The changing landscape of thyroid eye disease: current clinical advances and future outlook.

AIMS: This review aims to provide an overview of the current understanding of TED and its pathophysiology. To describe the evidence base for current consensus treatment recommendations and newer biological therapies available as well as to present future therapeutic research. METHODS: We reviewed and assessed the peer-reviewed literature placing particular emphasis on recent studies evaluating the pathophysiology of TED, landmark trials forming the basis of current management and recent clinical trials informing future therapeutics. Searched were made in MEDLINE Ovid, Embase Ovid, US National Institutes of Health Ongoing Trials Register and EU Clinical Trials Register. Keywords included: "Thyroid Eye Disease", "Graves Orbitopathy", "Thyroid Orbitopathy" and "Graves' Ophthalmopathy". RESULTS AND CONCLUSIONS: The pathophysiology of TED involves a complex array of cellular and humoral based autoimmune dysfunction. Previous therapies have been broad-based acting as a blunt instrument on this mechanism with varying efficacy but often accompanied with a significant side effect profile. The recent development of targeted therapy, spearheaded by Teprotumumab has led to an array of treatments focusing on specific components of the molecular pathway optimising their impact whilst possibly minimising their side effect profile. Future challenges involve identifying the most effective target for each patient rather than any single agent being a panacea. Long-term safety profiles will require clarification as unintended immunological consequence downstream may become manifest as seen in other diseases. Finally, future novel therapeutics will entail significant expenditure and may lead to a divergence of available treatment modalities between healthcare systems due to funding disparities.

Primary Ocular Toxoplasmosis Presenting to Uveitis Services in a Non-endemic Setting.

PURPOSE: This study sought to describe the different clinical features and presentations of primary ocular toxoplasmosis in a setting not demonstrating an outbreak of disease. METHODS: This was a retrospective review of patients presenting to uveitis management services in Auckland and Hamilton, New Zealand between 2003 to 2018 with uveitis and positive toxoplasmosis immunoglobulin M serology. RESULTS: We identified 16 patients with primary acquired toxoplasmosis infection and ocular involvement. The mean age was 53 years. Systemic symptoms were reported in 56% (9 / 16). Visual acuity was reduced to 20 / 30 or less in 50% of patients (8 / 16). A single focus of retinitis without a pigmented scar was the salient clinical feature in 69% (11 / 16). Optic nerve inflammation was the sole clinical finding in 19% (3 / 16). Bilateral arterial vasculitis was the sole clinical finding in 13% (2 / 16). A delay in the diagnosis of toxoplasmosis of more than two weeks occurred in 38% (6 / 16) due to an initial alternative diagnosis. Antibiotic therapy was prescribed in all cases. Vision was maintained or improved in 69% (11 / 16) at the most recent follow-up visit (15 months to 10 years). Relapse occurred in 69% (11 / 16), typically within four years from the initial presentation. CONCLUSIONS: Primary ocular toxoplasmosis presenting in adulthood is a relatively uncommon cause of posterior uveitis in New Zealand. This condition should be considered in any patient presenting with retinitis or optic nerve inflammation without a retinochoroidal scar. This disease tends to relapse; thus, close follow-up is required.

An update on the use of biologic therapies in the management of uveitis in Behçet's disease: a comprehensive review.

ᅟ: Behçet's disease (BD) is a systemic vasculitis characterised by a relapsing remitting course, affecting multiple organ systems. In the eye, it is a cause of potentially blinding inflammation in the form of uveitis. Management of uveitis in BD often requires the use of systemic immunosuppression, in order to reduce disease activity and prevent accumulation of irreversible damage. Whilst corticosteroids remain the mainstay of treatment, long-term use is limited by the development of adrenocorticotrophic side effects. There has therefore been significant interest in the use of corticosteroid-sparing immunosuppressive agents, and more recently, biologic therapies. Recent publications have demonstrated biologic therapy to have beneficial effects both on overall disease control, and quality of life for patients with BD. Widespread use of such agents is however limited, partly by the lack of high quality research evidence, and partly by the prohibitive cost of biologic treatments. In this review, we discuss the most recent research investigating the use of biologic therapy in uveitis due to BD, with consideration of health economics and quality of life outcomes.

Presumed tuberculous uveitis in non-endemic country for tuberculosis: case series from a New Zealand tertiary uveitis clinic.

BACKGROUND: To describe the clinical spectrum of presumed tuberculous (TB) uveitis in a developed, non-endemic country of high immigrant population. DESIGN: Retrospective review of a consecutive case series. PARTICIPANTS: All 39 patients diagnosed with presumed TB uveitis at the tertiary uveitis service in Auckland from 2007 to 2014. METHODS: Clinical chart review. MAIN OUTCOME MEASURES: Patient demographics, risk factors, ophthalmic manifestations, management and outcome. RESULTS: The median age was 37 years (interquartile range [IQR] 31-52) and 56% were female. The majority (97%) were born outside of New Zealand, and 77% had no TB-related history. Radiological abnormalities consistent with TB were evident in seven patients, including three who had culture positive pulmonary disease. Anterior uveitis was diagnosed in ten patients (26%), anterior and intermediate uveitis in eight (21%), posterior uveitis in 13 (33%) and panuveitis in eight (21%). Sixteen (41%) had retinal vasculitis, and five (13%) had multifocal serpiginoid choroiditis. Common complications included cataract (51%), ocular hypertension (36%), broad posterior synechiae (33%) and cystoid macular oedema (28%). Anti-TB treatment was initiated in 30 patients (76%). All but three patients completed the intended course of six to 12 months. Following anti-TB treatment, 67% remained in remission for at least 12 months, and all but two patients successfully stopped systemic steroids. The median initial and final visual acuity was 6/9 (IQR 6/6-6/18) and 6/6 (IQR 6/6-6/9), respectively. CONCLUSIONS: Despite a wide range of ocular presentations and complications, our cohort demonstrated good remission rate and visual prognosis following anti-TB treatment in carefully selected patients.

Sight-threatening diabetic retinopathy at presentation to screening services in Fiji.

PURPOSE: To report the spectrum of retinopathy at first presentation to photoscreening services, to determine the proportion of patients that present with sight-threatening diabetic retinopathy (STDR), and to raise awareness of the burden of diabetic eye disease in Fiji. METHODS: This retrospective observational cohort study used data from the initial visit of all new patients presenting to the diabetes retinal screening service at the Pacific Eye Institute in Fiji over the 3-month period between July and September 2012. Patients were assessed using a detailed questionnaire regarding diabetes type, duration of disease, medications, complications and co-morbidities, and blood sugar control. Patients subsequently underwent non-mydriatic fundus photography according to Pacific diabetes retinal screening guidelines. Images were graded at the time of acquisition, and data were entered onto a computerized database. For the purposes of this study, information regarding retinopathy grading, visual acuity and patient demographics was used. RESULTS: A total of 522 new patients were screened over the 3-month period. STDR was observed in 27% of patients, with 15% observed to have bilateral STDR. Diabetes control was generally poor. Blindness and visual impairment were observed in 2.7% and 6.7% of the cohort, respectively. CONCLUSION: Severe and advanced diabetic retinopathy was present in this population presenting to screening. This was observed 4 years after the formal expansion of the screening services and reflects the high prevalence of diabetes in the population. The need for increased public awareness and greater resource allocation into diabetes and its complications is emphasized.

Choroidal schwannoma: a case series of five patients.

AIM: To report a case series of five patients diagnosed with choroidal schwannoma at the Liverpool Ocular Oncology Centre. METHODS: Patients with choroidal schwannoma were identified by searching the computerised database of the Liverpool Ocular Oncology Centre. RESULTS: The patients (3 males, 2 females) ranged in age from 15 years to 45 years. Three tumours were treated by enucleation, trans-scleral local resection, and combined bevacizumab and photodynamic therapy, respectively. Two were observed after confirmation of the diagnosis by biopsy. CONCLUSIONS: Choroidal schwannoma has a variety of clinical manifestations. Associated features include hard exudates, retinal feeder vessels and serous retinal detachment. Biopsy with immunohistochemistry is required for diagnosis. Tumours not amenable to resection may respond to photodynamic therapy.

Vitreous analysis in the management of uveitis.

A correct diagnosis of uveitis is often challenging, given the wide range of possible underlying conditions and the lack of typical phenotypes. Management decisions may be difficult in view of the risk of visual loss with either inappropriate or delayed therapy. Analysis of the vitreous may therefore be used to provide the clinician with valuable information. In this paper, we describe the main clinical situations in which vitreous sampling is indicated and provide some guidance to clinicians for tailoring their requests. These situations include suspected intraocular infection and suspected intraocular malignancy. We describe the principal tests carried out on vitreous samples, including cultures, polymerase chain reaction-based testing, and cytokine analysis. Limitations of the tests used are likely to become less as more advanced testing methods are introduced. The importance of selecting the appropriate investigations to support a clinical suspicion is emphasised, as is the interpretation of test results within a clinical context.

Detection and time to treatment of uveal melanoma in the United Kingdom: an evaluation of 2,384 patients.

PURPOSE: To determine the mode of detection of uveal melanoma and time to treatment in the United Kingdom. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 2384 patients diagnosed with uveal melanoma at the Liverpool Ocular Oncology Center between 1996 and early 2011. METHODS: A questionnaire was completed with every new patient, and the results were correlated with clinical features and treatment. MAIN OUTCOME MEASURES: Tumor detection, practitioner initiating referral, referral pathway, time to treatment, baseline clinical features, and primary ocular treatment. RESULTS: The referral process was initiated by an optometrist, family doctor, or ophthalmologist in 68.0%, 18.2%, and 13.8% of patients, respectively. On referral, 30.2% of patients were asymptomatic. Twenty-three percent of patients reported that their tumor was initially missed; these tended to have a more advanced tumor when they reached our center. The time from referral to treatment had a median of 49 days, exceeding 6 months in 19.8% of patients. This delay was longer in patients who reported that their tumor was missed (median, 92 vs. 40 days; Mann-Whitney, P<0.001). Ophthalmologists delayed the referral process by more than 6 months in 10.9% of patients. Primary enucleation was performed in 33.3% of patients and was more likely in those who reported that their tumor was missed (44.8% vs. 29.8%; chi-square, P<0.001). CONCLUSIONS: Many patients with uveal melanoma experience long delays in treatment because their tumor was missed or misdiagnosed. Such patients tend to have a more advanced tumor by the time they reach an oncology center and are more likely to require enucleation.

Cancer-associated retinopathy presenting as retinal vasculitis with a negative ERG suggestive of on-bipolar cell pathway dysfunction.

A 62-year-old female patient presented to our clinic complaining of a 2 month history of shimmering photopsias and floaters. An ocular examination, fluorescein angiography, and electrophysiological testing were obtained that suggested either an inflammatory retinal vasculitis or a paraneoplastic syndrome. Melanoma-associated retinopathy was highly suspected despite the absence of previous history for cutaneous melanoma since an electronegative scotopic ERG was recorded on standard flash electroretinography. Additional investigations revealed the presence of a primary breast tumor with secondary lung and pancreatic metastasis that led to the diagnosis of cancer-associated retinopathy. The patient received chemotherapy and 4 months after the initial presentation her visual complaints but also her retinal function showed marked improvement. Cancer-associated retinopathy needs to be considered in patients presenting with retinal vasculitis and electrophysiological testing can tailor the approach in these cases.

Plasmapheresis in the management of choroidal vasculitis associated with C-anca positive renal vasculitis.

PURPOSE: The purpose of this study was to report the use of plasmapheresis in the management of choroidal vasculitis associated with Wegener granulomatosis. METHOD: Case report. PATIENT: A 50-year-old woman with acute renal failure as a result of glomerulonephritis of the Wegener granulomatosis type presented with sudden visual loss. Visual acuities at presentation were counting fingers in the left eye and 6/24 in the right eye. Clinical examination showed significant choroidal ischemia with no evidence of vitritis or anterior segment inflammation. Fluorescein and indocyanine green angiography confirmed choroidal vasculitis. RESULTS: The patient was treated with a course of seven plasmapheresis sessions, after which she was maintained on prednisolone and mycophenolate. One week after her presentation, vision improved to 6/6 bilaterally. The angiographic appearances resolved, and the patient was maintained on immunosuppression. CONCLUSION: We believe that the prompt use of plasmapheresis prevented irreversible visual loss in this patient. This case illustrates the dramatic improvement in choroidal perfusion presumably resulting from the removal of a circulating immune factor.

Serial retinal fluorescein angiography and immune therapy in Susac's syndrome.

We report a patient with Susac's disease presenting classically in a young female with an encephalopathy and visual disturbance with later deafness and tinnitus. Her encephalopathy settled, but subsequent serial fluorescein angiograms allowed sensitive monitoring of continuing sub-clinical disease activity, and provide evidence of a clear therapeutic response to immune suppression with tacrolimus (but not steroids alone)--and of a lack of efficacy of nimodipine and aspirin. We believe this single case study has both pathogenetic and useful practical implications: the apparently favourable response to immunosuppression lends support to the hypothesis that Susac's Syndrome is an immune-mediated disease; while the presence during symptomatic clinical remission of sporadic, multi-focal episodes of hyper-fluorescence, suggestive of breakthrough vasculopathy despite treatment, underlines the fact that the natural history of this rare condition is still not fully understood. Fluorescein angiography is proposed as a sensitive and important approach to the monitoring of sub-clinical disease activity, and so optimising immune suppressive treatment.