Macular Perfusion Changes in Proliferative Diabetic Retinopathy Following Anti-VEGF Therapy Versus Targeted and Pan-retinal Photocoagulation Using Optical Coherence Tomography Angiography
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Change in vascular density of the retinal capillary plexuses
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 18 years old
- •Type 1 or 2 diabetes mellitus
- •Central macular thickness less than 300 µm
排除标准
- •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.
- •Patients with previous cataract surgery within the last 3 months.
- •Uncontrolled glaucoma
- •Thromboembolic events within 6 months
- •Tractional retinal detachment.
研究组 & 干预措施
Anti-vascular endothelial growth factor agent
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.
干预措施: Bevacizumab Injection (Drug)
Targeted retinal photocoagulation
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.
干预措施: Targeted retinal photocoagulation (Procedure)
Standard pan-retinal photocoagulation
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.
干预措施: Standard pan-retinal photocoagulation (Procedure)
结局指标
主要结局
Change in vascular density of the retinal capillary plexuses
时间窗: 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.
Change in foveal avascular zone area
时间窗: 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.
次要结局
- Change in best corrected visual acuity(0, 3, 6, 9, and 12 months)
- Change in macular sensitivity(0, 3, 6, 9, and 12 months)
- Change in orbital blood flow(0, 3, 6, 9, and 12 months)
- Change in neovessels(0, 3, 6, 9, and 12 months)
- Change in central macular thickness(0, 3, 6, 9, and 12 months)
研究者
Ayman Gehad Elnahry
Lecturer of Ophthalmology
Cairo University