Corneal Neovascularization
Conditions
Brief summary
The purpose of this study is to determine the effectiveness and safety of Interleukin-1-Receptor Antagonist eye drops for the treatment of corneal blood vessels.
Detailed description
Normally avascular, under many pathologic conditions, vessels may invade the cornea from the limbal vascular plexus. Infection, inflammation, ischemia, degeneration, or trauma, and the loss of the limbal stem cell barrier can cause corneal neovascularization. Growth of new vessels may result in corneal scarring, edema, lipid deposition, and inflammation that may alter visual acuity and is a leading cause of monocular visual impairment and blindness. Additionally, it results in the loss of immune response across the cornea, thereby worsening the prognosis of a subsequent penetrating keratoplasty (PK). Growth of new blood and lymphatic vessels from preexisting vessels are mediated by members of the vascular endothelial growth factor (VEGF) family. This study is designed to investigate whether Interleukin-1-Receptor Antagonist is a drug that is both safe and effective in blocking VEGF pathways, stopping new growth, and reducing old vessel growth.
Interventions
DRUGPlacebo
Custom eye drop eye three times a day in both eyes for a period of 6 weeks
DRUGIL-1Ra
5% custom made topical IL-1Ra 3 times a day in both eyes for a period of 6 weeks
Sponsors
Reza Dana, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 18 years * Patients with superficial or deep corneal NV that extends farther than 1 mm from the limbus * Patients are in generally good stable overall health
Exclusion criteria
• Has received treatment with anti-VEGF agents (topical, intraocular or systemic) within 30 days of study entry * Corneal or ocular surface infection within 30 days prior to study entry• Ocular or periocular malignancy * Contact lens (excluding bandage contact lens) use within 2 weeks prior to study entry * Persistent epithelial defect (\>1mm and ≥14 days duration) within 2 weeks prior to study entry * Intravitreal or periocular steroids within 2 weeks prior to study entry * Change in dose/frequency of topical steroids and/or NSAIDs within 2 weeks prior to study entry * Pregnancy (positive pregnancy test) or lactation * Premenopausal women not using contraception * Signs of current infection, including fever and current treatment with antibiotics * Participation in another simultaneous medical investigation or trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Ocular Adverse Event | 64 Weeks | Incidence and severity of ocular adverse events, as identified by eye examination and visual acuity testing. |
| Extent of Neovascular Area (NA) | 64 weeks | The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis. |
| Vessel Caliber (VC), Measuring the Mean Diameter of the Corneal Vessels | 64 Weeks | The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis. |
| Invasion Area (IA), Measuring the Fraction of the Total Corneal Area Invaded by the Vessels | 64 Weeks | The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Central Corneal Thickness | 64 Weeks | The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis. |
| Best Spectacle-Corrected Visual Acuity (BSCVA) | 64 weeks | The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis. |
Countries
United States
Participant flow
Recruitment details
Patients in this study were recruited from Mass. Eye and Ear Infirmary from May 2009 - February 2010.
Pre-assignment details
This is a single site, randomized, double masked, crossover, phase I/II study of topical IL-1Ra (5.0%) in subjects with corneal neovascularization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo First, Then IL-1Ra 10 patients will complete a course of treatment with placebo, followed by a course of treatment with 5% custom made topical IL-1Ra.
IL-1Ra : 5% custom made topical IL-1Ra 3 times a day in both eyes for a period of 6 weeks
Placebo : Custom eye drop eye three times a day in both eyes for a period of 6 weeks | 5 |
| IL-1Ra First, Then Placebo 10 patients will complete a course of treatment with 5% custom made topical IL-1Ra, followed by a course of treatment with placebo
IL-1Ra : 5% custom made topical IL-1Ra 3 times a day in both eyes for a period of 6 weeks
Placebo : Custom eye drop eye three times a day in both eyes for a period of 6 weeks | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | IL-1Ra First, Then Placebo | Placebo First, Then IL-1Ra | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 4 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 19 | 53 years STANDARD_DEVIATION 24 | 56 years STANDARD_DEVIATION 22 |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 10 | 1 / 10 | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Extent of Neovascular Area (NA)
The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Time frame: 64 weeks
Population: The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Primary
Incidence and Severity of Ocular Adverse Event
Incidence and severity of ocular adverse events, as identified by eye examination and visual acuity testing.
Time frame: 64 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo First, Then IL-1RA | Incidence and Severity of Ocular Adverse Event | 2 participants |
| IL-1RA First, Then Placebo | Incidence and Severity of Ocular Adverse Event | 3 participants |
Primary
Invasion Area (IA), Measuring the Fraction of the Total Corneal Area Invaded by the Vessels
The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Time frame: 64 Weeks
Population: The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Primary
Vessel Caliber (VC), Measuring the Mean Diameter of the Corneal Vessels
The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Time frame: 64 Weeks
Population: The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Secondary
Best Spectacle-Corrected Visual Acuity (BSCVA)
The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Time frame: 64 weeks
Population: The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Secondary
Central Corneal Thickness
The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.
Time frame: 64 Weeks
Population: The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.