Evaluation of the Effect of Intravitreal Injections of Anti-VEGF on Macular Perfusion in Diabetic Patients Using OCTA

NCT03246152 | Completed Phase 4 Results FDA Drug

• 1 other identifier: N-79-2017
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-vascular endothelial growth factor (VEGF) drugs are the mainstay of therapy for diabetic macular edema (DME), substantially improving visual acuity for many diabetics worldwide, and proving effective for treatment of both non-proliferative and proliferative diabetic retinopathy. Many studies such as Diabetic Retinopathy Clinical Research Network studies, RESTORE Study, and The BOLT Study have supported the use of different anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments. Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract and retinal detachment. The effect of anti-VEGF drugs on macular perfusion has been inconclusive, with mixed reports of increase, decrease or no effect on perfusion in response to anti-VEGF treatment. In many of these studies, however, patients with more ischaemic retinas were not included. Retinal ischemia is an important factor in the progression and prognosis of diabetic retinopathy. Fluorescein angiography (FA) was the method used to assess changes in macular perfusion after anti-VEGF injections in most of the studies. Despite its clinical usefulness, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) is a new noninvasive method of acquiring high-resolution images of the retinal vasculature that can be utilized in the treatment of retinal disease without the need for dye injection. It allows the visualization of the superficial and deep retinal capillary layers separately and the construction of microvascular flow maps. Several studies have proved the reliability of OCTA in detecting and quantifying macular ischemia in diabetics. In this study, investigators aim to evaluate the effect of repeated intravitreal injections of different Anti-VEGF agents on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.

Conditions

Diabetic Macular Edema; Ischemic Maculopathy

Keywords

Anti-VEGF safety; Ischemic Maculopathy; Diabetic Macular Edema; OCTA

Outcome Measures

Primary Outcomes (2)

• FAZ Area Change

  Effect of repeated intravitreal Anti-VEGF injections on Foveal Avascular Zone (FAZ) area measured using the freehand tool of ImageJ

  At baseline and after 3-6 consecutive monthly injections.

• Macular Capillary Density Change at Full Retinal Thickness

  Effect of repeated intravitreal Anti-VEGF injections on macular capillary density using the change in the skeletonized vascular density and fractal dimension measured by ImageJ

  At baseline and after 3-6 consecutive monthly injections.

Secondary Outcomes (1)

• BCVA Change

  At baseline and after 3-6 consecutive monthly injections.

Study Arms (1)

Bevacizumab group

EXPERIMENTAL

Monthly intravitreal injection of 2.5 mg of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema.

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Repeated intravitreal injections of Bevacizumab monthly

Also known as: Avastin

Bevacizumab group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years old
• Type 1 or 2 diabetes mellitus
• Decreased BCVA due to diabetic macular edema
• Center involvement by the edema on spectral domain optical coherence tomography (SD OCT)
• Any stage of diabetic retinopathy

You may not qualify if:

• Ocular conditions that may affect macular perfusion (e.g. retinal vascular diseases, uveitis, vasculitis etc.)
• History of vitreoretinal surgeries (excluding intravitreal injections)
• Any previous treatment for diabetic macular edema
• Presence of epiretinal membrane involving the macula or vitreomacular traction
• Media opacity preventing good image quality
• Uncontrolled glaucoma
• Thromboembolic events within 6 months

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University Faculty of Medicine

Cairo, Egypt

Location

Related Publications (17)

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  PMID: 26959128 BACKGROUND

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  PMID: 20416952 BACKGROUND

• 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.

  PMID: 2866759 BACKGROUND

• Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina. 2006 Mar;26(3):352-4. doi: 10.1097/00006982-200603000-00016. No abstract available.

  PMID: 16508438 BACKGROUND

• Chapman JA, Beckey C. Pegaptanib: a novel approach to ocular neovascularization. Ann Pharmacother. 2006 Jul-Aug;40(7-8):1322-6. doi: 10.1345/aph.1G604. Epub 2006 Jul 18.

  PMID: 16849623 BACKGROUND

• Zhang X, Bao S, Hambly BD, Gillies MC. Vascular endothelial growth factor-A: a multifunctional molecular player in diabetic retinopathy. Int J Biochem Cell Biol. 2009 Dec;41(12):2368-71. doi: 10.1016/j.biocel.2009.07.011. Epub 2009 Jul 29.

  PMID: 19646547 BACKGROUND

• Hwang TS, Gao SS, Liu L, Lauer AK, Bailey ST, Flaxel CJ, Wilson DJ, Huang D, Jia Y. Automated Quantification of Capillary Nonperfusion Using Optical Coherence Tomography Angiography in Diabetic Retinopathy. JAMA Ophthalmol. 2016 Apr;134(4):367-73. doi: 10.1001/jamaophthalmol.2015.5658.

  PMID: 26795548 BACKGROUND

• Bradley PD, Sim DA, Keane PA, Cardoso J, Agrawal R, Tufail A, Egan CA. The Evaluation of Diabetic Macular Ischemia Using Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):626-31. doi: 10.1167/iovs.15-18034.

  PMID: 26903223 BACKGROUND

• Freiberg FJ, Pfau M, Wons J, Wirth MA, Becker MD, Michels S. Optical coherence tomography angiography of the foveal avascular zone in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2016 Jun;254(6):1051-8. doi: 10.1007/s00417-015-3148-2. Epub 2015 Sep 4.

  PMID: 26338819 BACKGROUND

• Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015 Jan;133(1):45-50. doi: 10.1001/jamaophthalmol.2014.3616.

  PMID: 25317632 BACKGROUND

• Yannuzzi LA, Rohrer KT, Tindel LJ, Sobel RS, Costanza MA, Shields W, Zang E. Fluorescein angiography complication survey. Ophthalmology. 1986 May;93(5):611-7. doi: 10.1016/s0161-6420(86)33697-2.

  PMID: 3523356 BACKGROUND

• Bonnin P, Pournaras JA, Lazrak Z, Cohen SY, Legargasson JF, Gaudric A, Levy BI, Massin P. Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin((R)) ) in neovascular age-related macular degeneration. Acta Ophthalmol. 2010 Sep;88(6):641-5. doi: 10.1111/j.1755-3768.2009.01526.x.

  PMID: 19563370 BACKGROUND

• Papadopoulou DN, Mendrinos E, Mangioris G, Donati G, Pournaras CJ. Intravitreal ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular age-related macular degeneration. Ophthalmology. 2009 Sep;116(9):1755-61. doi: 10.1016/j.ophtha.2009.03.017. Epub 2009 Jun 27.

  PMID: 19560206 BACKGROUND

• Manousaridis K, Talks J. Macular ischaemia: a contraindication for anti-VEGF treatment in retinal vascular disease? Br J Ophthalmol. 2012 Feb;96(2):179-84. doi: 10.1136/bjophthalmol-2011-301087.

  PMID: 22250209 BACKGROUND

• 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.

  PMID: 22330964 BACKGROUND

• 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.

  PMID: 21459215 BACKGROUND

• Elnahry AG, Abdel-Kader AA, Raafat KA, Elrakhawy K. Evaluation of Changes in Macular Perfusion Detected by Optical Coherence Tomography Angiography following 3 Intravitreal Monthly Bevacizumab Injections for Diabetic Macular Edema in the IMPACT Study. J Ophthalmol. 2020 Apr 27;2020:5814165. doi: 10.1155/2020/5814165. eCollection 2020.

  PMID: 32411431 DERIVED

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Ayman Elnahry
• Organization: Cairo University

ayman_elnahri@hotmail.com

00201224927604

Study Officials

• Khaled E El Rakhawy, PhD

  Cairo University

  STUDY DIRECTOR

• Karim A Raafat, PhD

  Cairo University

  STUDY DIRECTOR

• Ahmed AA Abdel Kader, PhD

  Cairo University

  STUDY CHAIR

• Ayman GA Elnahry, MSc

  Cairo University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Demonstrator

Study Record Dates

• First Submitted: August 6, 2017
• First Posted: August 11, 2017
• Study Start: October 23, 2017
• Primary Completion: December 24, 2018
• Study Completion: December 24, 2018
• Last Updated: January 30, 2020
• Results First Posted: January 30, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)