The course of uveitis in pregnancy and postpartum

Aim To examine the course of non-infectious uveitis during pregnancy.Methods This is a retrospective case series. The medical records of 47 subjects with a previous history of non-infectious uveitis pre-dating their pregnancy were reviewed. Uveitis activity during the periods 1 year before pregnancy, during pregnancy and 1 year postpartum, were recorded. Information on patient demographics, type of uveitis, medication use, sex of child and breastfeeding status were also collected. The main outcome measures were the events of flare-ups during the prepregnancy, pregnancy and postpartum periods.Results The rate of flare-up was 1.188 per person year prior to pregnancy, 0.540 per person year during pregnancy and 0.972 per person year in postpartum (p&lt;0.001 for comparison between prepregnancy and pregnancy; p=0.009 for comparison between pregnancy and postpartum). Rates of flare-up only began to decrease in the second trimester. After delivery, rates of flare-up rebounded and within 6 months postpartum, flare-up rates were not significantly different from prepregnancy levels (p=0.306). Even so, 40% of subjects were found to have remained inactive within 1 year postpartum.Conclusions Uveitis activity decreased by mid-pregnancy, but returned to prepregnancy levels within 6 months postpartum. These findings may be used to adjust uveitis management during pregnancy and the postpartum period.<br /

Outcome of Treatment of Uveitic Macular&nbsp;Edema The Multicenter Uveitis Steroid Treatment Trial 2-Year&nbsp;Results

PurposeTo evaluate the 2-year outcomes of uveitic macular edema.DesignLongitudinal follow-up of a randomized cohort.ParticipantsAt baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up.MethodsPatients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 μm) on time-domain optical coherence tomography (OCT) of macula.Main outcome measuresImprovement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA).ResultsBetween randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 μm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003).ConclusionsAbout two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema

Association of polymorphisms in MACRO domain containing 2 with thyroid-associated orbitopathy

Purpose: Thyroid-associated orbitopathy (TO) is an autoimmune-mediated orbital inflammation that can lead to disfigurement and blindness. Multiple genetic loci have been associated with Graves' disease, but the genetic basis for TO is largely unknown. This study aimed to identify loci associated with TO in individuals with Graves' disease, using a genome-wide association scan (GWAS) for the first time to our knowledge in TO. Methods: Genome-wide association scan was performed on pooled DNA from an Australian Caucasian discovery cohort of 265 participants with Graves' disease and TO (cases) and 147 patients with Graves' disease without TO (controls). Top-ranked single nucleotide polymorphisms (SNPs) then were genotyped in individual DNA samples from the discovery cohort, and two replication cohorts totaling 584 cases and 367 controls. Results: In the GWAS of pooled DNA samples, several SNPs showed suggestive association with TO at genome-wide P ≤ 10⁻⁶; rs953128 located on chr10q21.1, rs2867161 on chr7q11.22, rs13360861 on chr5q12.3, rs7636326 on chr3q26.2, rs10266576 on chr 7q11.22, rs60457622 on chr3q23, and rs6110809 on chr20p12.1. However, the only SNP consistently associated with TO on individual genotyping in the discovery and replication cohorts was rs6110809, located within MACROD2 on chromosome 20p12.1. On combined analysis of discovery and replication cohorts, the minor A allele of rs6110809 was more frequent in TO than in Graves' disease controls without TO (P = 4.35 × 10⁻⁵; odds ratio [OR] = 1.77; 95% confidence interval [CI], 1.35-2.32) after adjusting for age, sex, duration of Graves' disease, and smoking. Conclusions: In patients with Graves' disease, a common genetic variant in MACROD2 may increase susceptibility for thyroid-associated orbitopathy. This association now requires confirmation in additional independent cohorts.9 page(s

Outcome of Treatment of Uveitic Macular Edema

PURPOSE: To evaluate the clinical outcomes of uveitic macular edema through two years of treatment. DESIGN: Longitudinal follow-up of a randomized cohort. PARTICIPANTS: At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed two-year follow-up. METHODS: All patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness ≥240 µm) on time-domain optical coherence tomography (OCT) of macula. MAIN OUTCOME MEASURES: Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT) and best-corrected visual acuity (BCVA). RESULTS: Between randomization and 2-years’ follow-up, 62% and 25% of eyes in the systemic and implant groups respectively, received at least one supplemental regional corticosteroid injection. Overall, by 2-years’ follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%, P=0.20) and resolving (52% vs. 68%, P=0.28). However, on average, eyes randomized to implant had more improvement in macular thickness (median decrease of 180µm vs. 109µm in the systemic therapy group, P=0.04). Eyes with fluorescein angiographic leakage at baseline were more likely to improve in macular thickness than those without (76% vs. 58%, P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution,+10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, −16 letters (worsening acuity, P=0.0003). CONCLUSIONS: About two-thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Associated leakage on fluorescein angiography at baseline was associated with a greater likelihood of improvement in macular edema

Optical Coherence Tomography Evaluation in the Multicenter Uveitis Steroid Treatment (MUST) Trial

PURPOSE: To describe the evaluation of optical coherence tomography (OCT) scans in the Muliticenter Uveitis Steroid Treatment (MUST) trial and report baseline OCT features of enrolled participants. METHODS: Time domain OCTs acquired by certified photographers using a standardized scan protocol were evaluated at a Reading Center. Accuracy of retinal thickness data was confirmed with quality evaluation and caliper measurement of centerpoint thickness (CPT) was performed when unreliable. Morphological evaluation included cysts, subretinal fluid,epiretinal membranes (ERMs),and vitreomacular traction. RESULTS: Of the 453 OCTs evaluated, automated retinal thickness was accurate in 69.5% of scans, caliper measurement was performed in 26%,and 4% were ungradable. Intraclass correlation was 0.98 for reproducibility of caliper measurement. Macular edema (centerpoint thickness ≥ 240um) was present in 36%. Cysts were present in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement ranged from 78 − 82% for morphological features. CONCLUSION: Retinal thickness data can be retrieved in a majority of OCT scans in clinical trial submissions for uveitis studies. Small cysts and ERMs involving the center are common in intermediate and posterior/panuveitis requiring systemic corticosteroid therapy