Susan Lightman

Moorfields Eye Hospital NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (72)190.12 Total impact

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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.
    Ophthalmology 01/2014; · 5.56 Impact Factor
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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.
    Ophthalmology 09/2013; 120(9):1852-9. · 5.56 Impact Factor
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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.
    Ophthalmology 08/2013; 120(8):1571-9. · 5.56 Impact Factor
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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.
    Expert Opinion on Pharmacotherapy 07/2013; · 2.86 Impact Factor
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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.
    International journal of inflammation. 01/2013; 2013:434586.
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    ABSTRACT: BACKGROUND: To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN). METHODS: This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 1 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease. RESULTS: Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks). CONCLUSIONS: Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.
    BMC Ophthalmology 09/2012; 12(1):48. · 1.44 Impact Factor
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    ABSTRACT: To evaluate the impact of macular edema on visual acuity and visual field sensitivity in uveitis. This study utilized baseline data from the Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized, parallel treatment clinical trial comparing alternative treatments for intermediate, posterior and panuveitis. 255 patients (481 eyes with uveitis) recruited at 23 subspecialty centers. Visual acuity, optical coherence tomography and Humphrey 24-2 visual field testing. Macular edema was associated with impaired visual acuity (p < 0.01). Different phenotypes of macular edema were associated with different degrees of visual impairment: cystoid changes without retinal thickening were associated with moderately impaired visual acuity (-5 ETDRS letters), but visual acuity was worse in eyes with retinal thickening (-13 letters) and with both cysts and thickening (-19 letters). Uveitis sufficient to satisfy the study's inclusion criteria was associated with impaired visual field sensitivity, but eyes with macular edema had even worse visual field sensitivity (p < 0.01). The observation that macular edema substantially reduces visual function suggests macular edema itself is an important endpoint to study in the treatment of uveitis. As uveitis and macular edema both impair visual field sensitivity as measured by Humphrey 24-2 perimetry, both should be considered when evaluating patients with uveitis and raised intraocular pressure for glaucoma.
    Ocular immunology and inflammation 04/2012; 20(3):171-81. · 0.72 Impact Factor
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    BMJ (online) 02/2012; 344:e1121. · 17.22 Impact Factor
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    ABSTRACT: Raised intraocular pressure in uveitis, either due to the disease itself or secondary to treatment with steroids, is one of the most common causes of secondary glaucoma in clinical practice. There are currently no standardized criteria for the diagnosis nor guidelines for the management of raised intraocular pressure in uveitis. Intraocular pressure elevation may be due to any combination of several mechanisms and, as a result, the prognosis differs from primary glaucomas. In addition, the management of ongoing inflammation without elevating the intraocular pressure remains a challenge. Ideally, new anti-inflammatory agents should have better anti-inflammatory properties with safer intraocular pressure profiles, while sustained release medications to lower intraocular pressure would improve patient compliance.
    Expert Review of Ophthalmology 01/2012; 7(1):45-59.
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    International journal of inflammation. 01/2012; 2012:403520.
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    ABSTRACT: Wegener''s granulomatosis (newly renamed granulomatosis with polyangiitis [WG/GPA]) is a granulomatous autoimmune inflammatory disorder of unknown etiology that is associated with anti-neutrophil cytoplasm antibodies. It can involve any organ system, but most commonly affects the respiratory and renal systems and the head and neck, including the eye. The ophthalmic manifestations of WG/GPA are diverse and can affect any of the ocular structures. Despite continuing research, the exact pathogenesis of WG/GPA remains elusive, but there is increasing awareness of the disease, especially as its prevalence and incidence are both on the rise. Unhelpfully, the diagnosis and management of WG/GPA remains a challenge, especially in its limited form, as blood tests, imaging and tissue biopsies are often negative or nonspecific. Nevertheless, the emergence of new treatment regimens for WG/GPA, particularly target-specific drugs such as rituximab, the anti-CD20 antibody, is bringing promise in providing patients with better and potentially safer treatment for the disease.
    Expert Review of Ophthalmology 09/2011; 6(5):541-555.
  • The British journal of ophthalmology 05/2010; 94(5):665-6. · 2.92 Impact Factor
  • Article: Reply.
    Ahmed Sallam, Susan Lightman
    American Journal of Ophthalmology 03/2010; 149(3):526-7. · 4.02 Impact Factor
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    Patrick M K Tam, Claire Y Hooper, Susan Lightman
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    ABSTRACT: There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised.
    Clinical Ophthalmology 01/2010; 4:11-20.
  • Fiona Lyon, Richard P Gale, Susan Lightman
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    ABSTRACT: The management of complex uveitis is often based around the use of oral corticosteroids. To spare the side effects of corticosteroids, second-line oral immunosuppressant drugs are used. Newer systemic immunosuppressive drugs, including biologics, and locally delivered treatments are being evaluated. This article reviews current conventional treatments, discusses their limitations and evaluates newer treatment strategies. Current theories about the pathogenesis of uveitis and potential targets for treatment are discussed in this context. We are still in search of a low-risk, where possible, locally delivered and targeted treatment for uveitis.
    Expert Opinion on Investigational Drugs 06/2009; 18(5):609-16. · 4.74 Impact Factor
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    ABSTRACT: To compare the management and outcome of raised intraocular pressure (IOP) in uveitis patients with a corticosteroid hypertensive response and those who are noncorticosteroid responders and to determine the impact of intraocular corticosteroid use on IOP in uveitic eyes. Retrospective study. Eight hundred and ninety-one uveitis patients were observed in a specialized clinic over 3 months. The main outcome measures were frequency, characterization, management, and outcome of uveitis-related ocular hypertension and glaucoma. Of 891 patients with uveitis, 191 (275 eyes) had IOP elevation (21.4%). Of these, 95 (34.5%) eyes had glaucoma. IOP elevation attributed to corticosteroid-response (61.1%) was controlled more easily than that resulting from other causes (38.9%), requiring fewer eye drops (mean, 2.06 vs 2.52; P = .009) and less filtration surgery (8.9% vs 22.4%). Among eyes with uveitis and raised IOP, elevated IOP developed in 18 eyes (6.5%) after intravitreal triamcinolone, including 64.7% to 30 to 39 mm Hg and 35.3% to 40 mm Hg or more. Prostaglandin analogs were used in 49.2% of 246 eyes; no increase in inflammation was seen in these eyes. In this tertiary center series, most instances of raised IOP were attributable to corticosteroid response. Raised IOP induced by corticosteroid response was controlled more easily and less often resulted in optic nerve or visual field changes of glaucoma. Although intravitreous triamcinolone was associated with substantial risk of corticosteroid-response IOP elevation, all cases were controlled medically without experiencing glaucomatous injury. Prostaglandin-induced uveitis was not observed despite extensive use of prostaglandin IOP-lowering agents.
    American Journal of Ophthalmology 05/2009; 148(2):207-213.e1. · 4.02 Impact Factor
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    ABSTRACT: To investigate the efficacy of rituximab in patients with refractory ophthalmic Wegener's granulomatosis (WG). Data from 10 consecutive patients with refractory ophthalmic WG treated with rituximab were retrospectively reviewed. In all patients, the ophthalmic disease was driving treatment decisions, and disease activity had persisted despite standard immunosuppressive treatment. Patients had refractory scleritis (n=3), orbital granulomas causing optic nerve compromise (n=4), or a combination of both conditions (n=3). All patients had been treated with at least 3 different immunosuppressive agents, and 5 patients had previously been treated with tumor necrosis factor alpha blockade. Rituximab was administered intravenously in 2 doses, 2 weeks apart, in combination with standard treatment. Disease activity was monitored clinically by an interdisciplinary approach, including disease activity scoring, immunodiagnostics, and magnetic resonance imaging, as well as by corresponding reductions in the required dose of conventional medication. A beneficial response to treatment with rituximab was seen in all 10 patients, including induction of clinical remission. In all patients, the peripheral blood B cell count fell to zero during treatment with rituximab. Titers of classic antineutrophil cytoplasmic antibodies fell in association with B cell counts, and this reduction was correlated with improved clinical findings. In contrast to previous observations, this study showed that treatment with rituximab was associated with clinical improvement in patients with refractory ophthalmic WG.
    Arthritis & Rheumatology 05/2009; 60(5):1540-7. · 7.48 Impact Factor
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    ABSTRACT: A patient undergoing chemotherapy for treatment of acute lymphocytic leukemia developed septicemia that was treated with linezolid for 16 days. The patient subsequently reported reduced vision in both eyes and was found to have bilateral optic neuropathy. After the discontinuation of linezolid treatment, both the optic neuropathy and visual impairment resolved without sequelae.
    Clinical Infectious Diseases 03/2009; 48(7):e73-4. · 9.37 Impact Factor
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    ABSTRACT: To determine the type of ocular involvement in patients with neurosarcoidosis, and evaluate whether the type of eye involvement may help in the diagnosis of neurosarcoidosis. Retrospective, case history study. We reviewed the medical records of 46 patients who attended the sarcoidosis clinics at the Royal Brompton and Moorfields Eye Hospital over a 4-year period with a diagnosis of definite and probable neurosarcoidosis supported by laboratory investigations and exclusion of other causes for the neurological symptoms. Cranial nerve involvement was the most common neurological manifestation in this series. Among the 27 patients with cranial neuropathy, lower motor neurone facial palsy was the most frequently seen in 19 patients (70.4%). Diplopia was seen in four patients (14.9%). In three patients, this was because of common oculomotor nerve paresis. Uveitis was the most common intraocular manifestation in patients with neurosarcoidosis. The majority of these patients (9, 64.3%) suffered from anterior uveitis, but in 35.7% of them the inflammatory process involved the posterior segment. We found a higher incidence of ocular manifestations, including intraocular inflammation in neurosarcoidosis compared to that in systemic sarcoidosis elsewhere. The most common ocular complication seen in our series was anterior uveitis; however there were no associated clinical features of the uveitis in these series that could contribute to the differential diagnosis between neurosarcoidosis and other autoimmune disorders with neuro-ophthalmic features such as multiple sclerosis. Patients with neurological symptoms and associated intraocular inflammation should have a routine work-up for sarcoidosis. Investigations should include MRI scan of the brain and orbits and lumbar puncture in selected cases. Tissue biopsy should be attempted when clinically accessible lesions are available i.e., conjunctiva or lacrimal gland.
    Ocular immunology and inflammation 01/2009; 17(3):170-8. · 0.72 Impact Factor
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    Archives of ophthalmology 06/2008; 126(5):734. · 3.86 Impact Factor

Publication Stats

745 Citations
190.12 Total Impact Points

Institutions

  • 2001–2014
    • Moorfields Eye Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2007–2013
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2012
    • University of Oklahoma Health Sciences Center
      • Dean McGee Eye Institute
      Oklahoma City, OK, United States
    • National University of Malaysia
      Putrajaya, Putrajaya, Malaysia
  • 2010
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • The Chinese University of Hong Kong
      • Department of Ophthalmology and Visual Sciences
      Hong Kong, Hong Kong
  • 2009
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
    • York Hospital
      York, Pennsylvania, United States
  • 2006
    • University of Oxford
      Oxford, England, United Kingdom
  • 2003–2006
    • University College London
      • Institute of Ophthalmology
      London, ENG, United Kingdom
    • Rabin Medical Center
      Tell Afif, Tel Aviv, Israel
    • London College of Clinical Hypnosis
      Londinium, England, United Kingdom
    • UK Department of Health
      Londinium, England, United Kingdom