Susan Lightman

University of Bristol, Bristol, England, United Kingdom

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Publications (144)473.2 Total impact

  • Archana Airody · Greg Heath · Susan Lightman · Richard Gale
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    ABSTRACT: Non-infectious uveitis mainly affects the working-age population and can contribute to significant social and economic burden. It comprises a heterogeneous group of conditions with varied aetiology. Precise and early diagnosis, excluding masquerade syndromes, is the key to early therapeutic intervention. Treatment should be appropriately selected according to the anatomical sites of inflammation, the diagnosis and known prognosis, and whether there is a systemic inflammatory drive. Corticosteroids in the form of local or systemic therapy form the mainstay of treatment; however, due to unacceptable side effects, the need for long-term use or suboptimal response, corticosteroid-sparing medications may need to be considered early on in the management of non-infectious uveitis. With newer insights into the immunopathology of uveitis and the availability of biologic agents, treatment can be tailored according to individual needs. Many patients have systemic involvement, and hence a multidisciplinary approach is often required to achieve the best outcome in an individual. Patient involvement in the management of non-infectious uveitis, ensuring compliance, and continual monitoring of both the treatment and therapeutic response are the key to achieving optimal outcomes.
    No preview · Article · Dec 2015 · Drugs
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    ABSTRACT: Corticosteroids are the cornerstone of treating intraocular inflammation, but may be inadequate in controlling the disease, or related side effects preclude long-term treatment. Additional immunosuppressive drugs are used in these cases to augment the effect of corticosteroids and allow for their reduction to safe levels while maintaining control of the ocular inflammation. Here we review the different classes of immunosuppressive drugs and discuss their effect on ocular inflammation.
    No preview · Article · Oct 2015 · Developments in ophthalmology
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    ABSTRACT: Purpose: To identify factors associated with best-corrected visual acuity (BCVA) presentation and two-year outcome in 479 intermediate, posterior, and panuveitic eyes. Design: Cohort study using randomized controlled trial data METHODS: Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and 2 years' follow-up used gold standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and two-year change in BCVA. Results: Baseline factors significantly associated with reduced BCVA included: age≥50 vs. <50 years; posterior vs. intermediate uveitis; uveitis duration>10 vs. <6 years; anterior chamber (AC) flare>grade 0; cataract; macular thickening; and exudative retinal detachment. Over two years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (p=0.52) and 10 letters (p<0.001) respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or >10 vs. <6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening. Conclusions: Intermediate, posterior and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation.
    No preview · Article · Sep 2015 · American Journal of Ophthalmology
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    ABSTRACT: Purpose: To evaluate the 2-year outcomes of uveitic macular edema. Design: Longitudinal follow-up of a randomized cohort. Participants: At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up. Methods: Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness ≥240 μm) on time-domain optical coherence tomography (OCT) of macula. Main outcome measures: Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA). Results: Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P = 0.20) and resolving (52% vs. 68%; P = 0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 μm in the systemic therapy group; P = 0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P = 0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P = 0.92); little to no change, 6 letters (P = 0.19); and worsening, -16 letters (worsening acuity; P = 0.0003). Conclusions: About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema.
    No preview · Article · Sep 2015 · Ophthalmology
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    ABSTRACT: Purpose: To assess the clinical usefulness of chorioretinal biopsy in establishing a definitive diagnosis in intra-ocular lymphomas. Design: Retrospective, non-comparative, consecutive diagnostic case series. Methods: • Setting: Moorfields Eye Hospital, City Road, London, United Kingdom. • Patients: Twenty-nine consecutive patients presenting with severe uveitis that required an intra-ocular biopsy where underlying lymphoma was suspected. • Observation Procedure: A retrospective review of a 15-year period (1999-2014) was undertaken of all patients that have undergone to chorioretinal biopsy for suspected lymphoma at Moorfields Eye Hospital, London, United Kingdom. Patients were identified on the hospital's computerized database. • Main Outcome Measures: Effectiveness of chorioretinal biopsy in establishing a definitive diagnosis or in excluding malignancy. Results: A specific histological diagnosis was made in 17 cases (59%) while in 9 cases the biopsy combined with clinical data was effective in excluding malignancy. In the 3 remaining cases, no specific diagnosis was made. No intraoperative complications were reported. Postoperative complications other than cataract included 2 vitreous hemorrhages and 2 retinal detachments. Of the 17 cases with an histological diagnosis 15 were obtained in eyes with marked vitritis as opposed to 2 with minimal vitritis. Conclusions: Chorioretinal biopsy provided a definitive diagnosis of lymphoma in 59% of cases, and assisted in exclusion of a further 31% in this series. The level of vitritis appears to act as a strong index of likelihood in achieving a definitive histological diagnosis.
    No preview · Article · Sep 2015 · American Journal of Ophthalmology
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    X F Li · M H Hu · B P Hanley · Y.S Lin · L Poston · S L Lightman · K T O'Byrne
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    ABSTRACT: Obesity is the major risk factor for early puberty, but emerging evidence indicates other factors including psychosocial stress. One key brain region notable for its role in controlling calorie intake, stress and behavior is the amygdala. Early studies involving amygdala lesions that included the medial nucleus advanced puberty in rats. More recently, it was shown that a critical site for lesion-induced hyperphagia and obesity is the posterodorsal subnucleus of the medial amygdala (MePD), which may explain the advancement of puberty. Glutamatergic activity also increases in the MePD during puberty without a corresponding GABAergic change, suggesting an overall activation of this brain region. In the present study, we report that neurotoxic lesioning of the MePD advances puberty and increases weight gain in female rats fed a normal diet. However, MePD lesioned rats fed a 25% non-nutritive bulk diet also showed the dramatic advancement of puberty, but without the increase in body weight. In both dietary groups MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior. Chronic GABAA receptor antagonism in the MePD from postnatal day 21 for 14 days also advanced puberty, increased socialization and decreased play fighting without altering body weight, whereas glutamate receptor antagonism delayed puberty, decreased socialization without affecting play fighting. In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake. MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.
    Full-text · Article · Aug 2015 · Endocrinology
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    ABSTRACT: Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation respectively. Using bilateral micro-injections of recombinant adeno-associated virus encoding kisspeptin antisense (rAAV-Kisspeptin-AS) into the ARC or AVPV of female rats at postnatal day (pnd) 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured following ovariectomy. A 32% reduction of kisspeptin in ARC had no effect on the onset of puberty, but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signalling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity.
    Full-text · Article · Apr 2015 · Endocrinology
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    ABSTRACT: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.
    No preview · Article · Nov 2014 · Jama Ophthalmology
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    ABSTRACT: Objective To determine whether the addition of 26 weeks of subcutaneous peginterferon-α-2b could reduce the requirement for systemic corticosteroids and conventional immunosuppressive medication in patients with Behçet's disease (BD). Methods We conducted a multicentre randomised trial in patients with BD requiring systemic therapy. Patients were randomised to 26 weeks of peginterferon-α-2b in addition to their standard care or to standard care only and followed 6-monthly for 3 years with BD activity scores and quality of life questionnaires. Patients at one centre had blood taken to measure regulatory T cells (Tregs) and Th17 cells. Results 72 patients were included. At months 10–12, while among the entire patient population there was no difference in the corticosteroid dose or immunosuppression use between the treatment groups (adjusted OR 1.04, 95% CI 0.34 to 3.19), post hoc analysis revealed that in patients who were on corticosteroids at baseline the corticosteroid requirement was significantly lower in the peginterferon-α-2b (6.5 (5–15) mg/day) compared with the non-interferon group (10 (8.25–16.5) mg/day, p=0.039). Furthermore, there was a trend towards an improved quality of life that became significant by 36 months (p=0.008). This was associated with a significant rise in Tregs and a decrease in Th17 cells which was still present at 1 year and 6 months after the interferon was stopped. The safety profile was similar with adverse events in 10% in both groups. Conclusions The addition of peginterferon-α-2b to the drug regime of BD patients did not significantly reduce their corticosteroid dose required at 1 year. However, in those on corticosteroids at baseline post hoc analysis demonstrated that the addition of peginterferon-α-2b did result in a significant reduction in corticosteroid dose with a significantly improved quality of life and trend to reduce other required immunosuppressive agents. This effect was seen at 1 year and associated with a rise in Tregs suggesting a possible mode for interferon action. Trial registration number ISRCTN 36354474; EudraCT 2004-004301-18.
    No preview · Article · Sep 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal (HPG) axis. As corticotropin-releasing factor (CRF) expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, we tested the hypothesis that over-expression of CRF in the CeA of female rats alters anxiety behaviour, dysregulates the HPA axis response to stress, changes pubertal timing and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of pre-weaning (postnatal day 12) female rats. Over-expression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced, but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats over-expressing CRF. Despite the absence of change in basal or stress (lipopolysaccharide or restraint) induced corticosterone secretion, over-expression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in post pubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.
    Full-text · Article · Jul 2014 · Endocrinology
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    S. Y. Li · X. F. Li · M. H. Hu · B. Shao · L. Poston · S. L. Lightman · K. T. O'Byrne
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    ABSTRACT: The neural mechanisms controlling puberty onset remain enigmatic. Humans with loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with severe congenital gonadotrophin deficiency and pubertal failure. Animal studies have shown ambiguous actions of NKB-NK3R signalling in controlling puberty onset. The aims of this study were to elucidate the role of endogenous NKB-NK3R signalling in control of pulsatile luteinising hormone (LH) secretion and timing of puberty onset, and determine whether precocious pubertal onset due to an obesogenic diet is similarly regulated by this neuropeptide system. Prepubertal female rats, chronically implanted with intracerebroventricular cannulae, were administered SB222200, a NK3R antagonist, or artificial cerebrospinal fluid via an osmotic mini-pump for 14 days. SB222200 significantly delayed the onset of vaginal opening and first oestrus, as markers of puberty, compared to controls in both normal and high fat diet fed animals. Additionally, serial blood sampling, via chronic indwelling cardiac catheters, revealed that the increase in LH pulse frequency was delayed and LH pulse amplitude reduced in response to NK3R antagonism, regardless of dietary status. These data suggest that endogenous NKB-NK3R signalling plays a role in controlling the timing of puberty and associated acceleration of gonadotrophin-releasing hormone pulse generator frequency in the female rat.This article is protected by copyright. All rights reserved.
    Full-text · Article · May 2014 · Journal of Neuroendocrinology
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    P Grachev · X.F. Li · M.H. Hu · S.Y. Li · R.P. Millar · S.L. Lightman · K.T. O'Byrne
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    ABSTRACT: Acute systemic stress disrupts reproductive function by inhibiting pulsatile gonadotropin secretion. The underlying mechanism involves stress-induced suppression of the GnRH pulse generator, the functional unit of which is considered to be the hypothalamic arcuate nucleus (ARC) kisspeptin/neurokinin B/dynorphin A (KNDy) neurons. Agonists of the neurokinin B (NKB) receptor (NK3R) have been shown to suppress the GnRH pulse generator, in a dynorphin A (Dyn)-dependent fashion, under hypoestrogenic conditions, and Dyn has been well-documented to mediate several stress-related central regulatory functions. We hypothesized that the NKB/Dyn signaling cascade is required for stress-induced suppression of the GnRH pulse generator. To investigate this ovariectomized (OVX) rats, intravenously (iv) administered with Escherichia coli lipopolysaccharide (LPS) following intracerebroventricular (icv) pretreatment with NK3R or kappa-opioid receptor (KOR; Dyn receptor) antagonists, were subjected to frequent blood sampling for hormone analysis. Antagonism of NK3R, but not KOR, blocked the suppressive effect of LPS challenge on LH pulse frequency. Neither antagonist affected LPS-induced corticosterone (CORT) secretion. ARC NKB neurons project to the paraventricular nucleus (PVN) - the major hypothalamic source of the stress-related neuropeptides corticotropin releasing hormone (CRH) and arginine vasopressin (AVP), which have been implicated in the stress-induced suppression of the HPG axis. A separate group of OVX rats was, therefore, used to address the potential involvement of central CRH and/or AVP signaling in the suppression of LH pulsatility induced by icv administration of a selective NK3R agonist, senktide. Neither AVP nor CRH receptor antagonists affected the senktide-induced suppression of the LH pulse, however antagonism of type 2 CRH receptors attenuated the accompanying elevation of CORT levels. These data indicate that the suppression of the GnRH pulse generator by acute systemic stress requires hypothalamic NKB/NK3R signaling, and that any involvement of CRH therewith is functionally upstream of NKB.
    Full-text · Article · Apr 2014 · Endocrinology
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    ABSTRACT: To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. Retrospective cohort study. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. Our data suggest that control of inflammation can be achieved after switching or combining ISAs.
    No preview · Article · Jan 2014 · Ophthalmology
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    ABSTRACT: HMG-CoA reductase inhibitors (statins) have been demonstrated to be immunomodulatory for human immune-mediated disease and in experimental models. The aim of this study was to compare statin-mediated immunosuppressive effects on human T-cell responses in vitro with those of conventional immunosuppressives (dexamethasone, cyclosporin A (CsA), mycophenolate, and rapamycin). Statins (atorvastatin, lovastatin, and simvastatin) were investigated for their modulatory effects on human PBMC viability, cytokine profiles, and T-cell proliferation. At concentrations that inhibited anti-CD3/28-stimulated T-cell proliferation (P < 0.01), simvastatin significantly decreased intracellular CD4(+) T-cell expression of IFN-γ (P < 0.01) to levels similar to those induced by conventional immunosuppressives. Atorvastatin and lovastatin also decreased IFN-γ expression, although to a lesser degree (P < 0.05). All three statins reduced levels of IL-17 production (P < 0.01). However, in response to anti-CD3/28 stimulation, simvastatin significantly upregulated IL-1β production (P < 0.05). The profile of cytokines produced in response to anti-CD3/28 stimulation was similar when both atorvastatin and dexamethasone were added as compared with dexamethasone alone, suggesting that atorvastatin can synergise with dexamethasone with respect to immunomodulation of cytokines. This data supports the hypothesis of selective statin-mediated immunomodulatory effects on human immune cells.
    Full-text · Article · Sep 2013
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    ABSTRACT: Ocular inflammation and its related complications are important causes of vision loss. Inflammatory processes have long been implicated in the pathogenesis and sequelae of noninfectious uveitis and understood to underlie the macular edema which may arise following even uncomplicated intraocular surgeries [1]. More recently, evidence has also arisen supporting a prominent role for inflammation underlying the pathogenesis of a wide array of retinal diseases, including age-related macular degeneration (AMD) [2], diabetic retinopathy (DR) [3], retinal vein occlusion (RVO) [4], and retinitis pigmentosa (RP) [5], and has suggested a role for anti-inflammatory therapies to potentially alter the severity and course of these disorders. The goal of this special issue is to highlight the latest understanding of the role of inflammation in retinal diseases, to address current questions and controversies, and to facilitate future research.
    Preview · Article · Sep 2013
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    ABSTRACT: OBJECTIVE: To evaluate agreement between fluorescein angiography (FA) and optical coherence tomography (OCT) results for diagnosis of macular edema in patients with uveitis. DESIGN: Multicenter cross-sectional study. PARTICIPANTS: Four hundred seventy-nine eyes with uveitis from 255 patients. METHODS: The macular status of dilated eyes with intermediate uveitis, posterior uveitis, or panuveitis was assessed via Stratus-3 OCT and FA. To evaluate agreement between the diagnostic approaches, κ statistics were used. MAIN OUTCOME MEASURES: Macular thickening (MT; center point thickness, ≥240 μm per reading center grading of OCT images) and macular leakage (ML; central subfield fluorescein leakage, ≥0.44 disc areas per reading center grading of FA images), and agreement between these outcomes in diagnosing macular edema. RESULTS: Optical coherence tomography (90.4%) more frequently returned usable information regarding macular edema than FA (77%) or biomicroscopy (76%). Agreement in diagnosis of MT and ML (κ = 0.44) was moderate. Macular leakage was present in 40% of cases free of MT, whereas MT was present in 34% of cases without ML. Biomicroscopic evaluation for macular edema failed to detect 40% and 45% of cases of MT and ML, respectively, and diagnosed 17% and 17% of cases with macular edema that did not have MT or ML, respectively; these results may underestimate biomicroscopic errors (ophthalmologists were not explicitly masked to OCT and FA results). Among eyes free of ML, phakic eyes without cataract rarely (4%) had MT. No factors were found that effectively ruled out ML when MT was absent. CONCLUSIONS: Optical coherence tomography and FA offered only moderate agreement regarding macular edema status in uveitis cases, probably because what they measure (MT and ML) are related but nonidentical macular pathologic characteristics. Given its lower cost, greater safety, and greater likelihood of obtaining usable information, OCT may be the best initial test for evaluation of suspected macular edema. However, given that ML cannot be ruled out if MT is absent and vice versa, obtaining the second test after negative results on the first seems justified when detection of ML or MT would alter management. Given that biomicroscopic evaluation for macular edema erred frequently, ancillary testing for macular edema seems indicated when knowledge of ML or MT status would affect management. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
    Full-text · Article · Sep 2013 · Ophthalmology
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    ABSTRACT: OBJECTIVE: To report the 2-year incidence of raised intraocular pressure (IOP) and glaucomatous optic nerve damage in patients with uveitis randomized to either fluocinolone acetonide (FA) implants or systemic therapy. Secondarily, we sought to explore patient and eye characteristics associated with IOP elevation or nerve damage. DESIGN: A randomized, partially masked trial in which patients were randomized to either FA implants or systemic therapy. PARTICIPANTS: Patients aged ≥13 years with noninfectious intermediate, posterior, or panuveitis active within the prior 60 days for which systemic corticosteroids were indicated were eligible. METHODS: Visual fields were obtained at baseline and every 12 months using the Humphrey 24-2 Swedish interactive threshold algorithm fast protocol. Stereoscopic optic nerve photos were taken at baseline and at 3-, 6-, 12-, and 24-month follow-up visits. Masked examiners measured IOP at every study visit. MAIN OUTCOME MEASURES: Glaucoma was diagnosed based on an increase in optic nerve cup-to-disc ratio with visual field worsening or increased cup-to-disc ratio alone, for cases where visual field change was not evaluable, because of missing data or severe visual field loss at baseline. RESULTS: Most patients were treated as assigned; among those evaluated for glaucoma, 97% and 10% of patients assigned to implant and systemic treatment, respectively, received implants. More patients (65%) assigned to implants experienced an IOP elevation of ≥10 mmHg versus 24% assigned to systemic treatment (P<0.001). Similarly, 69% of patients assigned to the implant required IOP-lowering therapy versus 26% in the systemic group (P<0.001). Glaucomatous optic nerve damage developed in 23% versus 6% (P<0.001) of implant and systemic patients, respectively. In addition to treatment assignment, black race, use of IOP-lowering medications, and uveitis activity at baseline were associated with incident glaucoma (P<0.05). CONCLUSIONS: Implant-assigned eyes had about a 4-fold risk of developing IOP elevation of ≥10 mmHg and incident glaucomatous optic neuropathy over the first 2 years compared with those assigned to systemic therapy. Central visual acuity was unaffected. Aggressive IOP monitoring with early treatment (often including early filtration surgery) is needed to avoid glaucoma when vision-threatening inflammation requires implant therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
    Full-text · Article · Aug 2013 · Ophthalmology
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    ABSTRACT: To report the 2-year incidence of raised intraocular pressure (IOP) and glaucomatous optic nerve damage in patients with uveitis randomized to either fluocinolone acetonide (FA) implants or systemic therapy. Secondarily, we sought to explore patient and eye characteristics associated with IOP elevation or nerve damage.DesignA randomized, partially masked trial in which patients were randomized to either FA implants or systemic therapy.ParticipantsPatients aged ≥13 years with noninfectious intermediate, posterior, or panuveitis active within the prior 60 days for which systemic corticosteroids were indicated were eligible.Methods Visual fields were obtained at baseline and every 12 months using the Humphrey 24-2 Swedish interactive threshold algorithm (SITA) fast protocol. Stereoscopic optic nerve photos were taken at baseline and at 3-, 6-, 12-, and 24-month follow-up visits. Masked examiners measured IOP at every study visit.Main Outcome MeasuresGlaucoma was diagnosed based on an increase in optic nerve cup-to-disc ratio with visual field worsening or increased cup-to-disc ratio alone, for cases where visual field change was not evaluable, because of missing data or severe visual field loss at baseline.ResultsMost patients were treated as assigned; among those evaluated for glaucoma, 97% and 10% of patients assigned to implant and systemic treatment, respectively, received implants. More patients (65%) assigned to implants experienced an IOP elevation of ≥10 mmHg versus 24% assigned to systemic treatment (P<0.001). Similarly, 69% of patients assigned to the implant required IOP-lowering therapy versus 26% in the systemic group (P<0.001). Glaucomatous optic nerve damage developed in 23% versus 6% (P<0.001) of implant and systemic patients, respectively. In addition to treatment assignment, black race, use of IOP-lowering medications, and uveitis activity at baseline were associated with incident glaucoma (P<0.05).Conclusions Implant-assigned eyes had about a 4-fold risk of developing IOP elevation of ≥10 mmHg and incident glaucomatous optic neuropathy over the first 2 years compared with those assigned to systemic therapy. Central visual acuity was unaffected. Aggressive IOP monitoring with early treatment (often including early filtration surgery) is needed to avoid glaucoma when vision-threatening inflammation requires implant therapy.Financial Disclosure(s)Proprietary or commercial disclosure may be found after the references.
    No preview · Article · Aug 2013 · Ophthalmology
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    ABSTRACT: Introduction: Although rarer than its adult counterpart, non-infectious uveitis remains a significant cause of ocular morbidity in children. Owing to the chronicity of the disorder and when refractory to first-line treatment, namely corticosteroids, systemic immunosuppressive treatment may be required to control the disease. Areas covered: Following a literature search using the keywords 'paediatric uveitis', 'juvenile idiopathic arthritis-associated uveitis', 'immunosuppression' and 'treatment', we reviewed the range and effectiveness of treatments employed in the management of non-infectious, paediatric uveitis. Expert opinion: Corticosteroids (topical, periocular, intraocular or systemic) remain the initial drug of choice in ameliorating the signs and symptoms of non-infectious paediatric uveitis. Failure to control the disease and/or failure to reduce the oral dose of prednisolone at least 0.15 mg/kg within 4 weeks often requires additional immunosuppressant therapy. Methotrexate and azathioprine have shown to be effective in the management of juvenile idiopathic arthritis (JIA)-associated uveitis with the former considered the first-line corticosteroid-sparing agent. Biologic therapies are increasingly used earlier in the disease with investigators in the UK currently recruiting patients for the SYCAMORE trial evaluating the efficacy of methotrexate and adalimumab vs methotrexate alone for the treatment for JIA-associated uveitis. Until further randomised controlled trials are conducted, the use of other biologic agents should only be used with an appreciation that there are potentially unknown side-effects and that there is not a full knowledge of their efficacy.
    No preview · Article · Jul 2013 · Expert Opinion on Pharmacotherapy
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    ABSTRACT: Purpose: To evaluate the effect of a single treatment with dexamethasone intravitreal implant (DEX implant) on patient-reported visual functioning in patients with noninfectious intermediate or posterior uveitis. Methods: Patient eyes with noninfectious intermediate or posterior uveitis were randomized to a single treatment with DEX implant 0.70 mg (n=77), DEX implant 0.35 mg (n=76), or a sham procedure (n=76) and followed for 26 weeks. Vision-related functioning was measured using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) assessed at baseline and at weeks 8, 16, and 26 or early exit. Analysis of covariance and mixed model analysis of covariance were used to compare vision-related functioning between the DEX implant 0.70 and 0.35 mg groups and the sham group. Results: By 8 weeks, the DEX implant 0.70 mg group demonstrated significant improvements in NEI VFQ-25 subscales near vision (P=0.031), distance vision (P=0.023), peripheral vision (P=0.045), vision-specific social functioning (P=0.019), and the NEI VFQ-25 composite score (P=0.007) compared with sham. After 26 weeks, the DEX implant 0.70 mg group reported significant improvements in NEI VFQ-25 subscales distance vision (P=0.003), vision-specific role difficulties (P=0.038), vision-specific dependency (P=0.017), vision-specific social functioning (P=0.009), vision-specific mental health (P=0.036), and the composite score (P=0.001) compared with sham. Conclusions: In patients with noninfectious intermediate or posterior uveitis receiving a single treatment of DEX implant 0.70 mg, significant and clinically meaningful improvements in patient-reported visual functioning were observed as early as week 8 and were maintained over 26 weeks. (ClinicalTrials.gov number, NCT00333814.).
    No preview · Article · Jun 2013 · Investigative ophthalmology & visual science

Publication Stats

3k Citations
473.20 Total Impact Points

Institutions

  • 2004-2015
    • University of Bristol
      • The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology
      Bristol, England, United Kingdom
  • 1996-2015
    • University College London
      • Institute of Ophthalmology
      Londinium, England, United Kingdom
  • 1992-2015
    • Moorfields Eye Hospital NHS Foundation Trust
      • Department of Medical Retina
      Londinium, England, United Kingdom
  • 2013
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
  • 2012
    • Royal Surrey County NHS Foundation Trust
      Guilford, England, United Kingdom
  • 2007-2011
    • Imperial College London
      • Section of Immunology
      Londinium, England, United Kingdom
  • 1994-2010
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2005
    • Middlesex Hospital
      मिडलटाउन, Connecticut, United States