Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa - a Safety and Efficacy Multicenter Study

The following proposed study (ICM1TES/RP) will investigate the therapeutic aspects of
transcorneal electrical stimulation (TES) on the eye in patients with retinitis pigmentosa
(RP). It will utilize the Okuvision TES system, a Wills Eye Hospital-sponsored FDA
non-significant risk (NSR) medical device, OkuStim® (CE-marked OkuStim®) for the application
of electrical stimulation directly to the eye via a corneal contact electrode.

Study Design - Multi-center, prospective, randomized sham controlled 1:1 Clinical trial.

Study treatments - Patients will be randomized in a 1:1 ratio. Patients in treatment group
will have TES at 200% of phosphene threshold for 30 minutes once weekly for 52 weeks in both
eyes. Patients in sham group will also wear electrodes on both eyes, but no energy is turned
on and both eyes are sham.

Duration of study - anticipated duration is 36 months, 12 months for recruitment, 12 months
for treatment and sham groups and followed for 18 months, plus 6 months for analysis.

Inclusion Criteria - Diagnosis of RP, 22-80 years of age, no other ocular disease, able to
complete all visits.

Treatments - TES, 30 minute treatment weekly for 52 weeks at 0.8mA

Number of patients - 90 patients in treatment arm and 90 patients in sham arm. Electrodes
will be placed on both eyes, both eyes will be treated in treatment group and in the sham
group both eyes will be considered. However due to the possibility of drop out using 15% we
will recruit 210 patients (15 patients per center).

Screening -

1. VA & Phosphene threshold evaluation

2. Vfiii4e, vfVe, Octopus 900, complete eye exam, fundus photo, OCT and Contrast
sensitivity, electro-physiology.

3. Eligibility requirements met, then schedule baseline.

Tests - Base Line: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, fundus photo, OCT,
Contrast sensitivity, NEI VFQ-25, Photopic B-wave ERG, blood draw for genetic test (unless
genetic profile has been done).

3 Month visit: VA, eye exam, Phosphene threshold, OCT & Photopic B-wave.

6 Month visit: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, OCT & Contrast sensitivity,
phosphine threshold & Photopic B-wave.

9 Month visit: VA, eye exam, Phosphene threshold, OCT & Photopic B-wave.

12 Month visit: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, OCT & Contrast
sensitivity, NEI VFQ-25, phosphene threshold & Photopic B-wave

18 Month visit: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, OCT & Contrast
sensitivity, NEI VFQ-25 & phosphene threshold & Photopic B-wave.

Inclusion Criteria:

1. Patients with Retinitis Pigmentosa.

2. Adult patients, 22-80 years of age, having provided written informed consent and HIPAA
authorization.

3. LogMAR VA 1.00 or better in both eyes.

4. Octopus 900 Central Visual Field ≥10 degrees diameter around central fixation using
stimulus sizes III4e and V4e in both eyes on kinetic testing.

5. Agree to discontinue Vitamin A use and no intake for at least 2 months prior to
baseline visit.

Exclusion Criteria:

1. Visual field loss as demonstrated by Octopus 900 kinetic perimetry as <10 deg of
remaining central visual field using stimulus sizes III4e and V4e.

2. Due to distance or other reason, patients unable to travel to Philadelphia or
respective centers for the treatment procedures and follow-up examinations.

3. Diabetic retinopathy

4. Ocular neovascularisation of any origin

5. After arterial or venous occlusion

6. After retinal detachment or any vitreoretinal surgery with or without implantation.

7. Silicone oil tamponade

8. Dry or exudative age-related macular degeneration

9. Macular edema involving the foveal center as determined by SD-OCT

10. All forms of glaucoma

11. Any form of corneal degeneration that reduces visual acuity

12. Systemic diseases that are difficult to control or manage, which could hinder regular
attendance at follow-up examinations

13. Patients in a permanently poor general condition, which could hinder regular
attendance at follow-up examinations

14. Patients in whom phosphenes are only inducible at greater than, but not including, 0.8
mA.

15. Forms of mental illness related to the bipolar affective and schizoid-affective
disorders, epilepsy, and all forms of dementia

16. Simultaneous participation in another interventional study or history of interventions
whose effect may still persist

17. Current pregnancy, or being a woman with childbearing potential who is unwilling to
use medically acceptable means of birth control for the study duration, or a woman
unwilling to perform a pregnancy test at study entry

18. Any patient can be excluded from the study as determined by the Principal
Investigator.