Proliferative Diabetic RetinopathyPhase 4PROPERNCT04674254
Macular Perfusion Changes After Anti-VEGF Versus Targeted Retinal Photocoagulation in Proliferative Diabetic Retinopathy
A Phase 4 study testing Bevacizumab Injection, Targeted retinal photocoagulation and Standard pan-retinal photocoagulation in people with Proliferative Diabetic Retinopathy and Vascular Endothelial Growth Factor Overexpression, run by Cairo University at 1 site in Egypt.
Trial summary
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM), while proliferative diabetic retinopathy (PDR) is the principal cause of severe visual loss in patients with diabetes. Since 1981, Panretinal photocoagulation (PRP) has been a standard of treatment for PDR. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Proliferative Diabetic Retinopathy, Vascular Endothelial Growth Factor Overexpression, Diabetic Retinopathy
- What is being tested?
- Bevacizumab Injection, Targeted retinal photocoagulation and Standard pan-retinal photocoagulation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteEgypt
- Study dates
- 30 Mar 2021to 15 Mar 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years old
- Type 1 or 2 diabetes mellitus
- PDR
- Central macular thickness less than 300 µm
Who cannot join
- Central macular thickness more than 300 µm
- Previous retinal laser treatment
- Ocular conditions that may affect macular perfusion (e.g. retinal vein occlusion, uveitis, vasculitis etc.)
- Any previous treatment for diabetic macular edema.
- Presence of epiretinal membrane involving the macula or vitreomacular traction
- Media opacity such vitreous hemorrhage and dense cataract.
Show all 10Show fewer
- Patients with previous cataract surgery within the last 3 months.
- Uncontrolled glaucoma
- Thromboembolic events within 6 months
- Tractional retinal detachment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Macular Perfusion Changes in Proliferative Diabetic Retinopathy Following Anti-VEGF Therapy Versus Targeted and Pan-retinal Photocoagulation Using Optical Coherence Tomography Angiography
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM), while proliferative diabetic retinopathy (PDR) is the principal cause of severe visual loss in patients with diabetes. Since 1981, Panretinal photocoagulation (PRP) has been a standard of treatment for PDR. However, PRP can be associated with adverse effects, including visual field constriction, decreased night vision, and worsening of coexisting diabetic macular edema (DME). For this reason, some authors have advocated targeted treatment with PRP. Targeted retinal laser photocoagulation (TRP) is designed to treat areas of retinal capillary non-perfusion and intermediate retinal ischemic zones in PDR that may spare better-perfused tissue from laser-induced tissue scarring.
Protocol S by Diabetic Retinopathy Clinical Research Network (DRCR.net) has shown that patients that receive ranibizumab as anti-vascular endothelial growth factor (anti-VEGF) therapy with deferred PRP are non-inferior regarding improving in visual acuity to those eyes receiving standard prompt PRP therapy for the treatment of PDR.
Read more
Retinal ischemia is an important factor in the progression and prognosis of diabetic retinopathy. Regarding the effect of anti-VEGF drugs on macular perfusion, several studies have shown mixed results with an increase, decrease, or no effect on perfusion in response to anti-VEGF treatment. In many of these studies, however, patients with more ischemic retinas were not included. Fluorescein angiography (FA) was the method used to assess changes in macular perfusion after anti-VEGF injections in most of the clinical trials. Despite its clinical usefulness, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) in macular perfusion evaluation in these cases was recommended by some investigators. Several studies have proved the reliability of OCTA in detecting and quantifying macular ischemia in diabetics.
The investigators aim to compare changes in the macular perfusion in patients with PDR after treatment with anti-VEGF therapy versus TRP versus Standard PRP using OCTA.
Read the detailed description
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM), while proliferative diabetic retinopathy (PDR) is the principal cause of severe visual loss in patients with diabetes.
Since 1981, PRP has been a standard of treatment for PDR. However, PRP can be associated with adverse effects, including visual field constriction, decreased night vision, and worsening of coexisting diabetic macular edema (DME). for this reason, some authors have advocated targeted treatment with PRP. Targeted retinal laser photocoagulation (TRP) is designed to treat areas of retinal capillary non-perfusion and intermediate retinal ischemic zones in PDR that may spare better-perfused tissue from laser-induced tissue scarring.
Protocol S by DRCR.net has shown that patients that receive ranibizumab as anti-vascular endothelial growth factor (anti-VEGF) therapy with deferred PRP are non-inferior regarding improving in visual acuity to those eyes receiving standard prompt PRP therapy for the treatment of PDR. However, the effect of both treatment modalities on macular perfusion has been inconclusive with no studies comparing the effect of both.
Regarding the effect of anti-VEGF drugs on macular perfusion, several studies have shown mixed results with an increase, decrease, or no effect on perfusion in response to anti-VEGF treatment. In many of these studies, however, patients with more ischemic 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 clinical trials. Despite its clinical usefulness, however, FA is known to have documented risks and is being replaced by optical coherence tomography angiography (OCTA) in macular perfusion evaluation in these cases.
OCTA is a new noninvasive method of acquiring high-resolution images of the retinal vasculature that can be utilized in the management and study of retinal diseases 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 allowing quantitative analysis of vascular parameters.
OCTA uses high-speed OCT scanning to detect the flow of blood by analyzing signal decorrelation between two sequential OCT cross-sectional scans repeated at the same location. Because of the movement of erythrocytes within a vessel, compared to stationary areas of the surrounding retina, only perfused blood vessels will result in signal decorrelation, leading to their imaging. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio.
Several studies have proved the reliability of OCTA in detecting and quantifying macular ischemia in diabetics.
The investigators aim to compare changes in the macular perfusion in patients with PDR without macular edema after treatment with anti-VEGF therapy versus TRP versus Standard PRP using OCTA.
- Conditions
- Proliferative Diabetic Retinopathy, Vascular Endothelial Growth Factor Overexpression, Diabetic Retinopathy
- Being tested
- Bevacizumab Injection, Targeted retinal photocoagulation, Standard pan-retinal photocoagulation
- Keywords
- Proliferative diabetic retinopathy, anti-vascular endothelial growth factor, optical coherence tomography angiography, macular perfusion, pan-retinal photocoagulation, fluorescein angiography, visual field
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab InjectionDrug
Also called Avastin
Bevacizumab will be intravitreally injected every 4 weeks through 12 weeks then pro re nata thereafter for 12 months.
Targeted retinal photocoagulationProcedure or surgery
Targeted retinal photocoagulation will be administered to nonperfused areas detected on fundus fluorescein angiography at baseline and repeated every 3 months as needed for 12 months.
Standard pan-retinal photocoagulationProcedure or surgery
Standard pan-retinal photocoagulation will be applied to perfused and nonperfused areas of the retinal periphery at baseline and every 3 months as needed for 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Anti-vascular endothelial growth factor agent | Active comparator | Intravitreal injections of 1.25 mg/0.05 ml of Bevacizumab every 4 weeks through 12- week visit then pro re nata to complete 12 months according to Protocol S. Receives: Drug: Bevacizumab Injection |
| Targeted retinal photocoagulation | Active comparator | Targeted retinal photocoagulation guided by fundus fluorescein angiography will be administered after topical anesthesia, directed to areas of nonperfused peripheral retina plus a 1-disc area margin using the Mainster lens. Subsequent treatments if needed will be delivered at 3 monthly intervals for a minimum follow-up of 12 months. The extent of the laser applied will be determined based on areas of nonperfusion identified by fundus fluorescein angiography. Receives: Procedure: Targeted retinal photocoagulation |
| Standard pan-retinal photocoagulation | Active comparator | Standard pan-retinal photocoagulation will be performed at baseline and then every 3 months thereafter if needed, for a minimum follow-up period of 12 months.
PRP will be performed at two consecutive sessions with adherence to the guidelines of the Early Treatment Diabetic Retinopathy Study Group. Following topical anesthesia, 1000 to 1200 laser spots will be applied to the retina at each session with a 532 nm frequency doubled Nd-YAG laser (VISULAS, Carl Zeiss, Germany) using a spot size of 300-500 μm. PRP will be applied in all 4 retina quadrants.
The Mainster lens will be used. Retreatment will be done according to the Diabetic Retinopathy Clinical Research network protocol S classification for patients with stable, worsening, or with failure of regression of neovascularization. Receives: Procedure: Standard pan-retinal photocoagulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in foveal avascular zone area
The change in the foveal avascular zone area will be compared between the different treatment arms as a measure of macular perfusion change.
Measured: 0, 3, 6, 9, and 12 months
Change in vascular density of the retinal capillary plexuses
The change in retinal capillary vascular densities at different capillary layers will be compared between the different treatment arms as a measure of macular perfusion change.
Measured: 0, 3, 6, 9, and 12 months
Secondary outcomes (5)
Change in neovessels
The change in neovessels following treatment with each modality will be evaluated clinically and by fundus fluorescein angiography and the response to treatment will be classified according to the criteria of protocol S of the DRCR network
Measured: 0, 3, 6, 9, and 12 months
Change in central macular thickness
The change in central macular thickness will be evaluated following treatment with each modality using optical coherence tomography.
Measured: 0, 3, 6, 9, and 12 months
Change in best corrected visual acuity
The change in best corrected visual acuity will be assessed following treatment with each modality using standard Snellen charts.
Measured: 0, 3, 6, 9, and 12 months
Change in macular sensitivity
The change in the macular sensitivity will be assessed following treatment with each modality using macular microperimetry.
Measured: 0, 3, 6, 9, and 12 months
Change in orbital blood flow
The change in orbital blood flow will be assessed following treatment with each modality using orbital color duplex imaging.
Measured: 0, 3, 6, 9, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start30 Mar 2021
- Primary completion15 Mar 2023
- Study completion15 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Proliferative Diabetic RetinopathyStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ayman Gehad Elnahry, Cairo University
- Investigators
- Mohamed A Eldaly, MD, PhD, Study chair, Cairo UniversityAyman G Elnahry, MD, PhD, Principal investigator, Cairo UniversityWael A Yussuf, MD, MSc, Study director, Cairo UniversityAhmed A Abdel-Kader, MD, PhD, Study director, Cairo UniversityAhmed A Mohalhal, MD, PhD, Study director, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04674254
- Sponsor's protocol ID
- MD-39-2021
- Acronym
- PROPER
- Status last verified
- Jan 2024
- First submitted
- 6 Dec 2020
- Last updated
- 19 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Results will be posted on clinicaltrials.gov when the study is concluded.
Publications
Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015 Sep 30;2:17. doi: 10.1186/s40662-015-0026-2. eCollection 2015.
PubMed 26605370Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984 Dec;91(12):1464-74. doi: 10.1016/s0161-6420(84)34102-1.
PubMed 6521986Riaskoff S. Photocoagulation treatment of proliferative diabetic retinopathy. Bull Soc Belge Ophtalmol. 1981;197:9-17. No abstract available.
PubMed 6182936Alagorie AR, Nittala MG, Velaga S, Zhou B, Rusakevich AM, Wykoff CC, Sadda SR. Association of Intravitreal Aflibercept With Optical Coherence Tomography Angiography Vessel Density in Patients With Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2020 Aug 1;138(8):851-857. doi: 10.1001/jamaophthalmol.2020.2130.
PubMed 32584384Muqit MM, Marcellino GR, Henson DB, Young LB, Patton N, Charles SJ, Turner GS, Stanga PE. Optos-guided pattern scan laser (Pascal)-targeted retinal photocoagulation in proliferative diabetic retinopathy. Acta Ophthalmol. 2013 May;91(3):251-8. doi: 10.1111/j.1755-3768.2011.02307.x. Epub 2011 Dec 16.
PubMed 22176513Nikkhah H, Ghazi H, Razzaghi MR, Karimi S, Ramezani A, Soheilian M. Extended targeted retinal photocoagulation versus conventional pan-retinal photocoagulation for proliferative diabetic retinopathy in a randomized clinical trial. Int Ophthalmol. 2018 Feb;38(1):313-321. doi: 10.1007/s10792-017-0469-7. Epub 2017 Feb 6.
PubMed 28168567Wessel MM, Aaker GD, Parlitsis G, Cho M, D'Amico DJ, Kiss S. Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy. Retina. 2012 Apr;32(4):785-91. doi: 10.1097/IAE.0b013e3182278b64.
PubMed 22080911Kozak I, Luttrull JK. Modern retinal laser therapy. Saudi J Ophthalmol. 2015 Apr-Jun;29(2):137-46. doi: 10.1016/j.sjopt.2014.09.001. Epub 2014 Sep 28.
PubMed 25892934Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015 Nov 24;314(20):2137-2146. doi: 10.1001/jama.2015.15217.
PubMed 26565927Elnahry 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.
PubMed 32411431Elnahry 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 Clin Trials. 2020;15(3):188-198. doi: 10.2174/1574887115666200519073704.
PubMed 32427087Elnahry 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. 2019 Apr 18;2019:3936168. doi: 10.1155/2019/3936168. eCollection 2019.
PubMed 31139483Ghasemi Falavarjani K, Iafe NA, Hubschman JP, Tsui I, Sadda SR, Sarraf D. Optical Coherence Tomography Angiography Analysis of the Foveal Avascular Zone and Macular Vessel Density After Anti-VEGF Therapy in Eyes With Diabetic Macular Edema and Retinal Vein Occlusion. Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):30-34. doi: 10.1167/iovs.16-20579.
PubMed 28114569Manousaridis 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.
PubMed 22250209Hsieh YT, Alam MN, Le D, Hsiao CC, Yang CH, Chao DL, Yao X. OCT Angiography Biomarkers for Predicting Visual Outcomes after Ranibizumab Treatment for Diabetic Macular Edema. Ophthalmol Retina. 2019 Oct;3(10):826-834. doi: 10.1016/j.oret.2019.04.027. Epub 2019 May 7.
PubMed 31227330
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Macular Perfusion Changes in Proliferative Diabetic Retinopathy Following Anti-VEGF Therapy Versus Targeted and Pan-retinal Photocoagulation Using Optical Coherence Tomography Angiography
- ClinicalTrials.gov ID
- NCT04674254
- Acronym / sponsor ID
- PROPER / MD-39-2021
- Conditions
- Proliferative Diabetic Retinopathy, Vascular Endothelial Growth Factor Overexpression, Diabetic Retinopathy
- Keywords
- Proliferative diabetic retinopathy, anti-vascular endothelial growth factor, optical coherence tomography angiography, macular perfusion, pan-retinal photocoagulation, fluorescein angiography, visual field
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 30 Mar 2021 (actual)
- Primary completion
- 15 Mar 2023 (actual)
- Study completion
- 15 Mar 2023 (actual)
- First posted
- 19 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM), while proliferative diabetic retinopathy (PDR) is the principal cause of severe visual loss in patients with diabetes. Since 1981, Panretinal photocoagulation (PRP) has been a standard of treatment for PDR. However, PRP can be associated with adverse effects, including visual field constriction, decreased night vision, and worsening of coexisting diabetic macular edema (DME). For this reason, some authors have advocated targeted treatment with PRP. Targeted retinal laser photocoagulation (TRP) is designed to treat areas of retinal capillary non-perfusion and intermediate retinal ischemic zones in PDR that may spare better-perfused tissue from laser-induced tissue scarring.
Protocol S by Diabetic Retinopathy Clinical Research Network (DRCR.net) has shown that patients that receive ranibizumab as anti-vascular endothelial growth factor (anti-VEGF) therapy with deferred PRP are non-inferior regarding improving in visual acuity to those eyes receiving standard prompt PRP therapy for the treatment of PDR.
Retinal ischemia is an important factor in the progression and prognosis of diabetic retinopathy. Regarding the effect of anti-VEGF drugs on macular perfusion, several studies have shown mixed results with an increase, decrease, or no effect on perfusion in response to anti-VEGF treatment. In many of these studies, however, patients with more ischemic retinas were not included. Fluorescein angiography (FA) was the method used to assess changes in macular perfusion after anti-VEGF injections in most of the clinical trials. Despite its clinical usefulness, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) in macular perfusion evaluation in these cases was recommended by some investigators. Several studies have proved the reliability of OCTA in detecting and quantifying macular ischemia in diabetics.
The investigators aim to compare changes in the macular perfusion in patients with PDR after treatment with anti-VEGF therapy versus TRP versus Standard PRP using OCTA.
Detailed description
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM), while proliferative diabetic retinopathy (PDR) is the principal cause of severe visual loss in patients with diabetes.
Since 1981, PRP has been a standard of treatment for PDR. However, PRP can be associated with adverse effects, including visual field constriction, decreased night vision, and worsening of coexisting diabetic macular edema (DME). for this reason, some authors have advocated targeted treatment with PRP. Targeted retinal laser photocoagulation (TRP) is designed to treat areas of retinal capillary non-perfusion and intermediate retinal ischemic zones in PDR that may spare better-perfused tissue from laser-induced tissue scarring.
Protocol S by DRCR.net has shown that patients that receive ranibizumab as anti-vascular endothelial growth factor (anti-VEGF) therapy with deferred PRP are non-inferior regarding improving in visual acuity to those eyes receiving standard prompt PRP therapy for the treatment of PDR. However, the effect of both treatment modalities on macular perfusion has been inconclusive with no studies comparing the effect of both.
Regarding the effect of anti-VEGF drugs on macular perfusion, several studies have shown mixed results with an increase, decrease, or no effect on perfusion in response to anti-VEGF treatment. In many of these studies, however, patients with more ischemic 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 clinical trials. Despite its clinical usefulness, however, FA is known to have documented risks and is being replaced by optical coherence tomography angiography (OCTA) in macular perfusion evaluation in these cases.
OCTA is a new noninvasive method of acquiring high-resolution images of the retinal vasculature that can be utilized in the management and study of retinal diseases 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 allowing quantitative analysis of vascular parameters.
OCTA uses high-speed OCT scanning to detect the flow of blood by analyzing signal decorrelation between two sequential OCT cross-sectional scans repeated at the same location. Because of the movement of erythrocytes within a vessel, compared to stationary areas of the surrounding retina, only perfused blood vessels will result in signal decorrelation, leading to their imaging. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio.
Several studies have proved the reliability of OCTA in detecting and quantifying macular ischemia in diabetics.
The investigators aim to compare changes in the macular perfusion in patients with PDR without macular edema after treatment with anti-VEGF therapy versus TRP versus Standard PRP using OCTA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Anti-vascular endothelial growth factor agent | Active comparator | Drug: Bevacizumab InjectionIntravitreal injections of 1.25 mg/0.05 ml of Bevacizumab every 4 weeks through 12- week visit then pro re nata to complete 12 months according to Protocol S. |
| Targeted retinal photocoagulation | Active comparator | Procedure: Targeted retinal photocoagulationTargeted retinal photocoagulation guided by fundus fluorescein angiography will be administered after topical anesthesia, directed to areas of nonperfused peripheral retina plus a 1-disc area margin using the Mainster lens. Subsequent treatments if needed will be delivered at 3 monthly intervals for a minimum follow-up of 12 months. The extent of the laser applied will be determined based on areas of nonperfusion identified by fundus fluorescein angiography. |
| Standard pan-retinal photocoagulation | Active comparator | Procedure: Standard pan-retinal photocoagulationStandard pan-retinal photocoagulation will be performed at baseline and then every 3 months thereafter if needed, for a minimum follow-up period of 12 months. PRP will be performed at two consecutive sessions with adherence to the guidelines of the Early Treatment Diabetic Retinopathy Study Group. Following topical anesthesia, 1000 to 1200 laser spots will be applied to the retina at each session with a 532 nm frequency doubled Nd-YAG laser (VISULAS, Carl Zeiss, Germany) using a spot size of 300-500 μm. PRP will be applied in all 4 retina quadrants. The Mainster lens will be used. Retreatment will be done according to the Diabetic Retinopathy Clinical Research network protocol S classification for patients with stable, worsening, or with failure of regression of neovascularization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients ≥ 18 years old
- Type 1 or 2 diabetes mellitus
- PDR
- Central macular thickness less than 300 µm
Key exclusion criteria (10 listed)
- Central macular thickness more than 300 µm
- Previous retinal laser treatment
- Ocular conditions that may affect macular perfusion (e.g. retinal vein occlusion, uveitis, vasculitis etc.)
- Any previous treatment for diabetic macular edema.
- Presence of epiretinal membrane involving the macula or vitreomacular traction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab InjectionAlso: AvastinBevacizumab will be intravitreally injected every 4 weeks through 12 weeks then pro re nata thereafter for 12 months. | Drug | Anti-vascular endothelial growth factor agent |
| Targeted retinal photocoagulationTargeted retinal photocoagulation will be administered to nonperfused areas detected on fundus fluorescein angiography at baseline and repeated every 3 months as needed for 12 months. | Procedure or surgery | Targeted retinal photocoagulation |
| Standard pan-retinal photocoagulationStandard pan-retinal photocoagulation will be applied to perfused and nonperfused areas of the retinal periphery at baseline and every 3 months as needed for 12 months. | Procedure or surgery | Standard pan-retinal photocoagulation |
Primary outcome
Change in foveal avascular zone area
Time frame: 0, 3, 6, 9, and 12 months
The change in the foveal avascular zone area will be compared between the different treatment arms as a measure of macular perfusion change.
Change in vascular density of the retinal capillary plexuses
Time frame: 0, 3, 6, 9, and 12 months
The change in retinal capillary vascular densities at different capillary layers will be compared between the different treatment arms as a measure of macular perfusion change.
5 secondary outcomes
Change in neovessels
Time frame: 0, 3, 6, 9, and 12 months
Change in central macular thickness
Time frame: 0, 3, 6, 9, and 12 months
Change in best corrected visual acuity
Time frame: 0, 3, 6, 9, and 12 months
Change in macular sensitivity
Time frame: 0, 3, 6, 9, and 12 months
Change in orbital blood flow
Time frame: 0, 3, 6, 9, and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2024.
- Results publication: PubMed 26605370Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015 Sep 30;2:17. doi: 10.1186/s40662-015-0026-2. eCollection 2015.
- Results publication: PubMed 6521986Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984 Dec;91(12):1464-74. doi: 10.1016/s0161-6420(84)34102-1.
- Results publication: PubMed 6182936Riaskoff S. Photocoagulation treatment of proliferative diabetic retinopathy. Bull Soc Belge Ophtalmol. 1981;197:9-17. No abstract available.
- Results publication: PubMed 32584384Alagorie AR, Nittala MG, Velaga S, Zhou B, Rusakevich AM, Wykoff CC, Sadda SR. Association of Intravitreal Aflibercept With Optical Coherence Tomography Angiography Vessel Density in Patients With Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2020 Aug 1;138(8):851-857. doi: 10.1001/jamaophthalmol.2020.2130.
- Results publication: PubMed 22176513Muqit MM, Marcellino GR, Henson DB, Young LB, Patton N, Charles SJ, Turner GS, Stanga PE. Optos-guided pattern scan laser (Pascal)-targeted retinal photocoagulation in proliferative diabetic retinopathy. Acta Ophthalmol. 2013 May;91(3):251-8. doi: 10.1111/j.1755-3768.2011.02307.x. Epub 2011 Dec 16.
- Results publication: PubMed 28168567Nikkhah H, Ghazi H, Razzaghi MR, Karimi S, Ramezani A, Soheilian M. Extended targeted retinal photocoagulation versus conventional pan-retinal photocoagulation for proliferative diabetic retinopathy in a randomized clinical trial. Int Ophthalmol. 2018 Feb;38(1):313-321. doi: 10.1007/s10792-017-0469-7. Epub 2017 Feb 6.
- Results publication: PubMed 22080911Wessel MM, Aaker GD, Parlitsis G, Cho M, D'Amico DJ, Kiss S. Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy. Retina. 2012 Apr;32(4):785-91. doi: 10.1097/IAE.0b013e3182278b64.
- Results publication: PubMed 25892934Kozak I, Luttrull JK. Modern retinal laser therapy. Saudi J Ophthalmol. 2015 Apr-Jun;29(2):137-46. doi: 10.1016/j.sjopt.2014.09.001. Epub 2014 Sep 28.
- Results publication: PubMed 26565927Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015 Nov 24;314(20):2137-2146. doi: 10.1001/jama.2015.15217.
- Results publication: PubMed 32411431Elnahry 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.
- Results publication: PubMed 32427087Elnahry 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 Clin Trials. 2020;15(3):188-198. doi: 10.2174/1574887115666200519073704.
- Results publication: PubMed 31139483Elnahry 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. 2019 Apr 18;2019:3936168. doi: 10.1155/2019/3936168. eCollection 2019.
- Individual participant dataSharing planned: No. Results will be posted on clinicaltrials.gov when the study is concluded.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohamed A Eldaly, MD, PhD study chair
Cairo University
Ayman G Elnahry, MD, PhD principal investigator
Cairo University
Wael A Yussuf, MD, MSc study director
Cairo University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bevacizumab Injection, Targeted retinal photocoagulation and Standard pan-retinal photocoagulation in people with Proliferative Diabetic Retinopathy and Vascular Endothelial Growth Factor Overexpression, run by Cairo University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in foveal avascular zone area (time frame: 0, 3, 6, 9, and 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04674254, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2024.