Characterization of Intraocular Pressure Increases and Management Strategies Following Treatment With Fluocinolone Acetonide Intravitreal Implants in the FAME Trials.

BACKGROUND AND OBJECTIVE: To compare elevated intraocular pressure (IOP) management and outcomes among patients with diabetic macular edema who received fluocinolone acetonide (FAc) implants versus sham-control treatment and explore the prior ocular steroid exposure impact on IOP outcomes. PATIENTS AND METHODS: Best-corrected visual acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study charts or electronic VA testers. Goldmann applanation tonometry was used to measure IOP. RESULTS: Elevated IOP was more common in FAc-versus sham control-treated patients. Medication, and less often trabeculoplasty or surgery, was used to lower IOP without affecting VA outcomes. No patient treated with 0.2 µg/day FAc who received prior ocular steroid required IOP-lowering surgery. CONCLUSION: Elevated IOP may occur following FAc implant receipt; however, in the present study, it was manageable and did not impact vision outcomes. Patients previously treated with ocular steroid did not require IOP-lowering surgery following 0.2 µg/day FAc implant administration. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:426-435.].

Use of the Fluocinolone Acetonide Intravitreal Implant for the Treatment of Noninfectious Posterior Uveitis: 3-Year Results of a Randomized Clinical Trial in a Predominantly Asian Population.

INTRODUCTION: The fluocinolone acetonide (FA) intravitreal implant 0.59 mg (Retisert(®), Bausch + Lomb, Rochester, NY, USA) provides sustained release of FA directly to the vitreous cavity over a prolonged period of time. The purpose of this study was to evaluate the safety and efficacy of a 0.59- and 2.1-mg FA intravitreal implant in patients with noninfectious posterior uveitis. METHODS: A prospective, multicenter, randomized, double-masked, dose-controlled study was performed. Patients were randomized to the 0.59- or 2.1-mg FA implant surgically placed in the vitreous cavity through a pars plana incision and were evaluated at visits through 3 years. Patients with bilateral disease had the more severely affected eye implanted. Outcomes included uveitis recurrence rate, best-corrected visual acuity (BCVA), use of adjunctive therapy, and safety. RESULTS: A total of 239 patients, predominantly Asian, were implanted (n = 117, 0.59-mg implant; n = 122, 2.1-mg implant). Approximately 80% of patients had bilateral disease. Recurrence rates for implanted eyes decreased from 42.3% during the 1-year pre-implantation period to 25.9% during the 3-year post-implantation period (P = 0.0003) and increased for nonimplanted fellow eyes from 19.8 to 59.7% (P < 0.0001). More implanted eyes gained ≥3 lines of BCVA compared to nonimplanted fellow eyes (P ≤ 0.0046); and implanted eyes required less adjunctive systemic therapy and fewer periocular injections (P < 0.0001). Elevations of intraocular pressure (≥10 mm Hg) were frequent in implanted eyes (67.8%, 0.59-mg implant; 71.3%, 2.1-mg implant); nearly all (94.9%) phakic implanted eyes required cataract surgery. CONCLUSION: The FA intravitreal implant significantly reduced uveitis recurrence rates and led to improvements in visual acuity and reductions in adjunctive therapy. Lens clarity and intraocular pressure require monitoring.

Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial.

PURPOSE: We studied the 3-year efficacy and safety results of a 4-year study evaluating fluocinolone acetonide (FA) intravitreal implants in eyes with persistent or recurrent diabetic macular edema (DME). DESIGN: Prospective, evaluator-masked, controlled, multicenter clinical trial. PARTICIPANTS: We included 196 eyes with refractory DME. METHODS: Patients were randomized 2:1 to receive 0.59-mg FA implant (n = 127) or standard of care (SOC additional laser or observation; n = 69). The implant was inserted through a pars plana incision. Visits were scheduled on day 2, weeks 1, 3, 6, 12, and 26, and thereafter every 13 weeks through 3 years postimplantation. MAIN OUTCOME MEASURES: The primary efficacy outcome was ≥15-letter improvement in visual acuity (VA) at 6 months. Secondary outcomes included resolution of macular retinal thickening and Diabetic Retinopathy Severity Score (DRSS). Safety measures included incidence of adverse events (AEs). RESULTS: Overall, VA improved ≥3 lines in 16.8% of implanted eyes at 6 months (P=0.0012; SOC, 1.4%); in 16.4% at 1 year (P=0.1191; SOC, 8.1%); in 31.8% at 2 years (P=0.0016; SOC, 9.3%); and in 31.1% at 3 years (P=0.1566; SOC, 20.0%). The number of implanted eyes with no evidence of retinal thickening at the center of the macula was higher than SOC eyes at 6 months (P<0.0001), 1 year (P<0.0001; 72% vs 22%), 2 years (P=0.016), and 3 years (P=0.861). A higher rate of improvement and lower rate of decline in DRSS occurred in the implanted group versus the SOC group at 6 months (P=0.0006), 1 year (P=0.0016), 2 years (P=0.012), and 3 years (P=0.0207). Intraocular pressure (IOP) ≥30 mmHg was recorded in 61.4% of implanted eyes (SOC, 5.8%) at any time and 33.8% required surgery for ocular hypertension by 4 years. Of implanted phakic eyes, 91% (SOC, 20%) had cataract extraction by 4 years. CONCLUSIONS: The FA intravitreal implant met the primary and secondary outcomes, with significantly improved VA and DRSS and reduced DME. The most common AEs included cataract progression and elevated IOP. The 0.59-mg FA intravitreal implant may be an effective treatment for eyes with persistent or recurrent DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Bilateral central retinal artery occlusion in a patient with acute pancreatitis.

PURPOSE: To illustrate a case of bilateral simultaneous central retinal artery occlusion in a patient with acute pancreatitis. METHODS: This patient presented to the emergency room with a 4-day history of acute painless bilateral loss of vision and was then immediately referred to the on-call ophthalmologist. PATIENT: This patient is a 47-year-old white man with a chronic history of alcohol abuse. RESULTS: Laboratory workup and computed tomography abdominal imaging were diagnostic of acute pancreatitis. DISCUSSION: It is postulated that the resultant complement activation with subsequent leukoembolization along with the combined effect of other variables led to microvascular damage resulting in bilateral central retinal artery occlusion.

Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results.

OBJECTIVES: To evaluate the safety and efficacy of 0.59-mg and 2.1-mg fluocinolone acetonide (FA) intravitreous implants in noninfectious posterior uveitis. DESIGN: A 3-year, multicenter, randomized, historically controlled trial of the 0.59-mg FA intravitreous implant in 110 patients and the 2.1-mg FA intravitreous implant in 168 patients. MAIN OUTCOME MEASURES: Recurrence rate, vision, and complications. RESULTS: Uveitis recurrence was reduced in implanted eyes from 62% (during the 1-year preimplantation period) to 4%, 10%, and 20% during the 1-, 2-, and 3-year postimplantation periods, respectively, for the 0.59-mg dose group (P < .01) and from 58% to 7%, 17%, and 41%, respectively, for the 2.1-mg dose group (P < .01). More implanted eyes than nonimplanted eyes had improved visual acuity (P < .01). Implanted eyes had higher incidences of intraocular pressure elevation (> or = 10 mm Hg) than nonimplanted eyes (P < .01), and glaucoma surgery was required in 40% of implanted eyes vs 2% of nonimplanted eyes (P < .01). Cataracts were extracted in 93% of phakic implanted eyes vs 20% of phakic nonimplanted eyes (P < .01). CONCLUSIONS: The FA implant significantly reduced uveitis recurrence and improved or stabilized visual acuity in subjects with noninfectious posterior uveitis. Most subjects required cataract extraction, and a significant proportion required intraocular pressure-lowering surgery. APPLICATION TO CLINICAL PRACTICE: The FA implant provides an alternative therapy for prolonged control of inflammation in noninfectious posterior uveitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00407082.

Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants.

OBJECTIVE: To report the incidence and management of elevated intraocular pressure (IOP) in patients with uveitis treated with the fluocinolone acetonide (FA) intravitreal implant. DESIGN: Pooled data from 3 multicenter, double-masked, randomized, controlled, phase 2b/3 clinical trials evaluating the safety and efficacy of the 0.59-mg or 2.1-mg FA intravitreal implant or standard therapy were analyzed. RESULTS: During the 3-year follow-up, 71.0% of implanted eyes had an IOP increase of 10 mm Hg or more than baseline and 55.1%, 24.7%, and 6.2% of eyes reached an IOP of 30 mm Hg or more, 40 mm Hg or more, and 50 mm Hg or more, respectively. Topical IOP-lowering medication was administered in 74.8% of implanted eyes, and IOP-lowering surgeries, most of which were trabeculectomies (76.2%), were performed on 36.6% of implanted eyes. Intraocular pressure-lowering surgeries were considered a success (postoperative IOP of 6-21 mm Hg with or without additional IOP-lowering medication) in 85.1% of eyes at 1 year. The rate of hypotony (IOP

Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study.

PURPOSE: To report the interim 34-week safety and efficacy results of a 3-year study to evaluate an investigational intravitreal fluocinolone acetonide (FA) implant in patients with noninfectious posterior uveitis. DESIGN: Prospective, dose-masked, dose-randomized, historically controlled, multicenter trial in patients with unilateral or bilateral disease. PARTICIPANTS: A total of 278 patients with recurrent noninfectious posterior uveitis were randomized to receive a 0.59-mg (n = 110) or 2.1-mg (n = 168) implant. In patients with bilateral disease, the more severely affected eye received the implant. METHODS: The implant was inserted surgically into the vitreous cavity through a pars plana incision. Follow-up visits were scheduled on day 2, week 1, and then every 4 to 6 weeks through 34 weeks after implantation. Systemic, periocular, and topical therapies were reduced as allowed by the clinical response. MAIN OUTCOME MEASURES: The primary efficacy outcome was a comparison of the recurrence rate in the implanted eye from the 34 weeks before implantation to the 34 weeks after implantation. Visual acuity (VA), need for adjunctive therapy, and safety also were assessed. RESULTS: Combining both doses, the FA implant reduced the rate of recurrences from 51.4% in the 34 weeks preceding implantation to 6.1% postimplantation (P<0.0001) in the study eyes. Comparatively, there was a significant increase in the recurrence rate in the fellow nonimplanted eyes from 20.3% preimplantation to 42.0% postimplantation (P<0.0001). Visual acuity was stabilized or improved in 87% of implanted eyes and generally was associated with reductions in the area of macular hyperfluorescence. The percentage of eyes that required systemic medications, periocular injections, and topical corticosteroids decreased from 52.9%, 63.0%, and 35.7%, respectively, preimplantation to 12.1%, 2.2%, and 16.5% postimplantation (P< or =0.0001 in all cases). At week 34, 51.1% of implanted eyes required ocular antihypertensive drops, and 5.8% underwent glaucoma filtering surgery. Lens opacity scores increased by > or =2 grades in 19.8% of phakic implanted eyes, and 9.9% required cataract surgery. There were no statistically significant differences in any of the parameters studied for the 0.59-mg implant, compared with the 2.1-mg implant. CONCLUSIONS: The FA implant significantly reduced uveitis recurrences, improved VA, and decreased the need for adjunctive therapy in the studied patient population. The most common side effects included increased intraocular pressure and cataract progression.

Ocular pharmacokinetics of fluocinolone acetonide after Retisert intravitreal implantation in rabbits over a 1-year period.

PURPOSE: The present study was designed to examine the pharmacokinetics of a fluocinolone acetonide (FA) intravitreal implant in pigmented rabbits. METHODS: Pigmented rabbits were randomly assigned to receive either a 0.5 mg or 2.0 mg FA intravitreal implant (Retisert). Four animals were sacrificed per time point (2 hours; 2 weeks; and 3, 6, 9, and 12 months after implantation) for FA intraocular levels determination. RESULTS: In the vitreous, concentration of FA was relatively constant from the first time point, 2 hours, through 1 year, and dose-related, approximately seven- to eight-fold greater in the 2-mg implant. Concentrations of FA were generally higher in the vitreous (11-18 and 75-146 ng/g) and retina (42-87 and 224-489 ng/g) than in the aqueous humor (0.21-1.1 and 2.6-13.0 ng/g) for the 0.5- and 2-mg implants, respectively. Urine and plasma values were below the lower limit of quantitation (200 pg/mL) for all observations, indicating no evidence of systemic absorption. CONCLUSIONS: In this rabbit study, the Retisert provides relatively constant levels of FA in the posterior pole, which is consistent with previous reports of its clinical utility.

Central retinal artery occlusion and disc edema in a child.

Obstruction of the retinal arterial system is most commonly associated with elderly patient populations. The major etiologic factor in adults has been attributed to emboli from atherosclerotic vascular disease of the carotid arteries, with about 75% of patients over the age of 40 years demonstrating this finding. Conversely, arterial obstruction in young patients is rarely secondary to atheromatous disease and has a variety of causative factors.(1) We describe an unusual case of a previously healthy 8-year-old boy who developed a unilateral central retinal artery occlusion in conjunction with marked optic disc edema. The etiology of these pathologic lesions was attributed to a viral-like syndrome. Vision rapidly deteriorated to no light perception and remained unchanged despite treatment.