Non-arteritic Anterior Ischemic Optic Neuropathy (NAION), Trauma, Multiple Sclerosis (MS)
Conditions
Keywords
NAION, Decreased vision, Eye trauma, TES, Electrical stimulation, Multiple Sclerosis, Optic Neuritis
Brief summary
Transcorneal Electrical Stimulation (TES) using the OkuStim® device delivers electrical impulses to damaged and/or diseased photoreceptor cells. This electric stimulation of the retina may help to preserve visual acuity and/or the visual field.
Detailed description
The finely detailed, precise anatomy of the retina and optic nerve capture light impulses from the environment through a biochemical process and then transmit these images to the brain via electrical impulses conducted from the inner retina to the optic nerve and ultimately to the occipital cortex. In the human eye, three types of specialized ganglion cells transmit electrical impulses to the brain. Among these three cell populations are rod and cone cells, which participate in the photo-transduction step of light perception, along with other light sensitive ganglion cells. It is a system whereby the photosensitive pigment rhodopsin (or one of its analogs) rearranges in response to light, and this change in chemical structure fires electrical impulses to the brain which in turn interprets the incoming impulses as a visual image. Transcorneal Electrical Stimulation (TES) using the OkuStim® device delivers electrical impulses to damaged and/or diseased photoreceptor cells. This electric stimulation of the retina may help to preserve VA and/or the visual field.
Interventions
The clinical trial will investigate whether Transcorneal Electrical Stimulation delivered by the Okuvision Stimulation Set manufactured by Okuvision GmbH, Reutlingen, Germany, is a potentially effective therapy for the restoration and rehabilitation of vision loss as measured by improvements in visual acuity in the following three patient populations: patients with ocular trauma, patients with optic neuritis associated with multiple sclerosis and patients with Non-arteritic Anterior Ischemic Optic Neuropathy.
DEVICESham
Sham
Sponsors
United States Department of Defense
Wills Eye
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* You are 18 years or older. * You have sustained trauma (more than 3 months before this study) OR been diagnosed with Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) (more than 6 months before this study) OR been diagnosed with Multiple Sclerosis (MS) and suffered visual loss (more than 3 months before this study). * You are willing and able to give written informed consent. * You are able to commit to enrolling in the study during the full time period of up to 6 months.
Exclusion criteria
* You have any other significant ophthalmologic disease or condition (such as glaucoma, retinal degeneration, proliferative diabetic retinopathy, +/- six diopters of myopia, retinal detachment, exudative age-related macular degeneration). * You have amblyopia (lazy eye) in affected eye, previously diagnosed. * You are participating in any other interventional clinical trial. * If you are pregnant OR a woman with childbearing potential who is unwilling to use medically acceptable means of birth control for study duration OR woman unwilling to perform a pregnancy test at study entry/screening. * You are unable to give signed consent due to memory, medical, communication, language, or mental health problems. * You are less than 18 years old. * You are unable or unwilling to complete the evaluation or questionnaire. * Visual acuity better than 20/40 * Inability to detect phosphenes during threshold detection * You are on seizure medications, or have a history of epilepsy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity | Change from Baseline (week 1) to 1-week post initial treatment (week 8) | The primary outcomes are change in high-contrast LogMar VA from baseline (week 1) to initial post treatment (week 8). Participants read letters from a chart and receive 1 point for each letter correctly identified. Scores are converted to logMAR scale and analyzed for changes in visual acuity. Improvement in visual acuity is defined as a decrease in logMAR of 0.2 or more. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Field Mean Deviation | Change from Baseline (week 1) to 1 - week post initial treatment (week 8) | The Humphrey 24-2 Swedish Interactive Threshold Algorithm Standard perimeter was used to test visual field. Reported values are a change from baseline to 1-week post initial treatment. |
| Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant | Change from Baseline (week 1) to 1 - week post initial treatment (week 8) | Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline |
| Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant | Change from Baseline (week 1) to 1 - week post initial treatment (week 8) | Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline |
| Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant | Change from Baseline (week 1) to 1 - week post initial treatment (week 8) | Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline |
| Intra-Ocular Pressure (IOP) | Change from Baseline (week 1) to 1-week post initial treatment (week 8) | Measured by Applanation (Galdmann) Tonometry method |
| Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant | Change from Baseline (week 1) to 1 - week post initial treatment (week 8) | Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline |
| National Eye Institute's Visual Functioning Questionnaire - 25 | Change from Baseline to 1 - week post initial treatment | Test to measure Unweighted of scores within test ranging from 0-100 with higher scores meaning better outcome |
| Symbol Digit Modality Testing | Change from Baseline to 1 - week post initial treatment | Scores range from 0-110 with higher scores meaning better visual information processing speed |
| Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant | Change from Baseline (week 1) to 1 - week post initial treatment (week 8) | Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-arteritic Ischemic Optic Neuropathy Treatment of decreased vision due to NAION with the transcorneal electrical stimulation device (6+ months post-event).
Transcorneal Electrical Stimulation: The clinical trial will investigate whether Transcorneal Electrical Stimulation delivered by the Okuvision Stimulation Set manufactured by Okuvision GmbH, Reutlingen, Germany, is a potentially effective therapy for the restoration and rehabilitation of vision loss as measured by improvements in visual acuity in the following three patient populations: patients with ocular trauma, patients with optic neuritis associated with multiple sclerosis and patients with Non-arteritic Anterior Ischemic Optic Neuropathy. | 46 |
| Non-arteritic Ischemic Optic Neuropathy Sham Sham comparator for the Non-arteritic ischemic optic neuropathy group | 23 |
| Multiple Sclerosis Treatment of decreased vision due to multiple sclerosis with the transcorneal electrical stimulation device (3+ months post visual changes).
Transcorneal Electrical Stimulation: The clinical trial will investigate whether Transcorneal Electrical Stimulation delivered by the Okuvision Stimulation Set manufactured by Okuvision GmbH, Reutlingen, Germany, is a potentially effective therapy for the restoration and rehabilitation of vision loss as measured by improvements in visual acuity in the following three patient populations: patients with ocular trauma, patients with optic neuritis associated with multiple sclerosis and patients with Non-arteritic Anterior Ischemic Optic Neuropathy. | 9 |
| Multiple Sclerosis Sham Sham comparator for the multiple sclerosis group | 5 |
| Ocular Trauma Treatment of decreased vision due to ocular trauma with the transcorneal electrical stimulation device (3+ months post-trauma).
Transcorneal Electrical Stimulation: The clinical trial will investigate whether Transcorneal Electrical Stimulation delivered by the Okuvision Stimulation Set manufactured by Okuvision GmbH, Reutlingen, Germany, is a potentially effective therapy for the restoration and rehabilitation of vision loss as measured by improvements in visual acuity in the following three patient populations: patients with ocular trauma, patients with optic neuritis associated with multiple sclerosis and patients with Non-arteritic Anterior Ischemic Optic Neuropathy. | 10 |
| Ocular Trauma Sham Sham comparator for the ocular trauma group | 4 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 4 | 1 | 2 | 3 | 1 |
Baseline characteristics
| Characteristic | Non-arteritic Ischemic Optic Neuropathy | Total | Ocular Trauma Sham | Ocular Trauma | Multiple Sclerosis Sham | Multiple Sclerosis | Non-arteritic Ischemic Optic Neuropathy Sham |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 8.8 | 50.8 years STANDARD_DEVIATION 10.9 | 45.5 years STANDARD_DEVIATION 13.2 | 49.2 years STANDARD_DEVIATION 14.2 | 41 years STANDARD_DEVIATION 9.2 | 40.6 years STANDARD_DEVIATION 9.7 | 66 years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 93 Participants | 4 Participants | 8 Participants | 5 Participants | 9 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 86 Participants | 4 Participants | 8 Participants | 3 Participants | 7 Participants | 21 Participants |
| Region of Enrollment United States | 46 participants | 97 participants | 4 participants | 10 participants | 5 participants | 9 participants | 23 participants |
| Sex: Female, Male Female | 13 Participants | 37 Participants | 1 Participants | 2 Participants | 3 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 33 Participants | 60 Participants | 3 Participants | 8 Participants | 2 Participants | 2 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 23 | 0 / 9 | 0 / 5 | 0 / 9 | 0 / 4 |
| other Total, other adverse events | 15 / 45 | 0 / 23 | 3 / 9 | 0 / 5 | 5 / 9 | 0 / 4 |
| serious Total, serious adverse events | 0 / 45 | 0 / 23 | 0 / 9 | 0 / 5 | 0 / 9 | 0 / 4 |
Outcome results
Primary
Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity
The primary outcomes are change in high-contrast LogMar VA from baseline (week 1) to initial post treatment (week 8). Participants read letters from a chart and receive 1 point for each letter correctly identified. Scores are converted to logMAR scale and analyzed for changes in visual acuity. Improvement in visual acuity is defined as a decrease in logMAR of 0.2 or more.
Time frame: Change from Baseline (week 1) to 1-week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity | -0.23 logMAR |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity | -0.14 logMAR |
| Multiple Sclerosis | Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity | -0.08 logMAR |
| Sham - Multiple Sclerosis | Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity | -0.06 logMAR |
| Ocular Trauma | Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity | -0.29 logMAR |
| Sham - Ocular Trauma | Evaluation of the Effectiveness and Safety of Transcorneal Electrical Stimulation to Improve Visual Acuity | -0.05 logMAR |
Secondary
Intra-Ocular Pressure (IOP)
Measured by Applanation (Galdmann) Tonometry method
Time frame: Change from Baseline (week 1) to 1-week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Intra-Ocular Pressure (IOP) | -0.32 mmHg |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Intra-Ocular Pressure (IOP) | -1.13 mmHg |
| Multiple Sclerosis | Intra-Ocular Pressure (IOP) | -0.27 mmHg |
| Sham - Multiple Sclerosis | Intra-Ocular Pressure (IOP) | 0.52 mmHg |
| Ocular Trauma | Intra-Ocular Pressure (IOP) | 0.52 mmHg |
| Sham - Ocular Trauma | Intra-Ocular Pressure (IOP) | -0.57 mmHg |
Secondary
National Eye Institute's Visual Functioning Questionnaire - 25
Test to measure Unweighted of scores within test ranging from 0-100 with higher scores meaning better outcome
Time frame: Change from Baseline to 1 - week post initial treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | National Eye Institute's Visual Functioning Questionnaire - 25 | -0.59 score on a scale - change from baseline |
| Sham - Non-arteritic Ischemic Optic Neuropathy | National Eye Institute's Visual Functioning Questionnaire - 25 | 0.16 score on a scale - change from baseline |
| Multiple Sclerosis | National Eye Institute's Visual Functioning Questionnaire - 25 | 4.59 score on a scale - change from baseline |
| Sham - Multiple Sclerosis | National Eye Institute's Visual Functioning Questionnaire - 25 | 4.57 score on a scale - change from baseline |
| Ocular Trauma | National Eye Institute's Visual Functioning Questionnaire - 25 | 3.64 score on a scale - change from baseline |
| Sham - Ocular Trauma | National Eye Institute's Visual Functioning Questionnaire - 25 | 5.27 score on a scale - change from baseline |
Secondary
Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant
Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline
Time frame: Change from Baseline (week 1) to 1 - week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant | -0.07 um |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant | 3.89 um |
| Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant | -2.83 um |
| Sham - Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant | -1.07 um |
| Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant | -0.62 um |
| Sham - Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Center Quadrant | -0.42 um |
Secondary
Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant
Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline
Time frame: Change from Baseline (week 1) to 1 - week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant | -0.04 um |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant | -0.64 um |
| Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant | -2.37 um |
| Sham - Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant | 1.07 um |
| Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant | 0.57 um |
| Sham - Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Inferior Quadrant | -1.53 um |
Secondary
Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant
Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline
Time frame: Change from Baseline (week 1) to 1 - week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant | -0.48 um |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant | -1.24 um |
| Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant | -3.60 um |
| Sham - Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant | 0.28 um |
| Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant | 0.49 um |
| Sham - Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Nasal Quadrant | -1.36 um |
Secondary
Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant
Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline
Time frame: Change from Baseline (week 1) to 1 - week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant | -0.70 um |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant | 12.41 um |
| Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant | -3.80 um |
| Sham - Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant | -5.97 um |
| Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant | 0.37 um |
| Sham - Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Superior Quadrant | 1.42 um |
Secondary
Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant
Assessed the change in thickness of the retinal nerve fiber layer 1-week post treatment compared to baseline
Time frame: Change from Baseline (week 1) to 1 - week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant | 2.15 um |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant | -0.64 um |
| Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant | -0.49 um |
| Sham - Multiple Sclerosis | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant | 1.07 um |
| Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant | -0.35 um |
| Sham - Ocular Trauma | Ocular Coherent Tomography, Retinal Nerve Fiber Layer Thickness in Temporal Quadrant | -1.53 um |
Secondary
Symbol Digit Modality Testing
Scores range from 0-110 with higher scores meaning better visual information processing speed
Time frame: Change from Baseline to 1 - week post initial treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Symbol Digit Modality Testing | -0.03 score on a scale - change from baseline |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Symbol Digit Modality Testing | -0.01 score on a scale - change from baseline |
| Multiple Sclerosis | Symbol Digit Modality Testing | 2.98 score on a scale - change from baseline |
| Sham - Multiple Sclerosis | Symbol Digit Modality Testing | -0.77 score on a scale - change from baseline |
| Ocular Trauma | Symbol Digit Modality Testing | 4.08 score on a scale - change from baseline |
| Sham - Ocular Trauma | Symbol Digit Modality Testing | 6.14 score on a scale - change from baseline |
Secondary
Visual Field Mean Deviation
The Humphrey 24-2 Swedish Interactive Threshold Algorithm Standard perimeter was used to test visual field. Reported values are a change from baseline to 1-week post initial treatment.
Time frame: Change from Baseline (week 1) to 1 - week post initial treatment (week 8)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Non-arteritic Ischemic Optic Neuropathy | Visual Field Mean Deviation | 1.49 Decibels (dB) |
| Sham - Non-arteritic Ischemic Optic Neuropathy | Visual Field Mean Deviation | 2.09 Decibels (dB) |
| Multiple Sclerosis | Visual Field Mean Deviation | 1.31 Decibels (dB) |
| Sham - Multiple Sclerosis | Visual Field Mean Deviation | 0.96 Decibels (dB) |
| Ocular Trauma | Visual Field Mean Deviation | 1.70 Decibels (dB) |
| Sham - Ocular Trauma | Visual Field Mean Deviation | 0.25 Decibels (dB) |