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

• ClinicalTrials.gov Identifier: NCT05408416
• Recruitment Status: Completed
• First Posted: June 7, 2022
• Last Update Posted: June 7, 2022
• Sponsor: Peking University People's Hospital
• Information provided by (Responsible Party): Peking University People's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Proliferative Diabetic Retinopathy	Procedure: preoperative group and intraoperative group	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of Surgery Outcome Between Preoperative and Intraoperative Intravitreal Injection of Ranibizumab for Vitrectomy in Proliferative Diabetic Retinopathy Patients
• Actual Study Start Date: September 1, 2021
• Actual Primary Completion Date: May 29, 2022
• Actual Study Completion Date: May 29, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. best-corrected visual acuity (BCVA) [ Time Frame: from preoperation to 3 months follow-up ]
   every visit time
2. central retinal thickness [ Time Frame: from preoperation to 3 months follow-up ]
   every visit time

Secondary Outcome Measures :

1. surgery time [ Time Frame: during surgery ]
   intraoperative index
2. intraoperative bleeding [ Time Frame: during surgery ]
   intraoperative index
3. intraocular electrocoagulation use [ Time Frame: during surgery ]
   intraoperative index
4. iatrogenic retinal breaks [ Time Frame: during surgery ]
   intraoperative index
5. relaxing retinotomy [ Time Frame: during surgery ]
   intraoperative index
6. silicone oil tamponade [ Time Frame: during surgery ]
   intraoperative index
7. postoperative vitreous hemorrhage [ Time Frame: during 3 months follow-up ]
   postoperative index
8. neovascular glaucoma [ Time Frame: during 3 months follow-up ]
   postoperative index
9. recurrent retinal detachment [ Time Frame: during 3 months follow-up ]
   postoperative index
10. postoperative fibrovascular proliferation progression [ Time Frame: during 3 months follow-up ]
    postoperative index
11. reoperation [ Time Frame: during 3 months follow-up ]
    postoperative index

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

China, Beijing

People's Hospital of Peking University

Beijing, Beijing, China, 100044

Sponsors and Collaborators

Peking University People's Hospital

Investigators

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

More Information

Publications:

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.

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. Review.

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.

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. Review.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 Jul 29. doi: 10.1007/s40123-022-00550-7. [Epub ahead of print]

• Responsible Party: Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT05408416
• Other Study ID Numbers: PekingUPHJinfeng Qu
• First Posted: June 7, 2022
• Last Update Posted: June 7, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peking University People's Hospital:

pars plana vitrectomy; ranibizumab; preoperative intravitreal injection; intraoperative intravitreal injection

Additional relevant MeSH terms:

Retinal Diseases; Diabetic Retinopathy; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases