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A 35-year-old woman presented with a constellation of systemic symptoms: rashes, weight loss, arthralgia and mouth ulcers. Six months afterwards, she experienced bilateral and sequential reduction in vision, and was found to have bilateral vaso-occlusive retinopathy, with critical macular ischaemia in the left eye. Her serological markers were consistent with a diagnosis of lupus. A lymph node biopsy confirmed Kikuchi-Fujimoto disease, a benign condition of unknown cause characterised by fever, cervical and axillary lymphadenopathy. Given that this overlap syndrome was associated with a number of systemic features and had affected the eyes, an immunosuppressive regime with rituximab was considered prudent. This rendered her vasculitis stable and non-progressive, and there were signs of partial retinal microvasculature recovery on optical coherence tomography angiography. There is increasing evidence of an overlap between Kikuchi-Fujimoto disease and systemic lupus erythematosus, which is associated with vaso-occlusive retinopathy. In these instances, a multidisciplinary approach is warranted, with consideration of appropriate treatment in order to prevent harmful sequelae of vasculitis. Our treatment with rituximab abated the disease process, although close follow-up is paramount to monitor results and side-effects of treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The importance of patient and public involvement (PPI) in healthcare decisions and research is increasingly recognised. This paper describes the aims, delivery, evaluation and impact of a 'Birdshot Day' organised for patients with birdshot uveitis, their carers and healthcare professionals., Methods: Delivery of this event involved the close collaboration of patients with a large number of different healthcare professionals. The event's evaluation used established social research methods including qualitative questionnaires pre, post and 6 months following the event. The results were statistically analysed., Results: Results indicated that this event significantly educated both patients and professionals. The sense of isolation felt by patients was reduced and networking was developed among all attendees. Patient priorities for research were recorded and invaluable insight into patients' needs for a better quality of life was gained., Conclusions: The first undertaking of this novel PPI event achieved all its aims. It became even clearer that fundamental questions remain about birdshot uveitis, including aetiology, pathogenesis, practical clinical issues and impact on quality of life. These questions can only be addressed in partnership with patients. To this end, patients and professionals came together under the banner 'Team Birdshot' and the National Birdshot Research Network was launched.

Aim: There is little information on the demographic and clinical characteristics of Behçet's disease in children in different parts of the world. We sought to provide this information through a questionnaire survey of specialist eye centres., Methods: Descriptive questionnaires were collected from 25 eye centres in 14 countries. The questionnaire surveyed details of juvenile-onset Behçet's disease with uveitis. Ethnic groups, clinical features, treatments and prognosis of paediatric-age Behçet's disease were examined on a worldwide scale., Results: The clinical data of 135 juvenile-onset and 1227 adult-onset patients with uveitis were collected. The average age of disease diagnosis in the children was 11.7 years old. Of the ethnic groups identified 54% were from Middle East, 43% from Europe, but only 2% from East/South Asian countries. By contrast, 19.2% of adult patients were from East or South Asia. The frequency of genital ulcers in juvenile patients was 38.7%, which was significantly lower than in adult cases (53.5%; p<0.01)., Conclusions: Behçet's disease with uveitis was less common in children than in adults in East/South Asia. Although the clinical features of the systemic disease were similar in children and adults, there was a lower frequency of genital ulceration in children.

Aims: To describe the clinical and radiological features of orbital apex syndromes caused by presumed tuberculosis (TB)., Methods: A review of the discharge summaries of all patients seen in the Medical Eye Unit (MEU), St Thomas' Hospital between 1975 and 2006 identified seven patients with a diagnosis of orbital apex syndrome or optic neuropathy attributable to TB. Case notes and radiology were reviewed retrospectively for each patient., Results: All of the patients were born outside the UK and were HIV-negative. Four presented during 2005-6. Six of the seven patients presented with a visual acuity (VA) of less than counting fingers (CF), but all achieved a VA of 6/9 or better after a median 3 weeks of treatment with antituberculous treatment and systemic corticosteroids. All patients had constitutional symptoms. Chest x ray and CSF were normal in each case, but MRI was abnormal in six., Conclusions: We report a recent cluster of tuberculous orbital apex syndromes, in the context of an increasing incidence of TB in the UK. The condition is difficult to diagnose, but the combination of high-dose corticosteroids and anti-TB medication was rapidly effective and achieved a good outcome in all cases.

Aim: To compare the clinical findings in children with symptomatic toxoplasmic ocular lesions attributable to infection acquired before or after birth., Methods: Cases were prospectively ascertained for 24 months through national surveillance units and reference laboratories in the British Isles. Age and presenting symptoms, site of lesion and visual impairment in children who were classified as acquiring infection either before or after birth on the basis of clinical and serological findings were compared., Results: 31 children had toxoplasmic retinochoroiditis, 15 had congenital infection and all but three of these presented before the age of 4 years. The remaining 16 children acquired toxoplasmosis postnatally, and 14 of 16 presented after the age of 10 years. A further four children had retinochoroiditis due to other causes. The presence of bilateral, multiple or posterior pole lesions did not distinguish between the two groups, but most children (16/19; 84%) presenting with acute ocular symptoms had postnatally acquired infection. Unilateral visual impairment (Snellen < or =6/18) was equally prevalent in the two groups (4/9 before birth v 7/16 after birth; p>0.5). Only two children had bilateral visual impairment, both of whom had congenital infection. No child was blind., Conclusions: About 50% of children with ocular lesions due to toxoplasmosis had postnatal infection. Retinochoroidal lesions due to infection before and after birth were indistinguishable. The prognosis for bilateral visual function was good, regardless of when infection was acquired.

Background/aim: Competing levels of cytokines, either locally within the eye or systemically, may influence the eventual outcome of ocular inflammation. Polymorphism in the promoter part of the genes controlling cytokine production may result in either higher or lower production of the relevant cytokine to a given stimulus. The authors hypothesised that such polymorphisms may relate to visual outcome in patients with idiopathic intermediate uveitis., Methods: DNA was obtained from 125 patients with idiopathic intermediate uveitis and analysed for the interleukin 10 IL-10-1082G/Alpha and IL-10-819C/T, and interferon gamma IFNgamma 874T/A gene polymorphisms. Associations with disease were calculated by both allelic frequency and haplotype analysis, and associations between ocular disease outcomes and the presence of polymorphisms were identified. A bad outcome was defined as loss of vision <6/12 Snellen in both eyes at 5 years from presentation when the eyes were quiet., Results: An initial screen showed that the 874T allele of the IFNgamma gene was more prevalent in patients than controls (chi2= 7.9; p = 0.004 OR 1.7; 95% CI 1.2 to 2.6 (Pc = 0.02), whereas the IL-10-1082/-819 AT haplotype of the interleukin 10 (IL-10) gene was not. Analysis of disease outcome showed an association between IL-10-1082 AA homozygosity and bad outcome (chi2= 13; p = 0.0003). Moreover, the two cytokine polymorphisms taken together showed that up to 75% of patients with a poor visual outcome had the combined IFNgamma 874TA or TT genotype together with the IL-10-1082AA genotype (chi2= 13.2 p = 0.0008 OR 6.4; 95% CI 1.85 to 23.6 Pc = 0.1)., Conclusion: These results show that disease outcome in intermediate uveitis may be partly determined by a complex interplay between cytokine genes and these results may have implications for future treatment with biological agents that target these cytokines.

Aims: To document loss of central field in patients with scars from toxoplasmic retinochoroiditis close to the disc after resolution of disease., Methods: Patients with a clinical diagnosis of toxoplasmic retinochoroiditis were enrolled from four centres. Automated central visual field testing was performed when their disease had settled and retinal photographs of the lesions were taken. The type of central field defect (whether absolute or relative) and whether it broke out to the periphery were correlated with the size of the retinochoroidal scar and its proximity to the optic nerve head., Results: 69 eyes were enrolled; 16 (26%) were discarded because of poor field performance. Of the 53 remaining eyes, 31 showed absolute defects and 20 relative defects. Scars within one disc diameter of the disc were more likely to be associated with absolute defects breaking out to the periphery., Conclusion: The scarring induced by toxoplasmic retinochoroiditis is associated with considerable field loss when it occurs close to the optic nerve head. Current treatment is unlikely to ameliorate this situation. The degree of visual field loss should be an outcome measure for future trials of the efficacy of treatment trials for the disease.

Aim: To compare the efficacy of two preoperative steroid regimens for cataract surgery in patients with uveitis., Methods: 40 uveitis patients with cataract underwent phacoemulsification and intraocular lens (IOL) implantation. Preoperatively they were randomised into two groups: group 1 (20 patients) received a single dose of intravenous methylprednisolone (15 mg/kg) half an hour before surgery, and group 2 (20 patients) received a 2 week course of oral prednisolone (0.5 mg/kg) which was tapered postoperatively. Preoperatively patients had aqueous flare and cells measured with the Kowa laser flare meter. On days 1, 7, 28, and 90 aqueous flare and cells were measured, and on days 7 and 90 fluorescein angiography was performed to determine the incidence of cystoid macular oedema (CMO)., Results: At all postoperative visits the mean increase in flare was greater for group 1 (intravenous steroid). Patients with posterior synechiae had greater blood-aqueous barrier damage (BAB) postoperatively. There were no statistically significant differences in logMAR visual acuity and incidences of CMO between the two groups at 7 and 90 days., Conclusion: A 2 week course of oral prednisolone, tapered postoperatively, produced a better recovery of the BAB than a single dose of intravenous methylprednisolone and is thus the recommended preoperative regimen.

Behçet's disease (BD) is characterised by recurrent episodes of orogenital aphthae, systemic vasculitis, and systemic and retinal venous thrombosis. An association between HLA-B51 and BD was first identified over 20 years ago, but recently identified gene associations implicate regions both within and without the MHC in the immunological events underlying the lesions in BD. These include allelic variants within the tumour necrosis factor gene region and within the MHC class I chain related gene region, the factor V Leiden mutation, which is associated with retinal vascular occlusion, and alleles of the intercellular adhesion molecule gene. No single causative gene for BD has emerged; the evidence indicates that the underlying immune events in BD are triggered by a microbial antigen and subsequently driven by genetic influences which control leucocyte behaviour and the coagulation pathways. Knowledge of these risk factors may permit a more accurate prognosis for a given patient, and identify new pathways for more targeted intervention than is currently available.

Aim: To report the presence of Behçet's disease with ocular involvement in patients of west African or Afro-Caribbean origin., Methods: Case series of eight patients reporting to a tertiary uveitis service., Results: Eight patients with typical features of the disease are presented. Six of the eight patients were tested and found to be HLA-B51 negative., Conclusion: Behçet's disease has only been reported in sporadic case reports in the indigenous west African and Afro-Caribbean populations, in whom the incidence of HLA B51 is also very low. A series of patients from the London region presented with the typical symptoms and signs of disease, most of whom were also HLA B51 negative. The presence of disease in this population, when absent in the indigenous population, suggests either that ascertainment of disease is poor in the indigenous population or that acquired factors may be important in the aetiology of the disease.

Aims: To measure agreement and estimate sensitivity and specificity of uveitis experts' interpretation of retinal photographs for the diagnosis of toxoplasma retinochoroiditis., Methods: The authors collated 96 retinal photographs from patients presenting with symptomatic posterior uveitis to ophthalmology clinics within a defined geographical area. Five uveitis experts independently ranked each photograph as definite, probable, possible, or not toxoplasma retinochoroiditis. They measured interobserver agreement based on an intraclass correlation coefficient and estimated sensitivity and specificity for each observer using a maximum likelihood model., Results: The intraclass correlation coefficient for all five observers was 0.62 (95% CI: 0.54 to 0.69). Estimates of sensitivity and specificity for individual observers ranged from 71% to 96% and 58% to 100% respectively when appearances were dichotomised as definite or probable toxoplasma retinochoroiditis, versus possible or not., Conclusion: Agreement between uveitis experts on the interpretation of retinal photographs was moderate to good, but the estimates of sensitivity and specificity of their interpretation for the diagnosis of toxoplasma retinochoroiditis were highly variable. Assuming that interpretation of photographs is similar to real time ophthalmoscopy, clinicians need to beware that treatment decisions made on the basis of a single assessment will include patients without toxoplasma retinochoroiditis and will miss patients with the disease.

Aims: To determine whether urinary neopterin:creatinine (UNC) ratios relate to disease activity in idiopathic retinal vasculitis (RV)., Methods: 18 patients with RV were prospectively recruited into a year long longitudinal study. Patients collected first morning urine samples on a weekly basis and on the same day completed a diary which documented their subjective view of RV activity and any concurrent infection. They were examined in clinic on a 6-8 weekly basis and an objective assessment was made of RV disease activity. 14 healthy controls collected urine samples in the same way., Results: UNC ratios were significantly higher in patients than in controls (p=0.004, Mann-Whitney U test). UNC ratios were significantly higher when, according to their diaries, the patients had a subjective flare up of RV (p=0.001, Mann-Whitney U test). Subjective increased RV activity occurred more often when the patients had a concurrent infection (p<0.0001, chi(2) test). There was no significant difference in the UNC ratio between objective clinical relapse and non-relapse of RV. There was moderate agreement between the clinical assessment and patients' subjective impression of RV activity (kappa=0.48)., Conclusions: Higher neopterin levels reflect cell mediated disease that occurs in RV, but UNC ratios are not recommended as a means of monitoring clinical disease activity in RV.

Aims: To determine whether patients with idiopathic retinal vasculitis have altered production of cortisol and dehydroepiandrosterone sulphate (DHEA-S), and whether differences in these variables occur between those who are sensitive (SS) and resistant (SR) to steroids., Methods: 20 patients with retinal vasculitis (off treatment) and 10 control subjects were prospectively recruited. Morning cortisol and DHEA-S levels were measured, and cortisol secretion rates and short synacthen tests (SST) carried out in patients before treatment, when on prednisolone 20 mg/day, and in controls., Results: There were no differences in any variables between patients and controls. For retinal vasculitis patients pretreatment, the SST was lower in SR patients (p=0.02). More of the SR patients had ischaemic retinal vasculitis ( p<0.001)., Conclusions: Cortisol and DHEA-S are not involved in the pathogenesis of retinal vasculitis. SR in retinal vasculitis may be associated with a defective hypothalamic-pituitary-adrenal axis.

Background/aims: Diabetic retinopathy screening guidelines recommend referral to an ophthalmologist if there is exudate within one disc diameter of the fovea. Many of these patients, however, have resolution of small amounts of exudate without treatment. This study aimed to assess whether patients with minimal streak or dot exudates within one disc diameter of the fovea can be monitored in a screening programme without compromising visual acuity., Methods: A retrospective review of records and Polaroid photographs obtained by one screening centre over a 10 year period was performed. Outcomes measured were referral rates, alteration of Snellen visual acuity, and the need for macular photocoagulation treatment., Results: 55 patients (74 eyes) fulfilled entry criteria (37 streak and 37 dot exudates). Mean follow up was 56.1 months (range 12-127 months). Twenty five patients (30 eyes) were referred to an ophthalmologist. 13 eyes (17.6%) required macular photocoagulation treatment. Four eyes (5.4%) lost two or more lines of Snellen acuity over the follow up period (three from macular oedema and one from macular ischaemia). There was no relation between the presence or resolution of minimal exudate and visual loss (p>0.2)., Conclusion: It is appropriate to monitor eyes with streak or dot macular exudates at 6-9 monthly intervals in a screening programme.

Background/aims: Toxoplasma retinochoroiditis (TR) is an important cause of blindness and visual morbidity, affecting young adults. It has been postulated that some of the retinal damage observed in TR is due to antiretinal autoimmune mechanisms., Methods: Humoral antiretinal autoimmunity in TR was investigated by indirect immunofluorescence (IIF) on normal human cadaveric retina and by a human retinal S-antigen ELISA. 36 patients with TR were separated on clinical grounds into those with first recurrence of disease (n = 18) or those with multiple recurrences (n = 18). Patients were also segregated into those with active (n = 28) or quiescent disease (n = 8). Serum from 16 normal controls (six with positive toxoplasma serology and 10 without) with no evidence of eye disease and 12 patients with idiopathic retinal vasculitis (IRV) were also tested., Results: Sera from 34 of the 36 patients (94%) with TR demonstrated photoreceptor layer reactivity by IIF contrasting with six of 16 normal controls (p = < 0.001) and three of 12 IRV patients (p = < 0.001). Titres of antiphotoreceptor antibody were also higher among TR patients than controls. Sera from 27 of the 36 TR patients, 10 of 16 normals, and nine of 12 retinal vasculitis patients possessed anti-human retinal S-antigen antibodies at a titre of 1:400 or more as assessed by ELISA (p = > 0.05). Antiretinal autoantibody as detected by IIF did not run in parallel with S-antigen reactivity., Conclusions: The data indicate that the extent of antiretinal reactivity within TR is not accounted for by anti-S-antigen antibodies alone. This remarkably high prevalence of antiphotoreceptor antibody in TR as opposed to that found in either healthy or disease controls suggest that these antibodies may be co-pathogenic in toxoplasma retinochoroiditis.

Twenty-six patients (39 eyes) with retinal neovascularisation associated with ocular inflammation were identified from the retinal vasculitis clinic at St Thomas's Hospital. Eight patients had sarcoidosis, seven patients Behçet's disease, and 11 had idiopathic retinal vasculitis. Twenty-three patients had required systemic therapy to control the inflammation and 11 patients received laser photocoagulation. Fluorescein angiography showed significant capillary closure in 15 eyes and diffuse microvascular leakage in the remaining 24 eyes. All patients had posterior vitreous detachment. The visual prognosis was good despite vitreous haemorrhage being the presenting feature in 22 eyes, and the new vessels resolved in 70% of cases. However, laser treatment was followed by a significant increase in cystoid macular oedema (p less than 0.01). This retrospective study suggests that medical therapy is the first line of treatment in this group of patients. Photocoagulation should be performed when the eye is quiet and should be reserved for patients with recurrent vitreous haemorrhages and significant capillary closure.

The clinical, angiographic, and histopathological features of experimental posterior uveitis in the black hooded Lister rat are described. This mild form of experimental allergic uveoretinitis (EAU) is induced by sensitisation with retinal S antigen in Freund's complete adjuvant, and the inflammation produced is confined to the posterior segment of the eye. This allows for the first time precise photographic and angiographic documentation of the evolution of clinical signs, because there is minimal clouding of the vitreous by inflammatory cells. Clinically the disease is characterised by the appearance of disc oedema and periphlebitis, followed by focal infiltrates in the deep retinal layers, with eventual atrophy of the pigment epithelium. Histologically, retinal vasculitis is associated with focal mononuclear cell infiltration and necrosis of the photoreceptor layers. This model closely resembles the clinical features of idiopathic retinal vasculitis seen in man.

Experimental posterior uveitis was induced by the inoculation of retinal S-antigen into black hooded Lister rats. The time course of the disease was monitored by electroretinography (ERG), and the ERG changes were correlated with clinical signs and underlying pathological damage. The ERG became supernormal in the third week after inoculation, with some loss of temporal resolution (lowered ERG flicker fusion frequency), though the disease was not clinically manifest at this time and histological examination was normal. The ERG became subnormal after 21 days as clinical signs of disease began to appear. This subnormality was associated with focal photoreceptor necrosis, the degree of destruction being proportional to the reduction in the ERG. The ERG recovered with resolution of disease in most cases, though return to control values was uncommon. We suggest that the initial supernormal ERG reflects an underlying biochemical change mediated by the action of anti retinal S-antigen antibodies.

This paper describes the ophthalmological features of 150 patients with idiopathic retinal vasculitis, 67 of whom had isolated retinal vasculitis (RV) and 83 had RV associated with systemic inflammatory disease (RV + SID). The diagnosis of retinal vasculitis was made by ophthalmoscopy and fluorescein angiography, and patients with any identifiable cause (infection, ischaemia, or malignancy) were excluded from the study. Patients with isolated RV tended to have peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. Those with RV accompanying Behçet's disease often had branch vein retinal occlusions and retinal infiltrates together with macular oedema and diffuse capillary leakage; the retinal infiltrates were pathognomonic for Behçet's disease. In sarcoidosis the retina typically showed features of periphlebitis associated with focal vascular leakage. Patients with uveomeningitis, multiple sclerosis, arthritis, or systemic vasculitis showed diffuse retinal capillary leakage associated with a mixture of the other features. Poor visual function was particularly associated with macular oedema and branch vein retinal occlusion, while the retina appeared to 'withstand' the impact of vascular sheathing, periphlebitis, or neovascularisation alone. Within the limitations of a point prevalence study it was concluded that different patterns of retinal vasculitis occur in different systemic inflammatory diseases, and that in isolated retinal vasculitis there is a particular association between peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. In Part 2 we describe the results of examining the sera of these patients for the presence of antiretinal antibodies and circulating immune complexes.

Fifty-two patients with retinal vasculitis--26 with idiopathic disease and 26 with associated systemic inflammatory disease--were followed up for periods ranging from six months to 12 years. The aim of the study was to determine the relationship between relapse of uveitis, visual outcome, and the occurrence of circulating immune complexes (CIC) and antiretinal antibodies. In a total of 69 relapses, CIC were increased in one-third of patients and antiretinal antibodies in one-half. In those 34 patients who expressed antiretinal antibodies 27 (79%) of the relapses were characterised by antiretinal antibodies in the absence of raised CIC levels (p less than 0.01). These findings support our previous hypothesis that CIC may have a protective role in autoimmune retinal vasculitis and that antiretinal autoimmunity is of pathogenetic importance in relapse. In individual patients the visual outcome was not related to the number of relapses or to the CIC-autoantibody pattern, suggesting the operation of additional features which merit identification.

The results in 90 patients with superior bullous rhegmatogenous detachments operated on over a period of 10 years are presented. In only 70% of cases treated by scleral buckling, with or without drainage of subretinal fluid, was retinal reattachment achieved with a single operation. More recently the treatment of patients by external drainage, air injection into the vitreous cavity, and subsequent buckling has improved the success rate to 96%. It is suggested that the latter method be the surgical treatment of choice in such cases.

This study describes the occurrence of antiretinal antibodies and circulating immune complexes in the sera of a large series of patients with idiopathic retinal vasculitis whose ophthalmological and clinical features are presented in Part 1. Antiretinal antibodies were measured by indirect immunofluorescence and passive haemagglutination, and circulating immune complexes were measured by polyethylene glycol precipitation and Clq binding. The occurrence of antiretinal antibodies and that of circulating immune complexes were analysed in relation to each other, to severity of retinal disease, to the type of associated systemic inflammatory disease, and to the presence of individual features of retinal inflammation. In patients with retinal vasculitis together with systemic inflammatory disease circulating immune complexes were usually accompanied by antiretinal antibodies. However, those patients with antiretinal antibodies in the absence of circulating immune complexes tended to have more severe retinal vasculitis, a feature particularly evident in Behçet's disease (p = 0.028). In patients with isolated retinal vasculitis, severity of disease was associated with antiretinal antibody (p = 0.013), as well as with the occurrence of both antiretinal antibody and circulating immune complexes together (p = 0.010). In the series as a whole there was a tendency for individual features of retinal vasculitis to be associated with antiretinal antibodies unaccompanied by circulating immune complexes; especially in macular oedema (p = 0.028). In isolated retinal vasculitis there was also an additive effect of antiretinal antibodies and circulating immune complexes in relation to disease severity; in contrast, in patients with systemic inflammatory disease, the coexistence of antiretinal antibodies and concluded that both antiretinal autoimmunity and circulating immune complexes may act as immunopathogenetic factors in idiopathic retinal vasculitis but that, in certain patients, circulating immune complex formation seems to protect against the more severe forms of autoimmune retinal inflammatory disease.