Retinal Vein Occlusion
Conditions
Keywords
Vision Loss, Eye Injections
Brief summary
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.
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.
Interventions
Anti-vascular endothelial growth factor intraocular injection
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
All patients will receive the same standard of care treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Macular Edema | Baseline through week 35 | 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 |
| Change in Macular Volume | Baseline through week 35 | 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 |
| Change in Vascular Endothelial Growth Factor (VEGF) Level in Anterior Chamber | Baseline through week 35 | Evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA) analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Analytes - Chemokine (C-C Motif) Ligand (CCL)s | Baseline through week 52 | 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 |
| Change in Analytes - Chemokine (C-X-C Motif) Ligand (CXCL)s | Baseline through week 52 | CXCL1/GRO alpha/KC/Cytokine-induced neutrophil chemoattractant (CINC-1) and CXCL2/GRO beta/MIP-s/CINC-3 - Analyzed using an ELISA multiplex |
| Change in Analytes - Growth Factors | Baseline through week 52 | 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 |
| Change in Best Corrected Visual Acuity (BCVA) | Baseline through week 35 | 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 |
| Change in Analytes - Proteins | Baseline through week 52 | Programmed death-ligand 1(PD-L1)/B7 homolog 1(B7-H1) Analyzed using an ELISA multiplex |
| Change in Analytes - Interleukins | Baseline through week 52 | 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 |
| Change in Analytes - Interferons | Baseline through week 52 | Interferon (IFN)-alpha 2/IFNA2, Interferon (IFN)-beta, and Interferon (IFN)-gamma - Analyzed using an ELISA multiplex |
| Change in Intraocular Pressure (IOP) | Baseline through week 52 | 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) |
| Number of Intravitreal Injections | Baseline through week 52 | Number of injections received during study participation |
Countries
United States
Participant flow
Recruitment details
Participants were inappropriately enrolled; IRB required early termination due to the number of protocol violations.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Aflibercept Ophthalmic: Anti-vascular endothelial growth factor intraocular injection | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | IRB Required Early Termination Due to Safety Concerns | 17 |
Baseline characteristics
| Characteristic | Aflibercept | — |
|---|---|---|
| Age, Continuous | 74.4 years STANDARD_DEVIATION 6.6 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 6 Participants | — |
| Sex: Female, Male Male | 4 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 17 |
| other Total, other adverse events | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
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
Time frame: Baseline through week 35
Population: IRB terminated study early and would not allow study team to access data further.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Macular Edema | -504.4 cubic microns | Standard Deviation 300.82 |
Primary
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
Time frame: Baseline through week 35
Population: IRB will not allow study team to access or analyze data any further.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Macular Volume | -5.2 cubic microns | Standard Deviation 4 |
Primary
Change in Vascular Endothelial Growth Factor (VEGF) Level in Anterior Chamber
Evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA) analysis
Time frame: Baseline through week 35
Population: IRB will not allow study team to access or analyze data any further.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Vascular Endothelial Growth Factor (VEGF) Level in Anterior Chamber | -203.5 pg/ml | Standard Deviation 203.5 |
Secondary
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
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination
Secondary
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
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination
Secondary
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
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination
Secondary
Change in Analytes - Interferons
Interferon (IFN)-alpha 2/IFNA2, Interferon (IFN)-beta, and Interferon (IFN)-gamma - Analyzed using an ELISA multiplex
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination
Secondary
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
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination
Secondary
Change in Analytes - Proteins
Programmed death-ligand 1(PD-L1)/B7 homolog 1(B7-H1) Analyzed using an ELISA multiplex
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination
Secondary
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
Time frame: Baseline through week 35
Population: IRB will not allow study team to access or analyze data any further.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aflibercept | Change in Best Corrected Visual Acuity (BCVA) | -0.33 LOGMAR Units | Standard Deviation 0.43 |
Secondary
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)
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination
Secondary
Number of Intravitreal Injections
Number of injections received during study participation
Time frame: Baseline through week 52
Population: Not measured prior to IRB-required termination