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BACKGROUND: Epinastine hydrochloride is an antihistamine with mast cell-stabilizing and anti-inflammatory activity. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of ophthalmic epinastine in patients with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens. METHODS: This randomized (age-stratified), double-masked, parallel-group, active- and vehicle-controlled, environmental, Phase III clinical trial was conducted at 6 ophthalmology clinics in the United States. Patients aged >or=9 years diagnosed with SAC and who had a positive reaction in a conjunctival allergen challenge were enrolled. Patients were randomly assigned in a 2:2:1 ratio to receive 1 drop/eye BID of epinastine hydrochloride 0.05% ophthalmic solution, levocabastine hydrochloride 0.05% ophthalmic suspension, or vehicle of epinastine, respectively, for 8 weeks. The primary end point was ocular itching, and secondary end points included ocular hyperemia, chemosis, ocular mucous discharge (all assessed on a 5-point scale), eyelid swelling (assessed on a 4-point scale), and tearing (present or absent). Efficacy analyses used assessments from the two 1-week periods with the highest pollen counts. For tolerability assessment slit-lamp biomicroscopy and visual acuity examinations were conducted at each study visit (weeks 0, 2, 4, 6, and 8). RESULTS: Two-hundred ninety-eight patients (159 females, 139 males; mean [SD] age, 32.7 [14.6] years [range, 9-71 years]) entered the study; 118 received epinastine, 118 received levocabastine, and 62 received vehicle. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P=0.045); scores for hyperemia were similar between these 2 groups. Ocular itching and hyperemia scores were similar between the epinastine and levocabastine groups. No clinically or statistically significant between-group differences were seen in slit-lamp biomicroscopy findings, changes in visual acuity from baseline, or the incidence of treatment-related adverse effects. CONCLUSIONS: In this study of patients with SAC, ophthalmic epinastine instilled twice daily was more effective than vehicle for the control of ocular itching and was similar in efficacy to levocabastine for control of ocular itching and hyperemia. Epinastine was well tolerated. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epinastine hydrochloride is a nonsedating antihistamine with a high affinity for histamine H(1) receptors, together with mast cell-stabilizing and anti-inflammatory activities. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of topically administered ophthalmic epinastine using the conjunctival antigen challenge (CAC) model in patients with a history of allergic conjunctivitis. METHODS: This prospective, single-center, randomized, double-masked, vehicle-controlled, Phase III clinical trial was conducted at the Ophthalmic Research Associates study center (North Andover, Massachusetts) from November 2000 to January 2001. Eligible participants were asymptomatic but had a history of allergic conjunctivitis and had positive CAC reactions at the initial screening (week 0) and at a confirmation visit (week 1). Patients were randomly assigned by eye to receive epinastine hydrochloride 0.05% ophthalmic solution in 1 eye and vehicle in the contralateral eye. Each eye received 1 drop of study medication 15 minutes before antigen application (onset challenge; week 3) or 8 hours before antigen application (duration challenge; week 5). Primary end points were ocular itching and conjunctival hyperemia. Itching was recorded 3, 5, and 10 minutes after antigen challenge. Hyperemia was recorded 5, 10, and 20 minutes after antigen challenge, as were secondary end points, which included eyelid swelling, episcleral and ciliary hyperemia, chemosis, tearing, and ocular mucous discharge. Tolerability was assessed by patient interview and slit-lamp biomicroscopy. RESULTS: Sixty-seven patients (37 females, 30 males; mean [SD] age, 38.4 [14.2] years [range, 12-67 years]) were included in the study. Mean severity scores for the following signs and symptoms were significantly lower with epinastine compared with vehicle at all time points after onset and duration challenges: ocular itching (P<0.001); eyelid swelling (P<0.001); conjunctival ( P<0.001), episcleral ( P<0.001), and ciliary hyperemia (P<0.001); and chemosis (Por=8 hours). The tolerability of epinastine was similar to that of vehicle. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia., Design: Phase II clinical trial. Stage 1 was a single center, open-labeled, vehicle-controlled study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled trial., Participants: Patients with primary or recurrent pterygia., Main Outcome Measures: The primary efficacy end point was lesion vascularity based on masked grading of photographs by an independent reading center. Other end points included dimensions of pterygia and safety., Methods: In stage 1, 24 eyes of 24 patients received 1 drop of CBT-001 in a dose escalation fashion (0.02%, 0.05%, and 0.2%) to determine the maximally tolerated dose based on adverse events (AEs) and blood drug levels. In stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed 3 times a day for 4 weeks with a 20-week follow-up., Results: In stage 1, the plasma maximum concentration values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/ml). The most commonly reported AEs were mild foreign body sensation and irritation. CBT-001 0.2% was evaluated in stage 2. Baseline demographic characteristics were similar between patients receiving CBT-001 (n = 25) and vehicle (n = 23). After 4 weeks of dosing, the mean change from baseline in pterygium vascularity scores was -0.8 ± 0.7 (mean ± standard deviation) in subjects receiving CBT-001 0.2% and 0.0 ± 0.5 in subjects receiving vehicle ( P  < 0.001; 95% confidence interval: -1.12, -0.40). Pterygium vascularity scores remained significantly decreased, after the 4-week dosing period, at weeks 8 and 16, but not at week 24. The mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared with vehicle at weeks 2, 4, and 8 ( P  ≤ 0.014). The most commonly reported AEs were ocular, mild in severity, resolved after therapy, and did not result in discontinuation., Conclusions: CBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated with minimal detected systemic drug levels., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Botulinum toxin is one of the most potent and deadliest substances on earth. Because of its unique mechanism of action at the synaptic junction and the ability to precisely deliver the toxin locally to where it is needed, botulinum toxin has been used as an effective treatment for a plethora of diseases from head to foot, from chronic migraine to ankle spasticity. Unlike systemic drugs, botulinum toxin is delivered by injection to the site of disease. As we will see from the history of botulinum toxin, the ability to deliver the drug locally to minimize the amount of botulinum toxin needed and thereby minimizing systemic exposure has been key to its medical utility. Botulinum toxin was first approved by the US Food and Drug Administration in 1989 for the treatment of blepharospasm and strabismus, but the history starts long before this, with outbreaks of food poisoning in the tenth century. Importantly, the development of botulinum toxins for medical use continues today with the engineering of novel toxins to treat disease.

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 determine whether the levels of cytokines and chemokines in tears differ in uveitis patients and healthy subjects., Methods: Ninety-two uveitis patients (mean age 46.4 years) and 157 control healthy subjects (mean age 49.5 years) were recruited. Subjects with ocular surface diseases such as dry eye were excluded from the study. Using multiplex bead-based assays, tears (4 μl) were analysed for the concentration of interleukin (IL)-1β, IL-1RA, IL-2, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12p70, IL-15, IL-17A, IL-23, epidermal growth factor (EGF), fractalkine/CX3CL1, interferon-γ, IP-10/CXCL10, monocyte chemo-attractant protein (MCP)-1/CCL2, tumour necrosis factor-α, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, TGF-β2 and TGF-β3. Tear molecule levels were compared between the groups and among the different forms of uveitis and disease severity., Results: Epidermal growth factor, IL-1RA, IL-7, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, TGF-β2 and VEGF were detected in more than 75% of the samples in both groups. Statistically significant differences in percentage of detection between control and patient groups were found for IL-23, IL-1β, IL-15, EGF, fractalkine/CX3CL1 and MCP-1/CCL2. The concentrations of IL-1RA, IL-8/CXCL8, fractalkine/CX3CL1, IP-10/CXCL10, VEGF and TGF-β2 in uveitis tear samples were elevated compared to controls (p < 0.05). Significant differences in tear levels of those molecules and also EGF were also present depending on the anatomic classification of uveitis., Conclusion: There were significant differences in the levels of several cytokines and chemokines in tears of patients with uveitis compared with healthy subjects. These results can help understand the underlying pathophysiology of the uveitis and could potentially aid in diagnosis., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the safety and intraocular pressure (IOP)-lowering effect of a biodegradable bimatoprost sustained-release implant (Bimatoprost SR)., Design: Phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial., Methods: At baseline following washout, open-angle glaucoma patients (n = 75) were administered Bimatoprost SR (6 μg, 10 μg, 15 μg, or 20 μg) intracamerally in the study eye; the fellow eye began topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or a single repeat treatment with implant was allowed. The primary endpoint was IOP change from baseline. The main safety measure was adverse events. Results through month 6 are reported., Results: Bimatoprost SR provided rapid, sustained IOP lowering. Overall mean IOP reduction from baseline through week 16 in study eyes was 7.2, 7.4, 8.1, and 9.5 mm Hg with the 6-μg, 10-μg, 15-μg, and 20-μg dose strengths of implant, respectively, vs 8.4 mm Hg in topical bimatoprost-treated pooled fellow eyes (data censored at rescue/retreatment). Rescue/retreatment was not required in 91% and 71% of study eyes up to week 16 and month 6, respectively. Adverse events in study eyes usually occurred within 2 days after the injection procedure and were transient. Conjunctival hyperemia with onset later than 2 days after the injection procedure was more common with topical bimatoprost than Bimatoprost SR (17.3% vs 6.7% of eyes)., Conclusions: Bimatoprost SR demonstrated favorable efficacy and safety through 6 months. All dose strengths were comparable to topical bimatoprost in overall IOP reduction through week 16. A single administration controlled IOP in the majority of patients for up to 6 months., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

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: Eyebrow loss may have substantial negative functional and social consequences., Objective: Evaluate the safety and efficacy of bimatoprost 0.03% in subjects with eyebrow hypotrichosis., Methods: This multicenter, double-masked study randomized adult females or males with eyebrow hypotrichosis to receive bimatoprost 0.03% twice (BID) or once daily (QD) or vehicle BID for 7 months. Primary endpoint was overall eyebrow fullness at Month 7. Secondary endpoints included eyebrow fullness (mm), darkness (intensity units), and subject satisfaction with treatment. Safety was also assessed., Results: At Month 7, the proportion of subjects with improvement was significantly higher in bimatoprost groups versus vehicle (both, p < .001). Improvements occurred in both bimatoprost groups versus vehicle after Month 1 and continued through follow-up; eyebrow fullness and darkness improved as early as Months 2 and 1, respectively (both, p < .001). Greater satisfaction was reported with bimatoprost versus vehicle at Month 2 and all subsequent time points. Overall, 38.1%, 42.4%, and 35.5% of subjects in the bimatoprost BID, QD, and vehicle groups, respectively, experienced ≥1 treatment-emergent adverse event (TEAE). Most frequent TEAEs were similar across groups. No skin or iris hyperpigmentation or conjunctival hyperemia occurred., Conclusion: Bimatoprost 0.03% BID and QD is safe, well tolerated, and effective for eyebrow hypotrichosis.

Uveitis is a group of ocular inflammatory disorders that can lead to severe vision loss. Despite advances in anti-inflammatory therapy, many patients are resistant to or intolerant of existing treatments. A biodegradable, sustained-release implant, dexamethasone intravitreal implant 0.7 mg (Ozurdex), has been developed to deliver dexamethasone to target tissues in the posterior segment of the eye, minimizing systemic drug exposure and limiting side effects. The implant releases dexamethasone over a period of up to 6 months as the poly(D,L-lactide-co-glycolide) polymer matrix of the implant is metabolized to carbon dioxide and water. The implant is placed in the vitreous of the eye with a single-use applicator in a sutureless, office-based procedure. Treatment with a single dexamethasone intravitreal implant in patients with noninfectious intermediate or posterior uveitis has been shown to produce significant improvements in intraocular inflammation and best-corrected visual acuity with treatment benefit sustained for 6 months. Dexamethasone intravitreal implant has also been shown to reduce central retinal thickness and improve best-corrected visual acuity in patients with macular edema of various etiologies. The implant has been approved for treatment of noninfectious uveitis involving the posterior segment, diabetic macular edema, and macular edema associated with branch and central retinal vein occlusion., (© 2015 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.)

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 efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD)., Procedures: This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection., Results: DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups., Conclusion: DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients., (© 2015 S. Karger AG, Basel.)

Discovery of the neuromuscular effects of botulinum toxin began in the early 19th century and has continued to evolve. Currently, onabotulinumtoxinA is approved by the U.S. Food and Drug Administration for two cosmetic and eight medical indications, including chronic migraine (CM). CM is a disabling form of migraine characterized by ≥15 headache days monthly and is believed to result from neuronal hypersensitivity to proinflammatory mediators, upregulation of sensory receptors, and consequent maladaptive pain responses with peripheral and central sensitization. OnabotulinumtoxinA achieves migraine prophylaxis in CM through regulation of vesicular trafficking and exocytosis, inhibition of peripheral release of neuropeptides and inflammatory peptides, and reduced cell surface expression of certain ion channels and receptors. Clinically, efficacy of onabotulinumtoxinA for CM has been shown in two phase III, placebo-controlled trials (PREEMPT 1 and PREEMPT 2). OnabotulinumtoxinA significantly reduced the number of headache days per 28-day cycle relative to placebo at week 24 (change from baseline: -8.4 days for onabotulinumtoxinA versus -6.6 days for placebo; P < 0.001, pooled data). OnabotulinumtoxinA improved health-related quality of life and had an acceptable safety profile. OnabotulinumtoxinA is the only approved treatment specifically for CM prevention and represents a safe and effective therapeutic for chronic migraineurs., (© 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.)

Background: Limited options are available for the treatment of brittle nail syndrome., Objective: To assess the efficacy and safety of topical cyclosporine emulsion (CsAE) versus emulsion (vehicle) alone in the treatment of brittle nail syndrome., Results: Twenty-four patients were randomized to topical CsAE emulsion or emulsion (vehicle) for 24 weeks. Four fingernails of each patient were included; the 2 most severe brittle nails and the second most normal nail were treated with the same medication. The fourth nail, the most normal nail, remained untreated and was used to assess nail growth. The prespecified primary endpoint was change from baseline in Physician Global Assessment (PGA) score (0 to 5 scale) at each follow-up visit. Safety evaluations were conducted at each visit., Results: In the intent-to-treat population (n=12 for each treatment arm), the PGA score for treated nails improved from baseline (CsAE, 0.7 to 1.4; emulsion, 0.7 to 1.5; P<0.05 for each), with no significant between-group differences. Untreated nails did not improve in overall appearance (0.0 to 0.3 grade; P>0.05). Statistically and clinically significant improvement from baseline was reported for nail length/appearance in both CsAE and vehicle groups., Limitations: Sample size was relatively small. The difference in PGA between treated and untreated nails was not analyzed. Baseline disease severity may have been too mild, limiting detection of efficacy., Conclusions: Both CsAE and emulsion vehicle applied topically appeared to improve signs and symptoms of brittle nail syndrome and were well tolerated. These findings warrant corroboration in a larger population and inclusion of comparison with an inactive control and a higher concentration of CsAE, the former which may help in distinguishing the efficacy of vehicle emulsion from CsAE.

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.)

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.).

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.)

Objective: The goal of this study was to examine the safety and effectiveness of the LAP-BAND System for patients with 30-39.9 BMI and associated comorbidities., Design and Methods: In this prospective, multicenter, interventional cohort study, subjects with a BMI between 30 and 39.9 who had failed prior weight loss attempts were recruited from 7 surgical centers. The primary effectiveness endpoint required that >40% of subjects achieve ≥30% excess weight loss (EWL) at 1 year. Secondary endpoints included assessment of comorbidities and quality-of-life., Results: Of 149 subjects, 90.6% were female, with mean BMI of 35.3 kg/m2 . At 1 year, 84.6% of subjects achieved ≥30% EWL (P < 0.0001), with 65.0% mean EWL; 66.4% of subjects were no longer obese (BMI < 30). Baseline comorbidities improved at 1 year for 64.4% with dyslipidemia, 59.6% with hypertension, and 85.7% with diabetes. Quality-of-life (IWQOL-Lite) also improved (P < 0.0001). The Year 1 results were maintained or improved at 2 years. Regression analysis indicates that each additional 10% weight loss at Year 2 was associated with an increase in IWQOL-Lite by 7.1 points and a decrease in triglycerides by 13.7 mg/dL, fasting glucose by 3.5 mg/dL, and systolic blood pressure by 3.3 mmHg. Most adverse events were mild to moderate and resolved without sequelae within 1 month. Five subjects (3.4%) had explantations., Conclusion: LAGB is safe and effective for people with 30-39.9 BMI, with weight loss and comorbidity improvement through at least 2 years., (Copyright © 2013 The Obesity Society.)

Objective: To compare vision-related functioning and health-related quality of life of patients with noninfectious intermediate or posterior uveitis with those of the US general population and normal-vision reference groups., Methods: Secondary analysis of health-related quality of life measures administered at baseline to patients with noninfectious intermediate or posterior uveitis participating in the HURON trial, a 26-week, multicenter, masked, randomized, sham-controlled trial of a dexamethasone intravitreal implant (n=224) was performed. Patient-reported outcome measures included the National Eye Institute Visual Function Questionnaire-25, the 36-Item Short-Form Health Survey, the Short Form-6 Dimensions, and the EuroQol-5D. The National Eye Institute Visual Function Questionnaire-25 scores from the HURON uveitis population were compared with published National Eye Institute Visual Function Questionnaire-25 scores from a normal-vision reference group (n=122). The 36-Item Short-Form Health Survey, Short Form-6 Dimensions, and EuroQol-5D scores were compared with the US general population using data from the National Health Measurement Study (n=3844) and the Medical Expenditure Panel Survey (n=955)., Results: Compared with a normal-vision population, the HURON uveitis population had clinically significant impairments across all National Eye Institute Visual Function Questionnaire-25 subscales and the composite score, with all subscale score differences exceeding 10 points (P< .001). The HURON uveitis population had significantly lower 36-Item Short-Form Health Survey mental component summary and Short Form-6 Dimensions scores compared with a US general population sample (P< .001). No significant differences were found for the 36-Item Short-Form Health Survey physical component summary and EuroQol-5D scores between the uveitis and US general population samples., Conclusions: Compared with the US general population and normal-vision reference groups, noninfectious intermediate or posterior uveitis results in meaningful reductions in mental health outcomes, health-related quality of life, and vision-related functioning., Trial Registration: clinicaltrials.gov Identifier:NCT00333814.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries; with the aging population, the negative health impacts and costs of the disease will increase dramatically over the next decade. Although the exact cause of AMD is unknown, genetic studies have implicated the complement system as well as other immune responses in disease pathogenesis and severity. Furthermore, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, in both atrophic lesions and with retinal neovascularization. This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force. These deliberations focused on the role of inflammatory immune responses, including complement, inflammasomes, adaptive immune responses, and para-inflammation, unanswered questions and studies to address these questions, and potential immune-related therapeutic targets for AMD.

The challenge in the treatment of chronic retinal diseases is to deliver effective therapy to the target tissues in the back of the eye while limiting drug exposure in nontarget tissues. Intravitreal placement provides the most targeted drug delivery, but repeated penetration of the globe to deliver intravitreal therapy can pose safety risks. A more effective strategy for the treatment of chronic retinal diseases would be to combine intravitreal placement with sustained drug delivery. The dexamethasone intravitreal (DEX) implant is a biodegradable sustained-release intravitreal drug delivery system that is approved for the treatment of macular edema following branch or central retinal vein occlusion and for noninfectious uveitis affecting the posterior segment of the eye. A single DEX implant has been shown to provide clinical benefits for up to 6 months in eyes with retinal vein occlusion or intermediate or posterior uveitis.

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 dexamethasone pharmacokinetics after implantation of a sustained-release dexamethasone (DEX) intravitreal implant in nonvitrectomized and vitrectomized eyes., Methods: The right eyes of 25 rabbits underwent vitrectomy; contralateral eyes served as nonvitrectomy controls. The 0.7-mg DEX implant was injected into both eyes, and drug concentrations were determined in the vitreous humor and retina for 31 days (on days 2, 8, 15, 22, and 31)., Results: DEX was present in nonvitrectomized and vitrectomized eyes for at least 31 days. There were no statistically significant differences in DEX concentration between nonvitrectomized and vitrectomized eyes at any time point (P > 0.05). The maximum concentration of DEX in nonvitrectomized versus vitrectomized eyes for vitreous humor was 791 ng/mL (day 22) versus 731 ng/mL (day 22), respectively, and for retina it was 4110 ng/mL (day 15) versus 3670 ng/mL (day 22), respectively. Mean absorption (AUC(0-tlast)) of dexamethasone in nonvitrectomized and vitrectomized eyes was not different for both the vitreous humor (13,600 vs. 15,000 ng/day/mL; P = 0.73) and retina (67,600 vs. 50,200 ng/day/mL; P = 0.47)., Conclusions: The vitreoretinal pharmacokinetic profiles were similar between nonvitrectomized and vitrectomized eyes. These observations are consistent with clinical findings of the DEX implant in patients who have undergone vitrectomy and should reduce concerns about the use of the DEX implant in eyes that have undergone vitrectomy.

Purpose: To assess the efficacy of a dexamethasone (DEX) intravitreal implant in a rabbit model of anterior and intermediate uveitis., Methods: Experimental anterior and intermediate uveitis was induced by a unilateral intracameral injection of Mycobacterium tuberculosis H37Ra antigen in preimmunized rabbits. Four days after uveitis induction, rabbits received DEX implant or underwent a sham procedure (no implant). Clinical and histopathologic signs of uveitis were assessed for 13 days, and levels of inflammatory markers in the iris/ciliary body were measured after 21 days., Results: All signs of anterior and intermediate uveitis were reduced by the DEX implant compared with sham procedure. At day 13, mean anterior chamber cell scores ± SD for the DEX implant versus the sham procedure were, respectively, 1.9 ± 1.3 versus 4.0 ± 0.0 (P = 0.04), and mean total histologic inflammatory scores were 3.9 ± 2.5 versus 15.4 ± 6.0 (P = 0.026). Similarly, at day 13, mean vitreous haze severity scores (SD) for the DEX implant versus the sham procedure were, respectively, 0.1 ± 0.2 versus 2.7 ± 1.5 (P = 0.026), and mean vitreous inflammatory cell infiltration scores were 0.0 ± 0.0 versus 1.5 ± 1.3. Treatment with the DEX intravitreal implant also significantly reduced the proinflammatory immune response, as measured by cytokine levels in iris/ciliary body., Conclusions: A single administration of DEX implant significantly reduced inflammation in an animal model of anterior and intermediate uveitis.

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.

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.

Purpose: To determine the pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone (DEX) intravitreal implant (Ozurdex; Allergan, Inc.)., Methods: Thirty-four male monkeys (Macaca fascicularis) received bilateral 0.7-mg DEX implants. Blood, vitreous humor, and retina samples were collected at predetermined intervals up to 270 days after administration. DEX was quantified by liquid chromatography-tandem mass spectrometry, and cytochrome P450 3A8 (CYP3A8) gene expression was analyzed by real-time reverse transcription-polymerase chain reaction., Results: DEX was detected in the retina and vitreous humor for 6 months, with peak concentrations during the first 2 months. After 6 months, DEX was below the limit of quantitation. The C(max) (T(max)) and AUC for the retina were 1110 ng/g (day 60) and 47,200 ng · d/g, and for the vitreous humor were 213 ng/mL (day 60) and 11,300 ng · d/mL, respectively. The C(max) (T(max)) of DEX in plasma was 1.11 ng/mL (day 60). Compared with the level in the control eyes (no DEX implant), CYP3A8 expression in the retina was upregulated threefold up to 6 months after injection of the implant (0.969 ± 0.0565 vs. 3.07 ± 0.438; P < 0.05 up to 2-month samples)., Conclusions: The in vivo release profile of the DEX implant in an animal eye was similar to the pharmacokinetics achieved with pulse administration of corticosteroids (high initial drug concentration, followed by a prolonged period of low concentration). These results are consistent with those in clinical studies supporting the use of the DEX implant for the extended management of posterior segment diseases.