Anterior Uveitis, Uveitis
Conditions
Keywords
Cystoid Macular Edema, Intermediate Uveitis, Uveitis, OCT, Interferon-Gamma (IFN-Gamma)
Brief summary
The objective of this study is to investigate the safety and efficacy of ocular instillations of interferon gamma-1b as a potential treatment for cystoid macular edema (CME) secondary to uveitis.
Detailed description
Objective: Information gathered from NEI laboratories suggests that cystoid macular edema (CME) is caused by the disequilibrium of the JakStat and mTor signal transduction pathways in the retinal pigment epithelium (RPE). We wish to investigate whether stimulating the JakStat pathway with topically applied interferon gamma-1b can be a therapeutic intervention for the treatment of CME secondary to uveitis. The objective of this study is to investigate the safety and efficacy of ocular instillations of interferon gamma-1b as a potential treatment for CME secondary to uveitis. Study Population: Five participants with CME as evidenced by OCT (\> 275 microns central macular thickness and/or loss of foveal contour) secondary to uveitis will receive topical ocular instillations of interferon gamma-1b. Up to seven participants may be enrolled in order to obtain the five participants to be included in the analysis if participants withdraw prior to receiving interferon gamma-1b. Design: This Phase I/II, non-randomized, prospective, uncontrolled, single-center study will involve instilling four drops of interferon gamma-1b (approximately 30 μg) topically on the cornea of the study eye four times a day for one week and measuring the potential response with optical coherence tomography (OCT). Outcome Measures: The primary outcome is the change in excess central macular thickening as measured by OCT in response to interferon gamma-1b. Treatment success is defined as a 25% decrease in excess central macular thickening at Week 1 as compared with baseline. Secondary efficacy outcomes include changes in macular volume as measured by OCT, visual acuity, intraocular pressure and intraocular inflammation as graded upon slit lamp examination. Secondary safety outcomes include ocular surface irritation assessed by fluorescein staining of the cornea and conjunctiva to assess toxicity, the number and severity of systemic and ocular toxicities, the number of adverse events and the proportion of participants with a visual loss of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters.
Interventions
DRUGInterferon Gamma-1b
Interferon gamma-1b (Actimmune®, InterMune, Inc, Brisbane, CA 94005) was supplied to participants in single-use dropperettes. Each dropperette contained approximately 0.2 mL of interferon gamma-1b (Actimmune®). Participants received 28 dropperettes at the baseline visit and were instructed to place four drops (approximately 7 μg per drop) topically on the cornea of the study eye four times per day for seven days.
Sponsors
National Eye Institute (NEI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant must be 18 years of age or older. 2. Participant must understand and sign the protocol's informed consent document. 3. Participant has a diagnosis of CME (central thickness of \>275 microns on OCT and/or disruption of foveal contour) secondary to uveitis in at least one eye (the study eye). 4. Participant is willing to comply with the study procedures and is expected to be able to return for all study visits. 5. Participant has visual acuity of 20/400 or better in the study eye. 6. Female participants of childbearing potential must not be pregnant or breast-feeding. 7. Both female participants of childbearing potential and male participants able to father a child must agree to practice two acceptable forms of contraception during the study and for six weeks following the last administration of investigational product. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones dermal patch or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation or vasectomy).
Exclusion criteria
1. Participant is unable to tolerate the ocular instillations or follow study procedures. 2. Participant has a significant active infection (an infection requiring treatment as determined by the medical team) that in the principal investigator's best medical judgment would preclude participation. 3. Participant has multiple sclerosis (MS), as interferon gamma may cause MS exacerbations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | Baseline and 1 Week | Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | Baseline and 2 Weeks | Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
| Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | Baseline and 2 Weeks | Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
| Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | Baseline and 1 Week | Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
| Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | Baseline and 1 Week | Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
| Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | Baseline and 2 Weeks | Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
| Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | Baseline and 2 Weeks | Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
| Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline | Baseline and 1 Week | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. |
| Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | Baseline and 1 Week | Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. |
| Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline | Baseline and 2 Weeks | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. |
| Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline | Baseline and 2 Weeks | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. |
| Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline | Baseline and 1 Week | Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. |
| Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline | Baseline and 1 Week | Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. |
| Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline | Baseline and 2 Weeks | Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. |
| Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline | Baseline and 2 Weeks | Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg. |
| Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye | Baseline and 2 Weeks | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. |
| Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline | Baseline and 1 Week | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Interferon Gamma-1b Interferon gamma-1b (Actimmune®, InterMune, Inc, Brisbane, CA 94005) was supplied to participants in single-use dropperettes. Each dropperette contained approximately 0.2 mL of interferon gamma-1b (Actimmune®). Participants received 28 dropperettes at the baseline visit and were instructed to place four drops (approximately 7 μg per drop) topically on the cornea of the study eye four times per day for seven days. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Interferon Gamma-1b |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age Continuous | 55 years FULL_RANGE 12.51 |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | -38.60 µm | Standard Deviation 130.26 |
Secondary
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week One Compared to Baseline | 1.60 ETDRS Letters | Standard Deviation 4.72 |
Secondary
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Fellow Eye at Week Two Compared to Baseline | 3.20 ETDRS Letters | Standard Deviation 6.87 |
Secondary
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week One Compared to Baseline | 0.20 ETDRS Letters | Standard Deviation 5.63 |
Secondary
Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in ETDRS Best-corrected Visual Acuity (BCVA) in the Study Eye at Week Two Compared to Baseline | 4.00 ETDRS Letters | Standard Deviation 9.03 |
Secondary
Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | 12.00 µm | Standard Deviation 29.12 |
Secondary
Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Excess Central Macular Thickening in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | 30.20 µm | Standard Deviation 64.43 |
Secondary
Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Central macular thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Excess Central Macular Thickening in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | -47.40 µm | Standard Deviation 85.96 |
Secondary
Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Intraocular Pressure (IOP) in the Fellow Eye at Week One Compared to Baseline | -1.60 mm Hg | Standard Deviation 7.02 |
Secondary
Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Intraocular Pressure (IOP) in the Fellow Eye at Week Two Compared to Baseline | -2.20 mm Hg | Standard Deviation 7.4 |
Secondary
Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Intraocular Pressure (IOP) in the Study Eye at Week One Compared to Baseline | 0.40 mm Hg | Standard Deviation 2.07 |
Secondary
Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline
Intraocular pressure was recorded using a standard Goldmann applanation tonometer, a device for the measurement of intraocular pressure between 0 to 78 mm Hg.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Intraocular Pressure (IOP) in the Study Eye at Week Two Compared to Baseline | 0.40 mm Hg | Standard Deviation 1.34 |
Secondary
Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | 0.14 mm^3 | Standard Deviation 0.21 |
Secondary
Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Macular Volume in the Fellow Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | 0.06 mm^3 | Standard Deviation 0.34 |
Secondary
Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 1 Week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week One Compared to Baseline | -0.02 mm^3 | Standard Deviation 0.36 |
Secondary
Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline
Macular volume was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interferon Gamma-1b | Change in Macular Volume in the Study Eye, as Measured by Optical Coherence Tomography (OCT), at Week Two Compared to Baseline | 0.00 mm^3 | Standard Deviation 0.32 |
Secondary
Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.
Time frame: Baseline and 2 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Interferon Gamma-1b | Proportion of Participants With a Visual Loss of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters in the Study Eye | 0 Percentage of Participants |