Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Change in corneal sensitivity to hyperosmotic eye drop |
A recording of the eyes will be performed using a multi-camera video platform for a period of 150 seconds at four different time points. The first will be a baseline, second after a drop of isotonic saline and 3 and 4 after drops of 2 increasing concentrations of Muro 128 (2% sodium chloride, and 5% sodium chloride). Each of these will be separated by a 5 minute rest period. After, this is completed each subject will also be asked to record their sense of pain to each eye drop solution on a scale of 1 to 10. Squinting (an analysis of the amount of time a extent that the eye is closed) and blinking (number of blinks during the procedure) will be quantified during each time point using an image analysis program which analyzes the recorded digital video frames. |
Done once as the primary outcome of phase 1 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Primary |
Change in cornea nerve density |
This is a primary endpoint for phase 2 of the study. Prior to beginning treatment with fish oil and 1 year later after fish oil intervention is complete the subjects cornea nerve density will be determined using cornea confocal microscopy. This is a non-invasive procedure that takes images on the sub-epithelial layer of the cornea. Six images will be collected at each of the two visits. From these images the total corneal nerve length will be determined and reported as mm/mm2 |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in corneal sensation threshold using Cochet Bonnet filament |
This test records the mechanical sensitivity of the cornea to a filament that is touched to the cornea. The rigidity of the filament can be adjusted and the outcome is the length of the filament (6 to 1 cm) when the subjects blinks. The data will be recorded as cm. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in Michigan neuropathy screening instrument |
All subjects will answer a 15 question survey that relates to symptoms of peripheral neuropathy. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in ocular coherence tomography. |
Ocular coherence tomography is a special camera that measures the neural structure of the retina. This device is often used as standard of care. The subject will rest their chin on a supporting device and the camera will be positioned to image the neural retina. The test will take about 5 minutes and will be performed twice at baseline and 12 months later. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in slit lamp examination of the eye. |
This examination will be the last test performed by each subject enrolled in the study. This device will shine light in the eye to examine the front and back portions of the eye. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in 10 g monofilament test |
The 10 g monofilament test is a routine evaluation used to screen the diabetic foot for loss of sensory sensation and part of the standard of care for any diabetic patient. The subject will remove their footwear and lie down on a table. The filament will be applied perpendicular to the skin surface on the bottom of the feet will sufficient force to allow the filament to bend. Each subject will be asked to tell the examiner if they feel it. A lack of sensation is a marker for diabetic neuropathy. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in vibratory sensation of the great toe. |
Vibratory sensation is a standard of care test used with patients with diabetes to test sensory nerve sensation. A 129 Hz tuning fork is used and placed over the dorsum of the great toe on the boney prominence of the distal interphalangeal joint. The subject is asked to tell the examiner if they feel the object touching their toe. A lack of sensation is a marker for diabetic neuropathy. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in reflex testing |
Reflex testing is commonly used to detect sensory neuropathy in diabetic patients. The ankle reflex is examined by aligning the subjects ankle into a neutral position and the examiner strikes the Achilles tendon with a neurological hammer. An abnormal result is recorded if the subject does not display any ankle plantarflexion. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in hot or cold sensation. |
Cold and warm thresholds measure response of A-delta and C fibers of sensory nerves. A Velcro strap containing a metal circular pad about the size of a half dollar is attached to the dorsal part of the right foot. The subject is asked to push a button on a hand held device when they feel hot or cold from the circular pad attached to their foot. The device is set to default before any damaging temperature is reached. First warm followed by cold will be tested and the temperature of the pad will be recorded when the patient pushes the button. The commercial TSA-II Neurosensory Analyzer will be used. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in visual acuity (subject's vision) |
A routine visual acuity eye examination will be used. Subjects vision will be measured by having the subject read the smallest letters on an eye chart with their glasses or best correction. This takes about 5 minutes or less. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in omega-3 polyunsaturated fatty acids and their metabolites in serum |
Blood will be collected at baseline and end of the phase 2 part of the study. Blood will be used to determine the omega-6 to omega-3 ratio in blood a marker of inflammatory stress. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Change in pupil responsiveness to light |
A hand-held pupillometer/electroretinogram device (RETeval, LKC) will be held in front of the subject s eye, but will not touch the eye. The device will provide a brief, a series of brief light stimuli and then record the pupil response and the elicited electrical response from the retina from a surface skin patch (electrode) placed below each eye, from the light as a measure of whether the inherent sensitivity of the eye in the retina is normal. The investigators will repeat this in the left eye. The visible light stimulus is safe and is given at an intensity experienced in normal daily light exposures. The test takes about 2 minutes per eye. |
Done once as a baseline measurement for phase 2 of the study and again at the end of the study after 12 months of fish oil treatment. |
|
Secondary |
Questionnaires for corneal sensitivity |
There will be two questionnaires, Ocular Surface Disease Index (OSDI which contains 12 questions eye sensitivity to light, vision acuity, dryness, and sensitivity when reading, using the computer, and watching TV) and the Dry Eye Questionnaire (DEQ which contains 5 questions relating to discomfort, dryness and watery eyes). |
Done once as baseline for phase 1 of the study and also will be repeated at the end of phase 2 of the study. |
|
Secondary |
Determination of tibial nerve conduction velocity |
This is a non-invasive method of determining conduction velocity of the tibial nerve. The subject will be instructed to lie down on a examination table with shoes and socks removed. Afterwards, the lower ankle will be swabbed with an alcohol patch and allowed to air dry. A device containing 2 posts (about 3 inches apart) will be placed on the lower ankle in the region of the Achilles and activated. For a period of 5-10 sec the device sends a pulse stimulating the nerve distally (post located at the lower part of the ankle) and the response recorded by the post located distally on the skin of the upper part of the ankle. The nerve conduction is recorded electronically by the device and data down loaded to a secured computer. During the time of the analyses the subject will feel dual pulsating sensation that will last up to 10 sec. |
Done once as baseline for phase 1 of the study and also will be repeated at the end of phase 2 of the study. |
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