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: PurposeTo determine the effectiveness of systemic antibiotic treatment for toxoplasmic retinochoroiditis.: Clinical relevanceToxoplasma retinochoroiditis is a significant cause of visual morbidity. Multiple different antibiotic regimens are used, but controversy about treatment effectiveness remains.: Literature reviewedSearches were conducted of Cochrane Controlled Trials Register, Medline (1966 onward), Embase (1980 onward), Dissertation Abstracts (1861 onward), Lilacs (1982 onward), and Pascal (1984 onward). Pharmaceutical companies were contacted for unpublished data. Any randomized controlled trials that compared antibiotics versus placebo in immunocompetent patients with toxoplasmic retinochoroiditis were retrieved. Primary outcome measures were long-term visual acuity and risk of recurrent retinochoroiditis. Secondary outcomes included duration and severity of acute symptoms, size of the lesion at end of follow-up, and adverse effects of treatment.: ResultsOnly 3 studies (total of 173 participants) were randomized controlled trials and hence met the inclusion criteria (level II). All 3 were methodologically poor, and 2 were carried out more than 35 years ago. None reported the effect on long-term visual outcome. We found no evidence for a beneficial effect on the duration and severity of signs of acute toxoplasmic retinochoroiditis (A,II). There was weak evidence for an effect of long-term treatment for chronic recurrent toxoplasmic retinochoroiditis on lesion recurrence. Treatment was associated with adverse effects.: ConclusionsThere is a lack of evidence to support routine antibiotic treatment for acute toxoplasmic retinochoroiditis. Placebo-controlled randomized trials of antibiotic treatment in patients presenting with acute or chronic toxoplasmic retinochoroiditis arising in any part of the retina are required. [Copyright &y& Elsevier]

Purpose: To describe characteristics of intraocular inflammation in eyes with active ocular toxoplasmosis and to identify relationships between signs of inflammation, complications (including elevated intraocular pressure [IOP]), other disease features, and host characteristics. Design: Multicenter, retrospective, cross-sectional study. Methods: We reviewed the medical records of 210 patients with toxoplasmic retinochoroiditis at seven international sites (North America, South America, and Europe) for information from the first examination at each site during which patients had active retinal lesions. Signs of inflammation included anterior chamber (AC) cells and flare and vitreous humor cells and haze. Retinal lesion characteristics included size (≤1 disc area [DA] or >1 DA) and presence or absence of macular involvement. Results: AC cells and flare were related to vitreous inflammatory reactions (P ≤ .041). One or more signs of increased inflammation were related to the following factors: older patient age, larger retinal lesions, and extramacular location. In 30% of involved eyes, there was evidence of elevated IOP (despite use of glaucoma medications by some patients); other complications were uncommon. IOP of more than 21 mm Hg was associated with both increased AC cells and elevated flare (both P ≤ .001) and with macular involvement (P = .009). Inflammation seemed to be more severe among patients in Brazil than among those at other sites. Conclusions: There is substantial variation between patients in the severity of intraocular inflammation associated with ocular toxoplasmosis, attributable to multiple host- and disease-related factors. Results suggest that disease characteristics also vary in different areas of the world. Elevated IOP at initial examination reflects the severity of inflammation. [Copyright &y& Elsevier]

Purpose: Reliable information is needed to counsel parents of children with congenital toxoplasmosis regarding the long-term risk of visual impairment resulting from ocular toxoplasmosis.Design: Prospective cohort study of children with congenital toxoplasmosis identified by prenatal or neonatal screening.Methods: After three years of age, ophthalmologists reported the site of retinochoroidal lesions and visual acuity and parents reported visual impairment. An ophthalmologist predicted the child's vision based on the last retinal diagram. Selection biases were minimized by prospective enrollment and data collection, high rates of follow-up, and exclusion of referred cases.Results: Two hundred and eighty-one of 284 infected children who underwent ophthalmic examinations were followed up to a median age of 4.8 years. One in six children (49/281; 17%) had at least one retinochoroidal lesion, two-thirds of whom (32/49; 65%) had a lesion at the posterior pole. In children with retinochoroiditis who had visual acuity measured after 3 years of age, 94% (31/33) had normal vision in the best eye (6/12 Snellen or better), as did 91% of those with a posterior pole lesion (21/23). Analyses based on affected eyes showed that 42% (29/69) had a posterior pole lesion, of which just more than half (15/29, 52%) had normal vision, as did 84% (16/19) of eyes with a peripheral lesion alone. Vision predicted by the ophthalmologist was moderately sensitive (59%) but overestimated impairment associated with posterior pole lesions. Of 44 children with information on acuity, four (9%) had bilateral visual impairment worse than 6/12 Snellen.Conclusions: Severe bilateral impairment occurred in 9% of children with congenital toxoplasmic retinochoroiditis. Half the children with a posterior pole lesion and one in six of those with peripheral lesions alone were visually impaired in the affected eye. [ABSTRACT FROM AUTHOR]

: PurposePediatric uveitis is rare and has been reported to cause increased rates of visual loss compared with adult patients. The reasons for this are unclear. Only one study has been population–based, so the effect of referral bias is not known. We examined the pattern of disease in primary and referral centers to establish the unique characteristics of uveitis in children.: DesignCase control study.: MethodsRetrospective, multicenter, observational study of uveitis starting before the age of 20 years. Two hundred forty-nine patients were recruited from three primary and two referral ophthalmic units. Age-related differences in types of uveitis and systemic disease between hospitals were characterized, as were associations with visual loss.: ResultsThe incidence of uveitis in district hospitals at less than 16 years of age was 4.9/100,000: the most frequent diagnosis was idiopathic uveitis (78%). In referral cohorts the most frequent diagnosis was juvenile idiopathic arthritis-associated uveitis (67%). Other systemic diseases were rare. The most frequent type of uveitis at 0 to 7 years of age was chronic anterior uveitis, posterior uveitis in 8- to 15-year-olds, and acute anterior uveitis in 16- to 19-year-olds. Visual loss (any eye < 6/12) occurred in 17% and was not associated with age, sex, or hospital cohort. It was most frequent in posterior uveitis (25%). Treatment variables were independent predictors of visual loss: systemic treatment 2.2 (1.1– 4.6), surgical intervention 8.2 (3.8–17.6).: ConclusionsIdiopathic uveitis was three times more common in district hospitals. Visual loss was similar to adult uveitis in this study. The increased frequency of severe chronic anterior uveitis in children aged 0 to 7 years and posterior uveitis in older children aged 8 to 15 years accounts for the rate of visual loss seen in previous studies. [Copyright &y& Elsevier]

Purpose: To study the effects of intravitreal foscarnet and the clinical differences between varicella zoster virus (VZV) and herpes simplex virus (HSV) induced acute retinal necrosis (ARN). Design: Retrospective comparative case series. Participants: Eighty-one eyes of 74 patients. Methods: A retrospective case note analysis was performed in 2 tertiary referral centers. Main Outcome Measures: Presenting and final visual acuity, and progression to retinal detachment. Results: Thirty-three eyes had HSV-ARN and 48 had VZV-ARN. The average age for HSV-ARN was 34 years and 51 for VZV-ARN (P<0.001). Visual acuity on presentation was similar (P = 0.48), but a larger proportion had better vision (≥20/60) in the HSV-ARN group (52%) than the VZV-ARN group (35%). A greater proportion of eyes with poor vision (≤20/200) was found at the 12-month follow-up in the VZV-ARN group (60%) compared with the HSV-ARN group (35%). A greater degree of visual loss in the VZV-ARN group (0.4 logarithm of the minimum angle of resolution [logMAR]) compared with the HSV-ARN group (0.04 logMAR) was detected (P = 0.016). Retinal detachment was 2.5-fold more common in VZV-ARN (62%) compared with HSV-ARN (24%). When comparing eyes treated with (n = 56) and without (n = 25) intravitreal foscarnet, there was a 40% lower rate in retinal detachment (53.6% vs 75.0%) for VZV-ARN (P = 0.23). The numbers with HSV-ARN were too small for analysis. Conclusions: The results support the difference of outcome in HSV-ARN and VZV-ARN. Therefore, viral identification serves as a key to predicting outcome in these patients. Intravitreal foscarnet seems to be a useful adjunct for the treatment of ARN in that it reduced rate of retinal detachment. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Abstract: Behçet’s disease (BD) is a multisystem inflammatory disease characterized by recurrent orogenital ulceration, ocular inflammation, and skin lesions. The etiology of the disease is currently unknown but evidence suggests that there is a strong genetic component mediating the chronicity of the disorder. We have examined the association between polymorphisms at position −1082, and −819 in the promoter region of the gene encoding IL-10 in patients with Behçet’s disease from two distinct patient populations. The IL-10 −1082AA genotype was weakly associated with BD when all patients were analyzed as a group (pc = 0.04, OR 1.4, 95% CI 1.1–1.9), but not in the UK or Middle Eastern (ME) cohorts of patients alone compared to local controls. An association with IL-10 −819T was evident in all BD patients, (pc = 0.02, OR 1.5, 95% CI 1.1–2.0), and this was because of an association in the UK but not ME patients (pc = 0.0004, OR 2.1, 95% CI 1.4–3.3). The −1082A/−819T haplotype, which is linked to low production of this cytokine, was not significantly associated with Behçet’s disease. This link between BD, a chronic, relapsing, autoinflammatory condition, and a genotype associated with low IL-10 production provides evidence that abnormalities in the genetic control of cytokine levels may be relevant in influencing the immune response in Behçet’s disease in some patient groups. [Copyright &y& Elsevier]

Retinal vasculitis (RV) is characterised pathologically by migration of leucocytes across the blood–retinal barrier leading to oedema and photoreceptor cell dysfunction. Chemokines are a family of small molecules involved in leucocyte migration. In this study, levels of chemokines were measured in serum from patients with RV and correlated with disease activity and drug treatment. Serum samples (n=100; 25 active, 75 inactive) were obtained from 50 patients with RV, and levels of the chemokines MIP-1α, macrophage inflammatory protein-1β (MIP-1β) and monocyte chemoattractant protein-1 (MCP-1) were measured by ELISA. For longitudinal analysis levels of the same chemokines were measured in six consecutive serum samples from 10 of the above patients. Chemokine levels were correlated with disease activity and current drug treatment for each sample. Sera from 20 healthy individuals were used as control samples. Serum levels of MIP-1β were significantly raised in patients with RV, whether active or not, compared to healthy controls (P=0.04). Levels of MIP-1β and MCP-1 correlated with disease activity in some patients and with prednisolone levels in patients on this treatment alone. MIP-1α levels were not detectable in all samples but were present in significantly more samples from patients with active or inactive RV compared with healthy controls. Serum levels of the chemokines MIP-1β and MIP-1α, but not MCP-1 were raised in patients with retinal vasculitis. Longitudinal analysis suggested that MIP-1β and MCP-1 levels were controlled by drug treatment, particularly prednisolone. These data demonstrate that chemokines are involved in the pathogenesis of RV and may act as novel therapeutic targets. [Copyright &y& Elsevier]

Endogenous bacterial endophthalmitis is a rare but serious condition that occurs when bacteria cross the blood–ocular barrier and multiply within the eye. We provide an overview of endogenous bacterial endophthalmitis by reviewing 267 reported cases and integrating this with our experience of an additional 19 cases. The majority of patients with endogenous bacterial endophthalmitis are initially misdiagnosed and many have an underlying disease known to predispose to infection. This condition is often previously undiagnosed. Blood cultures are the most frequent means of establishing the diagnosis. The most common Gram positive organisms are Staphylococcus aureus, group B streptococci, Streptococcus pneumoniae,and Listeria monocytogenes.The most common Gram negative organisms are Klebsiella spp., Escherichia coli, Pseudomonas aeruginosa, and Neisseria meningitidis. Gram negative organisms are responsible for the majority of cases reported from East Asian hospitals, but Gram positive organisms are more common in North America and Europe. The visual outcome is poor with most cases leading to blindness in the affected eye. Many patients have extraocular foci of infection, with an associated mortality rate of 5%. The outcome of endogenous bacterial endophthalmitis has not improved in 55 years and clinicians need to have a high level of awareness of this commonly misdiagnosed condition. [Copyright &y& Elsevier]