Topical Interferon Gamma for Macular Edema Secondary to Uveitis (JakStat2)

The Treatment of Macular Edema Secondary to Uveitis Using Topical Interferon Gamma

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.

Study Overview

• Status: Completed
• Conditions: Uveitis; Anterior Uveitis
• Intervention / Treatment: Drug: Interferon Gamma-1b

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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.; Other Names: Actimmune®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 1 Week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 1 Week
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.	Baseline and 2 Weeks
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.	Baseline and 2 Weeks
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.	Baseline and 1 Week
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.	Baseline and 1 Week
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.	Baseline and 2 Weeks
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.	Baseline and 2 Weeks
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.	Baseline and 1 Week
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.	Baseline and 1 Week
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.	Baseline and 2 Weeks
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.	Baseline and 2 Weeks
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.	Baseline and 1 Week
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.	Baseline and 1 Week
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.	Baseline and 2 Weeks
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.	Baseline and 2 Weeks
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.	Baseline and 2 Weeks

Collaborators and Investigators

• Sponsor: National Eye Institute (NEI)
• Investigators: Principal Investigator: Hatice Nida Sen, MD, MHSc, National Eye Institute (NEI)

Publications and helpful links

General Publications

• Battle TE, Lynch RA, Frank DA. Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis. Cancer Res. 2006 Apr 1;66(7):3649-57. doi: 10.1158/0008-5472.CAN-05-3612.
• Khorana HG. Rhodopsin, photoreceptor of the rod cell. An emerging pattern for structure and function. J Biol Chem. 1992 Jan 5;267(1):1-4. No abstract available.
• Shi G, Maminishkis A, Banzon T, Jalickee S, Li R, Hammer J, Miller SS. Control of chemokine gradients by the retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4620-30. doi: 10.1167/iovs.08-1816. Epub 2008 Apr 30.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: June 17, 2011
• First Submitted That Met QC Criteria: June 17, 2011
• First Posted (Estimate): June 20, 2011

Study Record Updates

• Last Update Posted (Estimate): October 8, 2012
• Last Update Submitted That Met QC Criteria: September 6, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: OCT; Uveitis; Cystoid Macular Edema; Intermediate Uveitis; Interferon-Gamma (IFN-Gamma)
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Panuveitis; Uveal Diseases; Macular Degeneration; Iris Diseases; Macular Edema; Uveitis; Uveitis, Anterior; Iridocyclitis; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: 110167; 11-EI-0167 (Other Identifier: CNS IRB)