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Elevated soluble Fas in aqueous humor of patients with Behcet's uveitis: correlation with uveitis severity.

PURPOSE: To examine the role of soluble Fas (sFas) in patients with Behcet's uveitis. METHODS: We measured the sFas levels in both sera and aqueous humor (AH) of patients (n = 40) with uveitis and of non-uveitis controls (n = 27) using an enzyme-linked immunosorbent assay. The patients with uveitis comprised 24 with Behcet's disease, 6 pan-uveitis, 5 anterior uveitis, 2 lens-induced uveitis, 1 Vogt-Koyanagi-Harada disease, 1 sarcoidosis, and 1 retinal vasculitis. The severity of uveitis was determined by the Hogan grading method (0--4 grade) at the time of sampling. RESULTS: The concentration of aqueous sFas in uveitis patients was significantly higher than that in non-uveitis controls, while there was no difference in the serum concentration of sFas between the two groups. In the paired samples of serum and AH, obtained simultaneously, the aqueous sFas levels were higher than serum Fas levels in patients with uveitis, whereas the non-uveitis controls displayed significantly lower sFas levels in AH than in the serum. The sFas levels in AH or serum were not different between Behcet's uveitis patients and non-Behcet's uveitis patients. However, in patients with Behcet's uveitis, circulating sFas strongly correlated with aqueous sFas, which was not so in those with non-Behcet's uveitis. Patients (n = 29) with more active (grade greater-than-or-equal 2) uveitis had significantly higher levels of aqueous sFas than those (n = 11) with less active (grade < 2) uveitis. After treatment with steroids and/or immunosuppressive agents, aqueous sFas levels decreased in parallel with a reduction in the number of inflammatory cells. CONCLUSIONS: The levels of sFas were elevated in patients with Behcet's uveitis and correlated well with the uveitis severity in these patients.

Adolescent↗

Pattern of uveitis in a referral uveitis clinic in India.

This report describes a retrospective study of all new patients in our uveitis clinic between January 1992 and December 1994, undertaken to identify the pattern of uveitis in the Indian subcontinent. A standard clinical protocol, and the naming-meshing system with tailored laboratory investigations were used to arrive at a final uveitic diagnosis. Uveitis comprised 1.5% of new cases seen at the centre. Out of 1,273 uveitis cases, anterior uveitis was the most common type (39.28%), followed by posterior uveitis (28.75%), intermediate uveitis (17.44%), and panuveitis (14.53%). The most commonly affected age group were patients in their forties (23.57%). Uveitis was less common in children below 10 years (3.61%) and in adults over 60 years of age (6.44%). Men (62.21%) were more commonly affected than women (37.79%). Aetiology remained undetermined in 59.31% of cases. Anterior uveitis was most commonly idiopathic (58.6%). The most common cause of posterior uveitis was toxoplasmosis (27.87%), and that of panuveitis was the Vogt-Koyanagi-Harada syndrome (21.08%). A higher incidence of microbiologically proven tubercular uveitis (5 cases), and uveitis due to live intraocular nematode (4 cases), and malaria (1 case), were seen, in contrast to other studies. Only 2 cases of AIDS with ocular lesions were seen. This paper reveals the pattern of uveitis seen at a major referral eye institute in India.

Adolescent↗

[Ocular hypertension and uveitis. Study of 374 cases of uveitis].

OBJECTIVES: To study the frequency of ocular hypertension in uveitis and its correlations with the characteristics of uveitis. To analyze the mechanisms of hypertension and the influence of different etiologies. To evaluate the prognosis of increased intraocular pressure secondary to uveitis. MATERIAL AND METHODS: Retrospective, single-center, mono-observer study of 374 consecutive cases of uveitis. RESULTS: Ocular hypertension was observed in 45 of 374 cases (12%). Hypertension was observed only in 2 cases without any sign of anterior chamber inflammation. Increased intraocular pressure was more frequently observed in granulomatous uveitis [15 of 33 cases (45.4%)] than in non granulomatous uveitis [30 of 341 cases (8.9%)] (p < 0.001). There were 2 cases of Posner-Schlossman syndrome. Herpetic uveitis was otherwise the most frequent etiology of uveitis associated with secondary ocular hypertension [8 of 22 cases (36.3%)]. The ocular hypertension was most often in phase with intraocular inflammation [17 of 45 cases (37.8%)], suggesting a mechanism of trabecular obstruction. Corticosteroid-induced hypertension was only noted in 2 cases. In 12 cases the mechanisms of ocular hypertension could not be determined. Glaucomatous optic neuropathy was only observed in 3 patients. Filtering surgery was performed in 4 cases. CONCLUSIONS: Among uveitis cases, findings linked to a higher frequency of ocular hypertension were identified. There was a discrepancy between the low frequency of corticosteroid induced hypertension and the broad use of topical corticosteroids in cases of uveitis. The analysis of the mechanisms involved is necessary for an adequate treatment. The prognosis of hypertensive uveitis was more frequently linked to the consequences of intraocular inflammation than to hypertension.

Adrenal Cortex Hormones↗

Prevalence of uveitis in an outpatient juvenile arthritis clinic: onset of uveitis more than a decade after onset of arthritis.

PURPOSE: To determine the prevalence and severity of uveitis in an outpatient pediatric arthritis clinic in the midwestern United States during the 1990s. METHODS: The prevalence and clinical characteristics of uveitis were studied retrospectively for all children diagnosed with arthritis at Shriner's Hospital for Crippled Children and followed by the pediatric rheumatology and ophthalmology units of the St Louis Children's Hospital between 1992 and 1995. RESULTS: Seven children (9%) developed uveitis in a population of 78 patients with juvenile arthritis. Six of the seven children were female, and all six females had anti-nuclear antibody (ANA)-positive, juvenile rheumatoid arthritis (JRA). The prevalence of anterior uveitis in females with ANA-positive, pauciarticular JRA was 20%, and in polyarticular JRA, 17%. One of the girls with uveitis had combined JRA and sarcoidosis; the boy with uveitis had juvenile spondylitis. Arthritis preceded the onset of uveitis in each child by 1 to 13 years (average, 6.4 years). Progression of the uveitis in three of the children resulted in band keratopathy and cataract, causing significant visual loss in two (i.e., in 29% of the children who developed uveitis). CONCLUSION: The prevalence and ocular morbidity of uveitis in juvenile arthritis appears to have remained relatively stable over the last 2 decades. Onset of the uveitis in several of the children in our study population occurred more than a decade after the diagnosis of arthritis. Girls with ANA-positive JRA and boys with juvenile spondylitis may need to be followed by periodic slit-lamp examination for longer periods than recommended previously.

Adolescent↗

Causes of uveitis in the general practice of ophthalmology. UCLA Community-Based Uveitis Study Group.

PURPOSE: Most uveitis case series have come from tertiary care centers, and the relative frequencies of disorders they report may reflect referral bias. We sought information about the types of uveitis encountered in the general practice of ophthalmology. METHODS: We prospectively examined 213 consecutive cases of general uveitis, defined as intraocular inflammation other than cytomegalovirus retinopathy, seen by a group of community-based comprehensive ophthalmologists. This group of cases was compared with 213 consecutive cases of general uveitis examined by a uveitis specialist at a university referral center in the same community. All cases were categorized by anatomic site of inflammation and disease course, and, if possible, they were assigned a specific diagnosis. Cases of cytomegalovirus retinopathy and masquerade syndrome seen during the same intervals were recorded separately. RESULTS: The distribution of general uveitis cases by anatomic site of disease was significantly different between the community-based practices (anterior, 90.6%; intermediate, 1.4%; posterior 4.7%; panuveitis, 1.4%) and the university referral practice (anterior, 60.6%; intermediate, 12.2%; posterior, 14.6%; panuveitis, 9.4%; P < .00005). A cause or clinical syndrome could be assigned to 47.4% of cases in the community-based practices, and to 57.8% of cases in the university referral practice (P = .03). HLA-B27-associated anterior uveitis, cytomegalovirus retinopathy, and toxoplasmic retinochoroiditis were among the five most common forms of uveitis in both practice settings. CONCLUSION: The relative frequencies with which various forms of uveitis are seen in a tertiary referral center do not necessarily reflect the experience of ophthalmologists from the community in which the center is located. Anterior uveitis and disorders of sudden onset constitute a greater proportion of cases seen by community-based comprehensive ophthalmologists.

Adolescent↗

Pattern of uveitis in a referral uveitis clinic in India.

The pattern of uveitis changes over time with the emergence or identification of new uveitic entities. The aim of this prospective study was to obtain a correct incidence pattern and aetiology of uveitis cases seen in a uveitis clinic. We studied all new uveitic cases seen in a-one year period. A standard clinical protocol was followed for each case. Of the 465 new uveitic cases, anterior uveitis was most commonly encountered (170 cases, 36.5%), followed by posterior uveitis (132 cases, 28.4%), intermediate uveitis (92 cases, 19.8%) and panuveitis (71 cases, 15.3%). The aetiology remained undetermined in majority of the cases (58.7%): anterior uveitis (48.8%), posterior uveitis (45.45%), panuveitis (53.52%). The most common cause was collagen disease (29.4%) in anterior uveitis; toxoplasmosis (30.3%) in posterior uveitis; and Vogt-Koyanagi Harada's disease (25.35%) in panuveitis.

Adolescent↗

Murine endotoxin-induced uveitis, but not immune complex-induced uveitis, is dependent on the IL-8 receptor homolog.

PURPOSE: To determine the roles of the murine interleukin-8 receptor homolog (mIL-8Rh, neutrophil chemokine CXC receptor 2) and macrophage inflammatory protein-1alpha (MIP-1alpha, a CC chemokine) in two eye inflammation models: endotoxin-induced uveitis (EIU) and immune complex-induced uveitis (reverse passive Arthus reaction (RPAR) uveitis). METHODS: For the EIU model, 250 ng E.coli endotoxin was injected into the vitreous of mIL-8Rh-/- mice or heterozygous littermate mIL-8Rh+/- controls and into MIP-1alpha-/- mice or congenic MIP-1alpha+/+ controls. Eyes were harvested after 24 h for histologic characterization of infiltrating cells and IL-6 bioassays. For the RPAR model, mouse antiserum against human serum albumin (HSA) was injected into the vitreous of mIL-8Rh-/-, mIL-8Rh+/-, MIP-1alpha-/-, and MIP-1alpha+/+ mice. Twenty-four hours later, animals were challenged with intravenous HSA. Eyes were harvested after 4 h for analysis. RESULTS: RPAR resulted in the deposition of immune complexes at the ciliary area and iris with the subsequent development of uveitis. Genetic deficiency of mIL-8Rh reduced the median number of infiltrating cells in EIU by 63% (p < 0.01) but had no effect on RPAR-induced inflammation. In the EIU model, macrophages comprised a much higher percentage (45%) of infiltrating cells in mice lacking mIL-8Rh than in controls (17%). Loss of the MIP-1alpha gene had no apparent effect on RPAR uveitis and a 39% reduction of infiltrating cells in EIU that was not statistically significant. IL-6 activity in aqueous humor was much less in mice with RPAR uveitis than in those with EIU. Neither gene deletion had a significant impact on IL-6 levels in either disease model. CONCLUSIONS: Chemokines acting via mIL-8Rh have a significant role in the induction of neutrophil infiltration during EIU but not during RPAR uveitis. MIP-1alpha is not critical for either EIU or RPAR-induced uveitis. The differential dependence on IL-8-like chemokines is in accord with the two forms ofuveitis having different etiologies and, therefore, potentially different optimal therapies.

Animals↗

Uveitis associated with inflammatory bowel disease compared with uveitis associated with spondyloarthropathy.

BACKGROUND: Inflammatory bowel disease (IBD) and spondyloarthropathy (SA) such as Reiter syndrome may be characterized by diarrhea, arthritis, stomatitis, and uveitis. OBJECTIVE: To determine if the characteristics of the eye disease could help distinguish these 2 diagnoses. DESIGN: Seventeen patients with uveitis and IBD referred to a university clinic were compared retrospectively with 89 patients with uveitis and SA referred to the same clinic. RESULTS: Twelve (80%) of the 15 patients with evaluable IBD had Crohn disease. In marked contrast to patients with SA, patients with IBD were usually female (82%). Whereas uveitis with SA was predominantly anterior, unilateral, sudden in onset, and limited in duration, patients with IBD frequently had uveitis that was bilateral, posterior, insidious in onset, and/or chronic in duration. Results for 89% of the patients with SA who underwent HLA-B27 typing were positive, compared with only 46% of such patients with IBD. Episcleritis, scleritis, and glaucoma were more common among patients with IBD. Arthritis did not easily distinguish the 2 groups, as 13 (76%) of the patients with IBD had a history of joint disease. In 10 (59%) of the patients with IBD, the diagnosis of uveitis preceded that of IBD. CONCLUSION: The hallmarks of uveitis can often distinguish SA and IBD.

Adolescent↗

Endogenous uveitis in Chinese--an analysis of 240 cases in a uveitis clinic.

A review of 240 consecutive Chinese patients with endogenous uveitis seen over a 3-year period was made in Taiwan. The frequency of major types of uveitis was 110 cases (45.8%) of acute anterior uveitis, 43 cases (17.9%) of Behçet's disease, 22 cases (9.2%) of Harada's disease, 10 cases (4.2%) of peripheral uveitis, 6 cases (2.5%) of virus-induced uveitis and 5 cases (2.1%) of Fuchs' heterochromic cyclitis. Only 1 case (0.4%) of sarcoidosis was found. Of the 110 cases of acute anterior uveitis, 80.9% presented with HLA-B27 antigen. The incidences of types of endogenous uveitis in Chinese differ from those in Caucasians, Japanese and Negro races in the USA.

Adult↗

An evaluation of baseline risk factors predicting severity in juvenile idiopathic arthritis associated uveitis and other chronic anterior uveitis in early childhood.

BACKGROUND/AIMS: The clinical course for childhood chronic anterior uveitis can vary from mild, self limiting disease to bilateral blindness. The purpose of this study was to identify those risk factors at onset that predict disease severity. METHODS: A retrospective case note review of all patients with painless anterior uveitis diagnosed from 1982 to 1998. Patients were divided into two cohorts based on route of referral, diagnosis, and compliance with treatment. The standard cohort consisted of only those diagnosed from routine screening of juvenile idiopathic arthritis. RESULTS: Complications-cataract surgery, ocular hypertension treatment, and visual acuity <6/24. Remission: inactive uveitis on no topical treatment for >6 months. Results-163 patients were included. 34 patients (21%) developed at least one complication. The most significant predictor of complications was severe disease at onset (p = 0.001). Other factors included uveitis at the first examination (p = 0.034), membership of the non-standard cohort (p = 0.0001), non-oligoarticular disease (p = 0.02), and late onset arthritis (p = 0.024). Male sex was associated with increased complications in the standard cohort (p = 0.001). Factors predisposing to remission included membership of the standard cohort (p = 0.003), onset after 1990 (p = 0.016), white race (p = 0.015), mild disease onset (p = 0.003), and a long gap between arthritis and uveitis onset (p = 0.015). CONCLUSIONS: It is possible to characterise the severity of those with childhood chronic anterior uveitis at the onset of disease. The majority of patients remit without visually disabling complications. It may be possible to reduce the complication rate by targeting aggressive immunosuppression on high risk patients before complications develop.

Adolescent↗

Herpes simplex uveitis in immune rabbits. Priming effect of nonherpetic uveitis.

Systemic immunization of rabbits with herpes simplex virus (HSV) had two opposite effects on the outcome of subsequent efforts to produce primary HSV uveitis, the difference depending on whether or not the rabbits had had nonherpetic uveitis before the HSV challenge. In normal eyes, systemic immunization with HSV provided complete protection against the production of primary uveitis by an intraocular injection of HSV; but in eyes that had had a bout of experimentally induced nonherpetic uveitis before the challenge, the same systemic immunization was not protective. In these eyes, an immune-mediated uveal inflammation developed. Nonherpetic uveitis had apparently "primed" the eyes of the HSV-immune rabbits for subsequent immune-mediated HSV uveitis.

Animals↗

Experimental autoimmune anterior uveitis (EAAU), a new form of experimental uveitis. I. Induction by a detergent-insoluble, intrinsic protein fraction of the retinal pigment epithelium.

The uveitogenicity of several protein fractions of the bovine retinal pigment epithelium (RPE) was studied in Lewis rats, and a major pathogenic fraction was selected. Fresh RPE cells were carefully isolated and purified in order to minimize the presence of rod outer segments (ROS). The buffer-insoluble part of the cells was extracted by Triton X-100. Most uveitogenicity was found in the Triton-insoluble pigment and cytoskeleton-containing fraction of RPE (RPE-TI). The S-antigen and opsin contents of RPE-TI were too low to induce an inflammatory response, while transducin, IRBP and cGMP-phosphodiesterase were absent. Hence, a hitherto unknown uveitogenic RPE protein, called PEP-X, evoked the pathogenic response. A typical dose-dependent experimental autoimmune anterior uveitis (EAAU) developed when the rats were immunized with RPE-TI. Initially, mononuclear cells infiltrated the anterior segment. In subsequent severe stages polymorphonuclear cells predominated in the anterior chamber. EAAU differed in particular from the known forms of EAU induced by photoreceptor proteins in that the inflammation remained exclusively anterior and the photoreceptor cells and the pineal gland were not affected. In immunized rats the immune responses to ROS proteins were very low. In contrast, there were consistently high cellular and humoral immune responses to RPE-TI. As in experimental autoimmune (uveo)retinitis (EAU), the development of EAAU could be inhibited by cyclosporin treatment indicating T-cell-dependency. A combination of histopathological, immunological and biochemical results indicates that PEP-X is an intrinsic RPE protein that is highly pathogenic. In view of its characteristics, EAAU may be a valuable model for human acute anterior uveitis, the most prevalent form of uveitis.

Animals↗

Uveitis in adult patients with poststreptococcal reactive arthritis: the first two cases reported associated with uveitis.

We describe two adult patients with poststreptococcal reactive arthritis (PSRA), both of whom concomitantly developed uveitis. These are the first two cases reported. Because uveitis may result in permanent damage to visual acuity, this complication should be widely recognised in patients with PSRA and antibiotic prophylaxis should be considered for those with recurrent streptococcal infection.

Adult↗

Controlled evaluation of loteprednol etabonate and prednisolone acetate in the treatment of acute anterior uveitis. Loteprednol Etabonate US Uveitis Study Group.

PURPOSE: To compare the safety and efficacy of loteprednol etabonate 0.5% ophthalmic suspension with prednisolone acetate 1.0% ophthalmic suspension in reducing the ocular signs and symptoms associated with acute anterior uveitis. METHODS: Two prospective studies were conducted in sequence. Both were parallel, randomized, double-masked, active-controlled comparisons conducted at academic or private practice clinics in the United States. Efficacy was evaluated by the proportion of patients with a score of 0 for key signs and symptoms of uveitis. Intraocular pressure was increased regularly. The first study involved up to 42 days of treatment, starting with a dose of eight times per day. The second study involved up to 28 days of treatment, starting with a dose of 16 times per day. RESULTS: In the first study (N = 70), the proportion of patients achieving resolution by the final visit was anterior chamber cell (74% loteprednol etabonate, 88% prednisolone acetate, P = .194) and flare (71% loteprednol etabonate, 81% prednisolone acetate, P = .330). In the second study (N = 175), the proportion of patients achieving resolution by the final visit was anterior chamber cell (72% loteprednol etabonate, 87% prednisolone acetate, P = .015) and flare (66% loteprednol etabonate, 82% prednisolone acetate, P = .017). In both studies, intraocular pressure increase of more than 10 mm Hg was observed more frequently in patients receiving prednisolone acetate (seven patients) than those receiving loteprednol etabonate (one patient). CONCLUSIONS: Although a clinically meaningful reduction of signs and symptoms was noted in both treatment groups, loteprednol etabonate was less effective than prednisolone acetate in both of these controlled studies. However, the more favorable profile of loteprednol etabonate with respect to intraocular pressure increase may make it useful in many patients.

Acute Disease↗

Synthetic lipid A-induced uveitis and endotoxin-induced uveitis--a comparative study.

Endotoxin-induced uveitis (EIU) is an animal model of ocular inflammation induced by lipopolysaccharide (LPS). The lipid A (LA) region of the LPS chemical structure is believed to be responsible for virtually all the biological activities induced by LPS. The aim of this study was to perform a more detailed investigation of the potency of LA in reproducing EIU. Various doses of either LPS or LA were injected into the footpad of an inbred strain of Lewis rat and the inflammation patterns were compared by assessing the protein concentration, by cytological study, and by determining the inflammatory cell content in samples of aqueous humor obtained during 96-hour follow-up. Evaluation of the cell number and protein concentration ratio of both groups showed the LA-stimulated group presented a higher ratio than the LPS group (Welch's t-test, (P < 0.00001). It was noteworthy that even the injection of high doses of LPS could not reproduce the level of cellular infiltration induced by LA. Histological study confirmed the enhanced cellularity in the LA group, neutrophils being predominant in both the LPS- and the LA-stimulated groups. The divergent findings in these two models of uveitis may be valuable to further investigations of the process of inflammatory cell migration into the anterior chamber of the eye.

Animals↗

[Acute recurrent uveitis and idiopathic interstitial nephritis-- a nosologic entity (tubulo-interstitial nephritis and uveitis)].

So far 34 cases of idiopathic acute tubulo-interstitial nephritis and uveitis (TINU syndrome) have been reported by nephrologists. The patients have mainly been girls and only female adults. The authors describe a 53-year-old woman with this nosological entity, presenting with a granulomatous anterior uveitis and chronic course of nephritis. This is the first such case reported. All other cases described in the literature are compared and an attempt is made to locate the immune deficiency.

Acute Disease↗

[Secondary glaucoma and uveitis: hypertensive uveitis (author's transl)].

The secondary rise of i.o. pressure in uveitis may lead to a true secondary glaucoma or to hypertensive uveitis. The etiology of the endogenous inflammation does not seem to play a role. Pathogenetically the occlusion of the pupil with the formation of iris bombé and the obliteration of the chamber angle by exudate are important factors, while the hypersecretion of aqueous humor plays a minor role. Medical treatment consists in mydriatics and steroids. Surgical treatment depends on the pathogenetic mechanism and consists either in sector iridectomy or a filtering procedure.

Behcet Syndrome↗

Immunologic and biochemical properties of several retinal proteins bound by antibodies in sera from animals with experimental autoimmune uveitis and uveitis patients.

Sera from guinea pigs and rabbits with and without experimental autoimmune uveitis (EAU) induced by immunization with retina, choroid, optic nerve, retinal rod outer segments (ROS) and purified bovine S-antigen were tested for the ability to immunoprecipitate 125I-labeled, detergent-solubilized bovine retinal proteins. The results demonstrate that three major protein antigens with m.w. of 50,000 (p50), 35,000 (p35) and 27,000 (p27) and several minor activities between 30,000 and 60,000 m.w. are recognized by antibodies from these animals. The p50 component was immunoprecipitated by sera from animals immunized with whole retina homogenate, the high speed supernatant of whole retina homogenate, ROS, and S-antigen, and has been identified as S-antigen in competition experiments. The p35 band appeared when sera were used that were raised against antigen preparations containing membrane-bound retinal protein, i.e., whole retina homogenate, ROS, and washed ROS, and thus appears to be an ROS membrane protein. The p27 band was found when sera raised against ROS, washed ROS, optic nerve and whole retina homogenate were used, suggesting it is a membrane-bound antigen common to ROS and optic nerve. Serum from animals immunized with homologous choroid did not immunoprecipitate a detectable product. S-antigen and p35 were also precipitated by some uveitis patient sera. Because S-antigen is also an ROS protein as is rhodopsin, a putative uveitogenic retinal antigen, ROS appear to be an unusually rich source of autoantigenic proteins. S-antigen was also shown to be synthesized in the retina, and the primary translation product was indistinguishable from purified S-antigen by SDS-PAGE, thus eliminating the possibility that it is derived from or is cross-reactive with the 67,000 m.w. rhodopsin kinase.

Animals↗