Peter A Campochiaro1, Quan Dong Nguyen2, Gulnar Hafiz2, Steven Bloom3, David M Brown4, Miguel Busquets5, Thomas Ciulla6, Leonard Feiner7, Nelson Sabates8, Kathleen Billman9, Barry Kapik9, Ken Green9, Frances E Kane9. 1. The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: pcampo@jhmi.edu. 2. The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. Bennett and Bloom Eye Centers, Louisville, Kentucky. 4. Retinal Consultants of Houston, Houston, Texas. 5. Associates in Ophthalmology, Pittsburgh, Pennsylvania. 6. Midwest Eye Institute, Indianapolis, Indiana. 7. Retina Associates of New Jersey, Teaneck, New Jersey. 8. Department of Ophthalmology, University of Missouri-Kansas City School of Medicine, Truman Medical Centers, Kansas City, Missouri. 9. Alimera Sciences, Inc., Alpharetta, Georgia.
Abstract
PURPOSE: To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY). DESIGN: Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials. PARTICIPANTS: Thirty-seven patients with diabetic macular edema (DME) (Fluocinolone Acetonide in Human Aqueous [FAMOUS] Study, C-01-06-002) and 7 patients with uveitis (NA-00019318). METHODS:Aqueous FAc was measured after administration of FAc implants or 0.2 μg/day (low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 μg/day (high dose) FAc inserts. MAIN OUTCOME MEASURES: The primary end point was aqueous levels of FAc. RESULTS: At 1 month after administration for subjects who received 1 treatment, mean aqueous FAc levels were 2.17 (low dose) and 3.03 ng/ml (high dose) for FAc inserts and 6.12 ng/ml for FAc implants with maximum levels of 3.83, 6.66, and 13.50 ng/ml, respectively. At 3 months, mean FAc levels were 1.76, 2.15, and 6.12 ng/ml, respectively. Between 6 and 36 months after low-dose inserts, aqueous levels of FAc were remarkably stable, ranging from 1.18 to 0.45 ng/ml. After high-dose inserts, mean FAc levels were stable between 6 and 24 months, ranging from 1.50 to 0.84 ng/ml and then decreasing to 0.35 ng/ml at 30 months and 0.15 ng/ml at 36 months. In implant-containing eyes, mean FAc levels remained >6 ng/ml through 15 months, the last time point with measurements from at least 6 eyes. CONCLUSIONS:Low- and high-dose FAc inserts both provide stable long-term release of FAc with comparable peak levels in the aqueous: slightly >2 ng/ml for approximately 3 months followed by steady-state levels between 1.0 and 0.5 ng/ml through 36 months for low-dose inserts versus levels between 1.5 and 1.1 ng/ml through 24 months for high-dose inserts. Steady-state aqueous levels after FAc implants were >6 ng/ml. These results provide new insights that aid in the interpretation of efficacy trials and indicate that there is a dose effect for steroid-induced ocular hypertension. In susceptible patients, prolonged aqueous levels of FAc >1 ng/ml moderately increased the risk of glaucoma and levels >6 ng/ml posed a markedly increase risk.
RCT Entities:
PURPOSE: To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY). DESIGN: Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials. PARTICIPANTS: Thirty-seven patients with diabetic macular edema (DME) (Fluocinolone Acetonide in Human Aqueous [FAMOUS] Study, C-01-06-002) and 7 patients with uveitis (NA-00019318). METHODS: Aqueous FAc was measured after administration of FAc implants or 0.2 μg/day (low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 μg/day (high dose) FAc inserts. MAIN OUTCOME MEASURES: The primary end point was aqueous levels of FAc. RESULTS: At 1 month after administration for subjects who received 1 treatment, mean aqueous FAc levels were 2.17 (low dose) and 3.03 ng/ml (high dose) for FAc inserts and 6.12 ng/ml for FAc implants with maximum levels of 3.83, 6.66, and 13.50 ng/ml, respectively. At 3 months, mean FAc levels were 1.76, 2.15, and 6.12 ng/ml, respectively. Between 6 and 36 months after low-dose inserts, aqueous levels of FAc were remarkably stable, ranging from 1.18 to 0.45 ng/ml. After high-dose inserts, mean FAc levels were stable between 6 and 24 months, ranging from 1.50 to 0.84 ng/ml and then decreasing to 0.35 ng/ml at 30 months and 0.15 ng/ml at 36 months. In implant-containing eyes, mean FAc levels remained >6 ng/ml through 15 months, the last time point with measurements from at least 6 eyes. CONCLUSIONS: Low- and high-dose FAc inserts both provide stable long-term release of FAc with comparable peak levels in the aqueous: slightly >2 ng/ml for approximately 3 months followed by steady-state levels between 1.0 and 0.5 ng/ml through 36 months for low-dose inserts versus levels between 1.5 and 1.1 ng/ml through 24 months for high-dose inserts. Steady-state aqueous levels after FAc implants were >6 ng/ml. These results provide new insights that aid in the interpretation of efficacy trials and indicate that there is a dose effect for steroid-induced ocular hypertension. In susceptible patients, prolonged aqueous levels of FAc >1 ng/ml moderately increased the risk of glaucoma and levels >6 ng/ml posed a markedly increase risk.
Authors: Stephanie K Lynch; Kyungmoo Lee; Zhi Chen; James C Folk; Ursula Schmidt-Erfurth; Bianca S Gerendas; Andreas Wahle; Charles C Wykoff; Michael D Abràmoff Journal: Invest Ophthalmol Vis Sci Date: 2019-05-01 Impact factor: 4.799
Authors: Christopher J Brady; Andrea C Villanti; Hua Andrew Law; Ehsan Rahimy; Rahul Reddy; Pamela C Sieving; Sunir J Garg; Johnny Tang Journal: Cochrane Database Syst Rev Date: 2016-02-12