- People with rod-cone dystrophy (RCD) or enhanced S-cone syndrome (ESCS) have excess fluid
under the retina of their eye. This can cause vision loss. The medicine interferon gamma-1b
may help people with these diseases.
- To see if interferon gamma-1b eyedrops are safe for people with RCD or ESCS. To see if the
medicine can decrease retina fluid and help prevent vision loss.
- People at least 12 years old with RCD or ESCS. Those with ESCS must have two mutations in
the NR2E3 gene.
- Participants will be screened with medical history, physical exam, eye exam, and blood
- Participants will stay at NIH for 2 days and get the first eyedrops.
- Participants will give themselves 4 study eyedrops 4 times daily for 2 weeks and keep a
- Participants will have 2 phone calls and 5 outpatient visits over 8 weeks. They may
- Repeats of screening tests.
- Small piece of skin removed.
- Eye exams, including eye dilation and tasks on computer screens.
- Fluorescein angiography. A dye injected into an arm vein will travel to the blood
vessels in the eyes. A camera will take pictures.
- Electroretinography. Participants will sit in the dark wearing eyepatches. A small
electrode will be taped to the forehead. After 30 minutes, researchers will remove the
eyepatches and put in numbing eyedrops and contact lenses. Participants will watch
- Electrooculography. Electrodes will be attached outside of the eyes and eye function
will be measured in the dark and the light.
- Participants will have a follow-up visit after 52 weeks.
Rod-cone dystrophy (RCD) is a term applied to a number of genetically heterogenous diseases
presenting with night vision abnormalities, visual field defects and reduced rod
electroretinography responses. Enhanced S-Cone syndrome (ESCS) is a rare autosomal recessive
retinal disease with a developmental and a degenerative aspect. Macular cystic changes, often
florid and usually resulting in a reduction of central acuity, are frequently associated with
both diseases. The reason for this association is not well understood. Acetazolamide (Diamox)
and Dorzolamide (Trusopt) have been reported to have variable success in reducing these
cystic changes but the effect is frequently inadequate. The objective of this study is to
evaluate the safety and potential efficacy of Interferon (IFN) gamma-1b administered
topically for macular edema/retinal schisis cysts in RCD and ESCS. Possible disease-related
pathophysiologic mechanisms will be explored using induced pluripotent stem cell (iPSC)
protocols leading to iPSC-derived retinal pigment epithelium (RPE) and photoreceptor
Up to five participants with RCD with significant macular cystic changes and up to five
participants with ESCS with significant macular cystic changes will be enrolled to receive
IFN gamma-1b administered topically in one eye. However, up to an additional two participants
may be enrolled in order to obtain the five participants in each disease group to be included
in the primary analysis if any participants withdraw from the study prior to receiving five
days of treatment.
This is a single-center, prospective, uncontrolled, unmasked pilot Phase I/II study of the
safety, tolerability and possible efficacy of IFN gamma-1b in participants with RCD and ESCS
and macular cystic changes. One eye of up to five participants with RCD with significant
macular cystic changes and up to five participants with ESCS with significant macular cystic
changes [evidenced by optical coherence tomography (OCT) >275 microns central macular
thickness and/or disruption of foveal contour] will receive topical IFN gamma-1b instilled as
drops on the cornea. The initial stage of the study will include two participants from each
disease category. Once all four participants have completed the 8-week visit, enrollment will
be halted. Safety Adverse Event Review Committee members unaffiliated with the study will
review the data as a preliminary assessment of safety and efficacy and to determine whether
enrollment should continue. If the committee determines enrollment will continue, three
additional participants with RCD and three participants with ESCS will be enrolled. The study
will be completed once the final participant has received one year of follow-up.
The primary outcome measure related to the safety and tolerability of IFN gamma-1b
administered topically at the prescribed dosage for macular cystic changes in participants
with RCD and ESCS will be assessed by the number and severity of adverse events related to
the IP and the number of withdrawals at 52 weeks (one year) post-administration. Additional
safety of IFN gamma-1b administered topically in participants with RCD and ESCS will be
determined from the assessment of retinal function, ocular structure and occurrence of
adverse events at all time points. Secondary outcomes include changes in visual function
including visual acuity and microperimetry, and retinal imaging with OCT and fluorescein
- INCLUSION CRITERIA:
To be eligible, the following inclusion criteria must be met, where applicable.
1. Participant must be 12 years of age or older.
2. Participant (or legal guardian or legal representative) must understand and sign the
protocol informed consent.
3. Participant is willing to comply with the study procedures and is expected to be able
to return for all study visits.
4. Participant must carry a clinical diagnosis of RCD or ESCS.
5. ESCS participant must have molecular confirmation with two alleles for NR2E3 gene
6. Female participant of childbearing potential must not be pregnant or breast-feeding,
must have a negative pregnancy test at screening and must be willing to undergo
pregnancy tests at scheduled study visits.
7. Female participant of childbearing potential, and any male participant able to father
children must have (or have a partner who has) had a hysterectomy or vasectomy, be
completely abstinent from intercourse or must agree to practice two reliable methods
of contraception while taking the IP and six weeks after completion. Acceptable
methods of contraception include:
- Hormonal contraception (i.e., birth control pills, injected hormones, dermal
patch or vaginal ring);
- Intrauterine device;
- Barrier methods (diaphragm, condom) with spermicide; or
- Surgical sterilization (tubal ligation).
A participant is not eligible if any of the following exclusion criteria are present.
1. Participant has a history of other ocular disease likely to contribute significantly
to visual disruption (e.g., optic neuropathy, glaucoma, uveitis, or other retinal
2. Participant has had diagnosis or treatment of a malignancy (excluding non-melanoma
skin cancer) within the previous five years.
3. Participant has received investigational treatment in another clinical study related
to an ocular condition in the last six months.
4. Participant is pregnant, lactating, planning to become pregnant (or father a child)
during the study follow-up period.
5. Participant is allergic to fluorescein dye.
6. Participant has a systemic condition that, in the opinion of the investigator, would
preclude participation in the study (e.g., multiple sclerosis (MS), as IFN gamma may
cause MS exacerbations).
Study Eye Eligibility Criteria
A participant must have at least one eye meeting all inclusion criteria and none of the
exclusion criteria listed below.
Study Eye Inclusion Criteria
1. The study eye must retain adequate fixation to allow for completion of protocol
2. The study eye must have macular cystic changes (>275 microns and/or disruption of
foveal contour on OCT).
Study Eye Exclusion Criteria
1. The study eye has lens, cornea, or other media opacities that preclude adequate
visualization and testing of the retina.
2. The study eye has undergone intraocular surgery within 6 months prior to enrollment.
3. The study eye has a disease that may confound the outcome of the study [e.g.,
choroidal neovascularization (CNV) in the fovea or parafoveal area].
4. Participant is unwilling to discontinue wearing a contact lens in the study eye during
Study Eye Selection Criteria in Cases of Bilateral Disease
RCD and ESCS usually affect both eyes to a similar degree. In case both eyes of a
participant meet the study eye eligibility criteria, the following criteria will be used to
select the study eye:
- The eye with more intraretinal fluid will be selected as the study eye;
- If both eyes have similar levels of intraretinal fluid, the eye with worse visual
acuity will be selected as the study eye;
- If both eyes have the similar levels of intraretinal fluid and visual acuities, the
right eye will be selected as the study eye.