Celecoxib or Naproxen Treatment Does Not Benefit Depressive Symptoms in Persons Age 70 and Older: Findings From a Randomized Controlled Trial

Background: Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression. One pathway implicated is the production of prostaglandins via the enzyme cyclooxygenase (CO

Role of APOE and Age at Enrollment in the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT)

Background: The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) tested whether non-steroidal anti-inflammatory drugs (NSAIDs) can prevent Alzheimer’s disease (AD). The results were null. We analyzed ADAPT data to examine if the effects of NSAIDs on AD risk differed depending upon APOE genotype or age as has been suggested by previous observational studies. Methods: ADAPT randomized 2,528 cognitively intact older adults to either celecoxib, naproxen sodium or placebo; 2,388 participants provided blood samples for APOE genotyping. Proportional hazards regression was used to estimate the effects of naproxen or celecoxib versus placebo on incident AD by age at enrollment and APOE genotype. Results: The proportion of subjects providing a biological sample did not differ between the treatment groups. In models of AD risk, none of the tests for 2-way interactions between either NSAID and age or APOE genotype were significant (p > 0.05). Conclusions: The data did not support the hypothesis that the association between NSAIDs and AD risk differed by age or APOE genotype

Outcome of Treatment of Uveitic Macular Edema The Multicenter Uveitis Steroid Treatment Trial 2-Year 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

Outcome of Treatment of Uveitic Macular Edema: the Multicenter Uveitis Steroid Treatment Trial 2-Year Results

© 2015 American Academy of Ophthalmology. Purpose To evaluate the 2-year outcomes of uveitic macular edema. 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 2-year follow-up. Methods 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\u27 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\u27 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). 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. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema

Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, or Panuveitis Fifty-foure-Month Results of the Multicenter Uveitis Steroid Treatment Trial and Follow-up Study

Purpose: To evaluate the risks and quality-of-life (QoL) outcomes of fluocinolone acetonide implant versus systemic therapy with corticosteroid and immunosuppression when indicated for intermediate uveitis, posterior uveitis, and panuveitis. Design: Additional follow-up of a randomized trial cohort. Participants: Two hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis, randomized to implant or systemic therapy. Methods: Randomized subjects with intermediate uveitis, posterior uveitis, or panuveitis (479 eyes) were followed up over 54 months, with 79.2% completing the 54-month visit. Main Outcome Measures: Local and systemic potential complications of the therapies and self-reported health utility and vision-related and generic health-related QoL were studied prospectively. Results: Among initially phakic eyes, cataract and cataract surgery occurred significantly more often in the implant group (hazard ratio [HR], 3.0; P = 0.0001; and HR, 3.8; P < 0.0001, respectively). In the implant group, most cataract surgery occurred within the first 2 years. Intraocular pressure elevation measures occurred more frequently in the implant group (HR range, 3.7-5.6; all P < 0.0001), and glaucoma (assessed annually) also occurred more frequently (26.3% vs. 10.2% by 48 months; HR, 3.0; P = 0.0002). In contrast, potential complications of systemic therapy, including measures of hypertension, hyperlipidemia, diabetes, bone disease, and hematologic and serum chemistry indicators of immunosuppression toxicity, did not differ between groups through 54 months. Indices of QoL initially favored implant therapy by a modest margin. However, all summary measures of health utility and vision-related or generic health-related QoL were minimally and nonsignificantly different by 54 months, with the exception of the 36-item Short-Form Health Survey physical component summary score, which favored implant by a small margin at 54 months (3.17 on a scale of 100; P = 0.01, not adjusted for multiple comparisons). Mean QoL results were favorable in both groups. Conclusions: These results suggest that fluocinolone acetonide implant therapy is associated with a clinically important increased risk of glaucoma and cataract with respect to systemic therapy, suggesting that careful monitoring and early intervention to prevent glaucoma is warranted with implant therapy. Systemic therapy subjects avoided a significant excess of toxicities of systemic corticosteroid and immunosuppressive therapies in the trial. Self-reported QoL measures initially favored implant therapy, but over time the measures converged, with generally favorable QoL in both groups. (C) 2015 by the American Academy of Ophthalmology