Effect of Dexamethasone on Reduction of Macular Thickness in Diabetic Patients, a Randomized Clinical Trial

Overview

Purpose: To determine the impact of short-term 4mg/ml dexamethasone solution treatment in diabetic macular edema (DME).

Design: Phase II, randomized, prospective, parallel, interventional study.

Participants: Pseudophakic patients with central-involved DME.

Methods: Twenty-seven patients with visual impairment caused by DME were randomized in a 1:1:1 ratio, in order to investigate treatment with 0.01 ml, 0.03 ml and 0.05 ml intravitreous dexamethasone solutions, and followed-up over 28 days

Outcome Measures: The primary outcome was macular thickness at three days after intravitreous dexamethasone. The secondary outcomes were macular thickness at 28 days after intravitreous dexamethasone, best-corrected visual acuity (BCVA) and intraocular pressure (IOP) at three and 28 days after intravitreous dexamethasone

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 20, 2017

Detailed Description

This is a prospective, phase II, randomized, interventional, monocentric study. Data of consecutive patients with DME who volunteered to participate in the research at the department of ophthalmology of State University of Campinas (UNICAMP) – Brazil between May 2016 and December 2017 were analysed.

At the screening visit, all patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), slit-lamp biomicroscopy, applanation tonometry, fundus biomicroscopy, fluorescein angiography (Visucam NM/ FA Carl Zeiss; Carl Zeiss Meditec, California, USA), SD- OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Central macular thickness was obtained through 7 horizontal lines ( 30° x 5° area), centered on the fovea, with 1536 A scans per line at 240 µm intervals.

At the baseline study visit, patients were randomized with a 1:1:1 allocation to receive dexamethasone solution 4 mg/ml: 0,01 ml (40 µg) ; or 0,03 ml (120 µg); or 0,05 ml (200 µg). In follow up visits (1, 3, 7, 14, 21, 28 days after) were performed BCVA, slit-lamp biomicroscopy, applanation tonometry, fundus biomicroscopy, SD- OCT.

Interventions

  • Drug: Intravitreous Dexamethasone Solution 4mg/ml – vol 0,01 ml
    • 0,01 ml intravitreous dexamethasone solution 4mg/ml injection.
  • Drug: Intravitreous Dexamethasone Solution 4mg/ml – vol 0,03 ml
    • 0,03 ml intravitreous dexamethasone solution 4mg/ml injection.
  • Drug: Intravitreous Dexamethasone Solution 4mg/ml – vol 0,05 ml
    • 0,05 ml intravitreous dexamethasone solution 4mg/ml injection.

Arms, Groups and Cohorts

  • Experimental: 0,01ml dexamethasone solution
    • One intravitreous injection of 0,01 ml dexamethasone solution 4 mg/ml.
  • Experimental: 0,03 ml dexamethasone solution
    • One intravitreous injection of 0,03 ml dexamethasone solution 4 mg/ml.
  • Experimental: 0,05 ml dexamethasone solution
    • One intravitreous injection of 0,05 ml dexamethasone solution 4 mg/ml.

Clinical Trial Outcome Measures

Primary Measures

  • Macular Thickness at 3 Days After Intravitreous Dexamethasone
    • Time Frame: Three days after intravitreous dexamethasone
    • Measure macular thickness at 3 days after intravitreous dexamethasone with OCT – unit µm

Secondary Measures

  • Macular Thickness at 28 Days After Intravitreous Dexamethasone
    • Time Frame: 28 days after intravitreous dexamethasone
    • Measure macular thickness at 28 days after intravitreous dexamethasone with OCT – unit µm
  • Best Corrected Visual Acuity (BCVA) at 3 Days After Intravitreous Dexamethasone
    • Time Frame: Three days after intravitreous dexamethasone
    • Measure best corrected visual acuity (BCVA) at 3 days after intravitreous dexamethasone with ETDRS chart
  • Best Corrected Visual Acuity (BCVA) at 28 Days After Intravitreous Dexamethasone
    • Time Frame: 28 days after intravitreous dexamethasone
    • Measure best corrected visual acuity (BCVA) at 28 days after intravitreous dexamethasone with ETDRS chart
  • Intraocular Pressure (IOP) at 3 Days After Intravitreous Dexamethasone
    • Time Frame: 3 days after intravitreous dexamethasone
    • Measure intraocular pressure (IOP) 3 days after intravitreous dexamethasone – unit mmHg
  • Intraocular Pressure (IOP) at 28 Days After Intravitreous Dexamethasone
    • Time Frame: 28 days after intravitreous dexamethasone
    • Measure intraocular pressure (IOP) 28 days intravitreous dexamethasone – unit mmHg

Participating in This Clinical Trial

Inclusion Criteria

  • age > = 18 years;
  • diagnosis of DM type 2;
  • pseudophakic patients
  • presence of clinically significant DME according to ETDRS guidelines;
  • best correct visual acuity (BCVA) between 20/400 and 20/40;
  • central macular thickness (CMT) >= 300 µm measured by spectral domain optical coherence tomography ( Spectralis® Heidelberg). If both eyes of the patient met the elegibility criteria, the eye with worse BCVA at baseline was designated as the study eye.

Exclusion Criteria

  • any treatment of DME in the previous 4 months;
  • pan retinal photocoagulation (PRP) in the previous 4 months or antecipated need of PRP for the next 6 months;
  • any ophthalmologic surgery performed in the previous 4 months;
  • history of pars plana vitrectomy;
  • history of open-angle glaucoma or intraocular pressure elevation induced by corticosteroids that required anti-glaucomatous treatment or anti- hypertensive ocular treatment;
  • intraocular pressure >= 21 mmHg;
  • patients with characteristics that meet the inclusion criteria, but refused to sign the written general consent.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Universidade Federal de Pernambuco
  • Provider of Information About this Clinical Study
    • Principal Investigator: Rodrigo Pessoa Cavalcanti Lira, Principal Investigator – Universidade Federal de Pernambuco
  • Overall Official(s)
    • Rodrigo PC Lira, MD, Study Chair, University of Campinas, Brazil

References

Maturi RK, Glassman AR, Liu D, Beck RW, Bhavsar AR, Bressler NM, Jampol LM, Melia M, Punjabi OS, Salehi-Had H, Sun JK; Diabetic Retinopathy Clinical Research Network. Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2018 Jan 1;136(1):29-38. doi: 10.1001/jamaophthalmol.2017.4914.

Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.

Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14. doi: 10.1016/j.ophtha.2010.12.033.

Tamura H, Miyamoto K, Kiryu J, Miyahara S, Katsuta H, Hirose F, Musashi K, Yoshimura N. Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1440-4.

Wang K, Wang Y, Gao L, Li X, Li M, Guo J. Dexamethasone inhibits leukocyte accumulation and vascular permeability in retina of streptozotocin-induced diabetic rats via reducing vascular endothelial growth factor and intercellular adhesion molecule-1 expression. Biol Pharm Bull. 2008 Aug;31(8):1541-6.

Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.

Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.

Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec;103(12):1796-806.

Bandello F, Battaglia Parodi M, Lanzetta P, Loewenstein A, Massin P, Menchini F, Veritti D. Diabetic macular edema. Dev Ophthalmol. 2010;47:73-110. doi: 10.1159/000320075. Epub 2010 Aug 10. Review.

Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):552-63.

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