Comparison of Surgery Outcome Between Preoperative IVR and Intraoperative IVR in PPV for PDR

Comparison of Surgery Outcome Between Preoperative and Intraoperative Intravitreal Injection of Ranibizumab for Vitrectomy in Proliferative Diabetic Retinopathy Patients

Proliferative diabetic retinopathy (PDR) is the most common causes of irreversible blindness in diabetic retinopathy (DR).Intravitreal injection of anti-VEGF drugs is a good adjunct to vitreous surgery for severe PDR. Some studies have confirmed that the application of anti-VEGF drugs before vitrectomy for PDR patients can reduce the difficulty of surgery and improve postoperative best corrected visual acuity (BCVA), but very few researches focused on the injections of anti-VEGF during surgery.Therefore, investigators carry out this clinical trial to compare the effects of preoperative and intraoperative intravitreal injections of ranibizumab (IVR) on vitrectomy outcomes for PDR patients.One group receive ranibizumab injection (0.5mg/0.05ml) 3-5 days before vitrectomy. Another group receive ranibizumab injection (0.5mg/0.05ml) at the end of vitrectomy. Intraoperative and postoperative indices are collected for further comparison.Investigators enroll PDR patients whose baseline characteristics including age, sex, BMI, type of diabetes, HbA1c level, duration of DM, hypertension, previous history of laser photocoagulation, status of lens, indication for surgery, baseline BCVA, IOP, baseline CRT and extent of VAG are comparable.The enrolled eyes are randomly assigned according to the Central Randomization System with a ratio of 1:1 to preoperative IVR group and intraoperative IVR group. Intraoperative including surgery time, intraoperative bleeding, intraocular electrocoagulation use, iatrogenic retinal breaks, relaxing retinotomy and silicone oil tamponade, and postoperative indices including postoperative best-corrected visual acuity (BCVA), central retinal thickness (CRT), postoperative vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, postoperative fibrovascular proliferation progression and reoperationare collected for further comparison.

Study Overview

• Status: Completed
• Conditions: Proliferative Diabetic Retinopathy
• Intervention / Treatment: Procedure: preoperative group and intraoperative group

Detailed Description

Proliferative diabetic retinopathy (PDR) is the most common causes of irreversible blindness in diabetic retinopathy (DR).It is characterized by progressive loss of vision, retinal edema, vitreous hemorrhage (VH), retinal neovascularization, fibrovascular proliferation, tractional retinal detachment (TRD) and neovascular glaucoma (NVG).Although pars plana vitrectomy (PPV) is the cornerstone for treatment of advanced PDR, related postoperative complications such as recurrent VH, NVG, and progressive fibrovascular proliferation may still cause serious visual impairment.It is well known that vascular endothelial growth factor (VEGF) is a leading role of the neovascularization, vascular permeability, and diabetic macular edema.Intravitreal injection of anti-VEGF drugs before or during PPV maybe a good adjunct to vitreous surgery for severe PDR. Some studies have confirmed that the application of anti-VEGF drugs before vitrectomy for PDR patients can reduce the difficulty of surgery and improve postoperative best corrected visual acuity (BCVA),but very few researches focused on the injections of anti-VEGF during surgery.Therefore, investigators carried out this study to compare the effects of preoperative and intraoperative intravitreal injections of ranibizumab (IVR) on vitrectomy outcomes for PDR patients.Investigators enroll PDR patients whose baseline characteristics including age, sex, BMI, type of diabetes, HbA1c level, duration of DM, hypertension, previous history of laser photocoagulation, status of lens, indication for surgery, baseline BCVA, IOP, baseline CRT and extent of VAG are comparable.The enrolled eyes are randomly assigned according to the Central Randomization System with a ratio of 1:1 to preoperative IVR group and intraoperative IVR group. Intraoperative and postoperative indices are collected for further comparison. Intraoperative indices including surgery time, intraoperative bleeding, intraocular electrocoagulation use, iatrogenic retinal breaks, relaxing retinotomy and silicone oil tamponade. Investigators compare whether there are statistical differences in the above indicators between the two groups. Meanwhile, postoperative indices are collected during 1week, 1 month, 3 month follow-up, including best-corrected visual acuity (BCVA), central retinal thickness (CRT), postoperative vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, postoperative fibrovascular proliferation progression and reoperation. Investigators compare whether there are statistical differences in the above indicators between the two groups at different visit time.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • People's Hospital of Peking University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients aged 18 years or more with type 1 or 2 diabetes who were clinically diagnosed with PDR;
• persistent VH for more than 1 month or recurrent VH with or without panretinal photocoagulation (PRP);
• TRD detected by indirect ophthalmoscope or B-scan ultrasonography.

Exclusion Criteria:

• previous vitrectomy or intravitreal injection in the study eyes;
• eyes with any ocular disease that may hinder visual improvement other than PDR, such as optic atrophy or macular hole;
• poor control of diabetes mellitus (DM) with hemoglobin A1c (HbA1c) > 12%;
• history of thromboembolic events (including cerebral vascular infarctions or myocardial infarctions) or coagulation system disorders or receiving anticoagulant or antiplatelet therapy;
• eyes given gas tamponade or additional treatment during follow-up periods.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: preoperative group; PDR patients who received ranibizumab injection (0.5mg/0.05ml) 3-5 days before vitrectomy were assigned to preoperative group	Procedure: preoperative group and intraoperative group; ranibizumab injection (0.5mg/0.05ml) 3-5 days before vitrectomy or ranibizumab injection (0.5mg/0.05ml) at the end of vitrectomy
Experimental: intraoperative group; PDR patients who received ranibizumab injection (0.5mg/0.05ml) at the end of vitrectomy were assigned to intraoperative group	Procedure: preoperative group and intraoperative group; ranibizumab injection (0.5mg/0.05ml) 3-5 days before vitrectomy or ranibizumab injection (0.5mg/0.05ml) at the end of vitrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
best-corrected visual acuity (BCVA)	every visit time	from preoperation to 3 months follow-up
central retinal thickness	every visit time	from preoperation to 3 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
surgery time	intraoperative index	during surgery
intraoperative bleeding	intraoperative index	during surgery
intraocular electrocoagulation use	intraoperative index	during surgery
iatrogenic retinal breaks	intraoperative index	during surgery
relaxing retinotomy	intraoperative index	during surgery
silicone oil tamponade	intraoperative index	during surgery
postoperative vitreous hemorrhage	postoperative index	during 3 months follow-up
neovascular glaucoma	postoperative index	during 3 months follow-up
recurrent retinal detachment	postoperative index	during 3 months follow-up
postoperative fibrovascular proliferation progression	postoperative index	during 3 months follow-up
reoperation	postoperative index	during 3 months follow-up

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Study Chair: Jinfeng Qu, MD, Peking University People's Hospital

Publications and helpful links

General Publications

• Tseng VL, Greenberg PB, Scott IU, Anderson KL. Compliance with the American Academy of Ophthalmology Preferred Practice Pattern for Diabetic Retinopathy in a resident ophthalmology clinic. Retina. 2010 May;30(5):787-94. doi: 10.1097/IAE.0b013e3181cd47a2.
• Bressler SB, Qin H, Melia M, Bressler NM, Beck RW, Chan CK, Grover S, Miller DG; Diabetic Retinopathy Clinical Research Network. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial. JAMA Ophthalmol. 2013 Aug;131(8):1033-40. doi: 10.1001/jamaophthalmol.2013.4154.
• Ehrlich R, Harris A, Ciulla TA, Kheradiya N, Winston DM, Wirostko B. Diabetic macular oedema: physical, physiological and molecular factors contribute to this pathological process. Acta Ophthalmol. 2010 May;88(3):279-91. doi: 10.1111/j.1755-3768.2008.01501.x. Epub 2010 Mar 11.
• Wang X, Wang G, Wang Y. Intravitreous vascular endothelial growth factor and hypoxia-inducible factor 1a in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 2009 Dec;148(6):883-9. doi: 10.1016/j.ajo.2009.07.007. Epub 2009 Oct 17.
• He YN, Zhao WH, Bai GY, Fang YH, Zhang J, Yang XG, Ding GG. [Relationship between meat consumption and metabolic syndrome in adults in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2018 Jul 10;39(7):892-897. doi: 10.3760/cma.j.issn.0254-6450.2018.07.006. Chinese.
• Ferenchak K, Duval R, Cohen JA, MacCumber MW. Intravitreal bevacizumab for postoperative recurrent vitreous hemorrhage after vitrectomy for proliferative diabetic retinopathy. Retina. 2014 Jun;34(6):1177-81. doi: 10.1097/IAE.0000000000000058.
• Comyn O, Wickham L, Charteris DG, Sullivan PM, Ezra E, Gregor Z, Aylward GW, da Cruz L, Fabinyi D, Peto T, Restori M, Xing W, Bunce C, Hykin PG, Bainbridge JW. Ranibizumab pretreatment in diabetic vitrectomy: a pilot randomised controlled trial (the RaDiVit study). Eye (Lond). 2017 Sep;31(9):1253-1258. doi: 10.1038/eye.2017.75. Epub 2017 May 12.
• Simunovic MP, Maberley DA. ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR PROLIFERATIVE DIABETIC RETINOPATHY: A Systematic Review and Meta-Analysis. Retina. 2015 Oct;35(10):1931-42. doi: 10.1097/IAE.0000000000000723.
• di Lauro R, De Ruggiero P, di Lauro R, di Lauro MT, Romano MR. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2010 Jun;248(6):785-91. doi: 10.1007/s00417-010-1303-3. Epub 2010 Feb 5.
• Ren X, Bu S, Zhang X, Jiang Y, Tan L, Zhang H, Li X. Safety and efficacy of intravitreal conbercept injection after vitrectomy for the treatment of proliferative diabetic retinopathy. Eye (Lond). 2019 Jul;33(7):1177-1183. doi: 10.1038/s41433-019-0396-0. Epub 2019 Mar 14.
• Li S, Tang J, Han X, Wang Z, Zhang L, Zhao M, Qu J. Prospective Comparison of Surgery Outcome Between Preoperative and Intraoperative Intravitreal Injection of Ranibizumab for Vitrectomy in Proliferative Diabetic Retinopathy Patients. Ophthalmol Ther. 2022 Oct;11(5):1833-1845. doi: 10.1007/s40123-022-00550-7. Epub 2022 Jul 29.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): May 29, 2022
• Study Completion (Actual): May 29, 2022

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: ranibizumab; pars plana vitrectomy; preoperative intravitreal injection; intraoperative intravitreal injection
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: PekingUPHJinfeng Qu

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No