Intravitreal Infliximab for Proliferative Vitreoretinopathy (FIXER)

January 18, 2024 updated by: Ayman Gehad Elnahry, Cairo University

Treatment of Proliferative Vitreoretinopathy With Intravitreal Infliximab

Proliferative vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenous retinal detachment repair and is characterized by the growth and contraction of cellular membranes within the vitreous cavity on both sides of the retinal surface as well as intraretinal fibrosis.

Multiple therapeutic agents have been tried as an adjunctive to retinal detachment surgery for PVR with no consistent efficacy. Tumor necrosis factor-α (TNF-α), which is a prominent inflammatory cytokine, is secreted in response to trauma, infection, and inflammation. It is a key mediator of ocular inflammation and its interactions with the retinal pigment epithelium (RPE) cell contribute to the initiation of PVR. This may occur through the action of TNF-α on the RPE cells inducing changes in cellular morphologies that lead to the formation of fibroblastic cells.

Infliximab (Remicade; Janssen Biotech, Horsham, PA, USA) is a mouse-human chimeric antibody that neutralizes the biological activity of TNF-α by high-affinity binding to the soluble and transmembrane forms of TNF-α, therefore preventing the effective binding of TNF-α with its receptors. Infliximab is used in the treatment of various ocular and systemic inflammatory conditions. Furthermore, intravitreal infliximab has been used for the treatment of various ocular diseases and has proven to be generally safe for the short term in inflammatory ocular conditions. A recent study showed that intravitreal infliximab can inhibit the development of PVR and reduce levels of cytokines in an experimental dispase-induced PVR model.

The purpose of this randomized controlled trial is to evaluate the efficacy of intravitreal infliximab injection as an adjunct to pars plana vitrectomy in the treatment of PVR associated with primary rhegmatogenous retinal detachment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Proliferative vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenous retinal detachment repair and is characterized by the growth and contraction of cellular membranes within the vitreous cavity on both sides of the retinal surface as well as intraretinal fibrosis.

The incidence of PVR in all cases of retinal detachment is estimated to be 5- 10%. The incidence of PVR has largely remained unchanged in prospective studies despite the evolution of vitreoretinal techniques over the past 25 years, including valved trocars and smaller gauge instrumentation.

Numerous risk factors for the development of PVR have been identified. Almost all risk factors for PVR are associated with intravitreal dispersion of retinal pigment epithelial cells or breakdown of the blood-ocular barrier. Following a retinal break, the retinal pigment epithelial (RPE) cells are exposed to the vitreous cavity to react to growth factors and cytokines in the vitreous, resulting in a forward feedback to secret more growth factors and cytokines to further stimulate cellular responses.

Multiple therapeutic agents have been tried as an adjunctive to retinal detachment surgery for PVR with no consistent efficacy. Tumor necrosis factor-α (TNF-α), which is a prominent inflammatory cytokine, is secreted in response to trauma, infection, and inflammation. It is a key mediator of ocular inflammation and its interactions with RPE cells contribute to the initiation of PVR. This is because TNF-α was found to act on the RPE cells consequently inducing changes in cellular morphologies leading to the formation of fibroblastic cells. Additionally, if TNF-α is combined with other growth factors, a strong synergistic effect can be induced to form epithelial-mesenchymal transition (EMT)-associated fibrotic focus.

Infliximab (Remicade; Janssen Biotech, Horsham, PA, USA) is a mouse-human chimeric antibody that neutralizes the biological activity of TNF-α by high-affinity binding to the soluble and transmembrane forms of TNF-α, therefore preventing the effective binding of TNF-α with its receptors. Infliximab is used in the treatment of various ocular and systemic inflammatory conditions. Furthermore, intravitreal infliximab has been used for the treatment of various ocular diseases and has proven to be generally safe for the short term in inflammatory ocular conditions. A recent study showed that intravitreal infliximab can inhibit the development of PVR and reduce levels of cytokines in an experimental dispase-induced PVR model.

The purpose of this randomized controlled trial is to evaluate the efficacy of intravitreal infliximab injection as an adjunct to pars plana vitrectomy in the treatment of PVR associated with primary rhegmatogenous retinal detachment.

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt, 11956
        • Cairo University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age: more than or equal to 18 years
  • Primary rhegmatogenous retinal detachment with proliferative vitreoretinopathy more than or equal to grade C

Exclusion Criteria:

  • Patients with a history of open globe injury
  • Recurrent retinal detachment or primary failed retinal detachment surgery
  • History of vitreoretinal procedure
  • Retinal vascular diseases (Diabetic retinopathy, retinal vein occlusion,...etc)
  • Pregnant or breastfeeding females
  • Inability to attend regular follow-up visits
  • History of pulmonary or extra-pulmonary tuberculosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Infliximab group
This group will receive 1 mg/0.05 mL of intravitreal infliximab at the end of standard pars plana vitrectomy.
Drug: Intravitreal infliximab
1 mg/0.05 mL of infliximab will be injected intravitreally at the end of pars plana vitrectomy.
Other Names:
  • Remicade
Procedure: Pars plana vitrectomy
Standard pars plana vitrectomy
Sham Comparator: Standard of care group
This group will undergo standard pars plana vitrectomy.
Procedure: Pars plana vitrectomy
Standard pars plana vitrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anatomical success
Time Frame: 9 months
Anatomical Success will be defined as stable complete retinal reattachment following pars plana vitrectomy and silicone oil removal.
9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual acuity
Time Frame: 1, 3, 6, and 9 months
Best corrected visual acuity will be measured at follow up visits using standard Snellen charts.
1, 3, 6, and 9 months
Macular structure
Time Frame: 1, 3, 6, and 9 months
Optical coherence tomography will be done at each follow up visit to assess the structure of the macula.
1, 3, 6, and 9 months
Macular vascularity
Time Frame: 7 months
Optical coherence tomography angiography will be done at each follow up visit to assess macular vascular density.
7 months
Macular function
Time Frame: 7 months
Macular function will be assessed during follow up visits using multifocal electroretinography
7 months
Single operation success rate
Time Frame: 9 months
The rate of successful retinal reattachment following a single operation will be calculated.
9 months
Recurrence rate
Time Frame: 9 months
Cumulative rate of recurrence of retinal detachment and reoperation following the primary surgery will be calculated during the study period.
9 months
Epiretinal proliferative
Time Frame: 1, 3, 6, and 9 months
The formation of significant epiretinal proliferation will be assessed clinically at each follow up visit.
1, 3, 6, and 9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Investigators

  • Principal Investigator: Ayman G Elnahry, MD, PhD, Cairo University
  • Study Chair: Hany S Hamza, MD, PhD, Cairo University
  • Principal Investigator: Ahmed M Younes, MD, MSc, Cairo University
  • Study Director: Ahmed A Abdel-Kader, MD, PhD, Cairo University
  • Study Director: Ahmed M Abdelbaki, MD, PhD, Cairo University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 26, 2021

Primary Completion (Actual)

November 10, 2023

Study Completion (Actual)

November 10, 2023

Study Registration Dates

First Submitted

May 10, 2021

First Submitted That Met QC Criteria

May 13, 2021

First Posted (Actual)

May 19, 2021

Study Record Updates

Last Update Posted (Estimated)

January 19, 2024

Last Update Submitted That Met QC Criteria

January 18, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CU272021

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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