INTRAOCULAR PRESSURE IN PATIENTS WITH DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE INTRAVITREAL IMPLANT IN THE 3-YEAR MEAD STUDY.

PURPOSE: To evaluate the occurrence, management, and clinical significance of increases in intraocular pressure (IOP) in patients with diabetic macular edema treated with dexamethasone intravitreal implant (DEX implant). METHODS: Randomized, multicenter, 3-year, Phase III study. Patients (N = 1,048) with diabetic macular edema were randomized to DEX implant 0.7-mg, DEX implant 0.35-mg, or sham procedure with retreatment allowed at ≥6-month intervals (seven injections maximum). RESULTS: In the DEX implant 0.7-mg, DEX implant 0.35-mg, and sham groups, respectively, ≥10-mmHg IOP increases from baseline occurred in 27.7%, 24.8%, and 3.7% of patients, and their frequency did not increase with repeat injections. IOP-lowering medication was used by 41.5%, 37.6%, and 9.1% of patients. Only one patient (0.3%) in each DEX implant group had filtering surgery to manage a steroid-induced IOP increase. Among DEX implant 0.7-mg-treated patients with and without a ≥10-mmHg IOP increase, 21.9% (21 of 96) and 22.4% (57 of 255), respectively, achieved ≥15-letter best-corrected visual acuity gain at the end of the study, and mean average change in central retinal thickness from baseline was -127 µm and -106 µm, respectively. CONCLUSION: DEX implant demonstrated clear benefit of treatment despite increases in IOP. Sequential implants had no cumulative effect on IOP.

Anatomical effects of dexamethasone intravitreal implant in diabetic macular oedema: a pooled analysis of 3-year phase III trials.

BACKGROUND/AIM: To assess long-term effects of dexamethasone intravitreal implant (DEX implant) monotherapy on retinal morphology in diabetic macular oedema (DME). METHODS: Two multicentre, masked, phase III studies with identical protocols randomised patients with DME, best-corrected visual acuity of 34-68 Early Treatment Diabetic Retinopathy Study letters and central subfield retinal thickness (CSRT) ≥300 µm to DEX implant 0.7, 0.35 mg or sham procedure. Patients were followed up for 3 years (39 months if treated at month 36), with retreatment allowed at ≥6-month intervals. Patients needing other macular oedema (ME) therapy exited the study. Changes from baseline in CSRT, macular volume and ME grade, area of retinal thickening, macular leakage, macular capillary loss and diabetic retinopathy severity were assessed. RESULTS: After 3 years, more eyes treated with DEX implant 0.7 and 0.35 mg than sham showed improvement (although small) in ME grade (p<0.05 vs sham). DEX implant 0.7 mg delayed time to onset of two-step progression in diabetic retinopathy severity by ∼12 months. DEX implant 0.7 and 0.35 mg produced small, non-sustained reductions in macular leakage but had no significant effect on macular capillary loss. CONCLUSIONS: DEX implant 0.7 or 0.35 mg, administered at ≥6-month intervals over 3 years, produced sustained retinal structural improvement in DME. TRIAL REGISTRATION NUMBER: NCT00168337 and NCT00168389.

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema: subgroup analysis of the MEAD study.

BACKGROUND: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. METHODS: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34-68 Early Treatment Diabetic Retinopathy Study letters (20/200-20/50 Snellen equivalent), and central retinal thickness (CRT) ≥ 300 µm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥ 15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. RESULTS: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n = 261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5% of DEX 0.7 patients versus 11.1 % of sham had ≥ 15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 µm with DEX 0.7 versus -39.0 µm with sham (P < .001). Cataract-related adverse events were reported in 70.3% of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. CONCLUSIONS: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00168337 and NCT00168389, registered 12 September 2005.

Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.

PURPOSE: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME). DESIGN: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis. PARTICIPANTS: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 µm by optical coherence tomography. METHODS: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months. MAIN OUTCOME MEASURES: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP). RESULTS: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (-111.6 µm) and DEX implant 0.35 mg (-107.9 µm) than sham (-41.9 µm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy. CONCLUSIONS: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

Vision-related functioning outcomes of dexamethasone intravitreal implant in noninfectious intermediate or posterior uveitis.

PURPOSE: To evaluate the effect of a single treatment with dexamethasone intravitreal implant (DEX implant) on patient-reported visual functioning in patients with noninfectious intermediate or posterior uveitis. METHODS: Patient eyes with noninfectious intermediate or posterior uveitis were randomized to a single treatment with DEX implant 0.70 mg (n=77), DEX implant 0.35 mg (n=76), or a sham procedure (n=76) and followed for 26 weeks. Vision-related functioning was measured using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) assessed at baseline and at weeks 8, 16, and 26 or early exit. Analysis of covariance and mixed model analysis of covariance were used to compare vision-related functioning between the DEX implant 0.70 and 0.35 mg groups and the sham group. RESULTS: By 8 weeks, the DEX implant 0.70 mg group demonstrated significant improvements in NEI VFQ-25 subscales near vision (P=0.031), distance vision (P=0.023), peripheral vision (P=0.045), vision-specific social functioning (P=0.019), and the NEI VFQ-25 composite score (P=0.007) compared with sham. After 26 weeks, the DEX implant 0.70 mg group reported significant improvements in NEI VFQ-25 subscales distance vision (P=0.003), vision-specific role difficulties (P=0.038), vision-specific dependency (P=0.017), vision-specific social functioning (P=0.009), vision-specific mental health (P=0.036), and the composite score (P=0.001) compared with sham. CONCLUSIONS: In patients with noninfectious intermediate or posterior uveitis receiving a single treatment of DEX implant 0.70 mg, significant and clinically meaningful improvements in patient-reported visual functioning were observed as early as week 8 and were maintained over 26 weeks. (ClinicalTrials.gov number, NCT00333814.).

Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis.

OBJECTIVE: To evaluate the safety and efficacy of 2 doses of dexamethasone intravitreal implant (DEX implant) for treatment of noninfectious intermediate or posterior uveitis. METHODS: In this 26-week trial, eyes with noninfectious intermediate or posterior uveitis were randomized to a single treatment with a 0.7-mg DEX implant (n = 77), 0.35-mg DEX implant (n = 76), or sham procedure (n = 76). MAIN OUTCOME MEASURE: The main outcome measure was the proportion of eyes with a vitreous haze score of 0 at week 8. RESULTS: The proportion of eyes with a vitreous haze score of 0 at week 8 was 47% with the 0.7-mg DEX implant, 36% with the 0.35-mg DEX implant, and 12% with the sham (P < .001); this benefit persisted through week 26. A gain of 15 or more letters from baseline best-corrected visual acuity was seen in significantly more eyes in the DEX implant groups than the sham group at all study visits. The percentage of eyes with intraocular pressure of 25 mm Hg or more peaked at 7.1% for the 0.7-mg DEX implant, 8.7% for the 0.35-mg DEX implant, and 4.2% for the sham (P > .05 at any visit). The incidence of cataract reported in the phakic eyes was 9 of 62 (15%) with the 0.7-mg DEX implant, 6 of 51 (12%) with the 0.35-mg DEX implant, and 4 of 55 (7%) with the sham (P > .05). CONCLUSIONS: In patients with noninfectious intermediate or posterior uveitis, a single DEX implant significantly improved intraocular inflammation and visual acuity persisting for 6 months. Application to Clinical Practice Dexamethasone intravitreal implant may be used safely and effectively for treatment of intermediate and posterior uveitis. Trial Registration clinicaltrials.gov Identifier: NCT00333814.

Celecoxib effectively treats patients with acute shoulder tendinitis/bursitis.

OBJECTIVE: Shoulder tendinitis and subacromial bursitis are acute, painful inflammatory musculoskeletal conditions that may recur as a result of overuse. We investigated the efficacy of celecoxib in managing patients with acute shoulder tendinitis/bursitis. METHODS: In this double blind, placebo controlled, parallel group study, patients with acute onset shoulder tendinitis and/or subacromial bursitis were randomized to receive one of: celecoxib 400 mg followed by 200 mg bid, naproxen 500 mg bid, or placebo bid for 14 days. The primary measure of efficacy was the mean reduction in Maximum Pain Intensity at Rest, measured using a 100 mm visual analog scale, from baseline to Days 7 and 14. RESULTS: Of the 306 patients randomized to treatment, 254 completed the study. On Day 7, the mean reduction from baseline in Maximum Pain Intensity at Rest was significantly greater in the celecoxib group compared with the placebo group (-27.7 +/- 2.75 mm vs -18.4 +/- 2.63 mm, respectively; p < 0.05). Similarly, on Day 14, the mean reduction from baseline in Maximum Pain Intensity at Rest was greater in the celecoxib group compared with placebo (-35.0 +/- 3.06 mm vs -25.0 +/- 3.05 mm; p < 0.05). The mean reduction from baseline in Maximum Pain Intensity at Rest was also greater in the naproxen group compared with the placebo group at Day 7 (-26.4 +/- 2.70 mm vs -18.4 +/- 2.63 mm; p < 0.05), but not on Day 14. Secondary measures of efficacy also showed treatment with celecoxib to be significantly better than placebo treatment and similar to treatment with naproxen. In addition, celecoxib was well tolerated in these patients. CONCLUSION: Celecoxib showed comparable efficacy to naproxen in relieving the pain of patients with acute shoulder tendinitis and/or subacromial bursitis.