Name: dynamic visual tests to identify and quantify visual damage and repair following demyelination in optic neuritis patients
Uploaded: 2014-04-14T17:30:00
Description: Watch this Scientific Journal Video about Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients at JoVE.com

This work was supported by the Caesarea Edmond &#38; Benjamin de Rothschild Foundations.

The protocol follows the Hadassah Hebrew University Ethics Committee guidelines for studies in human subjects. To avoid the effect of myopia or refractive errors on test results, the protocols should be performed while patients wear their eyeglasses (corrected vision).
Object From Motion (OFM) protocol:
1. Test Initiation and Instructing Subjects
<ol>
	<li>Seat the subject 50 cm in front of the computer screen.</li>
	<li>Open the OFM software.</li>
	<li>Instruct the...

<ol>
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Optic neuritis is a demyelinative disease of the optic nerve, causing acute visual loss. Though considered transient when using standard visual testing1, patients continue to perceive difficulties in performing everyday visual tasks. We argue that dynamic visual tests are adequate to identify and quantify these sustained deficits. This is since dynamic but not static visual functions depend on projection rates, and may be more vulnerable to delayed projection following demyelination.
T...

Optic neuritis as a model for tracking tissue degeneration and repair
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) and is the leading cause of nontraumatic neurological disability in young adults in developed countries. Demyelination is considered the most characteristic histopathological feature of MS. Recent studies, however, revealed that MS is also a neurodegenerative disease with early neuroaxonal damage1-3.
Optic neuritis (ON), inflammation of the optic nerve, is the presenting symptom in 20% of MS patients and at least 50% of those suffering from MS experience at least one episode of ON during their lifetime4. Unlike other locations of MS lesions that do not always correlate to the clinical manifestations, demyelinating episode of the optic nerve typically results in distinctive manifestation of acute visual loss. Given its comorbidity with MS and its prominent clinical features, ON offers a unique opportunity for tracking tissue degeneration and repair and their consequences in a single MS lesion.
The need for improved methods for tracking tissue degeneration and repair in vivo
Pathologic studies in MS implicate demyelination as a principal cause of axonal transection and subsequent axonal degeneration. Remyelination may prevent demyelinated axons from degenerating; however, effective remyelination may be limited as a result of repeated attacks. Therefore, current and evolving neuroprotective and regenerative therapeutic strategies in MS are aimed to prevent new attacks and promote remyelination processes in the CNS5.
In order to follow up optic neuritis patients and evaluate the efficacy of their treatment, a fine tool to quantify changes in myelination at the CNS is required. However, the standard measurements, including routine visual tests and MRI scans, are not sensitive enough for this purpose. Routine visual tests (i.e. visual acuity, contrast sensitivity, visual fields, and color perception) may reveal cases of reduced input projection along the visual pathways but are insensitive to identify delayed projection rates, which is the role of the demyelinated fibers6,7. T2 hyperintense lesions, which are the hallmark of the disease, result from residual mixture of edema, inflammation, demyelination, axonal loss and gliosis and thus cannot differentiate between demyelination and other brain pathologies. Furthermore, standard MRI is designed to reveal qualitative tissue contrast. While these are adequate for identifying the location of unusual tissue, they are insufficient to quantitatively assess tissue properties.
Dynamic visual tests may be used as markers of demyelination and remyelination
We argue that dynamic visual functions are more appropriate than static functions to identify and quantify changes in projection latencies along the visual pathways. While accomplishment of both static and dynamic visual functions requires sufficient amount of visual input projection, only dynamic visual functions depend on projection rates. Optic nerve demyelination may thus affect dynamic rather than static visual functions, implicating the need for rapid transmission of visual input in order to perceive motion.
We have developed two behavioral tasks to assess monocular and binocular visual functions which may closely associate with projection latencies along the visual pathways. These include Object From Motion (OFM) extraction and Time-constrained stereo protocols.
In the OFM test, an array of dots compose an object, by moving the dots within the image rightward while moving the dots outside the image leftward or vice versa. The dot pattern generates a camouflaged object that cannot be detected when the dots are stationary or moving as a whole. Importantly, object recognition is dependent on motion perception. Using the OFM protocol, we have demonstrated a sustained deficit in the affected eyes of ON patients, evident even 12 months following the optic neuritis attack, while standard visual functions had recovered8. Furthermore, impaired performance was associated with delayed conductions (delayed P100, reflecting demyelination) and improvement in motion perception was correlated with shortening of conduction rates (reflecting remyelination; linear least squares regression with calculation of the correlation coefficient F=27.3; p=0.0005; r=-0.87)9.
The currently presented OFM protocol was updated in order to fit the test for clinical usage, including test shortening, adjusting the test software to result in an automatic output file, and to result in a motion sensitivity score.
To assess the effect of projection latencies on binocular vision, the Time-constrained Stereo protocol was developed. In this protocol, spatially disparate images are presented for a limited length of time, challenging binocular integration in time. This test was designed to test the hypothesis that due to demyelination at the affected nerve, information from the two eyes will reach the cortex at different time points impairing binocular integration in time. Testing a group of recovered ON patients (1-2.5 years following the attack), we have shown that while most patients had intact performance levels in a standard static stereo task; performance on the time-constrained stereo task was impaired in most cases10.
The OFM and the time-constrained stereo protocols provide a simple, yet powerful, way to identify and quantify processes of demyelination and remyelination along the visual pathways. These protocols may be efficient to diagnose and follow up ON and MS patients in a cost effective manner using an easy to use computer based protocol.

<table border="0" cellpadding="0" cellspacing="0" width="638">
	<tbody>
		<tr height="167">
			<td dir="LTR" height="167" style="height:167px;width:231px;">Personal computer, including laptops</td>
			<td style="width:117px;"></td>
			<td style="width:119px;"></td>
			<td dir="LTR" style="width:171px;">The OFM software runs best on Mac or on Windows 7 (or higher) PC. The Stereo software runs on every personal computer.&#160;</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">Monitor&#160; specification</td>
			<td style="width:117px;"></td>
			<td style="width:119px;"></td>
			<td dir="LTR" style="width:171px;">Size: at least 15inch,&#160; Color: at least 16 bit</td>
		</tr>
		<tr height="109">
			<td height="109" style="height:109px;width:231px;">The OFM and the Stereo softwares</td>
			<td dir="LTR" style="width:117px;">These are self-developed softwares</td>
			<td style="width:119px;"></td>
			<td dir="LTR" style="width:171px;">Researchers &#38; physicians who are interested in these softwares may contact us at: fmri-hadassah.org</td>
		</tr>
		<tr height="209">
			<td dir="LTR" height="209" style="height:209px;width:231px;">Red/Cyan 3D glasses (We had tested the Stereo software on the two following 3D glasses):</td>
			<td style="width:117px;">Nvidia &#38; American Paper Optics</td>
			<td dir="LTR" style="width:119px;">3D Vision Ultimate Anaglyph 3D Glasses &#38; Pro X Style Red/Cyan 3D Glasses for Movies and Games on Flat Screens&#160;&#160;</td>
			<td style="width:171px;"></td>
		</tr>
		<tr height="63">
			<td dir="LTR" height="63" style="height:63px;width:231px;">Performance on our stereo task was compared to performance on the standard Randot stereo test</td>
			<td dir="LTR" style="width:117px;">Stereo Optical Co.</td>
			<td dir="LTR" style="width:119px;">Randot SO-002&#160;</td>
			<td></td>
		</tr>
	</tbody>
</table>

dynamic visual tests to identify and quantify visual damage and repair following demyelination in optic neuritis patients

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to assess changes in myelination at the central nervous system (CNS). However, standard measurements, including routine visual tests and MRI scans, are not sensitive enough for this purpose. We present two visual tests addressing dynamic monocular and binocular functions which may closely associate with the extent of myelination along visual pathways. These include Object From Motion (OFM) extraction and Time-constrained stereo protocols. In the OFM test, an array of dots compose an object, by moving the dots within the image rightward while moving the dots outside the image leftward or vice versa. The dot pattern generates a camouflaged object that cannot be detected when the dots are stationary or moving as a whole. Importantly, object recognition is critically dependent on motion perception. In the Time-constrained Stereo protocol, spatially disparate images are presented for a limited length of time, challenging binocular 3-dimensional integration in time. Both tests are appropriate for clinical usage and provide a simple, yet powerful, way to identify and quantify processes of demyelination and remyelination along visual pathways. These protocols may be efficient to diagnose and follow optic neuritis and multiple sclerosis patients.
In the diagnostic process, these protocols may reveal visual deficits that cannot be identified via current standard visual measurements. Moreover, these protocols sensitively identify the basis of the currently unexplained continued visual complaints of patients following recovery of visual acuity. In the longitudinal follow up course, the protocols can be used as a sensitive marker of demyelinating and remyelinating processes along time. These protocols may therefore be used to evaluate the efficacy of current and evolving therapeutic strategies, targeting myelination of the CNS.

OFM protocol
The protocol results in a text file, automatically summarizing subject's responses. Outcome can be analyzed in two ways:
Total score: Each stimulus presented is assigned with a stimulus weight, and the sum of weights of all identified stimuli is set as the subject's response score. The weight of a particular stimulus is set based on the speed of the stimulus, with higher weights to lower speeds. Unidentified stimuli are assigned with a zero weight. General...

Watch this Scientific Journal Video about Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients at JoVE.com

Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

Object From Motion (OFM) and Time-constrained stereo protocols are sensitive tools to identify monocular and binocular dynamic visual function deficits, which are uniquely affected in optic neuritis patients. Furthermore, these tests may be used as quantitative noninvasive tools to assess the extent of myelination along visual pathways.

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to ...

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