Diabetic retinopathy (NPDR, PDR)
🌎Overview:
Population based studies: DCCT, UKPDS
Laser: DRS, ETDRS
Vitrectomy: DRVS
Ranibizumab: Protocol S
Aflibercept: CLARITY, PANORAMA
Diabetic retinopathy study (DRS), 1981 ⏩
n=1727
Study question: PRP for NPDR or PDR to reduce vision loss
Study results: Defined High Risk PDR and levels of NPDR. Defined PRP. Study showerd that PRP for High risk PDR lowered the risk for severe vision loss (<5/200). This article established laser retinal treatment for diabetic retinopathy.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy, 1984 and on ⏩
n= 1210 type 1, 1780 type 2. 25y+
Risk factors for retinopathy: males, high HbA1C, elevated diastolic Blood pressure. Risk for PDR: HbA1c, systolic hypertension, proteinuria, high BMI at baseline. Most importantly the duration of the disease: after 20 years: 99% of type 1 and 60% for type 2. PDR was found in 50% of type 1 and 25% in type 2. Note this study was based on a mainly white population.
Early Vitrectomy for Severe Vitreous Hemorrhage in Diabetic Retinopathy
Two-Year Results of a Randomized Trial Diabetic Retinopathy Vitrectomy Study Report 2, The Diabetic Retinopathy Vitrectomy Study Research Group (DRVS), 1985 ⏩
n=616, 2y
Study question: Early (<6m) Vs deferred (1y) PPV for VH d/t PDR.
Study results: 25% of the early vitrectomy group had visual acuity of 10/20 or better compared with 15% in the deferral group. In patients with Type I diabetes (younger and more-severe PDR) early PPV resulted in 36% of the eyes returned to 10/20 or better VS 12% in the deferral group. In the Type II diabetes VA of 10/20 or better 16% in the early group vs 18%. Evidence that this advantage differed by diabetes type was of borderline significance.
Early Treatment Diabetic Retinopathy Study (ETDRS), 1991 ⏩
The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus (DCCT), 1993 ⏩
n=1441 n=124.
Study questions: Effect of tight hypoglycemic control (HbA1c<8%) on NPDR/DPR patients.
Study results Tight glycemic control reduces retinopathy. Fast reduction in blood suagar levels can worsen DR.
United kingdom Prospective Diabetes Study reports (UKPDS), 1998 ⏩
n=4209, 11y
Study question: Conventional control blood pressure (BP 180/105) and blood sugar (BS ) VS Tight control (A1C 7.0%, BP 150/85). Study results: HbA1c was 11% lower in the intense group (7% vs 7.9%). Risk for any diabetes related complication lowered by 12%. Diabetic retinopathy lowered by 21%. Overall microvascular complications lowered by 25%. Death realted to DM lowered by 10%. All cause mortality lowered by 6%. Tight blood pressure lowered by 34% risk for retinopathy deterioration and 47% reduction risk for VA loss. Reduction of death related to DM by 32%.
Population based studies: DCCT, UKPDS
Laser: DRS, ETDRS
Vitrectomy: DRVS
Ranibizumab: Protocol S
Aflibercept: CLARITY, PANORAMA
Diabetic retinopathy study (DRS), 1981 ⏩
n=1727
Study question: PRP for NPDR or PDR to reduce vision loss
Study results: Defined High Risk PDR and levels of NPDR. Defined PRP. Study showerd that PRP for High risk PDR lowered the risk for severe vision loss (<5/200). This article established laser retinal treatment for diabetic retinopathy.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy, 1984 and on ⏩
n= 1210 type 1, 1780 type 2. 25y+
Risk factors for retinopathy: males, high HbA1C, elevated diastolic Blood pressure. Risk for PDR: HbA1c, systolic hypertension, proteinuria, high BMI at baseline. Most importantly the duration of the disease: after 20 years: 99% of type 1 and 60% for type 2. PDR was found in 50% of type 1 and 25% in type 2. Note this study was based on a mainly white population.
Early Vitrectomy for Severe Vitreous Hemorrhage in Diabetic Retinopathy
Two-Year Results of a Randomized Trial Diabetic Retinopathy Vitrectomy Study Report 2, The Diabetic Retinopathy Vitrectomy Study Research Group (DRVS), 1985 ⏩
n=616, 2y
Study question: Early (<6m) Vs deferred (1y) PPV for VH d/t PDR.
Study results: 25% of the early vitrectomy group had visual acuity of 10/20 or better compared with 15% in the deferral group. In patients with Type I diabetes (younger and more-severe PDR) early PPV resulted in 36% of the eyes returned to 10/20 or better VS 12% in the deferral group. In the Type II diabetes VA of 10/20 or better 16% in the early group vs 18%. Evidence that this advantage differed by diabetes type was of borderline significance.
Early Treatment Diabetic Retinopathy Study (ETDRS), 1991 ⏩
N=3711, 5y
In light of the DRS results: laser photocoagulation reduced SVL in advanced stage of DR. Study Question: NPDR\DME early vs deferred laser. Early: full scatter\mild\focal. Aspirin vs placebo. Results: Defined ETDRS VA and "clinically significant macular edema". Scatter worsened VA in DME. Focal for DME imrpoved *2 visual angle. NPDR Early scatter – small reduction in severe VA loss. Mild/Mod NPDR-not for scatter. Aspirin-no effect on retinopathy, reduction of CV morbidity.The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus (DCCT), 1993 ⏩
n=1441 n=124.
Study questions: Effect of tight hypoglycemic control (HbA1c<8%) on NPDR/DPR patients.
Study results Tight glycemic control reduces retinopathy. Fast reduction in blood suagar levels can worsen DR.
United kingdom Prospective Diabetes Study reports (UKPDS), 1998 ⏩
n=4209, 11y
Study question: Conventional control blood pressure (BP 180/105) and blood sugar (BS ) VS Tight control (A1C 7.0%, BP 150/85). Study results: HbA1c was 11% lower in the intense group (7% vs 7.9%). Risk for any diabetes related complication lowered by 12%. Diabetic retinopathy lowered by 21%. Overall microvascular complications lowered by 25%. Death realted to DM lowered by 10%. All cause mortality lowered by 6%. Tight blood pressure lowered by 34% risk for retinopathy deterioration and 47% reduction risk for VA loss. Reduction of death related to DM by 32%.
A systematic review and meta-analysis of clinical outcomes of vitrectomy with or without intravitreal bevacizumab pretreatment for severe diabetic retinopathy, 2011 ⏩
n=281, Meta-analysis
Study question: PPV with or without IVT bevacizumab pretreatment (3-20 days) for severe or complicated diabetic retinopathy. Study results: less intraoperative bleeding (OR 8.85) and less surgical time (WMD=14.13) in the tx group. Postoperative reabsorption time significantly shorter and final and BCVA was significantly better in the tx group. Other complications were statistically insignificant.
Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial (Protocol S), 2015 ⏩ and ⏩
n=393, 2y
Study question: Ranibizumab *4 then PRN VS PRP (and deferred Ranibizumab for DME) in patients with PDR (~40% were High Risk PDR).
Study Results: Similar mean VA letter improvement of +2.8 in the ranibizumab group versus +0.2 with PRP. Significantly bigger letter gain in patients with PDR and DME at baseline (+8 vs +2). PPV more frequent for the PRP group (15% vs 4%). About 50% of PRP groups had DME and Ranibizumab tx. DME 28% versus 9% in the Ranibizumab group. PDR regression was similar (47% improved in two severity scales). 6% of the ranibizumab group needed PRP. 35% of PRP group got Ranibizumab (for DME or as rescue).
Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy (CLARITY), 2017 ⏩
n= 232 ,52 weeks
Study Question: 3 Aflibercept then PRN Versus PRP for PDR
Study Results: Aflibercept group gained mean 1.3 letters vs loss of 2.9 in the laser group. CME increase in the PRP group. 30% more regression of NV in Aflibercept group.
Intravitreal aflibercept for moderately severe to severe non-proliferative diabetic retinopathy (PANORAMA), 2018 Not published, ASRS ⏩ or ⏩
n=402, 1y
Study question: Aflibercept (5 monthly then q8w ) VS 3 monthly then q16w VS Sham for moderately severe to severe NPDR in patients without DME.
Study results: Paitents that improved 2+ steps in the DRSS: 15% in sham, 65% in Aflibercept q16w, 80% in q8w. Patients who developed complications of NPDR (PDR, Anterior segment NV, Center involving DME): 41%, 10%, 11%). FDA approves Aflibercept for NPDR tx. $ - Regeneron. See also ongoing DRCR net protocol W.
Preoperative Bevacizumab for Tractional Retinal Detachment in Proliferative Diabetic Retinopathy: A Prospective Randomized Clinical Trial, 2019 ⏩
n=281, Meta-analysis
Study question: PPV with or without IVT bevacizumab pretreatment (3-20 days) for severe or complicated diabetic retinopathy. Study results: less intraoperative bleeding (OR 8.85) and less surgical time (WMD=14.13) in the tx group. Postoperative reabsorption time significantly shorter and final and BCVA was significantly better in the tx group. Other complications were statistically insignificant.
Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial (Protocol S), 2015 ⏩ and ⏩
n=393, 2y
Study question: Ranibizumab *4 then PRN VS PRP (and deferred Ranibizumab for DME) in patients with PDR (~40% were High Risk PDR).
Study Results: Similar mean VA letter improvement of +2.8 in the ranibizumab group versus +0.2 with PRP. Significantly bigger letter gain in patients with PDR and DME at baseline (+8 vs +2). PPV more frequent for the PRP group (15% vs 4%). About 50% of PRP groups had DME and Ranibizumab tx. DME 28% versus 9% in the Ranibizumab group. PDR regression was similar (47% improved in two severity scales). 6% of the ranibizumab group needed PRP. 35% of PRP group got Ranibizumab (for DME or as rescue).
Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy (CLARITY), 2017 ⏩
n= 232 ,52 weeks
Study Question: 3 Aflibercept then PRN Versus PRP for PDR
Study Results: Aflibercept group gained mean 1.3 letters vs loss of 2.9 in the laser group. CME increase in the PRP group. 30% more regression of NV in Aflibercept group.
Intravitreal aflibercept for moderately severe to severe non-proliferative diabetic retinopathy (PANORAMA), 2018 Not published, ASRS ⏩ or ⏩
n=402, 1y
Study question: Aflibercept (5 monthly then q8w ) VS 3 monthly then q16w VS Sham for moderately severe to severe NPDR in patients without DME.
Study results: Paitents that improved 2+ steps in the DRSS: 15% in sham, 65% in Aflibercept q16w, 80% in q8w. Patients who developed complications of NPDR (PDR, Anterior segment NV, Center involving DME): 41%, 10%, 11%). FDA approves Aflibercept for NPDR tx. $ - Regeneron. See also ongoing DRCR net protocol W.
Preoperative Bevacizumab for Tractional Retinal Detachment in Proliferative Diabetic Retinopathy: A Prospective Randomized Clinical Trial, 2019 ⏩
n=224, 12m
Study Question: RCT. PPV plus bevacizumab VS PPV plus sham for diabetic retinal detachment.
Study results: Tx group had less Iatrogenic retinal breaks intraoperatively (34.3% vs 58.9%), less intraoperative bleeding (31.3% vs 51.7 %), less endodiathermy use (27.4 % VS 66.9%) and shorter mean surgical time (71.3 ± 32.1 minutes VS 83.6 ± 38.7). 3% developed a TRD that may be related to bevacizumab membrane contraction.
Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial (DRCR net Protocol AB), 2020 ⏩
n=205, 24mo
Study question: multi-center RCT. 2 mg aflibercept (Protocol T) w/o laser VS PPV + PRP for eyes with vitreous hemorrhages secondary to diabetes.
Study results: Cross over occurred in ~1/3 of each group. Average duration of VH in each group was greater than 3 months. PPV group showed faster restoration of visual acuity at 4 weeks, but the aflibercept arm caught up by 12w and remained equivalent for the remainder of the study. BCVA, cataract formation or endophthalmitis did not differ between groups (despite higher rated of DME in the PPV group 31% vs 8%). Tractional retinal detachment higher in the aflibercept arm (22% versus 13%).
Abbreviations used on this page:
$ - study funding when relevant
CV - Cardio-cascular
DME - Diabetic macular edema
DRSS - Diabetic Retinopathy Severity Scale
NPDR - Non proliferative diabetic retinopathy
NV - Neo-vascularization
OR - odds ratio
PDR - Proliferative diabetic retinopathy
PRP - Pan-retinal photocoagulation
VA - Visual acuity
VH - vitreous hemorrhage
SVL - Severe vision loss
WMD -weighted mean difference
SVL - Severe vision loss
WMD -weighted mean difference
w/o - without
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This page is still being constructed, please feel free to suggest any other trials we should add to this page using the contact us form at the bottom of this page 🚧
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This page is still being constructed, please feel free to suggest any other trials we should add to this page using the contact us form at the bottom of this page 🚧
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