Noninfectious uveitis (NIU) is a collection of intraocular inflammatory disorders that may be associated with significant visual impairment. To our knowledge, few studies have investigated NIU ...prevalence overall or stratified by inflammation location, severity, presence of systemic conditions, age, or sex.
To estimate NIU prevalence using a large, retrospective, administrative claims database.
This analysis used the OptumHealth Reporting and Insights database to estimate 2012 NIU prevalence. Analysis was conducted in September 2016. The large administrative insurance claims database includes 14 million privately insured individuals in 69 self-insured companies spanning diverse industries. Included in the study were patients with NIU with 2 or more uveitis diagnoses on separate days in 2012 and continuous enrollment in a health plan for all of 2012 and categorized by inflammation site.
We estimated overall NIU prevalence by inflammation site, severity, sex, and age. Patients with anterior NIU were categorized by the presence of systemic conditions.
Of the approximately 4 million eligible adult patients, approximately 2.1 million were women, and of the 932 260 children, 475 481 were boys. The adult prevalence of NIU was 121 cases per 100 000 persons (95% CI, 117.5-124.3). The pediatric NIU prevalence was 29 cases per 100 000 (95% CI, 26.1-33.2). Anterior NIU accounted for 81% (3904 cases) of adult NIU cases (98 per 100 000; 95% CI, 94.7-100.9) and 75% (207 cases) of pediatric NIU cases (22 per 100 000; 95% CI, 19.3-25.4). The prevalences of noninfectious intermediate, posterior, and panuveitis were, for adults, 1 (95% CI, 0.8-1.5), 10 (95% CI, 9.4-11.5), and 12 (95% CI, 10.6-12.7) per 100 000, respectively, and for pediatric patients, 0 (95% CI, 0.1-1.1), 3 (95% CI, 1.8-4.1), and 4 (95% CI, 2.9-5.6) per 100 000, respectively. The prevalence of NIU increased with age and was higher among adult females than males. Application of these estimates to the US population suggests that NIU affected approximately 298 801 American adults (95% CI, 290 512-307 324) and 21 879 children (95% CI, 19 360-24 626) in 2015.
The estimated prevalence of NIU was 121 cases per 100 000 for adults (95% CI, 117.5-124.3) and 29 per 100 000 for children (95% CI, 26.1-33.2). Prevalence was estimated using administrative claims from a commercially insured population, which may have a different prevalence than other segments of the US population. A better understanding of the prevalence of NIU will help to determine the number of patients affected.
To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious ...intermediate, posterior, or panuveitis (uveitis).
Randomized controlled parallel superiority trial.
Patients with active or recently active uveitis.
Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (3 countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis.
Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life, ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked.
On evaluation of changes from baseline to 24 months among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), the implant and systemic therapy groups had an improvement in visual acuity of +6.0 and +3.2 letters (P = 0.16, 95% confidence interval on difference in improvement between groups, -1.2 to +6.7 letters, positive values favoring implant), an improvement in vision-related quality of life of +11.4 and +6.8 units (P = 0.043), a change in EuroQol-EQ5D health utility of +0.02 and -0.02 (P = 0.060), and residual active uveitis in 12% and 29% (P=0.001), respectively. Over the 24 month period, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio HR = 3.3, P < 0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, P < 0.0001), and glaucoma (17%, HR=4.2, P = 0.0008). Patients assigned to systemic therapy had more prescription-requiring infections than patients assigned to implant therapy (0.60 vs 0.36/person-year, P=0.034), without notable long-term consequences; systemic adverse outcomes otherwise were unusual in both groups, with minimal differences between groups.
In each treatment group, mean visual acuity improved over 24 months, with neither approach superior to a degree detectable with the study's power. Therefore, the specific advantages and disadvantages identified should dictate selection between the alternative treatments in consideration of individual patients' particular circumstances. Systemic therapy with aggressive use of corticosteroid-sparing immunosuppression was well tolerated, suggesting that this approach is reasonably safe for local and systemic inflammatory disorders.
Proprietary or commercial disclosure may be found after the references.
Mucous membrane pemphigoid and pseudopemphigoid Thorne, Jennifer E; Anhalt, Grant J; Jabs, Douglas A
Ophthalmology (Rochester, Minn.),
2004, 2004-Jan, 2004-1-00, 20040101, Letnik:
111, Številka:
1
Journal Article
Recenzirano
To describe the clinical characteristics of patients with mucous membrane pemphigoid (MMP) and pseudopemphigoid.
Retrospective cohort study.
Two hundred eighty consecutive patients referred for the ...evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001.
Information on patients presenting for evaluation of possible MMP was entered prospectively into a database, which was supplemented by a retrospective chart review. Mucous membrane pemphigoid was diagnosed in patients with a compatible clinical picture by the linear deposition of antibodies to the basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous membrane biopsy specimen or by the presence of circulating autoantibodies to epithelial BMZ.
Demographic and clinical characteristics of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with extraocular MMP without ocular disease.
Among patients with ocular MMP, extraocular disease was common (82.4% of patients). The risk of ocular involvement among patients with MMP seen without ocular disease was approximately 5% per year over the first 5 years of follow-up (cumulative risk at 5 years, 22%). Although immunohistologic confirmation of the diagnosis was obtained in all patients, the initial conjunctival biopsy was positive for MMP in 80% of the patients diagnosed with ocular MMP. The most frequent presumed causes of pseudopemphigoid were topical glaucoma medications (28.3%), rosacea blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and conjunctival lichen planus (8.3%).
Patients with ocular MMP typically have other systemic manifestations of MMP. Patients who are initially seen with extraocular MMP without ocular involvement are at risk for ocular disease developing. The clinical characteristics of ocular MMP and pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied tissue is needed to confirm the diagnosis of MMP.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new ...millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.
To develop classification criteria for 25 of the most common uveitides.
Machine learning using 5,766 cases of 25 uveitides.
Cases were collected in an informatics-designed preliminary database. Using ...formal consensus techniques, a final database was constructed of 4,046 cases achieving supermajority agreement on the diagnosis. Cases were analyzed within uveitic class and were split into a training set and a validation set. Machine learning used multinomial logistic regression with lasso regularization on the training set to determine a parsimonious set of criteria for each disease and to minimize misclassification rates. The resulting criteria were evaluated in the validation set. Accuracy of the rules developed to express the machine learning criteria was evaluated by a masked observer in a 10% random sample of cases.
Overall accuracy estimates by uveitic class in the validation set were as follows: anterior uveitides 96.7% (95% confidence interval CI 92.4, 98.6); intermediate uveitides 99.3% (95% CI 96.1, 99.9); posterior uveitides 98.0% (95% CI 94.3, 99.3); panuveitides 94.0% (95% CI 89.0, 96.8); and infectious posterior uveitides / panuveitides 93.3% (95% CI 89.1, 96.3). Accuracies of the masked evaluation of the “rules” were anterior uveitides 96.5% (95% CI 91.4, 98.6) intermediate uveitides 98.4% (91.5, 99.7), posterior uveitides 99.2% (95% CI 95.4, 99.9), panuveitides 98.9% (95% CI 94.3, 99.8), and infectious posterior uveitides / panuveitides 98.8% (95% CI 93.4, 99.9).
The classification criteria for these 25 uveitides had high overall accuracy (ie, low misclassification rates) and seemed to perform well enough for use in clinical and translational research.
To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN).
Literature searches of the PubMed and Cochrane Library databases ...were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective.
Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear.
Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time.
Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial ...to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.
This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported.
The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years).
In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).
To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation.
Retrospective cohort study.
Patients with noninfectious ocular inflammation managed at 4 tertiary ocular ...inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive.
Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers.
Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy.
Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for >or=28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone <or=10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%, 37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66% and 58.4% for sustained control and corticosteroid sparing (<or=10 mg), respectively. Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment.
Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving corticosteroid-sparing objectives, although many months may be required for therapeutic success. Methotrexate was well tolerated by most patients, and seems to convey little risk of serious side effects during treatment.
A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides ...did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known.
To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis.
Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016).
Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated.
Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death.
Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 interquartile range, 36-56 years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%).
In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up.
clinicaltrials.gov Identifier: NCT00132691.
PDF
