Topical Interferon Gamma-1b for Central Serous Chorioretinopathy

Objective: Central serous chorioretinopathy (CSC) is a retinal disorder characterized by an
accumulation of serous fluid under the retina thought to be due to excessive choroidal
hyperpermeability. The retinal pigment epithelium (RPE) plays a critical role in removing
fluid from the subretinal space. This RPE pump is believed to be a key player in the
reabsorption of subretinal fluid and maintenance of retinal attachment (9). Fluid transport
assays have examined whether interferon gamma induces changes in fluid transport (JV) across
human fetal RPE monolayers and showed an increase in fluid absorption from the retinal to
the choroidal side of the tissue. An in vivo rodent model of retinal detachment (11) has
been used to measure the effect of interferon gamma on re-absorption following retinal
detachment and showed that the addition of interferon gamma to the anterior eye surface
caused a significant, rapid decrease in retinal detachment volume in the first hour of
observation (10). This pilot study will investigate the safety, tolerability and potential
efficacy of serial ocular instillations of topical interferon gamma-1b for classic CSC.

Study Population: Five participants with subretinal fluid due to classic CSC will initially
be enrolled. However, up to an additional two participants may be enrolled in order to
obtain the five participants to be included in the analysis if any participants withdraw
from the study.

Design: In this Phase I/II, non-randomized, prospective, uncontrolled, dose-escalation,
single-center pilot study, a series of ocular instillations of topical interferon gamma-1b
will be administered in the study eye over a two-week period. If the fluid re-accumulates or
increases, participants will be eligible for re-challenging with topical interferon gamma-1b
in the study eye at Week 4. Participants will be followed for eight weeks. Participants may
be eligible for additional re-challenges after the initial eight week study period ends if
their fluid reaccumulates or increases further.

Outcome Measures: The primary outcome measure related to the safety and tolerability of
serial ocular instillations of topical interferon gamma-1b will be assessed by the number
and severity of adverse events (AEs) related to the investigational product and the number
of withdrawals. Secondary efficacy outcomes include changes in best-corrected visual acuity
(BCVA), central retinal thickness and maximum lesion volume as measured on optical coherence
tomography (OCT), leakage as observed on fluorescein angiograms (FA), autofluorescence
patterns as observed on fundus autoflourescence (FAF) imaging and mean macular sensitivity
as assessed by microperimetry.

- INCLUSION CRITERIA:

- Participant must be 18 years of age or older.

- Participant must understand and sign the protocol's informed consent document.

- Female participant of childbearing potential (see Appendix 1 for definition) 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.

- Female participant must be post-menopausal (see Appendix 1), must have had a
hysterectomy, have a partner with a vasectomy, be completely abstinent from
intercourse or must agree to practice two reliable methods of contraception
throughout the course of the study and for six weeks after 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 (diaphragm, condom) with spermicide; or

- surgical sterilization (tubal ligation).

EXCLUSION CRITERIA:

- Participant is actively receiving an investigational medication in another research
trial that may have unknown effects on CSC as determined by the investigator.

- Participant has evidence of ocular disease other than CSC in the study eye that may
confound the outcome of the study (e.g., neovascular age-related macular
degeneration).

- Participant has evidence of choroidal neovascularization (CNV) in the study eye.

- Participant is expected to need ocular surgery in the study eye during the eight
weeks of the study.

- Participant is expected to need focal laser treatment or photodynamic therapy (PDT)
in the study eye during the eight weeks of the study.

- Participant is on medications that enhance RPE pumping of fluid (e.g.,
acetazolamide).

- Participant is on steroid medication (oral (e.g., prednisone), topical (e.g.,
hydrocortisone cream) or inhaled (e.g., fluticasone inhaler)).

- Participant has a systemic condition that, in the opinion of the investigator, would
preclude participation in the study (e.g., Hypertension not controlled with
medications or active infection requiring treatment).

- Participant is allergic to fluorescein dye.

- Participant has multiple sclerosis (MS), as interferon gamma may cause MS
exacerbations.

- Participant is on anti-cortisol or anti-androgen medications (e.g., finasteride or
mifepristone), as there is some data suggesting that these medications may reduce CSC
fluid.