Diabetic Retinopathy, Proliferative Diabetic Retinopathy, Vascular Endothelial Growth Factor Overexpression
Conditions
Keywords
Proliferative diabetic retinopathy, anti-vascular endothelial growth factor, optical coherence tomography angiography, macular perfusion, pan-retinal photocoagulation, fluorescein angiography, visual field
Brief 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. 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.
Interventions
DRUGBevacizumab Injection
Bevacizumab will be intravitreally injected every 4 weeks through 12 weeks then pro re nata thereafter for 12 months.
PROCEDURETargeted retinal photocoagulation
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.
PROCEDUREStandard pan-retinal photocoagulation
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.
Sponsors
Cairo University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥ 18 years old 2. Type 1 or 2 diabetes mellitus 3. PDR 4. Central macular thickness less than 300 µm
Exclusion criteria
1. Central macular thickness more than 300 µm 2. Previous retinal laser treatment 3. Ocular conditions that may affect macular perfusion (e.g. retinal vein occlusion, uveitis, vasculitis etc.) 4. Any previous treatment for diabetic macular edema. 5. Presence of epiretinal membrane involving the macula or vitreomacular traction 6. Media opacity such vitreous hemorrhage and dense cataract. 7. Patients with previous cataract surgery within the last 3 months. 8. Uncontrolled glaucoma 9. Thromboembolic events within 6 months 10. Tractional retinal detachment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in foveal avascular zone area | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in best corrected visual acuity | 0, 3, 6, 9, and 12 months | The change in best corrected visual acuity will be assessed following treatment with each modality using standard Snellen charts. |
| Change in neovessels | 0, 3, 6, 9, and 12 months | 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 |
| Change in orbital blood flow | 0, 3, 6, 9, and 12 months | The change in orbital blood flow will be assessed following treatment with each modality using orbital color duplex imaging. |
| Change in macular sensitivity | 0, 3, 6, 9, and 12 months | The change in the macular sensitivity will be assessed following treatment with each modality using macular microperimetry. |
| Change in central macular thickness | 0, 3, 6, 9, and 12 months | The change in central macular thickness will be evaluated following treatment with each modality using optical coherence tomography. |
Countries
Egypt
Outcome results
None listed