To document the clinical presentation, treatment, and visual outcome of sarcoid uveitis and to determine the timing and potential risk factors of sarcoidosis progression to symptomatic systemic ...disease from the time of sarcoid uveitis diagnosis.
Retrospective, interventional case series.
Subjects: Patients with dual diagnoses of uveitis and presumed/biopsy-proven sarcoidosis. Procedure: Retrospective review of 143 patient records from the Royal Victorian Eye and Ear Hospital and Eye Surgery Associates in Melbourne, Australia, between October 1990 and April 2014 coded with the dual diagnoses of uveitis and sarcoidosis. Only patients with uveitis and presumed or biopsy-proven sarcoidosis (N = 113) were included. Main Outcome Measures: Ascertainment of rate and time (months) to the development of symptomatic systemic sarcoidosis from uveitis onset; comparison of the patient demographics, characteristics of uveitis, treatment, and visual outcome between those who developed systemic sarcoidosis and those who remained systemically asymptomatic.
Uveitis was the initial presenting complaint of sarcoidosis in 78.8% (n = 89). Twenty-three patients had concurrent undiagnosed systemic disease at presentation and 29 subsequently developed symptomatic sarcoidosis in an organ uninvolved at uveitis onset. The median time to the development of symptomatic systemic sarcoidosis was 12 months. No statistically significant association was ascertained between any particular uveitis characteristic and extraocular sarcoidosis progression.
Uveitis was the initial presentation of sarcoidosis in the vast majority of our subjects. Concurrent undiagnosed systemic sarcoidosis was common at the time of uveitis onset. A high index of suspicion for subsequent systemic progression should also be maintained, especially within the first 5 years of the uveitis diagnosis.
To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression.
...Cohort study of participants from a randomized clinical trial.
A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery.
The cumulative incidence of cataract surgery was 43% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age >50 years (hazard ratio HR 2.86, 95% CI 1.52, 5.42; P = .001), topical corticosteroid use (time-updated HR 3.13, 95% CI 1.42, 6.94; P = .005), glaucoma medication use (HR 2.75, 95% CI 1.38, 5.47; P = .004), and possibly history of anterior chamber inflammation (HR 1.90, 95% CI 0.95, 3.84; P = .07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data.
Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.
Primary choroidal lymphoma is a rare, slowly progressive intraocular malignancy. Most are low grade B cell lymphomas, often involving tissues adjacent to the choroid such as the subconjunctival ...space, lacrimal gland or orbit. Ideally, these lesions are biopsied to establish histopathological diagnosis. The most accessible ocular structure is biopsied. Obtaining tissue by transvitreal choroidal biopsy imparts a small but significant risk of ocular morbidity, including the need for multiple surgeries, retinal detachment and vision loss.
External beam radiotherapy (EBRT) is a common and effective treatment of low-grade lymphomas. EBRT has been found to very successfully treat primary marginal zone lymphomas of the ocular adnexa, which are typically of the same cell type as most primary choroid lymphomas. Ultra-low dose EBRT, most commonly using a total dose of 4 Gy, has been shown to be as effective as higher doses of radiotherapy for follicular or marginal zone lymphomas. The use of this low dose regimen for conjunctival lymphomas has been recently explored. The role of EBRT, and especially ultra-low dose EBRT, for treatment of primary choroidal lymphoma has been confined to case reports.
We describe a case of presumed primary choroidal lymphoma diagnosed on clinical findings alone as the risks of ocular biopsy were deemed too high, and report outcome following treatment with ultra-low dose EBRT.
Purpose: To determine clinical features, viral aetiology and treatment outcomes of eyes with acute retinal necrosis (ARN).
Methods: Retrospective, interventional, non‐comparative case series.
...Results: Twenty‐two patients (23 eyes) were identified between 1996 and 2007. Varicella zoster virus was the causative agent in 12 patients (nine confirmed by polymerase chain reaction), herpes simplex virus type 1 in six (five polymerase chain reaction‐confirmed) and unknown in three patients. Five patients had documented herpes zoster infection in the month prior to the onset of ARN. Twelve patients (55%) had identifiable (clinical or subclinical) immune dysfunction. At 6 months, 3 out of 15 eyes (20%) maintained vision 6/12 or better and 7 (47%) were 6/60 or worse. Median final VA was 6/60. Nine eyes developed retinal detachment and two‐thirds of these had received prior barrier laser. Poor prognostic factors for severe visual loss by univariate analysis were male gender (P = 0.019), and the development of retinal detachment (P = 0.05). Delay between onset of symptoms and diagnosis was associated with moderate visual loss (P = 0.018). Barrier laser did not reduce the risk of retinal detachment.
Conclusions: Acute retinal necrosis still has poor visual prognosis. Early diagnosis and initiation of treatment may improve outcome.
To examine the course of non-infectious uveitis during pregnancy.
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.
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<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.
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.
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.
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.
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.
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.
To evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), ...and the intravitreal dexamethasone implant (IDI).
Multicenter, randomized clinical trial.
Patients with uveitic ME.
Patients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes.
The primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included ≥20% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks.
All treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio HR, 0.79; 99.87% confidence interval CI, 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 0.56-0.86) had larger reductions in CST than PTA (P < 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P < 0.004). The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95% CI, 0.91-3.65 and HR, 2.52; 95% CI, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups.
Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments.
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 retinal thickness data were 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.98 for reproducibility of caliper measurement. Macular edema (centerpoint thickness ≥ 240 μm) was present in 36%. Cysts were present in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement ranged from 78 to 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.
To evaluate the 2-year outcomes of uveitic macular edema.
Longitudinal follow-up of a randomized cohort.
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 2-year follow-up.
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.
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).
Between 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).
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. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema.
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