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[Etiologies of intermediate, posterior, and panuveitis: a review of 201 cases].

The authors conducted a retrospective analysis of 201 patients with intermediate, posterior or panuveitis to determine the most frequent etiologies and collect some epidemiological data. A specific diagnosis was made in 70% of the cases: 35% were of infectious origin, 23% were associated with a systemic disease and 24% had a specific ocular condition. The most common entities included toxoplasmosis (24%), sarcoidosis (7.5%) and Behçet disease (5.5%). Birdshot retinochoroidopathy was the most frequent specific ocular disease (3.5%). The findings of this study are compared with those previously published in the literature.

Behcet Syndrome↗

Genetic susceptibility to early onset pauciarticular juvenile chronic arthritis: a study of HLA and complement markers in 158 British patients.

To investigate the genetics of susceptibility to early onset pauciarticular juvenile chronic arthritis (JCA), 158 unrelated ethnic British patients with a mean disease onset of 3.2 years, together with controls, were tested for HLA-A, B, C, and DR antigens. Additionally, 117 patients were also investigated for complement Bf and C4 markers. New observations included an increased frequency of the C4B 2 allotype (p corrected (pc) less than 0.02) and C4A 4,B 2 phenotype (p less than 0.0005). Findings suggested a unique increase of the haplotype HLA-DRw8, Bf*S, C4A*4, C4B*2, HLA-B39, possibly predisposing to more severe disease. Strong positive associations were confirmed with HLA antigens A2 (pc = 2.5 X 10(-8)), DRw8 (pc = 3.5 X 10(-14)), DR5 (pc less than 0.02), DRw52 (pc = 2.8 X 10(-6)) and DR5, w8 phenotype (pc = 3.9 X 10(-6)), and negative associations with DR7 (pc = 5.8 X 10(-7)), DR4 (pc less than 0.002), and DRw53 (pc = 0.004). Antinuclear antibody (ANA) seropositivity correlated with DR5 (p less than 0.02), and in children with chronic iridocyclitis (CIR) Bw62 incidence was raised (p less than 0.03) and B44 reduced (p less than 0.03). HLA-A2 was found in 88% of ANA+, CIR+ patients (p less than 0.01). A significant excess of DR5, w8 heterozygotes was present (relative risk = 41.1) and a lack of corresponding homozygotes. Results are inconsistent with a recessive, dominant, or intermediate mode of inheritance of susceptibility, and favour the existence of at least two DR linked 'disease' genes. Moreover, there may be an interaction in heterozygotes of combinatorial factors associated with DR5 and DRw8 in enhancing susceptibility. Possible immunogenetic mechanisms underlying the observed associations with three antigen classes are discussed. Evidence here suggests a role for the HLA-DQ locus in determining susceptibility to this disease.

Age Factors↗

Rhodopsin-induced experimental autoimmune uveoretinitis: dose-dependent clinicopathological features.

We have studied the clinicopathological features of experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by injection of different doses of rhodopsin and its illuminated form opsin. Rhodopsin consistently appears to be more pathogenic than opsin. Injected in Freund's complete adjuvant and pertussis adjuvant 50 micrograms of rhodopsin induces a frequency of severe EAU similar to 250 micrograms of opsin. Intensity, frequency and location of ocular inflammation are markedly dose dependent. At high dose (100-250 micrograms), rhodopsin induces severe bilateral uveoretinitis in all animals, which starts with acute inflammation of the anterior eye segment at day 10-12 followed by chorioretinitis (predominantly retinitis) which results in complete elimination of the photoreceptor cells. At low dose (20 micrograms), rhodopsin induces mild transient inflammation in 60% of the animals, mainly consisting of mild posterior retinitis which starts at day 20 and leads to a typical multiple focal destruction of the photoreceptor cells. Intermediate doses cause an intermediate type of disease. Omission of pertussis adjuvant lowers the frequency of severe disease at low doses of rhodopsin, delays its onset and changes its features. The last characteristic has been observed in particular at intermediate doses (50-100 micrograms). In these cases, EAU usually starts by cell infiltration of the vitreous, while the anterior segment is only mildly affected. Without pertussis adjuvant the pathogenicity of opsin is low. Even in both adjuvants severe EAU can only be evoked by a high dose of opsin. Although there exists a marked difference in uveitogenicity between rhodopsin and opsin, the immunogenicity is similar and seems not to be correlated with their pathogenicity.

Animals↗

Possible mechanism of immunosuppression by gramicidin S of S antigen-induced experimental autoimmune uveoretinitis.

Gramicidin S (GrS) suppressed the onset of experimental autoimmune uveoretinitis (EAU) induced with S-antigen in rats, and the proliferation of mitogen-stimulated lymphocytes in culture. As an immunosuppressive mechanism of the cyclic peptide antibiotic we first postulated that the drug exerts its effect as an ionophore. Although all ionophore compounds tested suppressed lymphocyte proliferation, no correlation was observed between changes in intracellular concentrations of Na+ and K+ and the degree of immunosuppression. For example, monensin inhibited lymphocyte proliferation without affecting intracellular Na+ and K+ levels. Thus it was likely that the immunosuppressive effects of the ionophore compounds including GrS were due to their ability to modify cell membrane properties rather than their ionophore activity. We then tested the hypothesis that GrS inhibits transport of metabolic intermediates or metabolites (thymidine and methionine) into lymphocytes. The idea was experimentally supported. Further, inhibition of metabolite transport by GrS was found to be reversible. To investigate whether inhibition of metabolite uptake can be a mechanism of immunosuppression of EAU, endogenously stimulated lymphocytes were isolated from S-antigen-immunized rats at different stages of EAU and the effect of GrS on metabolite uptake by the cells was determined. The activity of lymphocytes to transport metabolites was enhanced at pre-EAU stages and the enhanced metabolite uptake was markedly inhibited by GrS. We interpreted the result to support that inhibition of metabolite uptake by GrS is probably a mechanism of immunosuppression in vivo by this drug.

Animals↗

The Ahmed drainage implant in the treatment of pediatric glaucoma.

PURPOSE: To report the safety and efficacy of Ahmed Glaucoma Valve (New World Medical, Inc., Rancho Cucamonga, California, USA) implantation for the management of pediatric glaucoma in the early and intermediate follow-up period. DESIGN: Consecutive interventional case series. METHOD: A retrospective chart review was conducted on 60 eyes (44 patients, age range at surgery 1.5 months to 16 years, average 6 +/- 4.9 years), with pediatric glaucoma that underwent Ahmed Glaucoma Valve implantation for medically uncontrolled intraocular pressure (IOP) between the years 1995 and 2000. Outcome measures were control of IOP below 21 mm Hg, the need for antiglaucoma medications after surgery, and loss of 2 or more lines of Snellen acuity. Complications were monitored. RESULTS: The postoperative follow-up period for each eye averaged 24.3 +/- 16 months (range, 3 to 60 months). At last follow-up, IOP was controlled in 44 eyes (73%), 11 of which did not need antiglaucoma therapy. Kaplan-Meier life-table analysis showed probability of success with or without medications of 93% (95% confidence interval [CI], 86%-100%), 86% (95% CI, 77%-96%), 71% (95% CI, 59%-87%), and 45% (95% CI, 28%-80%) after 12, 24, 36, and 48 months of follow-up. Average IOP decreased from 32.8 +/- 6.2 before surgery to 16.6 +/- 8.0 postoperatively (P <.0001). The average number of medications used decreased from 4.4 +/- 1.97 to 2.0 +/- 2.0 (P <.0001). Kaplan-Meier survival analysis did not reveal any difference in survival profiles related to specific diagnosis of glaucoma, age (above or below 18 months), or prior surgery. Complications occurred in 30 eyes (50%). Although most resolved or were treated successfully, four patients had severe visual loss during the follow-up. Uveitis was a significant risk factor for tube exposure (Fisher exact test, P =.006). CONCLUSIONS: Ahmed Glaucoma Valve implantation is an effective treatment for pediatric glaucoma, although patients frequently require antiglaucoma medications. However, a high rate of potentially sight-threatening postoperative complications warrants ongoing close follow-up.

Adolescent↗

Contact transscleral Nd:YAG laser cyclophotocoagulation. Midterm results.

BACKGROUND: Early reports of both contact and noncontact transscleral Nd:YAG laser cyclophotocoagulation have been encouraging; however, recent evidence indicates a significant incidence of hypotony, visual loss, and phthisis with the noncontact technique with more than 6 months of follow-up. The authors sought to determine the intermediate term effects of contact transscleral Nd:YAG laser cyclophotocoagulation (CYC). METHODS: The authors followed 116 eyes of 114 patients for a minimum of 1 year after treatment of advanced glaucoma with CYC. RESULTS: The mean preoperative intraocular pressure (IOP) of 35.0 +/- 1.0 mmHg decreased to 18.6 +/- 1.1 mmHg (P less than 0.0001) during the average follow-up of 19.0 +/- 0.6 months (range, 12 to 36 months). Intraocular pressure control of 3 to 25 mmHg was achieved in 72%, 3 to 22 mmHg in 65%, and 3 to 19 mmHg in 56% of eyes. Retreatment was required in 31 of the 116 eyes (27%). Intraocular pressure decreased to less than 3 mmHg in 9 eyes and to 0 mmHg in 6 of these 9 eyes. Nineteen eyes, all with initial visual acuity of counting fingers or worse, progressed to no light perception; 17 of 36 eyes (47%) with visual acuity of 20/200 or better lost 2 or more Snellen lines. CONCLUSION: Midterm results of CYC continue to be encouraging but are tempered by a nearly 10% incidence of hypotony or phthisis and the progression of visual loss.

Adolescent↗