Noninfectious Posterior Uveitis Research Articles

Weitwinkelfundusautofluoreszenz bei nichtinfektiöser Uveitis posterior

Posterior uveitis comprises a heterogeneous group of diseases with inflammatory alterations of the posterior fundus and is a common cause of visual impairment and blindness. The goal of this study was to evaluate the diagnostic value of wide-field fundus autofluorescence (FAF) in patients with non-infectious posterior uveitis and chorioretinal alterations. In this study 73 eyes from 51 patients were included. Best-corrected visual acuity, wide-field color and FAF images achieved by a wide-field scanning laser opththalmoscope (SLO, Optomap P200Tx, Optos PLC, Dunfermline UK) and a full ophthalmological examination were obtained from each patient. A systematic analysis of chorioretinal alterations detected with FAF and color images was conducted followed by the evaluation of the diagnostic information of wide-field FAF compared to the clinical finding and wide-field color images. Of the 73 eyes included in the study 52 showed peripheral alterations. In 32 cases wide-field FAF images revealed a greater number and more extensive chorioretinal alterations than the corresponding wide-field color images of the posterior fundus. In this study wide-field FAF images showed more chorioretinal alterations than seen in funduscopy or in color SLO images. Therefore, wide-field FAF images offer important additional information for detection and documentation of peripheral and central chorioretinal alterations.

Toxoplasma Serotype Is Associated With Development of Ocular Toxoplasmosis

Worldwide, ocular toxoplasmosis (OT) is the principal cause of posterior uveitis, a severe, life-altering disease. A Toxoplasma gondii enzyme-linked immunoassay that detects strain-specific antibodies present in serum was used to correlate serotype with disease. Toxoplasma serotypes in consecutive serum samples from German uveitis patients with OT were compared with non-OT seropositive patients with noninfectious autoimmune posterior uveitis. OT patients were tested for association of parasite serotype with age, gender, location, clinical onset, size, visual acuity, or number of lesions (mean follow-up, 3.8 years) to determine association with recurrences. A novel, nonreactive (NR) serotype was detected more frequently in serum samples of OT patients (50/114, 44%) than in non-OT patients (4/56, 7%) (odds ratio, 10.0; 95% confidence interval 3.4-40.8; P < .0001). Non-OT patients were predominantly infected with Type II strains (39/56; 70%), consistent with expected frequencies in Central Europe. Among OT patients, those with NR serotypes experienced more frequent recurrences (P = .037). Polymerase chain reaction detected parasite DNA in 8/60 OT aqueous humor specimens but failed to identify Type II strain alleles. Toxoplasma NR and Type II serotypes predominate in German OT patients. The NR serotype is associated with OT recurrences, underscoring the value of screening for management of disease.

Vision-Related Functioning Outcomes of Dexamethasone Intravitreal Implant in Noninfectious Intermediate or Posterior Uveitis

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. 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. 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. 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.).

Psychometric evaluation of the National Eye Institute Visual Function Questionnaire and Visual Function Questionnaire Utility Index in patients with non-infectious intermediate and posterior uveitis

To evaluate the psychometric properties of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and Visual Function Questionnaire Utility Index (VFQ-UI) in patients with non-infectious intermediate and posterior uveitis. Secondary analysis of pooled data from a 26-week, multicenter, masked, randomized, sham-controlled Phase 3 clinical trial. Health-related quality of life was assessed using the NEI VFQ-25, the EQ-5D, and SF-36. Internal consistency reliability, reproducibility, convergent validity, and known groups of BCVA and vitreous haze severity were assessed. Clinically significant difference was assessed using anchor-based and distribution-based methods. The study included 224 subjects with non-infectious intermediate (80.4%) or posterior uveitis (19.6%). The NEI VFQ-25 and the VFQ-UI demonstrated good internal consistency (Cronbach's alpha 0.87-0.94) and test-retest reliability (ICCs 0.58-0.88). Spearman's product-moment rank correlations between the NEI VFQ-25 and VFQ-UI scores and the SF-6D, EQ-5D, and BCVA ranged from small to moderate. There was a significant association between visual functioning and known groups of visual acuity (p<0.05). Clinical significance, using the anchor-based method (difference between visual acuity groups≥10-<15 letter better and no change), was 10.2 for change from baseline to week 26 for the NEI VFQ-25 composite score and 0.05 for the VFQ-UI. Using the distribution-based method, the clinical significance was 3.86 for the composite score and 0.04 for the VFQ-UI. The NEI VFQ-25 and the VFQ-UI are reliable and valid measures of vision-related functioning and preference-based status in patients with non-infectious intermediate and posterior uveitis.

Dexamethasonimplantat zur Behandlung des Makulaödems bei retinalen venösen Gefäßverschlüssen und entzündlichen Augenerkrankungen

The efficacy of a single dose of Ozurdex® was evaluated over a 6-month period in eyes with macular edema due to retinal vein occlusion and intraocular inflammatory disease. 20 eyes of 20 consecutive patients with macular edema received a single injection of Ozurdex® (intravitreal dexamethasone implant 0.7 mg). Patients with branch retinal vein occlusion (n = 11), central retinal vein occlusion (n = 6), non-infectious posterior uveitis (n = 1) and Irvine-Gass Syndrome (n = 2) were included. In 10 patients Ozurdex® was used as the first treatment, 10 patients had undergone previous treatments for macular edema. The mean duration from the symptoms to the initiation of the treatment was 14.2 (1-60) months. The follow-up measurements were performed 1, 3 and 6 months after treatment. The main interest of the study was the visual and structural development over the duration of 6 months after a single dose of Ozurdex® with outcome measures including changes in best-corrected visual acuity and central retinal thickness. At baseline, the mean best-corrected visual acuity of all patients was 50 (± 16) ETDRS letters and the mean central retinal thickness was 632 (± 168.3) microns. Mean follow-up time was 3.4 (± 1.5) months and 7 patients dropped out during the follow-up period (4 patients after 3 months, additional 3 patients after 6 months). One month after treatment, 14 out of 20 patients (70%) showed a complete regression of macular edema, and in 6 cases (30%) it was partially recurrent. The mean best-corrected visual acuity improved to 56 (± 20.8) ETDRS. Central retinal thickness showed a mean decrease to 278 (± 84.9) microns. 6 months after treatment, recurrence was observed in 9 cases out of the remaining 13 patients (69.2%). In 3 cases, macular edema persisted (23.1%) and in one case (7.7%) the macula remained dry. The mean best-corrected visual acuity was 55 (± 13.9) ETDRS letters. The mean central retinal thickness decreased to 603 (± 174.6) microns. Ozurdex® showed a good effect in the treatment of macular edema one month after its application, namely a temporary decrease in central retinal thickness and a corresponding increase in best-corrected visual acuity. 6 months after treatment, the recurrence rate was high, and only one person with a branch retinal vein occlusion remained relapse-free over the entire follow-up. Based on our data, the patients should be checked at the latest after 3 months and then monthly in order to detect relapse in time and to initiate another treatment if needed.

Normative Comparison of Patient-Reported Outcomes in Patients With Noninfectious Uveitis

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. 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). 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. 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. clinicaltrials.gov Identifier:NCT00333814.

Dexamethasone intravitreal implant (Ozurdex) in the treatment of pediatric uveitis

The dexamethasone (Ozurdex) implant (Allergan Inc, Irvine, CA) is an implantable biodegradable polymer containing of 0.7 mg of dexamethasone. It is approved for the treatment of non-infectious uveitis in adults. To our knowledge its use in the treatment of pediatric uveitis has not been reported. A retrospective chart review of all pediatric patients at our institution with noninfectious posterior uveitis unresponsive to standard treatment that received the Ozurdex implant. Thirteen eyes of 10 patients (mean age 9.5 years range 4-12 years) underwent one to three Ozurdex implants (total 18 implants) in 2011-2012. Seven patients (10 eyes) had idiopathic intermediate or posterior uveitis. The remaining 3 patients had sympathetic ophthalmia, juvenile idiopathic arthritis and sarcoidosis. All patients were uncontrolled with standard treatments including topical corticosteroids, subtenon’s corticosteriod injections and systemic corticosteroid and/or immune-modulation. Improvement was noted initially in all patients. Initial implantation allowed for reduction of topical treatment in 8/13 eyes. Four eyes (31%) underwent 2 or 3 implantations for recurrent inflammation. Complications included implant migration into the anterior chamber in aphakic eyes (5 implants), increased IOP (>10 mm Hg from baseline)3 eyes, and progression of a preexisting cataract (1 eye). The Ozurdex implant should be considered in pediatric patients with refractory uveitis. The adverse events identified in our study are similar to those identified in adult studies. The dexamethasone intravitreal implant can be used safely and effectively in the pediatric population as an adjunctive treatment for intraocular inflammation in noninfectious intermediate and posterior uveitis.

Migration en chambre antérieure de l’implant intravitréen de dexaméthasone Ozurdex® chez le pseudophake : à propos de trois cas

Intravitreal implantation of Ozurdex(®) (Allergan Inc., Irvine, CA, USA) is being used widely for the treatment of macular edema secondary to retinal vein occlusion and in the setting of non-infectious posterior uveitis. We describe a complication little reported in the literature until now: migration of the dexamethasone implant into the anterior chamber. We report three cases of migration in two pseudophakic patients with iris claw lenses (on the anterior and posterior aspects of the iris) and in one pseudophakic patient with a posterior chamber IOL and zonular rupture. The risk of anterior chamber migration of the Ozurdex(®) implant is increased in cases of prior vitrectomy (three cases), prone positioning and dilation of the pupil (mydriasis). Clinical tolerability of the implant in the anterior chamber is poor in all cases, with diffuse corneal edema. Endothelial cell loss occurs, as demonstrated by specular microscopy performed in two of our patients. Removal or repositioning of the Ozurdex(®) implant into the posterior segment must be performed without delay because of the risk of endothelial toxicity. Patients without perfect zonular/posterior capsular integrity present a high risk of anterior chamber migration of the Ozurdex(®) implant. In such cases, anti-VEGF therapies should be discussed as an alternative.

Update on the Principles and Novel Local and Systemic Therapies for the Treatment of Non-Infectious Uveitis

Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.

Dexamethasone Intravitreal Implant: An Effective Adjunctive Treatment for Recalcitrant Noninfectious Uveitis

Purpose: To describe our experience in treating recalcitrant and severe cases of noninfectious posterior uveitis with the 0.7-mg dexamethasone intravitreal implant as adjunctive anti-inflammatory treatment. Procedures: Retrospective study. Twelve patients (8 females; 4 males; 14 affected eyes, 15 implants) with severe recalcitrant uveitis were treated. Patients had an inadequate control of uveitis despite different immunosuppressants and periocular corticosteroid therapy. Primary outcome measures evaluated were: decrease in uveitis activity, improvement in visual acuity, reduction of macular thickness, and occurrence of adverse events. Results: Uveitis activity decreased in all patients after the implant. The mean follow-up time from injection was 9 months. Best-corrected visual acuity improved from 20/80 to 20/40 at the end of follow-up. The mean retinal thickness improved from 496 to 226 µm. Adverse events encountered were: 3 eyes with intraocular pressure elevation, 1 vitreous hemorrhage and 1 subconjunctival hemorrhage. Three patients reduced the daily systemic corticosteroid dosage after treatment. Conclusions: The 0.7-mg dexamethasone intravitreal implant appears to be a novel and promising adjunctive treatment for patients with severe posterior noninfectious uveitis recalcitrant to different immunosuppressive agents.

Long-Term Effects of Intravitreal Infliximab for Treatment of Sight-Threatening Chronic Noninfectious Uveitis

This study aimed to evaluate the safety and long-term effects of infliximab on chronic noninfectious uveitis with measuring best corrected visual acuity (BCVA) and central macular thickness (CMT). Ten eyes of 7 patients were included in this prospective case series. All the patients had noninfectious anterior and posterior uveitis that was unresponsive to conventional treatments for 3 months. About 1.5 mg of infliximab in 0.15 cc was injected intravitreally and the patients were followed for 6 months. BCVA was measured by Snellen chart and grading of vitritis was measured according to binocular indirect ophthalmoscope score before injection, 4 weeks, 3 months, and 6 months after the injection. CMT was measured 1 day before injection and compared with the same factors 4 weeks and 6 months after the injection. Mean of LogMAR before injection was 1.37±0.43 that changed to 0.67±0.55 and 1.38±0.36 one month and 6 months after the injection, respectively. Mean CMT before injection was 673.2±338.39 that changed to 456.4±317.46 and 659.3±342.48, 4 weeks and 6 months after the injection, respectively. Mean vitreous haziness grade before injection, 4 weeks, 3 months, and 6 months after the injection was 2.7, 0.95, 2.3, and 2.6, respectively. Intravitreal Infliximab may be used in treatment of noninfectious uveitis. It probably improves the vision and decreases the macular edema but its effect is temporary and repeated injections may be needed to achieve the best therapeutic goal.

Wide-field Retinal Imaging in the Management of Noninfectious Posterior Uveitis

To determine whether the use of ultra wide-field imaging changes the management or determination of disease activity in patients with noninfectious posterior uveitis. Prospective, observational case series. setting: Divisions of Retina and Ocular Immunology at single academic medical center. patient population: Total of 43 patients with noninfectious posterior uveitis seen by 4 investigators at the Wilmer Eye Institute. procedures: Each patient underwent standard clinical examination, followed by ultra wide-field scanning laser ophthalmoscope (SLO) imaging and angiography. Investigators successively determined disease activity and management decisions based on clinical examination, examination plus simulated 30- or 60-degree fluorescein angiography (FA) (obtained by physically narrowing the field of view of the wide-field images), examination plus ultra wide-field SLO images, and examination plus wide-field FA. main outcome measures: The primary outcome was the percentage of patients whose management changed based on the availability of wide-field imaging, compared with standard examination and imaging. The secondary outcome was detection of disease activity with and without wide-angle imaging. Management was altered in 7 of 43 patients (16%) based on examination and limited FA, whereas 21 of 43 patients (48%) had management change with the use of the ultra wide-field imaging and angiography (P < .001). Disease activity was detected in 22 of 43 patients (51%) based on examination and simulated conventional imaging, and in 27 of 43 (63%) with wide-field imaging (P = .27). The index study, with several design limitations, has suggested that ultra wide-field imaging may alter management decisions compared to standard-of-care imaging and clinical examination. Additional studies, including longitudinal evaluations, are needed to determine whether these findings, or the subsequent management alterations, may improve patient outcomes.

Post-cataract outcomes in patients with noninfectious posterior uveitis treated with the fluocinolone acetonide intravitreal implant

PurposeTo describe visual acuity (VA) and inflammation following cataract surgery in eyes with noninfectious posterior uveitis (NIPU) that were being treated with a fluocinolone acetonide (FA) intravitreal implant compared with those that were not.DesignPost hoc, subgroup analysis of data from a 3-year, dose-masked, randomized, multicenter trial evaluating the FA implant for the treatment of NIPU.Participants and controlsThe subset of eyes that underwent cataract surgery during the 3-year trial. Eyes were either implanted with a 0.59- or a 2.1-mg FA implant, or, in the case of affected fellow eyes, received standard-of-care local treatment.Main outcome measuresVA, anterior and posterior chamber inflammation at 1 and 3 months after surgery, and rate of uveitis recurrence and serious postoperative ocular adverse events.ResultsOf 278 patients enrolled in the main trial, 132/142 phakic implanted eyes and 39/186 phakic non-implanted eyes underwent cataract surgery. Mean improvement in VA was significantly greater in implanted than non-implanted eyes at 1 (P = 0.0047) and 3 months (P = 0.0015) postoperatively; significantly fewer anterior chamber cells were seen in implanted than non-implanted eyes at 1 (P = 0.0084) and 3 months (P = 0.0002). Severity of vitreous haze was less in implanted than non-implanted eyes at 3 months postoperatively (P = 0.0005). The postsurgical uveitis recurrence rate was lower in implanted than non-implanted eyes (26.5% vs 44.4%; P = 0.0433). Glaucoma was reported in 19.7% of implanted eyes and no non-implanted eyes (P = 0.0008) postoperatively.ConclusionIn this post hoc subgroup analysis, eyes with NIPU treated with the FA intravitreal implant demonstrated better vision and less intraocular inflammation following cataract surgery than non-implanted eyes. Recurrent uveitic inflammation did not appear to be triggered by cataract surgery. Glaucoma occurred more frequently in implanted eyes.

Anterior chamber migration of dexametasone intravitreal implant (Ozurdex®)

Dear Editor, Ozurdex® (Allergan Inc., Irvine, CA, USA) is an intravitreal implant containing the dexamethasone. It uses NOVADUR® drug delivery technology, in which a biodegradable material is combined with the active drug dexamethasone to form a small rod-shaped implant of 0.46 mm in diameter and 6 mm in length. Inside the eye, the implant is progressively dissolved in the vitreous gel, as it slowly releases dexamethasone (0.7 mg). This biodegradable device is indicated for the treatment of macular edema following branch or central retinal vein occlusions. In large clinical trials, Ozurdex® has also proved effective in the treatment of posterior non-infectious uveitis, and diabetic and macular edema to and pseudophakic macular edema [1, 2]. Herein we report the case of a 68-year-old male diagnosed with macular edema following branch retinal vein occlusion in his left eye. Visual acuity was 0.6 logMAR. The patient had undergone cataract surgery years before, with intraoperative violation of the lens posterior capsula, anterior vitrectomy assisted with triamcinolone and iris-claw intraocular lens implantation. An intravitreous injection of Ozurdex® (Allergan Inc., Irvine, CA, USA) was performed without remarkable complications. Three weeks later, the patient attended our emergency department complaining of blurred vision in his left eye. Slit-lamp examination revealed the presence of diffuse corneal edema, and anterior migration of the implant (Fig. 1). The intraocular pressure measured 18 mmHg. The implant was surgically removed from the anterior chamber 48 hours later. However, corneal edema did not resolve, and the patient finally underwent corneal transplantation. The anterior chamber transit has been previously described for triamcinolone acetonide, resulting in pseudohypopion [3, 4]. Probably due to a similar mechanism, the dexamethasone implant may also migrate into the anterior chamber, with secondary corneal descompensation due to the contact of the implant with the endothelium. This may be more frequent in pseudophakic cases with Nd-YAG capsulotomy, or posterior capsule violation during phacoemulsification. Nevertheless, pseudohypopion after intravitreal triamcinolone injection has been described in both phakic or pseudophakic patients with posterior capsule integrity, it being presupposed then that the zonula is not complete or that the crystals are capable of crossing through it [3, 4]. In this particular case, the lack of anterior hyaloid may facilitate the penetration of Ozurdex into the anterior chamber too. In our opinion, the state of anterior hyaloid can be assessed by slit-lamp examination only. However, ecography could be useful in cases of uncertain anterior hyaloid status. The authors certify that they have not been published or are being considered for publication elsewhere. The authors also transfer property rights (copyright) of this work to Graefe’s Archive for Clinical and Experimental Opthalmology. D. Pardo-Lopez : E. Frances-Munoz :R. Gallego-Pinazo : M. Diaz-Llopis Department of Ophthalmology, University and Polytechnic Hospital La Fe, Valencia, Spain

Intraocular Pressure Outcome of Patients with Fluocinolone Acetonide Intravitreal Implant for Noninfectious Uveitis

To evaluate the intraocular pressure (IOP) outcomes of patients with noninfectious posterior uveitis treated with a fluocinolone acetonide (FA) intravitreal implant over an 8-year period. Retrospective clinical case series. Forty-seven eyes of 35 patients. Retrospective review of medical records of all patients receiving FA implants between June 2001 and March 2009 was performed. Data were pooled to record visual acuity (VA) and to characterize the incidence and outcome of glaucoma surgical intervention. Incidence of glaucoma surgery and IOP before and after glaucoma surgical intervention. Visual acuity before and after FA implant placement. Nineteen of 42 eyes (45%) receiving FA implants over the course of the study period required glaucoma surgical intervention. Success of IOP-lowering surgery was achieved in 94%, 94%, and 92% of eyes at 6, 12, and 24 months postoperatively. No patient lost more than 1 line of VA. There was an average 2-line gain of acuity at 3 years after FA implant placement for those patients who underwent IOP-lowering surgery. Patients receiving FA implants have a significant risk of increased IOP that frequently necessitates glaucoma surgery. Glaucoma surgery, when necessary, offers an effective method to decrease IOP. Proprietary or commercial disclosure may be found after the references.

Dexamethasone for ocular inflammation

Introduction: Corticosteroids, administered systemically and periocularly, have long been used to treat intermediate and posterior segment noninfectious uveitis. In addition to systemic immunosuppressive medications, these therapies are used to reduce inflammation, prevent structural complications and prevent long-term visual loss in patients with uveitis. While systemic immunosuppressive therapies carry their own set of side effects, treatment with local steroids is associated with the risk of development of cataract and glaucoma.Areas covered: Intravitreal delivery of fluocinolone acetonide via a sustained-release implant (Retisert) was approved by the FDA in 2005 for the treatment of noninfectious intermediate and posterior uveitis. Recently, the FDA also approved the biodegradable dexamethasone implant (Ozurdex) for the treatment of noninfectious uveitis involving the posterior segment.Expert opinion: The single injection, 26-week data indicate that the implant is well tolerated and produces meaningful improvements in intraocular inflammation and visual acuity that persist through 6 months. The available 6-month data also indicate that this implant confers much less of a risk of ocular hypertension than other forms of intraocular steroid therapy. However, future longer-term trials are needed to evaluate the efficacy and safety data in patients who receive multiple injections. The newly approved dexamethasone implant, Ozurdex, is a useful addition to our local armamentarium in the treatment of noninfectious intermediate and posterior uveitis given its efficacy, safety, and ease of use in the outpatient setting.

The dexamethasone drug delivery system: Indications and evidence

The Ozurdex(®) (Allergan Inc., Irvine, CA, USA) dexamethasone drug delivery system (DDS) was recently developed as a biodegradable intravitreal implant to provide sustained delivery of 700 μg of preservativefree dexamethasone to the retina and vitreous, and is approved by the United States Food and Drug Administration (FDA) for the treatment of macular edema associated with retinal vein occlusion, as well as for noninfectious posterior uveitis. This review summarizes the rationale behind the development of the dexamethasone DDS, evidence for its use in various clinical scenarios, and compares its efficacy to other available treatment options. Published data regarding the dexamethasone DDS as well as unpublished data that has been presented at national meetings were reviewed. The dexamethasone DDS has evidence for efficacy in multiple clinical situations, including macular edema associated with retinal vein occlusion (RVO), macular edema associated with uveitis or Irvine-Gass syndrome, diabetic macular edema in vitrectomized eyes, persistent macular edema, noninfectious vitritis, and as adjunctive therapy for age-related macular degeneration. Safety concerns include cataract formation and intraocular pressure elevation that is most often temporary and amenable to medical management. The dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.

Fluocinolone Acetonide Implantable Device for Diabetic Retinopathy

Diabetic retinopathy remains a major worldwide cause of preventable visual loss. Although photocoagulation and improved metabolic control are effective for patients with diabetic macular edema and proliferative diabetic retinopathy, some patients continue to lose vision despite treatment. Various classes of pharmacotherapy have shown promise in the treatment of diabetic retinopathy, including corticosteroids, anti-vascular endothelial growth factor agents, and others. Off-label intravitreal corticosteroids are associated with short-term anatomic and visual improvement in some patients, but these patients may require repeated intravitreal injections with cumulative risks of cataract formation, intraocular pressure elevation, and endophthalmitis. Various sustained-release corticosteroid delivery systems have been investigated for this purpose. The first to become widely available is the fluocinolone acetonide intravitreal implant (Retisert, Bausch & Lomb, Rochester, NY), which received U.S. Food and Drug Administration approval to treat chronic, noninfectious posterior segment uveitis in 2005. This device also has been investigated as a treatment for diabetic macular edema. Multiple randomized clinical trials have demonstrated medium-term anatomic and visual improvement, but the device is associated with high risks of cataract formation and intraocular pressure elevation. At this time, the device is not widely used in the treatment of diabetic retinopathy. A smaller device, designed to be injected in a clinic setting (Iluvien, Alimera Sciences, Alpharetta, GA) is currently being investigated for the treatment of diabetic macular edema. Results from a phase 3 randomized controlled trial have recently reported medium-term efficacy and safety in the treatment of diabetic macular edema. Combination photocoagulation and pharmacotherapy with these devices has not yet been reported.

Dexamethasone Intravitreal Implant for Noninfectious Intermediate or Posterior Uveitis

To evaluate the safety and efficacy of 2 doses of dexamethasone intravitreal implant (DEX implant) for treatment of noninfectious intermediate or posterior uveitis. 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). The main outcome measure was the proportion of eyes with a vitreous haze score of 0 at week 8. 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). 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.

Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis.