Vascular Endothelial Growth Factor (VEGF) Levels in Retinal Vein Occlusion (RVO) During Anti-VEGF Treatment

Correlation of Vascular Endothelial Growth Factor Levels in Anterior Chamber Fluid to Disease State in Patients With Retinal Vein Occlusion Receiving Standard of Care Treatment

The purpose of this study is to treat patients with retinal vein occlusion with standard of care anti-vascular endothelial growth factor therapy and to correlate levels of vascular endothelial growth factor in the anterior chamber fluid of the eye. This study will evaluate if measuring the vascular endothelial growth factor will help predict the timing of when anti-vascular endothelial growth factor therapy will be needed.

Study Overview

• Status: Terminated
• Conditions: Retinal Vein Occlusion
• Intervention / Treatment: Drug: Aflibercept Ophthalmic

Detailed Description

Ten patients, 5 with branch retinal vein occlusion and 5 with central retinal vein occlusion, will receive stand of care anti-vascular endothelial growth factor over the course of 52 weeks while undergoing a paracentesis prior to each treatment. During the paracentesis anterior chamber fluid will be removed to evaluate vascular endothelial growth factor levels along with other cytokines present in the anterior chamber fluid. Ocular coherence tomography will also be collected at each visit to evaluate macular thickness which will be used to help determine treatment windows along with levels of vascular endothelial growth factor. Patients with high levels of vascular endothelial growth factor and the presence of macular edema on ocular coherence tomography will be treated every four weeks. Once vascular endothelial growth factor levels are reduced along with improvements of macula edema treatment windows will be extended to 8 weeks and then to 12 weeks once levels are normal and edema is no longer present.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Blair Gordy; Phone Number: 336-716-3937; Email: bgordy@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Health Sciences

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Willingness and ability to provide written informed consent.
• Diagnosis of Retinal Vein Occlusion with macular edema and central foveal thickness of greater than or equal to 300 microns confirmed by intravenous fluorescein angiography and Optical Coherence Tomography
• Visual Acuity between 20/25 and 5/200

Exclusion Criteria:

• Bilateral Retinal Vein Occlusion
• Vision worse than 5/200 in study eye
• History of myocardial infarction, ischemia, or cerebrovascular accident within 6 weeks of screening
• Concurrent Proliferative Diabetic Retinopathy and/or Maculopathy
• Concurrent Exudative Age-related Macular Degeneration
• Concurrent optic neuropathy with the presence of an afferent pupillary defect
• Previous vitrectomy in the study eye
• Currently pregnant or planning to become pregnant during the duration of the study. Women currently breastfeeding are also excluded.
• Previous treatment for retinal vein occlusion in the study eye
• Any current medical condition which, in the opinion of the investigator is considered to be uncontrolled
• History of allergy or hypersensitivity to study treatment, fluorescein, or any study procedure and treatment related ingredients (e.g. topical anesthetics, betadine, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Aflibercept; All subjects will receive aflibercept every 4 weeks. Once vascular endothelial growth factor levels become normal and macular edema improves treatment windows will be extended up to every 12 weeks.	Drug: Aflibercept Ophthalmic; Anti-vascular endothelial growth factor intraocular injection; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Macular Edema	Measured by central retinal thickness using optical coherence tomography - OCT is an imaging method used to generate a picture of the back of the eye, called the retina. The picture is made by precisely measuring the amount of a dim red light that reflects off the retina	Baseline through week 52
Change in Macular Volume	Measured by central retinal thickness using optical coherence tomography - OCT is an imaging method used to generate a picture of the back of the eye, called the retina. The picture is made by precisely measuring the amount of a dim red light that reflects off the retina	Baseline through week 52
Change in Vascular Endothelial Growth Factor (VEGF) level in Anterior Chamber	Evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA) analysis	Baseline through week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Best Corrected Visual Acuity (BCVA)	Using Snellen Visual Acuity charts - The results are based on what line the patient can read with ease - If a subject's visual acuity is so poor that the subject can't see any letters on the charts, finger counting and/or hand motions will be checked	Baseline through week 52
Change in Intraocular Pressure (IOP)	Evaluated by tonometry - Tonometry is the procedure eye care professionals perform to determine the intraocular pressure (IOP), the fluid pressure inside the eye - Most tonometers are calibrated to measure pressure in millimeters of mercury (mmHg)	Baseline through week 52
Number of Intravitreal Injections	Number of injections received during study participation	Baseline through week 52
Change in Analytes - Chemokine (C-C motif) ligand (CCL)s	Chemokine (C-C motif) ligand 2 (CCL2)/(JE/MCP-1) Monocyte chemoattractant protein 1 and C-C motif chemokine 11(CCL11)/Eotaxin - Analyzed using an ELISA multiplex	Baseline through week 52
Change in Analytes - chemokine (C-X-C motif) ligand (CXCL)s	CXCL1/GRO alpha/KC/Cytokine-induced neutrophil chemoattractant (CINC-1) and CXCL2/GRO beta/MIP-s/CINC-3 - Analyzed using an ELISA multiplex	Baseline through week 52
Change in Analytes - Growth factors	Epidermal growth factor (EGF) and basic fibroblast growth factor (FGF basic)/FGF2/bFGF - and Transforming growth factor alpha (TGF-alpha) - and Platelet-derived growth factor (PDGF)-AA and PDGF-AB/BBA analyzed using an ELISA multiplex Analyzed	Baseline through week 52
Change in Analytes - Interferons	Interferon (IFN)-alpha 2/IFNA2, Interferon (IFN)-beta, and Interferon (IFN)-gamma - Analyzed using an ELISA multiplex	Baseline through week 52
Change in Analytes - Interleukins	IL-1 alpha/IL-1F1; IL-1 beta/IL-1F2; IL-1ra/IL-1F3; IL-2; IL-3; IL-4; IL-5; IL-6; IL-7; IL-8/CXCL8; IL-10; IL-12 p70; IL-13; IL-15; IL-17/IL-17A; IL-17E/IL-25; IL-33 Analyzed using an ELISA multiplex	Baseline through week 52
Change in Analytes - Proteins	Programmed death-ligand 1(PD-L1)/B7 homolog 1(B7-H1) Analyzed using an ELISA multiplex	Baseline through week 52

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Mark Nelson, MD, Wake Forest Baptist Medical Center

Publications and helpful links

General Publications

• Falavarjani KG, Nguyen QD. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye (Lond). 2013 Jul;27(7):787-94. doi: 10.1038/eye.2013.107. Epub 2013 May 31.
• Clark WL, Boyer DS, Heier JS, Brown DM, Haller JA, Vitti R, Kazmi H, Berliner AJ, Erickson K, Chu KW, Soo Y, Cheng Y, Campochiaro PA. Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study. Ophthalmology. 2016 Feb;123(2):330-336. doi: 10.1016/j.ophtha.2015.09.035. Epub 2015 Oct 30.
• Ogura Y, Roider J, Korobelnik JF, Holz FG, Simader C, Schmidt-Erfurth U, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, Zeitz O, Sandbrink R; GALILEO Study Group. Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study. Am J Ophthalmol. 2014 Nov;158(5):1032-8. doi: 10.1016/j.ajo.2014.07.027. Epub 2014 Jul 25.
• Heier JS, Clark WL, Boyer DS, Brown DM, Vitti R, Berliner AJ, Kazmi H, Ma Y, Stemper B, Zeitz O, Sandbrink R, Haller JA. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014 Jul;121(7):1414-1420.e1. doi: 10.1016/j.ophtha.2014.01.027. Epub 2014 Mar 27. Erratum In: Ophthalmology. 2014 Nov;121(11):2293.

Helpful Links

• Eyla prescribing information

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Actual): December 18, 2023
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: January 11, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Vision Loss; Eye Injections
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Retinal Vein Occlusion; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: IRB00064405

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD at this time.

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