Diabetic Macular Edema
Conditions
Brief summary
To measure various pro-permeability factors in the aqueous humor of patients with persistent/recurrent diabetic macular edema
Detailed description
Patients with Diabetic Macular Edema (DME) are increasingly being treated with molecules targeting vascular endothelial factor (VEGF). One potential advantage of a dexamethasone implant over specific VEGF antagonists is that steroids suppress production of multiple pro-permeability factors. Our primary objective is to measure the pro-permeability factors in the aqueous humor of patients with persistent/recurrent macular edema despite prior treatment with anti-VEGF agents at baseline and at 1, 2, 3, and 4 months after intraocular injection of a dexamethasone implant.
Interventions
Patients will receive a single injection of a dexmethasone implant
DRUGAnti-VEGF injection
Patients will receive PRN injections of an anti-VEGF agent
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* • Signed informed consent and authorization of use and disclosure of protected health information * Age more than or equal to 18 years * Diagnosis of diabetic macular edema * Intraretinal or subretinal fluid in the macula determined by Spectralis OCT * Best corrected visual acuity score in the study eye of 20/30 to 20/400 inclusive (Snellen equivalents using the ETDRS protocol at a distance of 4 meters) * In the opinion of the investigator, decreased vision in the study eye is due to foveal thickening from DME and not from other obvious causes of decreased vision * Persistent or recurrent edema despite prolonged treatment with an anti-VEFG agent
Exclusion criteria
* • Scatter laser photocoagulation or macular photocoagulation within 3 months of study entry in the study eye * Intraocular surgery in the study eye within 3 months of study entry * Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 4 months of study entry * Previous use of an anti-VEGF drug within 1 month of study entry * Yttrium-Aluminum-Garnet (YAG) laser capsulotomy within 1 month of study entry * Any condition that the investigator believes would pose a significant hazard to the subject if investigational therapy were initiated. * Inability to comply with study or follow up procedures * History of glaucoma. (Patients who have undergone filtration surgery may be included) * Patients with active or suspected ocular or periocular infection, including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. * Aphakic eyes with rupture of the posterior lens capsule. * Eyes with ACIOL and rupture of the posterior lens capsule. * Patients with hypersensitivity to dexamethasone or to any other components of the product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | 1, 2, 3, and 4 months after injection of a dexamethasone implant or anti-VEGF agent | Changes in propermeability factor levels were correlated with changes in edema using the person correlation coefficient (this was calculated using data from all time points). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 61.8 years |
| Baseline Best Corrected Visual Acuity | 56.1 ETDRS Score |
| Baseline Central Subfield Thickness | 464.3 Microns |
| Baseline Intraretinal Fluid Mild | 3 participants |
| Baseline Intraretinal Fluid Moderate | 14 participants |
| Baseline Intraretinal Fluid Severe | 3 participants |
| Mean Disease Duration | 48.1 Months |
| Prior Anti-VEGF injections | 13.3 Injections |
| Prior Intraocular Steroids | 5 participants |
| Prior Laser Grid Laser | 6 participants |
| Prior Laser Scatter Laser Photocoagulation | 6 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 20 |
| serious Total, serious adverse events | 4 / 20 |
Outcome results
Primary
Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent
Changes in propermeability factor levels were correlated with changes in edema using the person correlation coefficient (this was calculated using data from all time points).
Time frame: 1, 2, 3, and 4 months after injection of a dexamethasone implant or anti-VEGF agent
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | MMP-9 | 0.45 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Persephin | 0.35 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Endostatin | 0.41 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | MIP-1a | 0.34 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Prolactin | 0.45 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | THSP-2 | 0.33 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Angiopoietin-2 | 0.40 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | HGF | 0.31 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | EG-VEGF | 0.43 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | IL-8 | 0.30 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | IGF-BP3 | 0.36 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | CXCL16 | 0.29 Pearson correlation coefficient (r) |
| Dexamethasone Implant | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | IGF-BP1 | 0.47 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | CXCL16 | 0.027 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | IGF-BP1 | 0.059 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Prolactin | 0.369 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | MMP-9 | 0.29 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | EG-VEGF | -0.004 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Endostatin | 0.189 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Angiopoietin-2 | 0.229 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | IGF-BP3 | 0.435 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | Persephin | 0.114 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | MIP-1a | -0.107 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | THSP-2 | 0.064 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | HGF | 0.226 Pearson correlation coefficient (r) |
| Anti-VEGF Agent | Correlation Between Change in Level of Propermeability Factors With Change in Edema After Treatment With a Dexamethasone Implant or Anti-VEGF Agent | IL-8 | -0.184 Pearson correlation coefficient (r) |