom being blurred vision. The most common finding in symptomatic patients was cataract with almost a quarter of patients having posterior subcapsular lens opacity that could be attributed to steroid therapy. CONCLUSION: Patients had surprising low incidences of ocular infective complications despite previous reports. It is likely that this is due to improved immunosuppression regimes and improved monitoring of immunosuppression in the early post-transplant period. The screening of asymptomatic individuals following heart, lung or heart-lung transplantation was not supported by this study.

Adolescent↗
PubMed2006

Cytokine gene polymorphisms involved in chronicity and complications of anterior uveitis.

The aim of this study was to identify key cytokine polymorphisms associated with disease susceptibility, clinical phenotype, and outcome in patients with chronic anterior uveitis (CAU) as compared to those with recurrent self-limiting anterior uveitis (RAU). One hundred fifty seven British Caucasian patients with anterior uveitis were identified and divided into those where the inflammatory process lasted less than 3 months (RAU=118) and those where the inflammation persisted longer than 3 months (CAU=39). Patients with CAU were further sub-divided into idiopathic CAU, CAU associated with systemic disease, CAU with and without complications (posterior synechiae, posterior subcapsular lens opacity, raised intraocular pressure, cystoid macular oedema, and poor response to treatment). Sixty-six healthy controls were ethnically matched. TaqMan PCR amplification was used to genotype five single nucleotide polymorphisms in cytokine genes; IL-1RN+2018, IL-6-174, IL-10-1082, TNF-238, TNF-308 and these were correlated with clinical phenotype.

Adult↗
PubMed2006

Normalized CD8+ but not CD4+ lymphocyte IL-2 expression is associated with early treatment with highly active antiretroviral therapy.

CD4+ and CD8+ lymphocyte cytokine production in patients with HIV/AIDS and Controls, in response to stimulation with phorbol-12-myristate-13-acetate (PMA) and ionomycin was assessed using single cell flow cytometric methods. Sixty-eight patients with HIV were divided into those on no antiretroviral therapy and those on highly active antiretroviral therapy (HAART). Patients on HAART were analyzed further on the basis of gender, ethnicity, viral load (> or </=50 copies/ml), CD4 count change from nadir (>100 or <100 cells/mm(3)) and CD4 count (>200 or <200 cells/mm(3)). Interferon gamma (IFNgamma) expression by CD4+ and CD8+ lymphocytes was elevated in HIV-infected groups as compared to Controls. This elevation was statistically significant for patients on HAART but not for those not on HAART. The most significant difference was seen when the CD4+ count reached >200 cells/mm(3) (p=0.018 for CD4+ IFNgamma production and p=0.004 for CD8+ IFNgamma production). CD4+ interleukin-2 (IL-2) expression was significantly lower in HIV patients as compared to Controls but did not significantly improve however good the response to HAART. IL-2 expression by CD8+ lymphocytes was also lower in HIV patients as compared to Controls. IL-2 expression by CD8+ lymphocytes significantly improved in all patients on HAART as compared to HIV patients on no HAART. IL-2 expression was not significantly different from that of the Controls when the HIV viral load was less than 50 copies/ml. These results demonstrate improvements in both CD4+ and CD8+ responsiveness with HAART. IFNgamma production was elevated in response to HAART and was maximal only with significant CD4 count recovery. In contrast, normalization of IL-2 production by CD8+ lymphocytes was seen early in patients receiving HAART even when there was only a small increase in CD4+ lymphocyte numbers.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Ocular cicatricial pemphigoid.

PURPOSE OF REVIEW: To review the content and importance of articles on ocular cicatricial pemphigoid (OCP), or mucous membrane pemphigoid (MMP) with relevance to ocular involvement, published from 2005 to 2006. RECENT FINDINGS: There is wide antigenic heterogeneity in MMP and OCP and attempts are being made to link this with clinical variations with varying degrees of success. A larger study demonstrates a link between multiple autoantibody reactivity and disease severity. Details of epitope specificity are emerging. A highly sensitive ELISA for laminin 5 has been developed which may provide prognostic information.Clinically, younger OCP patients show more severe ocular disease and are less well controlled by medication. A systematic review shows good evidence only for steroids and cyclophosphamide in OCP. Continued small trials suggest some role for the expensive intravenous immunoglobulin therapy in OCP where conventional treatment fails. Ocular reconstruction surgery has made some progression, and is enhanced by adjunctive medical therapy; osteo-odonto-keratoprosthesis offers some hope of prolonged retention of limited vision in end-stage disease. SUMMARY: OCP remains a difficult disease to manage well and the progress being made in understanding disease mechanisms is whence true disease-modifying, safe therapy is likely to emerge in the future.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

The ocular manifestations of inflammatory bowel disease.

PURPOSE OF REVIEW: The purpose of this review is to present the literature on the ocular complications of inflammatory bowel disease, their pathogenesis, manifestation and treatment options. In particular, the literature pertaining to recently available treatments will be reviewed. RECENT FINDINGS: Although the pathogenesis of inflammatory bowel disease remains incompletely understood, treatment options for ocular and systemic disease have expanded with the introduction of newer steroid-sparing agents such as mycophenolate mofetil and a new class of immunomodulatory agents targeting cytokines, in particular infliximab, a monoclonal antibody directed against tumour necrosis factor-alpha. SUMMARY: That inflammatory bowel disease can have ocular manifestations has been known for over 80 years. Knowing of their occurrence and treatment options enables the treating clinician to recognize their cause and treat them appropriately.

Anti-Inflammatory Agents↗
PubMed2006

Intravitreal steroids in the management of macular oedema.

The use of intravitreal corticosteroids in the management of macular oedema has recently gained widespread acceptance. New long-acting steroid preparations and methods of delivery have facilitated the use of these new modalities. This review describes the various types of macular oedema for which this therapeutic option is used and the results.

Dexamethasone↗
PubMed2005

Outcome of intravitreal triamcinolone in uveitis.

PURPOSE: To report the short-term outcome of intravitreal triamcinolone acetate (TA) in the treatment of uveitic cystoid macular edema (CME). DESIGN: Retrospective noncomparative (nonrandomized, uncontrolled) interventional case series. PARTICIPANTS: Sixty-five eyes of 54 patients with uveitis-related CME inadequately responsive to treatment combinations of oral corticosteroid, periocular orbital floor corticosteroid injections, and second-line immunosuppressive agents. INTERVENTION: Intravitreal injection of 4 mg/0.1 ml of TA. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP), levels of inflammation, and immunosuppressive therapy were assessed. Other potential complications, including cataract progression, vitreous hemorrhage, endophthalmitis, and retinal detachment (RD), were looked for. RESULTS: The mean follow-up was 8.0 months (range, 3-51), and the mean improvement of VA after intravitreal TA was 0.26 (from 0.65 to 0.39 logarithm of the minimum angle of resolution; Snellen, 6/24-6/12, approximately). This occurred at a mean of 4 weeks (range, 1-30). The improvement in VA was more significant if the duration of CME before intravitreal TA was < or =12 months (P = 0.006) and if patients were < or =60 years old (P = 0.005). Patients with the worst vision before treatment also improved the least. The most important side effect was raised IOP (mean rise, 10.3 mmHg), with 28 eyes (43.1%) experiencing an IOP rise of >10 mmHg. Patients younger than 40 years were more likely to experience this IOP rise than those older than 40. Thirty-three eyes (51%) were treated with antiglaucoma medications, with a mean duration of treatment of 17.4+/-13.3 weeks, and no patient required trabeculectomy or lost vision. The dosage of oral corticosteroids and/or second-line immunosuppressive medication was reduced or stopped altogether in 18 of 33 eyes (54.5%) during the study period. There were no cases of injection-related vitreous hemorrhage, endophthalmitis, or RD. CONCLUSIONS: In patients with uveitic CME, intravitreal TA can effectively reduce CME and improve VA and, in some eyes, allows the cessation and/or reduction of immunosuppressive therapy. The period of effectivity varies in different patients and, in some eyes, is limited. Treatment was associated in 43.1% with a rise in IOP, which was transient and treatable medically.

Adolescent↗
PubMed2005

The development of complications in patients with chronic anterior uveitis.

PURPOSE: This study aimed to identify the factors determining the ocular complications and visual outcome in patients with chronic anterior uveitis. DESIGN: Retrospective, noncomparative case study. METHODS: Ninety-one eyes of 68 patients with anterior uveitis that lasted longer than 3 months were assessed. Patients were divided into idiopathic and nonidiopathic chronic anterior uveitis and Fuchs' heterochromic uveitis. Visual acuity and complications such as posterior synechiae, cataract formation, raised intraocular pressure (IOP), and posterior segment complications (i.e., cystoid macular edema and optic nerve involvement) were evaluated. Poor visual outcome measured by life-table analysis was considered when logMAR (log of the reciprocal of Snellen visual acuity) visual acuity was 0.3 or worse. RESULTS: No statistically significant differences in the visual outcome were found between the three groups of patients with chronic anterior uveitis. Posterior synechiae formation was, as expected, significantly increased in patients with chronic anterior uveitis compared with those with Fuchs' heterochromic uveitis. There was a trend for patients with nonidiopathic chronic anterior uveitis to have an increased risk of cystoid macular edema compared with those with idiopathic disease. There were no significant differences in visual outcome between any of the groups with time. CONCLUSIONS: The visual prognosis for patients with chronic anterior uveitis is generally good. Posterior segment complications appear to be more likely to occur if there is an underlying associated disease. However, the presence of complications does not seem to affect the visual outcome in patients with chronic anterior uveitis.

Adult↗
PubMed2005

Clinical outcome of chronic immunosuppression in patients with non-infectious uveitis.

AIM: To determine the visual outcome and corticosteroid dose requirement in patients with non-infectious uveitis affecting the posterior segment treated with corticosteroids and additional second-line immunosuppression. METHOD: A retrospective, non-comparative case series was carried out. Seventy-two patients (141 eyes) with uncontrolled non-infectious uveitis on systemic prednisolone were treated with at least one second-line immunosuppressive agent in addition to systemic prednisolone and followed for at least 3 months. Visual acuity (VA), clinical disease activity, corticosteroid-sparing effect, disease relapses requiring corticosteroid dose increase,and side-effects from second-line agents were evaluated. RESULTS: At the end of the follow-up period (mean: 55.5 months),70 eyes (49.6%) had VA of 6/9 or better. There was a reduction in the mean maintenance dose of prednisolone required before the introduction of the second-line agent (19 mg/day +/- 2 SE)when compared to the mean maintenance dose of prednisolone at the end of the data collection (9 mg/day +/- 1 SE; P <0.001). There was also a significant reduction in the number of disease relapses requiring an increase in prednisolone dose after starting the second-line agents as compared to the year before (P <0.02). CONCLUSION: In patients with uveitis affecting the posterior segment, the addition of all second-line immunosuppressive therapy was effective in allowing reduction of the dose of systemic prednisolone to 10 mg/day or less, in controlling intraocular inflammation, reducing the number of relapses and in maintaining vision. Because of their side-effects, immunosuppressive treatment should be individualized and monitored closely but its addition is beneficial in the short and longer term.

Adolescent↗
PubMed2005

Clinical features and visual outcome of intermediate uveitis in children.

PURPOSE: To determine the presentation, course, treatment and outcome of idiopathic intermediate uveitis in children. METHODS: The records of all patients under the age of 16 presenting with idiopathic intermediate uveitis under the care of one consultant (SL) between 1990 and 2001 were reviewed. The case notes were analysed with respect to presenting symptoms, associated conditions, ocular signs, change in visual acuity, treatment and complications. All patients with systemic disease were specifically excluded from the study. RESULTS: Twenty-six patients (45 eyes) were identified with intermediate uveitis from 114 cases of childhood uveitis seen. The mean age at presentation was 10 years (range 7-13 years) and the average follow-up time was 3 years (range 0-7 years). All patients had varying degrees of vitritis, 28 eyes had snowbanks and 5 had cystoid macular oedema at presentation. Six patients required no treatment, five received topical treatment only, five were managed with orbital floor steroids alone and a further two were managed with orbital floor steroids and oral prednisolone. Systemic steroids were required in eight patients, four of whom also required cyclosporin. Six of these children had successful disease control and maintained a visual acuity of 6/9 in at least one affected eye. CONCLUSION: Idiopathic intermediate uveitis is a relatively uncommon condition in children but can have severe effects on vision. With careful management, vision can be preserved in at least one eye. This study describes the course of the disease in a relatively large series. The variation in disease severity prompts the use of individually tailored immunosuppressive regimens.

Adolescent↗
PubMed2005

Use of PCR to diagnose Toxoplasma gondii chorioretinitis in eyes with severe vitritis.

Two cases are reported of intraocular inflammation in which severe vitritis hampered the fundal view, making an accurate clinical diagnosis impossible, and vitreous analysis using conventional techniques was unhelpful. PCR for Toxoplasma gondii was positive in both cases and provided the only way of confirming the diagnosis. Other ocular samples also underwent PCR for Toxoplasma DNA and the specificity of this approach is demonstrated.

Animals↗
PubMed2005

TNF-857T, a genetic risk marker for acute anterior uveitis.

PURPOSE: To determine the association between 17 single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha, lymphotoxin-alpha, and the TNF-receptors genes (TNF, LTA, and TNFRSF1A and -B) and idiopathic acute anterior uveitis (IAU) and to investigate their association with HLA-B27 and/or the development of visually significant complications. METHODS: Ninety-eight white patients in the United Kingdom were identified (by SL) from the uveitis clinics of Moorfields Eye Hospital (London, UK). Sequence-specific primers with 3' end mismatches were used to identify the presence of specific allelic variants by PCR amplification. RESULTS: There was a significant increase in the frequency of the TNF-857T allele in patients with IAU when compared with control subjects (15.3% vs. 7.3%, P = 0.0006). The frequency of haplotype 4, containing the T allele at nucleotide position -857, was also significantly increased in patients with IAU compared with control subjects (15.4% vs. 7.1%, P = 0.0003, OR 2.4, 95% confidence interval 1.4-4.0). In subgroup analysis, there were significant differences in the frequencies of the uncommon TNFRSF1A-201T and TNFRSF1A-1135T alleles between HLA-B27(+) patients with inflammation-related complications and those without complications (80.0% vs. 33.6%, P = 0.006; 80.0% vs. 36.6%, P = 0.01, respectively). CONCLUSIONS: A significant difference in the frequency of TNF-857T allele was found in patients with IAU. There was a trend toward the development of inflammation-related complications in HLA-B27(+) patients with IAU who were carriers of TNFRSF1A-201T or TNFRSF1A-1135T alleles. Genetic variations in these proinflammatory mediators and their receptors appear to influence the susceptibility and severity of the inflammatory response within the eyes of patients during the development of IAU.

Acute Disease↗
PubMed2004

Retinal and choroidal biopsies are helpful in unclear uveitis of suspected infectious or malignant origin.

OBJECTIVES: To assess the clinical value of retinal or choroidal biopsy in establishing a definitive diagnosis directing subsequent management and to assess the risk involved in such surgery. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Thirteen patients with uveitis of suspected malignant or infectious origin. One patient had 2 consecutive biopsies on the same eye. METHODS: A retrospective review of a 4-year period was undertaken of all those cases in which the biopsy was taken for diagnostic purposes at a single institution. MAIN OUTCOME MEASURES: Ability of biopsy to establish a pathologic diagnosis and guide treatment and surgical complications. RESULTS: A transscleral approach was used in 4 and a pars plana vitrectomy approach in 10 of the biopsies. The only operative complication was a retinal break in 1 case. Postoperative events that might be related to the surgery included 1 localized retinal detachment, 2 cataracts, and 1 phthisical eye. The pathologic diagnosis differed from the initial clinical diagnosis in 5 of the 13 cases. The biopsy result directed specific appropriate treatment in 7 of the 13 cases. In the 6 remaining cases, no specific diagnosis was confirmed, but the results of the biopsy were useful in excluding malignancy and in some cases allowing a therapeutic trial. CONCLUSIONS: Retinal or choroidal biopsy is a valuable investigation that often changes clinical management when carried out for specific indications in patients with uveitis of suspected malignant or infectious origin. Although it is likely to remain an investigation of last resort, it should be considered at an earlier stage when there is diagnostic uncertainty if severe visual loss is to be prevented.

Adult↗
PubMed2004

Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis.

AIM: To compare the efficacy and side-effects of posterior sub-Tenon injection of triamcinolone acetonide (Kenalog) with orbital floor injection of methylpredisolone acetate (Depomedrone) in the management of posterior uveitis. METHODS: Non-randomized comparative prospective clinical study. Sixty-four eyes from 60 consecutive patients with non-infectious posterior uveitis requiring treatment were allocated on an alternate 1:1 basis to receive either orbital floor methylprednisolone or sub-Tenon triamcinolone using standard procedures and assessed at 6 and 12 weeks. RESULTS: After five eyes of five patients who had received the same treatment bilaterally were excluded from the statistical analysis, 14 out of 29 eyes treated with orbital floor methylprednisolone and 10 out of the 30 eyes given sub-Tenon triamcinolone improved at 6 weeks. There was no statistically significant difference in the improvement rate between the two groups. However, two patients given triamcinolone had prolonged upper lid ptosis, which required surgery, and another two developed markedly raised intraocular pressure, neither of which occurred in the methylprednisolone-treated group. CONCLUSIONS: Although the two drugs and routes compared were of similar efficacy, lid ptosis occurred in the triamcinolone-treated but not the methylprednisolone group. This should be borne in mind when choosing the preferred route of delivery of periocular corticosteroid in the treatment of posterior uveitis.

Blepharoptosis↗
PubMed2003

T-cell characterization in chronic allergic eye disease.

Chronic allergic eye disease encompasses several disorders, but it is vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) that have sight-threatening sequelae. T cells, eosinophils, and mast cells are all found in the conjunctiva, and are thought to play a role in disease pathogenesis. Recently, the conjunctival epithelium has also been considered to play a key role. New and effective therapeutic strategies for the future for these patients depend on achieving a greater understanding of the roles and interactions of the cell populations in these sight-threatening disorders.

Chronic Disease↗