Intermediate uveitis in a child with phosphatase and tensin homolog gene mutation and Bannayan-Riley-Ruvalcaba syndrome.

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a congenital disorder characterised by macrocephaly, multiple hamartomas, lipomas, and pigmented macules of the glans penis. Intermediate uveitis is characterised by chronic inflammatory cells aggregates on the pars plana (snowbanks) and within the vitreous cavity (snowballs). We describe what we believe to be the first case of intermediate uveitis associated with BRRS. Early examination under anaesthesia should be considered in the management of young children diagnosed with this syndrome in order to provide appropriate ocular evaluation, treatment and follow-up. Further research is needed to establish a better understanding of the ophthalmic manifestations of this syndrome.

Biological Characterization and Inhibition of Streptococcus pyogenes ZUH1 Causing Chronic Cystitis by Crocus sativus Methanol Extract, Bee Honey Alone or in Combination with Antibiotics: An In Vitro Study.

Streptococcus pyogenes (S. pyogenes) ZUH1 was isolated and characterized using morphological, cultural and biochemical methods. The results showed that the marker genes (namely spyCEP, ssa, sic, sdaB and speG) indicating group A streptococci (GAS) were detected in the S. pyogenes genome. The results showed that the S. pyogenes strain was inhibited by Crocus sativus methanol extract (CSME), bee honey (BH) and catfish glycoprotein (CFG). The inhibitory activity of these natural agents were compared with standard antibiotics such as Ceftazidime (30 µg/mL), Cefoperazone (75 µg/mL), Cefoxitin (30 µg/mL) and Imipenem (10 µg/mL). There was a synergistic effect between certain antibiotics and CSME. GC-MS and IR analysis of CSME showed different cyclic ketones, aldehydes, esters, alcohols and acids. The main compounds were tetradecanoic acid, safranal and isophorone. Transmission electron microscopy (TEM) images of S. pyogenes cells treated with CSME showed signs of an irregular wrinkled outer surface, fragmentation, adhesion and aggregation of damaged bacterial cells or cellular debris. The marker genes (spyCEP, ssa, sic, sdaB and speG) could be used as a rapid diagnostic tool for GAS. CSME, BH and CFG showed distinctive anti-streptococcal activity either alone or in combinations with antibiotics; their action on S. pyogenes cells was studied by TEM. There was a synergistic effect between antibiotics and Crocus sativus, bee honey, and glycoprotein against S. pyogenes ZUH1. The action of natural agents on the pathogenic cells was shown using TEM.

Evaluation of vascular changes in intermediate uveitis and retinal vasculitis using swept-source wide-field optical coherence tomography angiography.

PURPOSE: To evaluate vascular changes in patients with intermediate uveitis with or without retinal vasculitis using swept-source wide-field optical coherence tomography angiography (OCTA). METHODS: This is a prospective cross-sectional study. Consecutive patients with intermediate uveitis were evaluated using wide-field OCTA. Wide-field OCTA and en-face OCT images were analysed for the presence of capillary non-perfusion and reduced perfusion, disruption of ellipsoid zone, and abnormalities on en-face wide-field retinal thickness maps, respectively, and compared with fluorescein angiography (FA) findings in a subcohort. RESULTS: 164 eyes of 88 patients with intermediate uveitis were included. Areas of capillary non-perfusion and reduced perfusion were more frequently observed in the choroidal OCTA slab (33.3% and 49.4%), choriocapillaris (CC; 31.4% and 48%) and deep capillary plexus (DCP; 9.6% and 34.6%) than in the superficial capillary plexus (SCP; 5% and 26.3%), respectively. Intermediate uveitis with vasculitis presented more frequently with non-perfusion and hypoperfusion in the DCP (p=0.003 and p=0.05, respectively) and SCP (p=0.007 and p=0.005, respectively) than intermediate uveitis without vasculitis. Peripheral capillary leakage on FA correlated with the presence of perivascular, macular and generalised thickening on en-face wide-field thickness maps (p=0.007). Ischaemia on FA was significantly associated with non-perfusion on wide-field OCTA in SCP and DCP (p=0.019 and p=0.027, respectively). CONCLUSION: Changes in the choroid, CC and DCP are more frequently found than in the SCP on wide-field OCTA in intermediate uveitis. While wide-field OCTA is a reliable tool to detect capillary non-perfusion in intermediate uveitis, it was not helpful in determining disease activity. TRIAL REGISTRATION NUMBER: NCT02811536.

Dexamethasone implants in paediatric patients with noninfectious intermediate or posterior uveitis: first prospective exploratory case series.

BACKGROUND: To evaluate the efficacy and safety of dexamethasone (DEX) implants in paediatric patients with noninfectious intermediate or posterior uveitis. METHODS: Prospective single center exploratory case series. Children and adolescents, 6 to 17 years old, with a vitreous haze score of ≥1.5+ or cystoid macular edema (CME) of >300 µm were enrolled. Vitreous haze score at month 2 was chosen as primary endpoint. Best corrected visual acuity (BCVA), central retinal thickness (CRT) and concomitant medication at month 6 were defined as secondary endpoints. Intraocular pressure (IOP) and cataract formation were determined as safety endpoints. RESULTS: Three out of 6 eligible patients participated in the case series. At month 2, vitreous haze was reduced from a score of 1.5+ to 0.5+ and 0 and BCVA improved by ≥3 lines, ≥4 lines and ≥2 lines of Early Treatment of Diabetic Retinopathy (ETDRS)-letters, respectively. Visual acuity gain was accompanied by a CRT reduction of -186 µm and -83 µm in the first and third patient, in whom CME was the indication for DEX implantation. A reduction of concomitant medication was achieved in 1 patient. IOP increase was seen in all 3 patients, but could be treated sufficiently with primarily IOP lowering medications and without need for glaucoma surgery. Cataract progression did not occur. CONCLUSIONS: DEX implants led to an improvement in all endpoints, especially BCVA. This study confirms that IOP rises may also occur in the paediatric population and should be monitored and treated appropriately. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials (EudraCT)- nr: 2013-000541-39.

[The effectiveness of Uroprofit in women with chronic cystitis].

AIM: To evaluate the effectiveness of the biologically active dietary supplement Uroprofit in the comprehensive management of exacerbations of chronic recurrent cystitis in women. MATERIALS AND METHODS: We examined 40 women with chronic cystitis aged 20-68 years. All patients were allocated to receive either monotherapy with fosfomycin (Monural) (control group, n=20) or combination therapy with fosfomycin and biologically active dietary supplement Uroprofit (study group, n=20). The results were evaluated at 1 and 2 months after treatment initiation. All patients before and after treatment underwent diagnostic work-up including standard laboratory tests, uroflowmetry, cystometry, cystoscopy, and laser Doppler flowmetry to assess microcirculation. RESULTS: The patients of the study group showed faster improvement in clinical manifestations of the disease, laboratory indicators, the dynamics of the endoscopic pattern and had positive changes in the bladder mucosa microcirculation. DISCUSSION: Uroprofit produces an antimicrobial and anti-inflammatory effect, helps normalize urodynamics of the lower urinary tract, improves microcirculation in the bladder wall and reduces the risk of repeated relapses of chronic cystitis. CONCLUSION: Uroprofit could be recommended as a component of the comprehensive management of exacerbations of chronic recurrent cystitis in women and as the means of preventing relapses in disease-free periods.

INFLIXIMAB THERAPY IN PATIENTS WITH NONINFECTIOUS INTERMEDIATE UVEITIS RESISTANT TO CONVENTIONAL IMMUNOMODULATORY THERAPY.

PURPOSE: To examine the efficacy and safety of infliximab therapy in the treatment for noninfectious intermediate uveitis resistant to conventional immunomodulatory therapy. METHODS: Forty-four eyes of 23 patients with resistant noninfectious intermediate uveitis who were treated with infliximab infusions for a minimum period of 3 months were included. Demographic data, clinical data, and fluorescein angiography and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution database between August 2005 and February 2014. Clinical response, improvement in ancillary test findings, and major side effects were evaluated. RESULTS: Nineteen patients (82.6%) achieved remission. The mean duration of treatment to induce remission was 3.99 ± 3.06 months (range, 2-14.7). Cystoid macular edema was the only complication observed during the course of the treatment in 1 eye (2.27%). One patient (4.3%) developed major side effects. None of the patients developed central or peripheral demyelinating neuropathies or multiple sclerosis. At 6 months after remission, logarithm of the minimum angle of resolution visual acuity (P = 0.006) and central macular thickness (P = 0.03) showed significant improvement in patients who achieved remission. CONCLUSION: A significant number of patients achieved remission on infliximab therapy. The incidence of major side effects in our cohort was low.

A cross-sectional study of submacular thickening in intermediate uveitis and determination of treatment threshold.

BACKGROUND: The aim of this work is to refine understanding of anatomical and functional alterations in eyes with Intermediate Uveitis (IU), their natural history in mild cases not necessitating treatment and their response to treatment in severely affected eyes with macular edema. METHODS: 61 consecutive patients with IU presenting over a 6-year period were prospectively recruited into the study. Two subgroups of patients with IU were identified on the basis of the need or not for systemic cortico-steroid treatment. A group of healthy volunteers was identified for determining normal average central foveal thickness (CFT) values. Statistical comparisons were sought between patient sub-groups and with the group of normal volunteers for CFT and Best Corrected Visual Acuity (BCVA) at baseline and after 6 months. In a post hoc analysis, a cut-off value of CFT for systemic treatment initiation in IU was statistically identified and its sensitivity and specificity determined. RESULTS: A statistically significant difference in mean CFT at baseline was observed between patients under systemic treatment and untreated patients (p = 0.0005) as well as between untreated patients and healthy volunteers. (p < 0.001) After six months difference in CFT between the two patients subgroups was no longer significant (p = 0.699). BCVA was worse for patients under systemic treatment. No statistically significant difference could be identified between the subgroup of untreated patients and the group of healthy volunteers either at baseline or after 6 months. Correlation between LogMAR visual acuity and central retinal thickness at baseline was strong (r = 0.7436, p < 0.0001, Pearson's correlation coefficient). The cut-off value of CFT for initiating systemic treatment was determined at 215.5 µm in a post hoc analysis (sensitivity 62.5 %, specificity 96.4 %). CONCLUSIONS: Subclinical retinal thickening of mildly inflamed eyes with IU can occur though bearing no functional clinical significance and spontaneously resolving within 6 months. A cut-off CFT value for treatment of macular edema in IU, in the presence of other relevant morphological features on Optical Coherence Tomography, seems to emerge from post hoc analysis of collected data demonstrating strong specificity and moderate sensitivity.

Analysis of a Functional IL-6 Gene Polymorphism in HLAB27 Associated and Intermediate Uveitis Gives New Insight in Disease Pathogenesis and Commonality with Other Autoimmune Diseases.

PURPOSE: Interleukin 6 (IL-6) plays a crucial role in both adaptive and innate immunity. The rs1800795 gene polymorphism of IL-6 is associated with various autoimmune diseases, like multiple sclerosis. METHODS: 134 patients with HLAB27 positive iridocyclitis, 84 patients with intermediate uveitis, 132 controls, and 65 HLAB27 positive controls were recruited for the present case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction. RESULTS: The frequency of carriers of the minor allele for rs1800795 was significantly higher in patients with intermediate uveitis compared to controls (p = 0.04; OR: 1.46; CI: 1.02-2.11). Frequencies of the minor allele for rs1800795 did not differ significantly in patients with HLAB27 associated uveitis when compared to controls (p > 0.05). CONCLUSION: These findings further deepen our understanding of the commonality between multiple sclerosis and intermediate uveitis. Given the functionality of the investigated polymorphism, new pathophysiological insights are gained that help to evaluate possible therapeutic targets.

Associations of Independent IL2RA Gene Variants with Intermediate Uveitis.

PURPOSE: The genetic background for the concomitance of uveitis and other autoimmune diseases remains elusive. Here the role of two IL2RA gene variants (rs11594656 and rs12722495) was investigated in intermediate uveitis and HLAB27 acute anterior uveitis. MATERIALS AND METHODS: One hundred fifty-nine patients with HLAB27 acute anterior uveitis, 85 patients with intermediate uveitis, 138 HLAB27 negative controls and 100 HLAB27 positive controls were recruited for this case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction. RESULTS: The frequencies of carriers of the minor allele at rs11594656 and rs12722495 were significantly different in patients with intermediate uveitis compared to HLAB27 positive and negative controls combined (p<0.05). For rs12722495 the minor G allele was protective (genotypic OR: 0.29 [0.12-0.69]), and for rs11594656 the minor A allele conferred risk (genotypic OR: 1.59 [1.09-2.32]). No significant differences in genotype distribution were found between patients with HLAB27 acute anterior uveitis and HLAB27 positive or negative control subjects. CONCLUSIONS: We found rs11594656 and rs12722495 to be associated with intermediate uveitis but not with HLAB27 acute anterior uveitis. The genetic heterogeneity found at the IL2RA locus could help explain patterns of concomitance with other autoimmune diseases.

Intraocular and serum cytokine profiles in patients with intermediate uveitis.

PURPOSE: To study the intraocular and serum cytokine and chemokine profile in patients with intermediate uveitis (IU) at various stages of inflammatory activity. METHODS: Institutional, prospective association study. Paired aqueous humor (AqH) and serum samples were collected from 36 consecutive IU patients and 10 controls. The concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF)-α, CC--chemokine ligand 5/regulated upon activation normal T-cell expressed, and secreted (CCL5/RANTES), CC--chemokine ligand 3/macrophage inflammatory protein 1alpha (CCL3/MIP-1α), CCL4/MIP-1ß, and CC--chemokine ligand 2/monocyte chemotactic protein--1 (CCL2/MCP-1) were measured in both AqH and serum by multiplex immunoassay. Main outcome measures were serum and intraocular levels of the analyzed cyto- and chemokines. RESULTS: Patients with IU had higher serum levels of TNF-α than non-uveitic controls (p<0.0001), whereas their AqH TNF-α levels did not show a difference (p=0.323). IU patients had higher intraocular levels of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and CCL2/MCP-1 than the controls (p=0.020, 0.001, <0.0001, 0.005, 0.003, and 0.003, respectively). Active stages of IU were characterized by higher levels of IL-6, IL-8, CCL5/RANTES and CCL2/MCP-1 (p=0.003, <0.0001, 0.033, and 0.033, respectively). Higher levels of IL-6 and IL-8 were found in IU patients with cystoid macular edema (CME) compared to non-CME IU patients (p=0.026 and 0.012, respectively). Significant positive correlations between various observed mediators were present in the AqH of IU patients only. CONCLUSIONS: Significantly elevated concentrations of multiple intraocular cytokines were found in IU patients, especially IL-6 and IL-8 in those with CME and active disease. In serum elevated TNF-α levels were observed in IU patients. Our findings improve the understanding of the pathogenesis of IU and contribute to the identification of factors which may contribute to the activity of IU.

Rubella-related intermediate uveitis in pregnancy--a rare presentation.

PURPOSE: To report a rare case of intermediate uveitis following rubella infection in pregnancy. DESIGN: Case report. METHODS: A 35-year-old pregnant woman, at 24 weeks of gestation, presented with sudden floaters and blurring of vision of the left eye. Ocular examination revealed vitritis 1-2+ with no retinal involvement. Rubella serology showed a high IgG titr eof 268 IU/mL. Treatment with periocular steroids (posterior subtenon triamcinalone) injection into the left eye was initiated. RESULTS: Improvement of vision with resolution of the vitritis was seen after 3 weeks. Repeat rubella IgG titer dropped to 20.4 IU/mL. Obstetrics evaluation of the fetus remained normal. CONCLUSIONS: Rubella-related intermediate uveitis is a very rare presentation during pregnancy. It is worthwhile to investigate for rubella infections in pregnant patients complaining of recent onset of visual disturbances. This type of intermediate uveitis can be treated successfully with minimal ocular complications if recognized early.

Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective, randomized pilot study.

PURPOSE: Comparison of pars plana vitrectomy (PPV) with immunomodulatory therapy (IMT) for patients with intermediate uveitis (IU). METHODS: A prospective, randomized pilot study was performed on patients with recalcitrant IU associated with degradation of visual acuity (VA) despite standard treatment. Outcome measures (VA, intraocular pressure, anterior chamber and vitreous cellular infiltrate) were collected. RESULTS: Sixteen patients (18 eyes) were randomized to the PPV IMT group. Nine of 11 eyes (82%) treated with PPV showed resolution of inflammation at follow-up, at 5.93 years. Four of 7 eyes (57%) given IMT had persistent inflammation requiring subsequent PPV. PPV patients showed greater improvement in Snellen line, IOP, and vitreous cell reduction. Three PPV patients had cystoid macular edema (CME) initially; all resolved postoperatively. CME improved in 2 of 3 eyes using IMT. CONCLUSIONS: A higher percentage of patients treated with PPV had improvement of uveitis compared to those given IMT. A multicentered clinical trial is needed to confirm and statistically validate these conclusions.

Nonprogressive tractional inferior retinal elevation in intermediate uveitis.

PURPOSE: To describe inferior peripheral retinal elevations associated with intermediate uveitis. METHODS: Retrospective review. RESULTS: Eleven eyes of 7 patients developed inferior retinal elevation secondary to intermediate uveitis. Six eyes (54.6%) were believed to have tractional retinoschisis, 2 (18.2%) had tractional retinal detachment, and the remaining 3 (27.3%) had flat retinal elevation of indeterminate type. In 10 eyes there was no evidence of progression during a mean 4-year follow-up. One eye developed extended tractional elevation with macular pucker and failed to respond to surgery. At the most recent visit, visual acuity ranged from 6/5 to NPL with a median of 6/12. CONCLUSION: Intermediate uveitis may cause inferior peripheral retinal elevation. The authors propose that preretinal and pars plana gliosis resulting from chronic pars planitis exerts traction on peripheral retina, causing elevation, but infer that such elevation removes traction and is self-limiting. Surgery should be reserved only for macula threatening lesions.

[Cellular characteristics of cultured non-pigmented ciliary epithelium from adult pigs].

PURPOSE: To compare the reactive proliferation of non-pigmented ciliary epithelial cells in patients with cyclitis, or after cyclophotocoagulation and cyclocryocoagulation, and the cultured non-pigmented ciliary epithelial cells from adult pigs. METHODS: Porcine ciliary epithelial cells were cultured and non-pigmented ciliary epithelial cells were isolated. Detection of DNA synthesis, morphological observation by a phase contrast microscope and a transmission electron microscope, and staining of senescence-associated beta-galactosidase were carried out. RESULTS: The cells proliferated without showing contact inhibition of growth or reconstitution of epithelial morphology. With a decrease of proliferative activity, the cultured cells expressed senescence-associated beta-galactosidase. Although DNA synthesis persisted for a long time, some cells in later culture periods showed morphologically abnormal nuclei or plural nuclei indicating dysfunction of cell division, or apoptotic features. CONCLUSION: The uncontrolled growth and loss of the epithelial nature of non-pigmented ciliary epithelial cells in vitro resembles the process of formation of cyclitic membrane and proliferation of ciliary epithelium after cyclophotocoagulation and cyclocryocoagulation in patients. Observatin of the behavior of cultured non-pigment epithelial cells could aid in understanding the mechanism of cyclitic membrane formation.

[Mesangial glomerulonephritis and intermediate uveitis]. / Glomerulonefritis mesangial asociada a uveítis intermedia (pars planitis).

Uveitis in children are less frequent than in adults. Their prognosis is variable because it may be found as an isolated and idiophatic condition or in association with definite clinical entities. The associated noninfectious diseases with predominantly renal involvement are tubulointerstitial nephritis and uveitis syndrome (TINU syndrome), mesangial glomerulonephritis isolated or in association with Behçet's disease. A case of 14-years-old girl with intermediate uveitis (pars planitis) and mesangial glomerulonephritis is presented. The ocular symptoms was eye redness and ocular pain and she has snow-banks in pars plana. She showed microscopic hematuria and intermitent proteinuria that increased during the ocular clinical exacerbation. Renal biopsy revealed both mild mesangial matrix increase and mesangial celullarity with normal tubulointerstitial structure and mesangial deposition of IgA and IgG immunoglobulins. This case is de first pediatric patient report in the literature with intermediate uveitis and mesangial glomerulonephritis with immune deposition. Mesangial glomerulonephritis were observed in patients whit Behçet disease, known etiological cause of uveitis in adults and children. These findings may suggest that uveitis and glomerulonephritis have common immunological pathogenesis including circulatory immune complexes. In uveitis patients, screening for associated extra-ocular and renal manifestations is mandatory and should have careful long-term follow-up with regular systemic evaluation.

Intermediate uveitis: a hospital based study.

UNLABELLED: Intermediate uveitis affecting pars plana, peripheral retina and underlying choroid affects primarily healthy children and young adults. OBJECTIVE: To study the components of intermediate uveitis at Nepal Eye Hospital in the year 2003 August to 2004 March. MATERIALS AND METHODS: A prospective study was done in patients with intermediate uveitis visiting Nepal Eye Hospital. Sample size was 50. Specially designed proforma of intermediate uveitis was used to collect particulars of the patients, history, clinical examination findings, investigation reports, management protocols used and the final visual outcome. RESULTS: Intermediate uveitis was seen more in 20 to 29 years age group (38%) and more prevalent in males (52%). Among the study population farmers constituted maximum proportion (36%) and Mongoloid origin was mostly affected (30%). High number of patients were from the central development region with highest proportion from Dhading district (34%). Anterior segment affection with keratic precipitates and anterior chamber cells were noted in 72% of involved eyes. Vitreous cells were noted in all affected eyes while 4% had vitreous snow banking and 3% had vitreous snow balls. Most of the patients (52%) received between topical steroid and posterior subtenon injection of Triamcinolone. Visual Acuity was improved in 52% of cases and remained static in 46%.while deteriorated in 2%. CONCLUSION: Significantly high number of patients with intermediate uveitis has been reported from the central development region mainly from Dhading Kathmandu and Nuwakot districts People in their third decade were found to be commonly involved and Mongloid origin were more commonly affected Anterior chamber spill over was seen in higher percentage of patients than described in literature As the patients presented in milder forms visual acuity improved is of cases with the treatment protocol followed.

Is granuloma annulare related to intermediate uveitis with retinal vasculitis?

AIM: To report on eight patients with severe idiopathic intermediate uveitis (IU) and granuloma annulare (GA), a self limiting cutaneous condition of unknown aetiology. METHODS: Retrospective case series. Clinical ophthalmic and dermatological data were studied and fluorescein angiography and skin biopsies were reviewed. RESULTS: All patients with idiopathic IU had similar ocular features (eight with vitritis, seven with retinal vasculitis) and developed complications such as cystoid macular oedema (n=5), cataract (n=4), and glaucoma (n=3). Systemic diseases were not found, but a localised type of GA was observed in all. CONCLUSION: Seven out of eight patients with IU and GA developed severe retinal vasculitis. Further studies are needed for a better understanding of this association, a common pathogenesis, and its eventual clinical consequences.

Glaucoma persistente secundário à injeção subtenoniana posterior de acetato de triancinolona (kenalog) - relato de casos / Persistent glaucoma secondary to posterior subtenon injection of triamcinolone acetate (Kenalog) - case reports

Objetivo: Descrever 3 casos de crianças submetidas à injeção subtenoniana posterior Objetivo.: acetato de triancinolona (Kenalog© 40mg) para tratamento de uveíte intermediária, com desenvolvimento de glaucoma secundário refratário. Métodos: Relato de caso. Resultados: Três crianças com diagnóstico de uveíte intermediária, submetidas à injeção subtenoniana posterior de acetato de triancinolona para tratamento de inflamação vítrea crônica e/ou edema macular cistóide,desenvolveram glaucoma refratário e foram submetidos à excisão cirúrgica do corticóide de depósito e/ou cirurgia filtrante para controle da pressão intra-ocular (PIO). Conclusão: Çorticóide de depósito periocular pode representar alto risco para desenvolvimento de glaucoma secundário, de difícil controle em crianças. Excisão cirúrgica do corticóide de depósito pode resultar em controle da PIO, porém, em alguns casos, a realização de cirurgia filtrante é necessária.

Uveitis associated with childhood rheumatic diseases.

Optimal management of childhood rheumatic diseases requires an appreciation of their multisystem nature. The eye represents an important site of involvement, and inflammation of the uveal tract is a particularly frequent and potentially debilitating extra-articular feature of some childhood rheumatic diseases. Anterior uveitis associated with oligoarticular juvenile idiopathic arthritis is an especially distinctive entity. Other disorders in children, however, can be associated with posterior and intermediate uveal tract inflammation. The potentially debilitating consequences of uveitis associated with childhood rheumatic diseases, the inadequacies of existing therapies, and the immunopathogenic basis for particular forms of uveitis have prompted the use of immunomodulatory therapy, including new biologic agents, to treat childhood uveitis. This review summarizes recent contributions to the literature that help to clarify the spectrum of conditions associated with uveitis in children, consider evidence for immunopathogenic processes associated with uveitis, and address new approaches to therapy.

Immunopathology of the noninfectious posterior and intermediate uveitides.

The posterior and intermediate uveitides share an underlying immune etiology; however, they can be clinically and immunopathologically distinguished. Although the initiating stimuli for posterior and intermediate uveities are not known, it is believed that an exogenous agent (such as a bacterium or a virus) or an endogenous molecule may induce disease. In either case, T-helper lymphocytes in conjunction with human leukocyte antigens are likely to be involved. This review examines the epidemiology, histology, immunopathology, and theories of pathogenesis of several posterior and intermediate uveitides, including sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, Behçet's disease, sarcoidosis, intermediate uveitis, white dot syndromes, and birdshot retinochoroidopathy.