Objective:
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 generation.
Study Population:
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.
Design:
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.
Outcome Measures:
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 angiography.
