The Risk of Intraocular Pressure Elevation in Pediatric Noninfectious Uveitis

To characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric non-infectious uveitis

The Risk of Intraocular Pressure Elevation in Pediatric Noninfectious Uveitis

PURPOSE: To characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric non-infectious uveitis. DESIGN: Multi-center retrospective cohort study. PARTICIPANTS: Nine hundred sixteen children (1593 eyes) <18 years old at presentation with non-infectious uveitis followed between January 1978 through December 2007 at five academic uveitis centers in United States. METHODS: Medical records review by trained, certified experts. MAIN OUTCOME MEASURES: Prevalence and incidence of IOP≥21 and ≥30mmHg and incidence of a rise in IOP by ≥10mmHg. To avoid under ascertainment, outcomes were counted as present when IOP-lowering therapies were in use. RESULTS: Initially 251 (15.8%) and 46 eyes (2.9%) had IOP≥21 and ≥30mmHg, respectively. Factors associated with presenting IOP elevation included age 6–12 years (versus other pediatric ages), prior cataract surgery (adjusted odds ratio≥21mmHg [aOR21]=2.42, P=0.01), pars plana vitrectomy (adjusted odds ratio≥30mmHg[aOR30]=11.1, P=0.03), duration of uveitis ≥6 months (aORs30 up to 11.8, P<0.001), contralateral IOP elevation (aOR21=16.9, aOR30=8.29; each P<0.001), visual acuity worse than 20/40 (aORs21 up to 1.73, P=0.02; aORs30 up to 2.81 P=0.03), and topical corticosteroid use (aORs up to 8.92, P<0.001 in a dose-response relationship). The median follow-up was 1.25 years (interquartile range 0.4–3.66). The estimated risk of any observed IOP elevation to ≥21 mmHg, ≥30 mmHg and of a rise in IOP by ≥10mmHg was 33.4%, 14.8% and 24.4% respectively within 2 years. Factors associated with IOP elevation included pars plana vitrectomy (adjusted hazard ratio≥21mmHg[aHR21]=3.36, P<0.001), contralateral IOP elevation (aHRs up to 9.54, P<0.001), the use of topical (aHRs up to 8.77 that followed a dose-response relationship, P<0.001), periocular (aHRs up to 7.96, P<0.001) and intraocular (aHRs up to 19.7, P<0.001) corticosteroids. CONCLUSIONS: IOP elevation affects a large minority of children with non-infectious uveitis. Statistically significant risk factors include IOP elevation or use of IOP-lowering treatment in the contralateral eye and local corticosteroid use – that demonstrated a dose-and route of administration-dependent relationship. In contrast, use of immunosuppressive drug therapy did not increase such risk. Pediatric eyes with non-infectious uveitis should be followed closely for IOP elevation when strong risk factors such as the use of local corticosteroids and contralateral IOP elevation are present

Use of Immunosuppression and the Risk of Subsequent Overall or Cancer Mortality

OBJECTIVE: To determine the incidence of all-cause and cancer mortality in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and cancer mortality for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with non-infectious OID, excluding those with HIV infection or pre-existing cancer. INTERVENTIONS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this non-interventional cohort study. MAIN OUTCOMES AND MEASURES: Overall and cancer mortality. RESULTS: Over 187,151 person-years (median follow-up 10.0 years), during which 15,938 patients were at risk for mortality-we observed 1,970 deaths, 435 attributed to cancer. Both patients unexposed to immunosuppressants (Standardized Mortality Ratio (SMR)=0.95, 95% confidence interval (CI): 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SID) (SMR=1.04, 95% CI: 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents versus patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio (aHR)=0.88, 0.89, 0.90, 1.11) and cancer mortality (aHR=1.25, 0.89, 0.89, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3- or 5-year lags, and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and cancer mortality over a median cohort follow-up of 10.0 years. These results suggest safety of these agents with respect to overall and cancer mortality for patients treated with immunosuppression for a wide range of inflammatory diseases