Pars-plana Vitrectomy vs Panretinal Photocoagulation for Severe NPDR

Micro-invasive Pars-plana Vitrectomy vs Panretinal Photocoagulation for Severe Non-Proliferative Diabetic Retinopathy A Randomized Clinical Trial

It is estimated that there are about 600 million diabetes mellitus (DM) patients all over the world until 2040，and almost 50% of whom have some degree of diabetic retinopathy (DR) at any given time. About 5% to 10% diabetic retinopathy would develop vision-threatening complications, including proliferative diabetic retinopathy (PDR), capillary non-perfusion, or macular edema. Data from the DRS suggest that given long enough duration of diabetes, approximately 60% of patients with DR will develop PDR, and without intervention, 75% nonproliferative diabetic retinopathy (NPDR) will development PDR within 1 year follow up, 45% will develop high-risk PDR, nearly half of PDR will experience profound visual loss. panretinal photocoagulation (PRP) only reduced 50% risk of sever visual loss and about 25% of the sNPDR patients who finished PRP need Pars-plana vitrectomy (PPV) in a 5 year follow up.

Vitreous have been proven to play an important role in the development of NPDR to PDR, which were the collection of vascular endothelial growth factor (VEGF) factors and the major component of proliferative lesion in the later stage of PDR.

Micro-invasive Pars-plana vitrectomy has been shown as a safe and effective method in the treatment of PDR, through removing the pathological vitreous, proliferative membrane and also the VEGF factors. However, whether or not Micro-invasive Pars-plana vitrectomy will be more effective than PRP to control the progression of NDPR remained unknown.

Study Overview

• Status: Recruiting
• Conditions: Non Proliferative Diabetic Retinopathy
• Intervention / Treatment: Procedure: Prompt panretinal photocoagulation; Procedure: 25G Pars-plana vitrectomy

• Study Type: Interventional
• Enrollment (Anticipated): 272
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: tao li, Dr; Phone Number: +8620 66683995; Email: litao2@mail.sysu.edu.cn
• Study Contact Backup: Name: shida chen, Dr; Phone Number: +8620 66610721; Email: chenshd3@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Zhongshan Ophthalmic Center

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:

1. Aged ≥18 years, male or female
2. Type 1 or type 2 diabetes

3. Presence of severe NPDR according to the diagnosis of 4-2-1 rule,

   One or more of the following, in the absence of PDR:

   • More than 20 intraretinal hemorrhages in each of four quadrants
   • Definite venous beading in two or more quadrants
   • Prominent intraretinal microvascular abnormality (IRMA) in one or more quadrants
4. Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity letter score > 24 (approximate Snellen equivalent 20/320) on the day of randomization.
5. Media clarity, pupillary dilation, and study participant cooperation sufficient to administer PRP and obtain adequate fundus photographs and optical coherence tomography (OCT).
6. Able and willing to provide informed consent

Exclusion Criteria:

1. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant
2. In the opinion of the investigator, A condition that would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
3. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied.

4. Blood pressure > 180/110 (systolic above 180 or diastolic above 110).

   *If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.

5. Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization

6. Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization

   * These drugs should not be used during the study

7. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 3 years.

   * Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed

8. History of prior panretinal photocoagulation (prior PRP is defined as ≥100 burns outside of the posterior pole
9. If macular edema is present, it is considered to be primarily due to a cause other than diabetic macular edema.
10. An ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might alter visual acuity during the course of the study (e.g., retinal vein or artery occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.).
11. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye were otherwise normal).
12. History of intravitreal anti-VEGF treatment at any time in the past 2 months
13. History of corticosteroid treatment (intravitreal or peribulbar) at any time in the past 4 months.
14. History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.
15. History of laser capsulotomy performed within 2 months prior to randomization
16. Aphakia.
17. Uncontrolled glaucoma (in investigator's judgment).
18. Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis.

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
Experimental: Group A; Prompt panretinal photocoagulation	Procedure: Prompt panretinal photocoagulation; Study eyes that receive panretinal photocoagulation (prompt PRP eyes at baseline) should have 1200 to1600 burns with a spot size on the retina of approximately 500 microns given over 1 to 3 sittings and completed within 4 weeks of initiation
Experimental: Group B; Micro-invasive Pars-plana vitrectomy	Procedure: 25G Pars-plana vitrectomy; Study eyes that receive standard 25G Pars-plana vitrectomy that remove all the vitreous, without laser or Silicone oil tamponade, but filled with perfusion fluid. Surgery should be completed within 4 weeks after randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression rate of severe non proliferative diabetic retinopathy	the number of patients with severe non proliferative diabetic retinopathy progressed to proliferative diabetic retinopathy in each group from the baseline to 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of best corrected visual acuity	The mean change in best corrected visual acuity in each group from baseline to 12 months	12 months
the rate of re-treatment	The number of patients who need re-treatment including supplement laser or vitrectomy from baseline to 12 months	12 months
The occurrence of diabetic macular edema	The occurrence number of diabetic macular edema in each group from baseline to 12 months	12 months
The change of central retinal thickness	the change of central retinal thickness from baseline to 12 months	12 months
The change of visual field	the change of visual field from baseline to 12 months	12 months
The occurrence of cataract	the occurrence of cataract from baseline to 12 months	12 months
The change of quality of life	the change of quality of life as assessed by questionnaire at 12 months	12 months

Collaborators and Investigators

• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University

Publications and helpful links

General Publications

• Zheng W, Chen S, Ding X, Lai K, Xiao S, Lin Y, Liu B, Jin L, Li J, Wu Y, Ma Y, Lu L, Liu Y, Li T. Microinvasive pars plana vitrectomy versus panretinal photocoagulation in the treatment of severe non-proliferative diabetic retinopathy (the VIP study): study protocol for a randomised controlled trial. BMJ Open. 2021 Feb 22;11(2):e043371. doi: 10.1136/bmjopen-2020-043371.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2019
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: NPDR; Pars-plana vitrectomy; panretinal photocoagulation
• 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: 2019KYPJ108

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
• product manufactured in and exported from the U.S.: No