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

Risk of Retinal Neovascularization in Cases of Uveitis

OBJECTIVE: To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with uveitis at four US academic ocular inflammation subspecialty practices. METHODS: Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate. MAIN OUTCOME MEASURES: Prevalence and incidence of NV. RESULTS: Among uveitic eyes of 8931 patients presenting for initial evaluation, 106/13,810 eyes had NV (prevalence=0.77%, 95% confidence interval (CI): 0.60%–0.90%). Eighty-eight more eyes developed NV over 26,465 eye-years (incidence=0.33%/eye-year, 95% CI: 0.27–0.41%). Factors associated with incident NV include age <35 as compared to >35 years (adjusted hazard ratio (aHR) = 2.4, 95% CI: 1.5–3.9), current cigarette smoking (aHR=1.9, 95% CI: 1.1–3.4), and systemic lupus erythematosus (aHR=3.5, 95% CI: 1.1–11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared to patients diagnosed >5 years ago, aHR=2.4 (95% CI 1.1–5.0) and aHR=2.6 (95%CI 1.2–6.0) for diagnosis within <1 year vs. 1–5 years respectively). Compared to anterior uveitis, intermediate uveitis (aHR=3.1, 95% CI: 1.5–6.6), posterior uveitis (aHR=5.2, 95% CI: 2.5–11), and panuveitis (aHR=4.3, 95% CI: 2.0–9.3) were associated with a similar degree of increased NV incidence. Active (aHR=2.1, 95%CI: 1.2–3.7) and slightly active (aHR=2.4, 95%CI: 1.3–4.4) inflammation were associated with an increased incidence of NV as compared to inactive inflammation. NV incidence also was increased with retinal vascular occlusions (aHR=10, 95% CI: 3.0–33), retinal vascular sheathing (aHR=2.6, 95% CI: 1.4–4.9), and exudative retinal detachment (aHR=4.1, 95% CI: 1.3–13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR=2.3, 95% CI: 1.1–4.9); and systemic hypertension (aHR 1.5; 95% CI:0.89–2.4) was associated with non-significantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus. CONCLUSIONS: Retinal neovascularization is a rare complication of uveitis, which occurs more frequently in younger patients; smokers; and those with intermediate/posterior/panuveitis, systemic vasculopathy and/or retinal vascular disease; and active inflammation. Inflammation and retinal neovascularization likely are linked; additional studies are needed to further elucidate this connection

Incidence and remission of post-surgical cystoid macular edema following cataract surgery in eyes with intraocular inflammation

PURPOSE: To evaluate the incidence, remission and relapse of post-surgical cystoid macular edema (PCME) following cataract surgery in inflammatory eye disease. METHODS: A total of 1859 eyes that had no visually significant macular edema prior to cataract surgery while under tertiary uveitis management were included. Standardized retrospective chart review was used to gather clinical data. Univariable and multivariable logistic regression models with adjustment for inter-eye correlations were performed. RESULTS: PCME causing VA 20/50 or worse was reported in 286 eyes (15%) within 6 months of surgery. Adults age 18-64 years as compared to children (adjusted Odds ratio (aOR) 2.42, for ages 18-44 and aOR 1.93 for ages 45-64, overall p = 0.02); concurrent use of systemic immunosuppression (conventional aOR 1.53 and biologics aOR 2.68, overall p =0.0095); pre-operative VA 20/50 or worse (overall p \u3c0.0001); cataract surgery performed before 2000 (overall p=0.03) and PMCE in fellow eye (aOR 3.04, p=0.0004) were associated with development of PCME within 6 months of cataract surgery. PCME resolution was seen in 81% of eyes at 12 months and 91% of eyes at 24 months. CME relapse was seen in 12% eyes at 12 months and 19% eyes at 24 months. CONCLUSIONS: PCME occurs frequently in uveitic eyes undergoing cataract surgery, however, most resolve within a year. CME recurrences likely are due to the underlying disease process and not relapses of PCME

Incidence and Outcome of Cataract in Eyes with Scleritis and Episcleritis

PURPOSE: To estimate the incidence and predictive factors for cataract in eyes with episcleritis and scleritis, and to evaluate the outcome of cataract surgery in those eyes. DESIGN: Retrospective cohort study at uveitis subspecialty centers. METHODS: One thousand three hundred eighty-four eyes with non-infectious scleritis and episcleritis at risk of cataract were included. Predictive factors for cataract development were assessed by multivariable Cox regression. The main outcomes were development of cataract, defined as the first reduction of presenting visual acuity \u3c20/40 attributed to cataract or else occurrence of cataract surgery itself. A second cohort of eyes with episcleritis and scleritis that underwent cataract surgery was evaluated for postoperative outcomes. Logistic regression was utilized to assess variables associated with visual acuity 20/40 or better one year after cataract surgery. RESULTS: Seventy-six eyes developed cataract (incidence = 0.025/eye-year, 95% confidence interval: 0.019-0.031). Age ≥65 years, elevated intraocular pressure ≥30 mmHg, use of oral corticosteroids at the preceding visit, and anterior chamber inflammatory activity were associated with increased cataract incidence. Race/ethnicity, type of scleritis, and bilaterality were unassociated with cataract risk after adjustment. Among 79 cataractous eyes that underwent cataract surgery, median presenting visual acuity improved by 6 ETDRS lines. Pre-operative factors including duration of inflammation, immunotherapy use, and corticosteroid use were not significantly associated with odds of post-operative visual acuity 20/40 or better. CONCLUSIONS: Under subspecialty management, the incidence of cataract was low in eyes with episcleritis and scleritis. Cataract surgery was associated with large and sustained improvements in visual acuity

Effectiveness of Frequently Used TNF Inhibitors vs. Conventional Immunosuppressive Therapies for Noninfectious Uveitis

To compare the corticosteroid sparing efficacy of frequently used antimetabolites to tumor necrosis factor (TNF) inhibitors in the management of noninfectious ocular inflammation.PURPOSETo compare the corticosteroid sparing efficacy of frequently used antimetabolites to tumor necrosis factor (TNF) inhibitors in the management of noninfectious ocular inflammation.Retrospective analysis of patients with noninfectious uveitis on conventional antimetabolite (methotrexate, mycophenolate mofetil, azathioprine,or leflunomide, "CONV") or a TNF inhibitor (adalimumab or infliximab, "TNFi") with active inflammation or more than 7.5 mg daily prednisone. Eyes were assessed in three groups: CONV only, TNFi only and combination of both (COMB). Cox regression models compared treatment success, adjusted for age, race, smoking, anatomic location of uveitis, duration of uveitis and visual acuity. Corticosteroid sparing success was defined as: inactive or slightly active uveitis on <=7.5 mg daily oral prednisone and <=2 drops of prednisolone acetate 1%.METHODSRetrospective analysis of patients with noninfectious uveitis on conventional antimetabolite (methotrexate, mycophenolate mofetil, azathioprine,or leflunomide, "CONV") or a TNF inhibitor (adalimumab or infliximab, "TNFi") with active inflammation or more than 7.5 mg daily prednisone. Eyes were assessed in three groups: CONV only, TNFi only and combination of both (COMB). Cox regression models compared treatment success, adjusted for age, race, smoking, anatomic location of uveitis, duration of uveitis and visual acuity. Corticosteroid sparing success was defined as: inactive or slightly active uveitis on <=7.5 mg daily oral prednisone and <=2 drops of prednisolone acetate 1%.There were 1475 eligible patients in the analysis. By 6 and 12 months, respectively, the Cox model-predicted, percentage success was 27.6% and 44.9% for the CONV group; 34.2% and 53.9% in the TNFi group and 39.9% and 61.1% for the COMB group. COMB was more likely than CONV to achieve success (adjusted HR 1.58 (95% confidence interval (CI), 1.28, 1.95, p < 0.0001). Factors associated with lower success were age under 18 years, smoking, visual acuity worse than 20/50 at cohort entry, over 4-year duration of uveitis and daily baseline prednisone 7.5 mg or higher (all p < 0.05).RESULTSThere were 1475 eligible patients in the analysis. By 6 and 12 months, respectively, the Cox model-predicted, percentage success was 27.6% and 44.9% for the CONV group; 34.2% and 53.9% in the TNFi group and 39.9% and 61.1% for the COMB group. COMB was more likely than CONV to achieve success (adjusted HR 1.58 (95% confidence interval (CI), 1.28, 1.95, p < 0.0001). Factors associated with lower success were age under 18 years, smoking, visual acuity worse than 20/50 at cohort entry, over 4-year duration of uveitis and daily baseline prednisone 7.5 mg or higher (all p < 0.05).Our results suggest COMB is more effective than CONV at achieving disease quiescence and corticosteroid sparing success among patients with active noninfectious uveitis. More research is needed to determine if TNFi alone is superior to CONV for uveitic corticosteroid-sparing.CONCLUSIONOur results suggest COMB is more effective than CONV at achieving disease quiescence and corticosteroid sparing success among patients with active noninfectious uveitis. More research is needed to determine if TNFi alone is superior to CONV for uveitic corticosteroid-sparing

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