Risks of relapse in patients with acute anterior uveitis.

AIM: To quantify the rate of recurrence of acute anterior uveitis (AAU), and evaluate the influence of associated risk factors. METHODS: We retrospectively reviewed the case notes of 185 patients with acute anterior uveitis, from their time of presentation to August 2001. The time to the first three recurrences of AAU from the onset of the disease was recorded, as well as the site of recurrence. Information regarding risk factors (for example (HLA-B27) status, spondyloarthropathy (SpA), family history of AAU/SpA and history of non-specific joint pain) were also collected. RESULTS: Patients were followed up until their third relapse, or up to the censoring date (August 2001) if less than three relapses had occurred. The median length of follow-up was 35 months. One hundred and twenty-two patients (66%) developed at least one relapse and 67 (36%) had three or more relapses. Kaplan-Meier estimate of median interval between disease onset and the first relapse was 24 months 95% CI (16 to 34) and between the first and second relapse was 14 months 95% CI (9 to 22), and was 15 months 95% CI (10 to 25) months between the second and third relapse. Using Cox regression only the number of previous relapses was significantly associated with the risk of AAU recurrence. There was no significant association between other reported risk factors and the risk of relapse, and neither did any risk factor significantly modify the association between previous relapses and AAU recurrence (p>0.066 for all interactions). There was a borderline significant difference in survival according to the laterality pattern of recurrences (ipsilateral, alternate, or bilateral) with a slightly greater than expected number of events in those with bilateral recurrence (p = 0.048). CONCLUSION: Patients with previous relapse(s) of AAU have a greater risk of AAU recurrence compared to those at disease onset but the risk of recurrence appears not to increase in a dose-response manner with increasing number of previous relapses. Demographic and extraocular features do not appear to influence the rate, or risk of recurrence of AAU.

Are cytokine gene polymorphisms associated with outcome in patients with idiopathic intermediate uveitis in the United Kingdom?

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.

The risk of complications of uveitis in a district hospital cohort.

AIMS: To establish the frequency and risk factors for visual loss in a primary referral cohort of hospital patients with uveitis. METHODS: 561 consecutive uveitis patients attending three district hospitals were recruited and the acuity at the end of the study period recorded. A retrospective case-control study of risk factors for visual loss (permanent loss of acuity <6/9) was performed. Risk factors examined included type of uveitis, age at onset of uveitis, race, type of systemic inflammatory disease, length of follow up, and treatment variables. RESULTS: Visual loss of at least 6/12 in one eye was found in 111 patients (19.9%). Only four patients (0.7%) suffered severe bilateral visual loss (6/36 or less). Visual loss was associated with age at onset >60 years (odds ratio 3.9, 95% confidence interval (CI) 2.2 to 7.0, long follow up 2.0 (1.2 to 3.3) and a history of cataract surgery 3.9 (2.1 to 7.2). It was less likely in patients with acute anterior uveitis 0.2 (0.1 to 0.3). CONCLUSION: The frequency of visual loss associated with uveitis in a district hospital cohort is less than that found in referral centres and levels of legal blindness are low. Although acute anterior uveitis has a low frequency of visual loss it contributes significantly to the total burden. The ocular co-morbidity of the elderly may contribute to the increased visual loss of late onset uveitis.

Blindness following a diabetic foot infection: a variant to the 'eye-foot syndrome'?

AIMS: The 'eye-foot syndrome' was initially described by Walsh et al. to highlight the important association of foot lesions in patients with diabetic retinopathy. We present a case of a 58-year-old patient with Type 2 diabetes mellitus who developed blindness following endogenous staphylococcal endophthalmitis from an infected foot ulcer. RESULTS: Our case describes the link between the eye and the foot but is somewhat different to the association as described by Walsh et al. Endogenous endophthalmitis is rare with diabetic patients being especially at risk, and we report the first case of endogenous staphylococcal endophthalmitis related to a diabetic foot lesion. CONCLUSIONS: Our case illustrates several important issues in the management of diabetic patients admitted to hospital with infection; the need to thoroughly examine the feet to ascertain any foot lesions and any underlying peripheral vascular disease or peripheral neuropathy, to treat aggressively any infected foot lesions to prevent serious complications of septicaemia and to consider rare conditions like endogenous endophthalmitis in any diabetic patient presenting with acute visual impairment and septicaemia.

The ocular and systemic prognosis of patients presenting with sarcoid uveitis.

PURPOSE: To describe the visual and systemic outcomes in patients presenting with sarcoid uveitis. METHODS: Seventy-five patients with definite or presumed sarcoid uveitis were followed up for a median of 4 years. The patients came from a primary ophthalmic referral centre and a specialist uveitis centre. The prognostic value of demographic and clinical features at the onset of disease were studied. Baseline and outcome variables were analysed by survival analysis. RESULTS: After 10 years, 54% of patients retained normal visual acuity and 4.6% had lost vision to less than 6/36 in both eyes. Fifty-one per cent required oral steroids for uveitis and a further 11% needed additional immunosuppressants. Twenty-one per cent of patients had undergone a surgical procedure. At the onset of uveitis the lung was the most common organ involved (35%). After 10 years follow-up disease spread to other organs in 13 patients (17%); in 8 of 13 patients this was the central nervous system. The only outcome associated with baseline variables was bilateral visual loss, which was more likely in those over 40 years at presentation (p = 0.004). CONCLUSIONS: The ocular prognosis of sarcoid uveitis is unrelated to the extent of disease at onset. Patients with extraocular disease fared no differently from those with isolated ocular disease. Patients with sarcoid uveitis are at risk of neurological involvement for at least 15 years.

Antiendothelial cell antibodies (AECA) in patients with uveoretinitis.

AECAs have been found in 26% of patients with uveoretinitis in studies arising from three different laboratories, and their presence cannot simply be explained by coexisting extraocular disease. There is little correlation with ocular disease activity or other markers of systemic inflammation and vascular damage that can be found in this group of patients, but this lack of correlation has also been found in studies of more widespread inflammatory diseases. The changes found in the peripheral blood of patients with uveoretinitis are the result of a mixture of acute and chronic inflammation, reactions to coexisting tissue damage, as well as predisposing abnormalities of inflammation and hemostasis. Even patients with similar clinical appearances are unlikely to be pathologically homogeneous, and the reasons for the presence of AECA are likely to be various. Some patients may demonstrate a heightened antibody response to endothelium damaged by unknown mechanisms, whereas others may develop cytotoxic AECA as an integral part of the inflammatory process. The majority of serum samples with AECA demonstrated antibody-dependent cell-mediated cytotoxicity, but this potentially pathogenetic mechanism was only demonstrable in a minority of patients. It is unlikely that IgM AECA or complement-mediated cytotoxicity is a relevant mechanism of vascular damage in this group of patients. A subgroup of patients may be genetically predisposed to produce excess autoantibodies in response to tissue damage caused by a wide variety of insults. Sawyerr et al.(36) has suggested that increased serum levels of agalactosyl IgG may account for some of the AECA binding found in chronic inflammatory diseases: we have also found changes in agalactosyl IgG in patients with active isolated uveoretinitis (40), but levels did not correlate with levels of IgG AECA (unpublished results). Further longitudinal studies will be necessary on each subgroup of patients in order to determine the true clinical significance of these findings.

Acute angle closure glaucoma: relative failure of YAG iridotomy in affected eyes and factors influencing outcome.

The treatment of acute angle closure glaucoma has been influenced by the development of the YAG laser and its ability to perform iridotomies as an outpatient procedure. In this retrospective study the results of YAG iridotomy were compared with surgical peripheral iridectomy. When compared with surgical peripheral iridectomy patients, YAG iridotomy patients were at greater risk of proceeding to further surgery, with this risk being significantly associated with increasing duration of attack. The authors suggest that in selected cases, surgical iridectomy should be given consideration as a primary procedure.

The efficacy of systemic corticosteroids in sight-threatening retinal vasculitis.

This study was undertaken to assess the efficacy of a standard regime of high-dose systemic oral corticosteroids in the management of retinal vasculitis. The study was performed because the single most common reason for referral to our specialist clinic is the apparent failure of patients to respond to a course of systemic steroids, which in most cases appeared to be due to an inadequate initial dose. A retrospective study of 29 patients (30 treatment episodes) with sight-threatening retinal vasculitis managed initially with high-dose systemic steroids was evaluated 1 year after treatment. Patients included in the study all started treatment with > or = 1 mg/kg prednisolone and remained on a high steroid dose (> or = 40 mg prednisolone) for at least 5 weeks. No patient was on any other immunosuppressive agent at the start of the study. Therapeutic success for this regime, as judged by improvement in visual acuity, was 60%, improving to 77% with addition of other immunosuppressive agents. Eight patients required additional immunosuppressives. Although documented side-effects of steroids were common (50% of cases managed on steroids alone), in only 5 patients were they therapeutically important. Twelve of the 22 patients managed on high-dose steroids alone were off treatment at 12 months. There was no correlation at any stage between visual acuity, activity index or relapses and the final visual outcome at 12 months. Seven cases had a poor visual outcome and the causes for this included relapse in the twelfth month of follow-up, persistent cystoid macular oedema and lens opacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease relapse in idiopathic uveoretinitis.

This study reports the results of a point prevalence study of markers of endothelial dysfunction in the serum of patients with idiopathic uveoretinitis. sICAM-1, soluble endothelial leucocyte adhesion molecule (sELAM), anti-endothelial cell antibodies (AECA) and von Willebrand factor (vWF) levels were measured in 32 patients with isolated idiopathic uveoretinitis and seven with uveitis in association with systemic disease, using commercial and in-house ELISAs. Raised levels of AECA were found in 31% of patients with isolated uveitis, vWF in 28%, sELAM in 15.6% and sICAM-1 in 31%. Further analysis revealed that raised sICAM-1 levels were closely associated with recent relapse of disease (P = 0.00003). Patients with accompanying systemic disease were found to have a similar prevalence of these serum abnormalities to those with isolated ocular disease. In conclusion, vascular endothelial dysfunction may contribute to pathogenesis in uveoretinitis, and in particular sICAM-1 may prove a marker of disease relapse in this condition.

Experimental autoimmune uveoretinitis in the RCS rat: the influence of photoreceptor degeneration on disease expression.

S-antigen induced experimental autoimmune uveoretinitis (EAU) was produced in the Royal College of Surgeons (RCS) strain of rat which develops a photoreceptor dystrophy within 2 weeks of birth. Animals were sensitised at 60, 90, and 105 days of age: all animals developed disease, but onset was significantly delayed in older (105 day) animals compared with those aged 60 days at sensitisation (p 0.003). Disease was characterised by the early development of complete serous retinal detachment which resolved in a few days: the prevalence of retinal detachment was increased to 80% in dystrophic animals compared with 10% in the congenic, non-dystrophic controls (p < 0.001). Anterior uveitis was seen in 17/30 control strain eyes, but in none of 30 dystrophic eyes (p < 0.001). Genetically determined photoreceptor and retinal pigment epithelium dysfunction in the RCS rat, which may involve the local accumulation of altered S-antigen, predisposes the dystrophic strain to display an acute retinal detachment in the early stages of EAU. This phenomenon illustrates how biochemical dysfunction of a target organ may influence susceptibility, form, and severity of an experimental autoimmune disease.

Anti-endothelial cell antibodies in retinal vasculitis.

Auto-antibodies to endothelial cells are found in a variety of vasculitic disorders including two diseases associated with retinal vasculitis: Behcet's disease and multiple sclerosis. In this study we have examined the prevalence of anti-endothelial cell antibodies [AECA] in 15 patients with retinal vasculitis [RV] associated with Behcet's disease, multiple sclerosis or sarcoidosis and 20 patients with idiopathic retinal vasculitis. 47% of patients with RV associated with systemic disease and 35% of patients with idiopathic RV had AECA, compared to 1% of 70 normal controls. The mean levels of AECA were similar in both groups of patients, and comparable to levels found in other systemic vasculitides.