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Background/objectives: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO)., Subjects/methods: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses., Results: Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P < 0.001)., Conclusions: Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO.

Purpose: This post hoc analysis explores the relationship between early retinal anatomical response and long-term anatomical and visual outcomes with ranibizumab in center-involved diabetic macular edema., Methods: Eyes randomized to the ranibizumab plus prompt laser and ranibizumab plus deferred laser treatment arms in the Protocol I study were categorized according to their proportional reduction (<20 vs. ≥20%) in central retinal thickness (CRT) after 12 weeks. Adjusted and unadjusted analyses assessed the association between early (Week 12) anatomical response and long-term (Weeks 52 and 156) anatomical and best-corrected visual acuity outcomes., Results: Of 335 study eyes, 118 showed limited (<20%) and 217 showed strong (≥20%) CRT reduction at Week 12. In unadjusted and adjusted analyses, limited early CRT response was negatively and significantly associated with strong CRT response at Weeks 52 and 156. Sensitivity analyses indicated that this association was robust and unrelated to any "floor effect." In unadjusted analyses, a strong early CRT response was associated with greater long-term improvement in best-corrected visual acuity; after controlling for confounders, the association lost statistical significance., Conclusion: Early CRT response to ranibizumab is a significant prognostic indicator of medium- to long-term anatomical outcome in center-involved diabetic macular edema.

Purpose: Corticosteroids remain the mainstay of treatment for inflammatory diseases almost 80 years after their first clinical use. Topical ophthalmic formulations of corticosteroids have been available to treat disease of the anterior segment of the eye, but the approval of corticosteroids to treat vitreoretinal diseases, including vein occlusion, diabetic macular edema, and uveitis, has occurred only recently. Although most diseases respond to corticosteroid therapy, some patients are resistant to this therapy and side effects, including cataract and elevated intraocular pressure, can limit their use. The purpose of this review is to detail the basic science of corticosteroids focusing on differences in potency, drug delivery, pharmacokinetics, and gene activation, and how these differences affect safety and efficacy in the treatment of diabetic macular edema., Methods: A review was conducted of basic science and pharmacology of the corticosteroids used to treat diabetic macular edema., Results: Clinically available corticosteroids not only have differing potency and pharmacokinetics, but also activate different genes in different target tissues. These differences are associated with distinct efficacy, pharmacokinetic, and safety profiles. It is important to understand these differences in selecting corticosteroids to treat diabetic macular edema., Conclusions: Recent advances in our understanding of the basic science of corticosteroids can explain clinical differences in these agents regarding efficacy and safety. Importantly, this understanding should allow the future discovery of additional novel corticosteroids to treat diabetic macular edema.

Purpose: To evaluate whether treatment with dexamethasone intravitreal implant (DEX implant) 0.7 mg every 5 months provides a similar average change in best-corrected visual acuity (BCVA) from baseline as ranibizumab 0.5 mg administered as per its European Summary of Product Characteristics in patients with diabetic macular edema (DME)., Methods: This was a multicenter, open-label, 12-month, randomized, parallel-group, noninferiority study in patients with DME (one eye/patient). The primary efficacy measure was BCVA using the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Secondary efficacy measures included area of leakage on fluorescein angiography and central retinal thickness (CRT) on optical coherence tomography., Results: Baseline patient characteristics were similar in the two treatment groups (DEX implant, n = 181; ranibizumab, n = 182); mean DME duration was ∼33 months. The mean average BCVA change from baseline over 12 months was 4.34 letters with DEX implant and 7.60 letters with ranibizumab. The lower limit of the 95 % confidence interval of the between-group difference was -4.74 letters, and therefore, DEX was demonstrated to be noninferior to ranibizumab based on the prespecified noninferiority margin of 5 letters. At monthly follow-up visits, the percentage of patients with ≥15-letter BCVA gain from baseline ranged from 7.2 to 17.7 % with DEX implant and 4.4 to 26.9 % with ranibizumab. Both DEX implant and ranibizumab effectively reduced CRT and reduced the area of fluorescein leakage. Between-group differences in change from baseline CRT favored DEX implant at 1, 2, 6, and 7 months (p ≤ 0.007) and ranibizumab at 4, 5, 9, and 10 months (p < 0.001); the decrease in fluorescein leakage area was greater with DEX implant than ranibizumab at month 12 (p < 0.001). Ocular adverse events in the study eye were more frequent in the DEX implant group because of the occurrence of intraocular pressure (IOP) increases and cataract. IOP increases were transient and generally managed with topical medication., Conclusions: Both DEX implant and ranibizumab were well tolerated and improved BCVA and anatomic outcomes in patients with DME. DEX implant met the a priori criterion for noninferiority to ranibizumab in average change from baseline BCVA over 12 months. Noninferiority was achieved with an average of 2.85 DEX implant injections and 8.70 ranibizumab injections per patient.

Purpose: To determine whether early visual acuity response to ranibizumab in diabetic macular edema is associated with long-term outcome., Design: Post hoc analysis of randomized controlled trial data., Methods: Pooled data from the ranibizumab plus prompt and deferred laser treatment arms of the Diabetic Retinopathy Clinical Research Network's Protocol I study were used to explore the relationship between early (week 12) and late (weeks 52-156) visual acuity response (mean change from baseline in best-corrected visual acuity [CFB BCVA]; categorized improvement [<5, 5-9, or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] in BCVA)., Results: In the analysis population (340 eyes), <5-, 5- to 9-, and ≥10-letter BCVA improvements occurred in 39.7%, 23.2%, and 37.1% of eyes, respectively, at 12 weeks, and 34.2%, 16.5%, and 49.3% of eyes at 156 weeks. Within each early BCVA response category (<5, 5-9, and ≥10 letters of improvement at 12 weeks), mean CFB BCVA at 52-156 weeks varied by <5 letters from that at 12 weeks. CFB BCVA and <5-letter improvement at 12 weeks showed significant positive and negative association, respectively, with CFB BCVA and ≥10-letter improvement at 52 and 156 weeks. Similar relationships were demonstrated in eyes with baseline BCVA <69 letters, and associations remained significant after multivariate adjustment for potential confounders., Conclusions: Ranibizumab ± laser therapy resulted in similar rates (∼40%) of suboptimal (<5-letter) and pronounced (≥10-letter) BCVA improvement at 12 weeks. Eyes with suboptimal early BCVA response showed poorer long-term visual outcomes than eyes with pronounced early response (mean improvement 3.0 vs 13.8 letters at 156 weeks)., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: To evaluate the relationship between changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes from two clinical trials of dexamethasone intravitreal implant 0.7 mg for macular edema after branch or central retinal vein occlusion., Methods: Patients with vision loss as a result of macular edema (≥6-week duration) after branch retinal vein occlusion or central retinal vein occlusion were treated with a single dexamethasone intravitreal implant or sham. Prospectively defined outcomes included BCVA and CRT (as assessed by optical coherence tomography)., Results: There was a modest but statistically significant negative linear correlation between changes in CRT and changes in BCVA in both treatment groups at Days 90 and 180 (correlation coefficient: -0.23 to -0.34; P < 0.001). Improvements in BCVA at Day 180 were significantly greater (P < 0.001) in eyes that achieved and maintained CRT ≤250 μm from Day 90 to 180 (mean BCVA improvement: 14 letters; 49% of eyes with ≥15-letter gain) than in eyes that never achieved CRT ≤250 μm (mean BCVA improvement: 2 letters; 13% of eyes with ≥15-letter gain)., Conclusion: The greatest improvements in BCVA were seen in eyes that achieved and maintained the greatest improvements in CRT.

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.

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., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the onset and duration of improvement in best-corrected visual acuity (BCVA) in eyes treated with dexamethasone intravitreal implant 0.7 mg (DEX implant) for macular edema after branch or central retinal vein occlusion., Methods: Post hoc analysis of data from 2 previously reported multicenter, 6-month, randomized sham-controlled clinical trials. Patients received a single DEX implant (n = 427) or sham procedure (n = 426) in the study eye. The primary endpoint was the percentage of eyes with ≥ 15-letter improvement in BCVA from baseline at postimplant Day 7., Results: The baseline mean BCVA was 20/80. At Day 7, 10.3% of DEX implant-treated eyes versus 4.0% of sham-treated eyes (P < 0.001) had ≥ 15-letter improvement in the BCVA, and 27.2% of DEX implant-treated eyes versus 10.6% of sham-treated eyes had ≥ 10-letter improvement (P < 0.001). The mean improvement at Day 7 was 5.3 letters (branch retinal vein occlusion, 5.1; and central retinal vein occlusion, 5.8) with DEX implant and 1.6 letters (branch retinal vein occlusion, 2.3; and central retinal vein occlusion, 0.1) with sham (P < 0.001). The mean time from initial observation of ≥ 15-letter BCVA gain to the last observation of ≥ 15-letter BCVA gain was 70 days., Conclusion: Dexamethasone intravitreal implant treatment led to improvement in BCVA compared with sham procedure as early as postimplant Day 7. The duration of ≥ 3-line improvement was typically 2 to 3 months.

Purpose: To evaluate Ozurdex (dexamethasone intravitreal implant [DEX implant]; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic macular edema (DME)., Design: Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial., Participants: Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled., Intervention: Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed., Main Outcome Measures: The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP)., Results: The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 (P<0.001) and month 9 (P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P ≤ 0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P ≤ 0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required., Conclusions: There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the angiographic findings in eyes from 2 clinical trials of the dexamethasone intravitreal implant (DEX implant) 0.7 mg in the treatment of macular edema (ME) after branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)., Design: Post hoc analysis of pooled data from 2 identical phase 3 clinical trials., Participants: Patients with vision loss as a result of ME (≥ 6 weeks' duration) after BRVO or CRVO for whom angiographic data were available (n = 329 eyes)., Methods: Fluorescein angiography (FA) results assessed by masked, certified graders using standardized grading protocols., Main Outcome Measures: The primary outcome measure in the parent studies was change from baseline in best-corrected visual acuity. Prospectively defined secondary outcomes included FA measurements (to assess macular capillary leakage, neovascularization, and nonperfusion) and optical coherence tomography results (to assess central retinal thickness [CRT])., Results: At baseline, 42% of eyes in the DEX implant group and 38% of eyes in the sham group had unreadable assessments because of hemorrhage. At day 180, significantly fewer DEX implant-treated eyes (2%) than sham-treated eyes (9%) had unreadable assessments because of hemorrhage (P = 0.029). Among eyes with gradable assessments, the incidence of nonperfusion remained fairly steady from baseline to day 180. The proportion of eyes with active neovascularization increased from baseline to day 180 in the sham group, but stayed relatively constant in the DEX implant group (P = 0.026 for DEX vs. sham). The mean area of overall nonperfusion and the mean area of macular capillary nonperfusion increased from baseline to day 180 in both treatment groups (no statistically significant between-group difference). There was a statistically significant positive correlation between changes in macular leakage and changes in CRT in both the DEX implant group (r = 0.22; 95% confidence interval, 0.03-0.40; P = 0.023) and the sham group (r = 0.29; 95% confidence interval, 0.10-0.46; P = 0.003)., Conclusions: This study demonstrated that the clinical improvements observed with the DEX implant were accompanied by significant improvements in vascular parameters and suggests that treatment with the DEX implant may be associated with some clinically significant improvements in angiographic findings, specifically active neovascularization., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the effect of duration of macular edema (ME) on clinical outcomes after treatment with dexamethasone intravitreal implant 0.7 mg (Ozurdex; Allergan, Inc, Irvine, CA) in patients with ME following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)., Design: Post hoc analysis of pooled data from 2 randomized, controlled trials., Participants: Patients with vision loss resulting from ME of 6 weeks' duration or more after BRVO or CRVO (n = 690)., Methods: The relationship between ME duration at the time of first treatment and treatment outcomes was assessed using logistic regression. Other factors potentially associated with ME duration or patient outcomes were adjusted for in the analyses., Main Outcome Measures: The proportion of patients achieving at least 15 letters improvement in best-corrected visual acuity (BCVA) or at least 200-μm or more reduction in central retinal thickness 6 or 12 months after the first treatment with dexamethasone intravitreal implant 0.7 mg., Results: In the 6-month analysis, each 1-month increase in ME duration was associated with a significantly lower likelihood of achieving a BCVA improvement of 15 letters or more (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.83-0.94; P<0.001) or a CRT reduction of 200-μm or more (OR, 0.91; 95% CI, 0.86-0.97; P<0.01) 6 months after treatment. In the 12-month analysis, increased ME duration was associated with a significantly lower likelihood of achieving BCVA improvement of 15 letters or more improvement in BCVA (OR, 0.85; 95% CI, 0.76-0.95; P<0.01) 12 months after treatment; duration was not significantly associated with the likelihood of a CRT reduction of 200-μm or more at 12 months. In general, the effect of ME duration on outcomes was stronger and statistically significant in BRVO patients, but weaker and not statistically significant in CRVO patients., Conclusions: In eyes with retinal vein occlusion, longer ME duration at the time of first treatment with the dexamethasone intravitreal implant 0.7 mg was associated with a significantly lower likelihood of achieving clinically meaningful improvements in vision or CRT 6 or 12 months after treatment. This suggests that prompt treatment for retinal vein occlusion, particularly BRVO, may be associated with improved clinical outcomes., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the safety and efficacy of 1 or 2 treatments with dexamethasone intravitreal implant (DEX implant) over 12 months in eyes with macular edema owing to branch or central retinal vein occlusion (BRVO or CRVO)., Design: Two identical, multicenter, prospective studies included a randomized, 6-month, double-masked, sham-controlled phase followed by a 6-month open-label extension., Participants: We included 1256 patients with vision loss owing to macular edema associated with BRVO or CRVO., Methods: At baseline, patients received DEX implant 0.7 mg (n = 421), DEX implant 0.35 mg (n = 412), or sham (n = 423) in the study eye. At day 180, patients could receive DEX implant 0.7 mg if best-corrected visual acuity (BCVA) was <84 letters or retinal thickness was >250 μm., Main Outcome Measures: The primary outcome for the open-label extension was safety; BCVA was also evaluated., Results: At day 180, 997 patients received open-label DEX implant. Except for cataract, the incidence of ocular adverse events was similar in patients who received their first or second DEX implant. Over 12 months, cataract progression occurred in 90 of 302 phakic eyes (29.8%) that received 2 DEX implant 0.7 mg injections versus 5 of 88 sham-treated phakic eyes (5.7%); cataract surgery was performed in 4 of 302 (1.3%) and 1 of 88 (1.1%) eyes, respectively. In the group receiving two 0.7-mg DEX implants (n = 341), a ≥ 10-mmHg intraocular pressure (IOP) increase from baseline was observed in (12.6% after the first treatment, and 15.4% after the second). The IOP increases were usually transient and controlled with medication or observation; an additional 10.3% of patients initiated IOP-lowering medications after the second treatment. A ≥ 15-letter improvement in BCVA from baseline was achieved by 30% and 32% of patients 60 days after the first and second DEX implant, respectively., Conclusions: Among patients with macular edema owing to BRVO or CRVO, single and repeated treatment with DEX implant had a favorable safety profile over 12 months. In patients who qualified for and received 2 DEX implant injections, the efficacy and safety of the 2 implants were similar with the exception of cataract progression., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the safety and efficacy of Ozurdex (dexamethasone intravitreal implant) 0.7 mg in the treatment of diabetic macular edema in vitrectomized eyes., Methods: This was a prospective, multicenter, open-label, 26-week study. Fifty-five patients with treatment-resistant diabetic macular edema and a history of previous pars plana vitrectomy in the study eye received a single intravitreal injection of 0.7-mg dexamethasone intravitreal implant. The primary efficacy outcome measure was the change in central retinal thickness from baseline to Week 26 measured by optical coherence tomography., Results: The mean age of patients was 62 years. The mean duration of diabetic macular edema was 43 months. The mean (95% confidence interval) change from baseline central retinal thickness (403 μm) was -156 μm (-190, -122 μm) at Week 8 (P < 0.001) and -39 μm (-65, -13 μm) at Week 26 (P = 0.004). The mean (95% CI) increase in best-corrected visual acuity from baseline (54.5 letters) was 6.0 letters (3.9, 8.1 letters) at Week 8 (P < 0.001) and 3.0 letters (0.1, 6.0 letters) at Week 26 (P = 0.046). At Week 8, 30.4% of patients had gained ≥10 letters in best-corrected visual acuity. Conjunctival hemorrhage, conjunctival hyperemia, eye pain, and increased intraocular pressure were the most common adverse events., Conclusion: Treatment with dexamethasone intravitreal implant led to statistically and clinically significant improvements in both vision and vascular leakage from diabetic macular edema in difficult-to-treat vitrectomized eyes and had an acceptable safety profile.

Purpose: The purpose of this study was to evaluate the correlation between best-corrected visual acuity (BCVA) and macular thickness in patients with persistent macular edema treated with a dexamethasone intravitreal drug delivery system (dexamethasone DDS)., Methods: In a randomized, multicenter, controlled, parallel-group, dose-ranging study, patients with macular edema lasting at least 90 days despite treatment were randomized to observation or treatment with 350- or 700-microg dexamethasone DDS. Macular thickness was assessed in 80 patients using optical coherence tomography. Best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study methodology., Results: At baseline, macular thickness was significantly inversely correlated with BCVA (r = -0.406, P < 0.001). Patients treated with 350- or 700-microg dexamethasone DDS showed a significant decrease in macular thickness from baseline to Day 90 (P = 0.002). In the 700-microg dexamethasone DDS treatment group, there was a modest inverse correlation between changes in macular thickness from baseline to Day 90 and improvement in BCVA (r = -0.530, P = 0.009). In the 350-microg dexamethasone DDS treatment group, the correlation was weaker and not statistically significant (r = -0.206, P = 0.304)., Conclusion: The correlation between baseline BCVA and macular thickness in patients with persistent macular edema was modest. Improvement in BCVA after treatment with 700-microg dexamethasone DDS was consistent with changes in macular thickness measured using optical coherence tomography.

Objective: To evaluate the safety and efficacy of dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc., Irvine, CA) compared with sham in eyes with vision loss due to macular edema (ME) associated with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)., Design: Two identical, multicenter, masked, randomized, 6-month, sham-controlled clinical trials (each of which included patients with BRVO and patients with CRVO)., Participants: A total of 1267 patients with vision loss due to ME associated with BRVO or CRVO., Intervention: A single treatment with DEX implant 0.7 mg (n = 427), DEX implant 0.35 mg (n = 414), or sham (n = 426)., Main Outcome Measures: The primary outcome measure for the pooled data from the 2 studies was time to achieve a > or =15-letter improvement in best-corrected visual acuity (BCVA). Secondary end points included BCVA, central retinal thickness, and safety., Results: After a single administration, the time to achieve a > or =15-letter improvement in BCVA was significantly less in both DEX implant groups compared with sham (P<0.001). The percentage of eyes with a > or =15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90 (P<0.001). The percentage of eyes with a > or =15-letter loss in BCVA was significantly lower in the DEX implant 0.7-mg group compared with sham at all follow-up visits (P< or =0.036). Improvement in mean BCVA was greater in both DEX implant groups compared with sham at all follow-up visits (P< or =0.006). Improvements in BCVA with DEX implant were seen in patients with BRVO and patients with CRVO, although the patterns of response differed. The percentage of DEX implant-treated eyes with intraocular pressure (IOP) of > or =25 mmHg peaked at 16% at day 60 (both doses) and was not different from sham by day 180. There was no significant between-group difference in the occurrence of cataract or cataract surgery., Conclusions: Dexamethasone intravitreal implant can both reduce the risk of vision loss and improve the speed and incidence of visual improvement in eyes with ME secondary to BRVO or CRVO and may be a useful therapeutic option for eyes with these conditions., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the safety and efficacy of a dexamethasone intravitreous drug delivery system (DDS) in eyes with diabetic macular edema (DME)., Methods: Patients with persistent macular edema (> or = 90 days' duration) were randomized to treatment with 700 microg or 350 microg of dexamethasone DDS or observation. One eye from each patient was designated as the study eye. The analysis is of the eyes in this study with DME (n = 171)., Main Outcome Measures: The primary outcome measure was the proportion of eyes that achieved an improvement in best-corrected visual acuity (BCVA) of 10 letters or more from baseline at day 90. Other outcome measures included fluorescein leakage, central retinal thickness, and safety parameters., Results: At day 90, a BCVA improvement of 10 letters or more was seen in more eyes in the 700-microg group (33.3%) and 350-microg group (21.1%) than the observation group (12.3%; P = .007 vs 700-microg group). At day 180, a BCVA improvement of 10 letters or more was seen in 30% of eyes in the 700-microg group, 19% in the 350-microg group, and 23% in the observation group (P > or = .4 for treated vs observed eyes). There were also significantly greater improvements in central retinal thickness and fluorescein leakage in treated eyes than observed eyes (P = .03; day 90). Dexamethasone DDS was well tolerated., Conclusions: In eyes with persistent DME, treatment with 700 microg of intravitreal dexamethasone DDS is well tolerated and produces significant improvements in BCVA, central retinal thickness, and fluorescein leakage compared with observation (statistically significant at day 90)., Application to Clinical Practice: Dexamethasone DDS, 700 microg, may have potential as a treatment for persistent DME., Trial Registration: clinicaltrials.gov Identifier: NCT00035906.

Purpose: To evaluate the effects of a dexamethasone intravitreous drug delivery system (dexamethasone DDS) in patients with persistent macular edema (ME) resulting from uveitis or Irvine-Gass syndrome., Design: Randomized, prospective, single-masked, controlled trial., Methods: Three hundred and fifteen patients with persistent (>or= 90 days) ME were randomized in a multicenter study to surgical placement of 350 or 700 microg dexamethasone DDS or observation. This study evaluated the subset of patients with uveitis or Irvine-Gass syndrome (n = 41). The primary outcome measure was the proportion of patients achieving a 10-letter or more improvement in best-corrected visual acuity (BCVA) at day 90. Change in fluorescein angiographic leakage and safety also were evaluated., Results: At day 90, a 10-letter or more BCVA improvement was seen in 41.7% (5/12) of patients in the 350-microg group, in 53.8% (7/13) of patients in the 700-microg group, and in 14.3% (2/14) of patients in the observation group (P = .029 vs the 700-microg group). Improvement in visual acuity persisted to day 180. A 15-letter or more improvement was achieved in 53.8% (7/13) of 700-microg patients vs 7.1% (1/14) of observed patients (P = .008). There were significantly greater reductions in fluorescein leakage in treated patients than in observed patients. Dexamethasone DDS was well tolerated. Throughout the study, an increase in intraocular pressure of 10 mm Hg or more was seen in 5 of 13 patients in the 700-microg group, in 1 of 12 patients in the 350-microg group, and in no patients in the observation group. There were no reports of endophthalmitis., Conclusions: In patients with persistent ME resulting from uveitis or Irvine-Gass syndrome, 700-microg dexamethasone DDS was well tolerated and produced statistically significant improvements in visual acuity and fluorescein leakage.

Purpose: Evaluation of safety and performance of an applicator-inserted dexamethasone drug delivery system., Methods: Patients with clinically observable macular edema were randomized to receive 700 microg dexamethasone drug delivery system via a pars plana incisional placement (n = 10) or a 22-gauge applicator insertion (n = 20). Outcome measures included assessment of procedure duration, the postinsertion wound, adverse events, intraocular pressure, and best-corrected visual acuity at baseline and days 1, 7, 14, 30, 60, 90, and 180., Results: Both procedures were well tolerated and none of the patients in the applicator group required sutures to close the insertion wound. The overall incidence of ocular adverse events was less in the applicator group (13/19; 68.4%) than the incisional group (9/10; 90%), although the difference was not statistically significant in this pilot study. Vitreous hemorrhage occurred in two patients in the incisional group and none in the applicator group. Increases in intraocular pressure were less frequent in the applicator group (3/19; 15.8%) than the incisional group (3/10; 30%). No cases of endophthalmitis or retinal detachment occurred in either group. The percentage of patients achieving improvement in visual acuity of >/=15-letters at Day 90 was similar in both groups; 40% (8/20) in the applicator group and 30% (3/10) in the incisional group., Conclusion: The dexamethasone drug delivery system applicator system performed well, allowing safe, effective, and sutureless intravitreal placement of 700 microg dexamethasone drug delivery system.

Objective: To evaluate a dexamethasone intravitreous drug delivery system (DDS) in patients with persistent (> or =90 days despite treatment) macular edema., Methods: This 6-month study randomized 315 patients with persistent macular edema with best-corrected visual acuity (BCVA) of 20/40 to 20/200 in the study eye to observation or a single treatment with dexamethasone DDS, 350 or 700 microg., Main Outcome Measures: Proportion of patients achieving a BCVA improvement of 10 or more letters or 15 or more letters, safety measures, change in fluorescein angiographic leakage, and central retinal thickness., Results: At day 90 (primary end point), an improvement in BCVA of 10 letters or more was achieved by a greater proportion of patients treated with dexamethasone DDS, 700 microg (35%) or 350 microg (24%), than observed patients (13%; P<.001 vs 700-microg group; P = .04 vs 350-microg group); an improvement in BCVA of 15 letters or more was achieved in 18% of patients treated with dexamethasone DDS, 700 microg, vs 6% of observed patients (P = .006). Results were similar in patients with diabetic retinopathy, vein occlusion, or uveitis or Irvine-Gass syndrome. During 3 months of observation, 11% of treated patients and 2% of observed patients had intraocular pressure increases of 10 mm Hg or higher., Conclusion: In persistent macular edema, a single dexamethasone DDS treatment produced statistically significant BCVA improvements 90 days after treatment and was well tolerated for 180 days. Application to Clinical Practice Dexamethasone DDS, 700 microg, may have potential as a treatment for persistent macular edema.

Purpose: To ascertain the incidence of cystoid macular edema (CME) after phacoemulsification and its relationship to blood-aqueous barrier damage and visual acuity., Setting: A British teaching hospital., Methods: A prospective trial was performed to document the incidence of CME after routine phacoemulsification with continuous curvilinear capsulorhexis. LogMAR visual acuity and laser flare were measured using the KOWA FC 1000 laser cell-flare meter preoperatively and 1, 14, 30, and 60 days postoperatively. At day 60, a standardized fluorescein angiogram was performed and graded by masked observers., Results: The rate of angiographic CME on day 60 was 19%. Visual acuity at each visit was significantly worse in the CME group (P < .05). The flare and cell values at days 14, 30, and 60 were higher in the CME group at day 60; however, the difference was not statistically significance (P > .05)., Conclusions: The incidence of CME after routine phacoemulsification was 19%. Patients with CME at day 60 had significantly worse visual acuity than those who did not from the first postoperative day throughout the follow-up. There was a trend for patients who had CME at day 60 to have more postoperative inflammation.

Objective: To characterize a group of phakic patients with idiopathic intermediate uveitis as defined by vitritis, cystoid macular edema, and retinal periphlebitis., Design: Cross-sectional study., Participants: Nineteen phakic patients (35 eyes) with vitreous inflammation, cystoid macular edema, and/or retinal periphlebitis of unknown cause., Intervention: None., Main Outcome Measures: Best-corrected final visual acuities, standardized clinical examinations, photographic and fluorescein angiographic evaluations, and class I and II HLA analysis on all 19 patients., Results: Fifteen of the 19 patients were women. The mean age was 38 years, the mean follow-up was 104 months, and the mean duration of symptoms was 154 months. All 35 affected eyes had significant vitritis; 21 eyes (60%) had cystoid macular edema, 21 eyes (60%) had retinal periphlebitis. The median initial visual acuity was 20/30. The median final visual acuity was 20/20 with 32 (91%) of 35 eyes having 20/40 or better visual acuity at the final visit. No patient developed "snow-banks" or evidence of systemic disease, including multiple sclerosis or sarcoidosis, during the follow-up period. There were no statistically significant HLA associations in these patients compared with controls from another study from Iowa, but the Iowa phakic patients with cystoid macular edema did differ from the Iowa patients with pars-planitis at loci HLA-B8, HLA-B51, and HLA-DR2., Conclusions: We describe a disease entity of idiopathic intermediate uveitis that affects primarily young to middle-aged women and usually causes bilateral vitritis, cystoid macular edema, and retinal periphlebitis. Most patients retained good vision over a prolonged follow-up period. Multiple sequential examinations and HLA associations suggest that these conditions are distinct from other syndromes of intermediate uveitis, particularly parsplanitis.

Purpose: To study the effect of acetazolamide on cystoid macular edema in patients with uveitis., Methods: Forty patients with chronic intermediate, posterior, or panuveitis associated cystoid macular edema were randomized into a masked, cross-over trial comparing acetazolamide versus placebo. Patients received an initial 4-week course of either acetazolamide or placebo (course A) followed by a 4-week washout period. They then received a 4-week course of the opposite study medication (course B). Primary endpoints included area of cystoid macular edema measured on late-phase views of fluorescein angiography and visual acuity., Results: Thirty-seven patients completed the trial and were available for analysis; 17 (46%) were randomized to receive acetazolamide and 20 (54%) to receive placebo during course A. Acetazolamide resulted in a 0.5-disc area (25%) decrease in cystoid macular edema over that of placebo (P = 0.01; estimated treatment effect = -0.5 disc areas; 95% confidence interval, -0.9 to -0.1). However, there was no statistically significant effect of acetazolamide on visual acuity (P = 0.61; estimated treatment effect = 0.6 letters; 95% confidence interval, -2 to 3)., Conclusions: A 4-week course of acetazolamide therapy results in a statistically significant but small decrease in cystoid macular edema in patients with chronic uveitis, and does not improve visual acuity. In contrast to previous studies in the literature, acetazolamide may have a more limited clinical benefit in patients with long-standing cystoid macular edema associated with chronic uveitis.