title: SAFETY AND FEASIBILITY OF A NOVEL 25-GAUGE BIODEGRADABLE IMPLANT OF DEXAMETHASONE FOR TREATMENT OF MACULAR EDEMA ASSOCIATED WITH RETINAL VEIN OCCLUSION: A PHASE I CLINICAL TRIAL.
abstract: OBJECTIVE
  To evaluate the safety and feasibility of a 25-gauge biodegradable implant containing 350 μg of dexamethasone (DDS-25) for the treatment of decreased vision due to macular edema associated with central or branch retinal vein occlusion.
  
  
  METHODS
  Prospective, nonrandomized, open-label, Phase I clinical trial, including 10 patients with decreased vision (best-corrected early treatment diabetic retinopathy study visual acuity of 20/40 or worse) due to macular edema associated with central retinal vein occlusion (n = 4) or branch retinal vein occlusion (n = 6) for more than 4 months. Comprehensive ophthalmic evaluation, including best-corrected visual acuity, spectral domain optical coherence tomography (Spectralis Heidelberg Engineering) for determination of central subfield thickness, full-field electroretinography (ISCEV standard ERG), and fluorescein angiography, was performed at baseline, and 1, 4, 12, and 24 weeks after intravitreal DDS-25 insertion.
  
  
  RESULTS
  Mean best-corrected visual acuity was 0.72 ± 0.1 logMAR (20/100) at baseline and improved by 7 early treatment diabetic retinopathy study letters to 0.58 ± 0.08 logMAR (20/80 + 1) at 24 weeks (P = 0.049), with 3 central retinal vein occlusion and 3 branch retinal vein occlusion patients improving between 1 and 4 early treatment diabetic retinopathy study lines. Significant central subfield thickness reduction was observed at 24 weeks compared with baseline (P = 0.011); mean ± standard error (range) central subfield thickness (μm) was 461.2 ± 41.3 (288-701) at baseline, and 439.6 ± 40.4 (259-631), 442.5 ± 44.6 (255-632), 354.6 ± 31.2 (228-537), and 316.5 ± 26.4 (226-441) at 1, 4, 12, and 24 weeks, respectively. No significant changes in electroretinography responses or area of retinal nonperfusion were observed during 24 weeks of follow-up. There was no significant change in mean intraocular pressure at any of the study visits compared with baseline. One patient had mild anterior chamber inflammation (1-5 cells) at one week after DDS-25 insertion.
  
  
  CONCLUSIONS
  In this Phase I study demonstrating the feasibility of intravitreal DDS-25 insertion for the treatment of decreased vision due to macular edema associated with retinal vein occlusion, no safety concerns were observed. A larger prospective randomized study with longer follow-up is warranted to confirm these findings.
authors.affiliation: Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Renato B
authors.initials: RB
authors.lastname: Cunha
authors.affiliation: Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Rubens C
authors.initials: RC
authors.lastname: Siqueira
authors.affiliation: Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Messias
authors.affiliation: Departments of Ophthalmology and Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Ingrid U
authors.initials: IU
authors.lastname: Scott
authors.affiliation: Ezequiel Dias Foundation, FUNED, Minas Gerais, Brazil.
authors.forename: Silvia Ligorio
authors.initials: SL
authors.lastname: Fialho
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Brazil.
authors.forename: Armando da Silva
authors.initials: ADS
authors.lastname: Cunha-Junior
authors.affiliation: Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jorge
mesh_terms: D020341:Absorbable Implants; D000368:Aged; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004596:Electroretinography; D005240:Feasibility Studies; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012170:Retinal Vein Occlusion / Q000150:complications* / Q000175:diagnosis; D041623:Tomography, Optical Coherence
chemical_list: D004343:Drug Implants; D005938:Glucocorticoids; D003907:Dexamethasone