Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema

Diabetic Retinopathy Clinical Trial

— REBEL  

Official title:

Comparison of the Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema Using OCTA

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04991350
• Other study ID #: CU372021
• Status: Terminated
• Phase: Phase 4
• Start date: November 26, 2021
• Est. completion date: November 1, 2022

Study information

• Verified date: February 2023
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Early Treatment Diabetic Retinopathy Study (ETDRS) group founded guidelines for treating patients with clinically significant diabetic macular edema (DME) with focal/grid macular laser photocoagulation. Since then, macular laser, and steroids, were the main therapies for the treatment of DME until anti-vascular endothelial growth factors (anti-VEGF) drugs were developed after a growing body of scientific evidence implicated VEGF in the pathophysiologic process of DME. Anti-VEGF drugs have been implicated in the treatment of DME. VEGF has been shown to play an important role in the occurrence of increased vascular permeability in DME. VEGF levels are significantly higher in patients with DME and extensive leakage than in patients with minimal leakage. Many studies such as Diabetic Retinopathy Clinical Research [DRCR] Network studies, RESTORE Study, RISE and RIDE Research Group, and The BOLT Study have supported the use of 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 different effects on macular perfusion between different anti-VEGFs have yet to be fully concluded with mixed conclusions that it increases or decreases or has no effect on perfusion of the macula in response to Anti-VEGF treatment. In many of these studies, however, patients with more ischemic retinas were not included. Retinal ischemia is a vital factor determining the diabetic retinopathy progression and prognosis. Optical coherence tomography angiography (OCTA) detects blood flow by analyzing signal decorrelation between two sequential OCT cross-sectional scans at the same location. As it detects the movements of red blood corpuscles within the vessels, compared to the stationary retinal surroundings, which will result in signal disparity and imaging The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio. OCTA is considered a reliable tool in the detection and quantification of macular ischemia in diabetics. In this study, the investigators aim to compare the effect of repeated intravitreal injections of ranibizumab and bevacizumab on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.

Description:

Diabetic retinopathy is the major cause of blindness in developed but also in developing countries. The disruption of the blood-retinal barrier and the subsequent accumulation of fluid in the intraretinal layers result in diabetic macular edema (DME), the leading cause of central vision loss in these patients. The Early Treatment Diabetic Retinopathy Study (ETDRS) group founded guidelines for treating patients with clinically significant DME (CSME) with focal/grid macular laser photocoagulation. Since then, macular laser, and steroids, were the main therapies for treatment of DME until anti-vascular endothelial growth factors (anti-VEGF) drugs were developed after a growing body of scientific evidence implicated VEGF in the pathophysiologic process of DME. Anti-VEGF drugs have been implicated in the treatment of DME. VEGF has been shown to play an important role in the occurrence of increased vascular permeability in DME. VEGF levels are significantly higher in patients with DME and extensive leakage than in patients with minimal leakage. Many studies such as Diabetic Retinopathy Clinical Research [DRCR] Network studies, RESTORE Study, RISE and RIDE Research Group, and The BOLT Study have supported the use of anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments. DRCR network protocol T found statistically insignificant difference between ranibizumab and bevacizumab on visual acuity and central macular thickness in diabetic macular edema. Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract, and retinal detachment. The different effects on macular perfusion between different anti-VEGFs have yet to be fully concluded with mixed conclusions that it increases or decreases or has no effect on perfusion of macula in response to Anti-VEGF treatment.in many of these studies, however, patients with more ischemic retinas were not included. Retinal ischemia is a vital factor determining the diabetic retinopathy progression and prognosis. Using ocular ultrasound some studies showed retinal arteriolar vasoconstriction in eyes treated with anti-VEGF, while others showed decreased blood flow velocities in all retro-bulbar arteries after intravitreal injection of anti-VEGF. This may indicate that anti-VEGF may have an effect on ocular perfusion. 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 value, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) is an excellent non-invasive modality to acquire 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 both the superficial and deep retinal capillary layers separately and the construction of microvascular flow maps. OCTA detects blood flow by analyzing signal decorrelation between two sequential OCT cross-sectional scans at the same location. As it detects the movements of red blood corpuscles within the vessels, compared to the stationary retinal surroundings, which will result in signal disparity and imaging The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio. OCTA is considered a reliable tool in the detection and quantification of macular ischemia in diabetics. In this study, the investigators aim to compare the effect of repeated intravitreal injections of ranibizumab and bevacizumab on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: November 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients =18 years old with type 1 or 2 diabetes mellitus with decreased BCVA due to center involving diabetic macular edema on spectral-domain optical coherence tomography.

2. Patients with central macular thickness "CMT" of = 300 micrometers

Exclusion Criteria:

1. Ocular conditions that may affect macular perfusion (e.g. retinal vascular diseases, uveitis, vasculitis etc.)

2. History of vitreo-retinal surgeries.

3. Previous macular laser treatment

4. Presence of epi-retinal membrane involving the macula or vitreo-macular traction.

5. Media opacity preventing good image quality.

6. Uncontrolled glaucoma.

7. Thrombo-embolic events within 6 months

8. Previous intravitreal injections of anti-VEGF

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Diabetic Retinopathy
• Edema
• Ischemia
• Macular Edema
• Vascular Endothelial Growth Factor Overexpression

Intervention

Drug:
• Intravitreal ranibizumab
Intravitreal injection of 0.3 mg/0.05 ml ranibizumab will be performed monthly for 3 months.
• Intravitreal bevacizumab
Intravitreal injection of 1.25 mg/0.05 ml bevacizumab will be performed monthly for 3 months.

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

References & Publications (8)

Elnahry AG, Abdel-Kader AA, Habib AE, Elnahry GA, Raafat KA, Elrakhawy K. Review on Recent Trials Evaluating the Effect of Intravitreal Injections of Anti-VEGF Agents on the Macular Perfusion of Diabetic Patients with Diabetic Macular Edema. Rev Recent Cl — View Citation

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 O — View Citation

Elnahry AG, Abdel-Kader AA, Raafat KA, Elrakhawy K. Evaluation of the Effect of Repeated Intravitreal Bevacizumab Injections on the Macular Microvasculature of a Diabetic Patient Using Optical Coherence Tomography Angiography. Case Rep Ophthalmol Med. 201 — View Citation

Elnahry AG, Elnahry GA. Optical Coherence Tomography Angiography of Macular Perfusion Changes after Anti-VEGF Therapy for Diabetic Macular Edema: A Systematic Review. J Diabetes Res. 2021 May 22;2021:6634637. doi: 10.1155/2021/6634637. eCollection 2021. — View Citation

Elnahry AG, Ramsey DJ. Automated Image Alignment for Comparing Microvascular Changes Detected by Fluorescein Angiography and Optical Coherence Tomography Angiography in Diabetic Retinopathy. Semin Ophthalmol. 2021 Nov 17;36(8):757-764. doi: 10.1080/088205 — View Citation

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. — View Citation

Michaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F, Boos CJ, Xing W, Egan C, Peto T, Bunce C, Leslie RD, Hykin PG. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology. 2010 Jun;117(6):1078-1086.e2. doi: 10.1016/j.ophtha.2010.03.045. Epub 2010 Apr 22. — View Citation

Sorour OA, Elsheikh M, Chen S, Elnahry AG, Baumal CR, Pramil V, Abdelhalim TI, Nassar E, Moult EM, Witkin AJ, Duker JS, Waheed NK. Mean macular intercapillary area in eyes with diabetic macular oedema after anti-vascular endothelial growth factor therapy — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in foveal avascular zone area	The change in the foveal avascular zone area will be compared between the two treatment arms as a measure of macular perfusion change.	0 and 3 months.
Primary	Change in vascular density of the superficial retinal capillary plexus	The change in the superficial retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change.	0 and 3 months.
Primary	Change in vascular density of the deep retinal capillary plexus	The change in the deep retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change.	0 and 3 months.
Secondary	Change in best corrected visual acuity	The change in best corrected visual acuity will be assessed following treatment with both drugs using standard Snellen charts.	0 and 3 months
Secondary	Change in central macular thickness	The change in central macular thickness will be assessed following treatment with both drugs using optical coherence tomography.	0 and 3 months
Secondary	Change in intraocular pressure	he change in intraocular pressure will be assessed following treatment with both drugs using Goldman applanation tonometry.	0 and 3 months
Secondary	Change of severity of diabetic retinopathy	The change in the severity of diabetic retinopathy will be assessed following treatment with both drugs using color fundus photographs and clinical examination.	0 and 3 months