The authors wish to acknowledge the VISUALIA visual therapy clinic, which partially supported the development of the computer-based test, under agreement with the University of Oviedo (FUO-EM-104-12).

The study design was approved by the Basque Country Ethics Committee and followed the tenets of the Declaration of Helsinki. Written informed consent was obtained either from participants enrolled in the study or their legal guardians. Figure 1 represents the protocol steps.
1. Participant Recruitment
<ol>
	<li>Recruit patients with the following characteristics: between 7-14 years of age with refractive amblyopia and/or successfully treated strabismic amblyopia (strabismus children are only eligible to participate if misalignment of the visual axes has been successfully corrected with glasses, visual therapy, and/or strabismus surgery); with monocular best corrected distance visual acuity of &#8805;0.1 logMAR21; and stereoacuity measured in the 800&#34;-200&#34; range (coarse-moderate stereo-deficiency)22 according to a random-dot stereogram test23.
	<ol>
		<li>To determine &#34;refractive amblyopia&#34;, consider the interocular refractive difference error by means of autorefraction under cycloplegia. 
		NOTE: Anisometropic amblyopia is defined when a patient presents an interocular refractive difference error of &#8805;1 spherical dioptre (D), (spherical equivalent). Isometropic amblyopia is defined when the cycloplegic refractive error in each eye of &#8805;4.00 D hypermetropia or myopia and/or &#8805;2.00 D astigmatism and the interocular refractive difference error is &#60;1 D.</li>
		<li>To determine successfully treated strabismic amblyopia, check for the absence of strabismus using a monocular cover-uncover test and stimulating accommodation with a letter acuity score of 20/30 to ensure that the subject looks at the letter with the fovea when performing the fixing movement24.</li>
	</ol>
	</li>
	<li>Exclude patients with the following characteristics: strabismus; hyperphoria (upward deviation) of 2 prism diopters or more; nystagmus; hypermetropic anisometropia, in which the patient presents a spherical equivalent difference between the eyes of 3 diopters (or more) if corrected with glasses (to prevent aniseikonia); any ocular pathology; attention-deficit/hyperactivity disorder; and any cognitive disorder. Exclude patients without access to a computer or without internet connection at home.</li>
</ol>
2. Visual Evaluations
<ol>
	<li>Perform the Baseline Optometric Evaluation prior to beginning this section for collection of baseline data and ensure all appropriate inclusion/exclusion criteria.
	<ol>
		<li>Measure best corrected distance visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study (ETDRS visual acuity chart).</li>
		<li>Check for the absence of strabismus as explained in step 1.1.2.</li>
		<li>Measure stereoacuity at a constant distance of 40 cm, under light illumination of 120 cd/m2. 
		NOTE: Illumination control guarantees contrast consistency between dots and background in the test pattern. Patient head-to-test distance is a critical variable because it is included in the equation that sets stereoacuity result.
		<ol>
			<li>Measure global stereoacuity with a random-dot stereogram (to avoid monocular cues) conducted according to the test manufacturer&#39;s instructions.</li>
			<li>Measure local stereoacuity using a contour test despite the presence of monocular cues with a Wirt Circles test conducted according to the test manufacturer&#39;s instructions.</li>
		</ol>
		</li>
		<li>Measure the refractive error by cycloplegic refraction (1% cyclopentolate) following Pediatric Eye Disease Investigator Group (PEDIG) guidelines25,26.</li>
		<li>Rule out any ocular pathology with an in-depth study of the anterior (slit lamp) and posterior (indirect ophthalmoscope) poles.</li>
	</ol>
	</li>
	<li>Conducting the optometric center first visit with patients.
	<ol>
		<li>Create a patient profile in the game service application.
		<ol>
			<li>Set the patient&#39;s user identifier and password.</li>
			<li>Set the patient&#39;s interpupillary distance.</li>
		</ol>
		</li>
		<li>Install the computerized stereoscopic game on the patient&#39;s computer.</li>
		<li>Configure the game by clicking on the configuration panel.
		<ol>
			<li>Set the physical dimensions of the patient&#39;s computer screen.</li>
			<li>Ensure that the user is wearing the anaglyph glasses correctly (with the red filter over the left eye).</li>
		</ol>
		</li>
		<li>Measure the patient&#39;s stereopsis basal acuity using the computerized stereoscopic game.
		<ol>
			<li>Ask the patient to play the game under supervision, as explained in section 3.4.</li>
			<li>Consult the result stored in the cloud using the game service application.</li>
		</ol>
		</li>
		<li>Using patient stereopsis basal acuity, set the patient&#39;s basal level in the game service application.
		<ol>
			<li>The computerized stereoscopic game defines three stimulation categories, each associated with a stereoscopic acuity interval value: poor (840&#34;-300&#34;), coarse (480&#34; -210&#34;) and moderate-fine stereopsis (300&#34; -30&#34;). Patients begin with the finest level at which they can identify the stereopsis stimulus. For example, in a patient with a stereo threshold of 720&#34;, assign the poor stereopsis level on the patient&#39;s profile.</li>
		</ol>
		</li>
		<li>Explain to participants how to perform the exercises at home, as explained in section 3.</li>
	</ol>
	</li>
	<li>Perform check-up visits on completion of every 15 therapy sessions with the computerized stereoscopic game during the training period.
	<ol>
		<li>Open the game service application, open the patient profile and check both compliance and stereopsis results data.
		<ol>
			<li>Remind parents and participants about the importance of respecting the working distance from the screen.</li>
			<li>Remind parents and participants about the importance of compliance.</li>
		</ol>
		</li>
		<li>Evaluate the logMAR BCVA at distance with an ETRDS test to check for any deterioration from the starting values.</li>
		<li>Measure the patient&#39;s stereopsis acuity using the computerized stereoscopic game (step 2.2.4)</li>
		<li>Set the patient&#39;s basal level in the game service application (step 2.2.5).</li>
	</ol>
	</li>
	<li>Perform the final optometric evaluation on completion of 60 therapy sessions with the computerized stereoscopic game (end of treatment) to collect outcome data. 
	NOTE: This evaluation reproduces the baseline optometric evaluation, stressing the measurement of global and local stereopsis.</li>
	<li>Perform the follow-up optometric evaluation 6 months after completion to ensure stability of the results. 
	NOTE: This evaluation reproduces the baseline optometric evaluation, stressing the measurement of global and local stereopsis.</li>
</ol>
3. Treatment Exercises Performed at Home
<ol>
	<li>Explain to participants that they must follow a course of training using the computerized stereoscopic game at home for sixty 8 min sessions.</li>
	<li>Explain that each session must be performed on a different day and that five sessions per week must be completed. Explain to patients that the research team will have access to their compliance and results data in the cloud.</li>
	<li>Instruct patients to visit the optometry center for a check-up visit after every 15 sessions, which should be completed within 3 weeks to consider compliance as 100%, and in all cases, within a maximum of 6 weeks.</li>
	<li>Explaining how to use the computerized stereoscopic game
	<ol>
		<li>Ask the participant to sit at a distance of 80 cm from the computer screen. Make it clear that patients should not try to cheat the program by moving closer to the screen.</li>
		<li>Ensure that the room is dimly lit, avoiding any reflections on the computer screen.</li>
		<li>Explain that the program takes the form of a videogame, in which a random-dot image conceals a hidden silhouette. The silhouette can only be seen in three dimensions while wearing anaglyph glasses.</li>
		<li>Give the patient a pair of anaglyph glasses and explain how to wear them, focusing on which filter goes to which eye (with the red filter over the left eye).</li>
		<li>Provide the patient with an identifier and password to log in to the game (step 2.2.1).</li>
		<li>Instruct the patient to use the mouse to select which silhouette appears, selecting one figure from the four options shown at the bottom of the screen (Figure 2).</li>
		<li>Explain what happens after the selection of a silhouette.
		<ol>
			<li>If the answer is correct, the software emits a high-pitched sound, and the correct image appears in the form of a full-color picture as a reward.</li>
			<li>If the answer is incorrect, the software emits a deep sound. The player still has two more attempts to find the right answer.</li>
			<li>If there are three consecutive wrong answers, the software will show the correct answer.</li>
		</ol>
		</li>
		<li>Explain to the patient that after each trial, the software generates a new screen with a random-dot image concealing a new hidden silhouette.</li>
		<li>Explain to the patient that the hidden silhouette becomes more difficult to find as the session progresses and that this is normal.</li>
		<li>Explain to the patient that, once the session is complete, the software stores the outcomes in a cloud server, allowing the optometrist to track compliance and stereoacuity evolution remotely. 
		NOTE: Stress the importance of a stable Wi-Fi connection and of closing the computerized stereoscopic game properly.</li>
	</ol>
	</li>
</ol>

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The computer-based test was developed at the University of Oviedo by S.M.-G., who is a co-author of this manuscript. Subsequent to completion of this study, VISIONARY TOOL, S.L. (found at &#60;www.visionarytool.com&#62;), a private entity, approached S.M.-G. and J.A.P.-C. with an opportunity to take part in the development of a computerised visual training tool, which includes several games and tests, one of which is the random-dot hidden silhouette game used in this article.

Presented here is a protocol for the direct stimulation of stereoacuity, in which random-dot stereo images are used to enhance stereoscopic acuity in stereo-deficient subjects. Four preceding studies have evaluated the results of direct stimulation16,17,18,19. This latest protocol contributes additional features to the abovementioned interventional models.
The model of intervention proposed is intended for patients with a history of strabismic or anisometropic amblyopia, who have already received treatment (i.e., optical correction, occlusion, strabismus surgery, vision therapy) and achieved a best corrected visual acuity of at least 0.1 logMAR, but whose stereoacuity remains low (between 200&#34;-800&#34;). The goal of the protocol is to improve stereoacuity in cases like these.
Direct stimulation of stereopsis has already been shown to be effective in enhancing stereoacuity in stereo-deficient subjects16,17,18,19. However, for a stimulation system to be feasible, therapy must be performed in the patient&#39;s home to reach the 3,000-20,000 trials needed for learning to occur.
In the previously published study that validated this procedure and is summarized above, 11 subjects improved their stereoacuity20. However, five of the subjects experienced no increase in stereoacuity (Figure 3). This may be attributable to the presence of small-angle strabismus undetectable in a cover test. Read inferred that, since images from the left and right eyes should be located within Panum&#39;s area of fusion, normal stereoacuity should require alignment within 0.6 prism diopters28. Panum&#39;s fusional area is &#177;5-20 min of arc (0.1-0.6 prism diopter in the fovea), and it may be that alignment within this window is needed to support high-grade stereoscopic acuity29. A study conducted by Holmes et al. showed that a cover test failed to detect deviations below &#177;3 prism diopters; therefore, the presence of undetectable strabismus could compromise a patient&#39;s ability to acquire fine stereoacuity24.
Gamification has been used to enhance patient motivation and compliance. Moreover, the program stores data in the cloud after each session, making it possible for the practitioner to track a patient&#39;s activity remotely on a daily basis. Thanks to this feature, compliance results are excellent (88.36%) and comparable to those recorded in two earlier studies, in which amblyopic subjects received dichoptic stimulation treatment using an iPad at home10,11. They are also much better than the reported results of a PEDIG study under similar conditions, in which only 22.5% of the sample managed to complete over 75% of the treatment prescribed13. The compliance demonstrated here also exceeds that reported by studies that evaluated the effectiveness of occlusion treatment in amblyopia (70% compliance when 6 h of occlusion are prescribed, and 50% when 12 h are prescribed)30. A web application has the added advantage that parents are not required to keep a record of their child&#39;s compliance13. The optometrist&#39;s only duty is to access the server and check the data collected for each patient at the end of each session using the computerised stereoscopic game program.
During the training period, patients visit the optometry center (check-up visits), allowing the optometrist to stress the importance of user-to-screen distance. Optometrists also set the stimulation category (poor, coarse, moderate-fine) during these check-up visits. Perceptual learning theories predict that improvements are less likely if the patient does not work at his or her threshold (e.g., if the patient moves closer to the screen or works in an easier stimulation category). These findings were corroborated in the study carried out to validate this protocol20. User-to-screen distance is out of the software&#39;s control and is therefore the responsibility of the patient or patient&#39;s parents.
The decision to use a random-dot approach for the design of the computerized stereoscopic game may be critical. Stimulation through random-dot stereoscopic images is never inconsequential: even patients working below their threshold experience improvements. In a process of perceptual learning, repeated exposure to a random-dot stimulus alone will enhance binocular vision. The patient&#39;s task, and one that is particularly difficult for patients with a history of strabismus31, is to fuse the correlated random dots perceived by each eye12 without suppression. This enhances their ability to distinguish the correlated dots (signal) from those unable to be fused (noise). Training of this type may have improved the disparity detector response, given that the perceptual learning would have improved the fusional response and improved the patient&#39;s ability to detach the signal from noise32.
One of the risks of the perceptual learning approach is selectiveness. This method has demonstrated that random-dot stereogram training is not selective, because learning is transferred to medial lateral stereoacuity measured with a Wirt Circles test. Another finding that demonstrates the effectiveness of this treatment method is the stability of the results achieved. Different studies have examined whether improvements achieved in subjects with amblyopia as a result of perceptual learning training are stable16,17,19,33. This model has demonstrated the stability of the improvements measured with a random-dot stereoacuity test at a 6 month follow-up visit.
Several limitations have been detected. The software design requires the stimulation category to be set manually, when this process should ideally be automatic according to the patient&#39;s evolution. The pass level condition implemented could be improved by considering the possibility of moving the patient back to a coarse stereoacuity setting if the patient fails to pass a level on several consecutive occasions. In any case, a staircase procedure is discarded, because one of the goals of gamification is to improve patient motivation through game mechanics. The patient should experience the sensation of progress and success, regardless of whether their clinical condition is improving or deteriorating. This is achieved by concealing easier trials within the game flow (though not with a standard staircase procedure, whose goal is to quickly and accurately determine the threshold limit, at which performance is 50%). Another improvement is to monitor the patient&#39;s distance from the screen automatically. However, we are not aware of a solution that does not involve the use of special hardware, though it may be worth testing custom-built webcam head-tracking software.
Other limitations are due to the study design and include the following: (1) the majority of subjects had a history of strabismus (the sample of subjects with a history of anisometropic amblyopia was too small); (2) the age range was restricted to 7-14 years; and (3) the stereoacuity range was between 800&#34;-200&#34;. In future studies, it would be interesting to verify the therapeutic effect on anisometropic amblyopia and coarser stereoacuity and in older subjects.

Amblyopia is a developmental disorder of spatial vision frequently associated with the existence of strabismus, anisometropia, or form deprivation at a young age1. The incidence of amblyopia among the general population ranges from 1.3%-3.6%2. Conventional amblyopia therapy starts with the correction of any refractive error, followed by occlusion of the good eye with a patch or atropine penalization3. Although treatment outcomes of conventional treatment are initially good, with 73%-90% of patients experiencing improved visual acuity, this improvement does not equate to normal visual acuity in about 50% of patients. Moreover, children frequently experience deterioration even after successful treatment2. A previous study showed that, with respect to binocular vision, as few as 28% of anisometropic patients with amblyopia recorded two or more levels of improvement as a result of treatment4. There has been little research aimed at evaluating strategies for the improvement of stereopsis in cases of amblyopia, despite the fact that stereopsis is essential to visual perception in humans5. Conventional amblyopia therapy, which produces good results for visual acuity but poor outcomes in terms of binocular vision, can benefit from the development of an interventional model aimed at improving stereoacuity in patients with a history of amblyopia2.
Over the last 10 years, some researchers have proposed an alternative approach to understanding the course of amblyopia6,7. This understanding has motivated the proposal of a interventional model focused on anti-suppression dichoptic training for the recovery of binocular vision8,9. Amblyopia therapy involving targeted gamified activities for patient use at home has been reported successful in a number of cases10,11.
Notwithstanding, this dichoptic training is ineffective for improving stereoscopic acuity12. Two contemporary clinical trials using the anti-suppression dichoptic training model reported no stereoacuity improvement11,13. The most recent research indicates, however, that dichoptic stimulation is capable of reducing suppression depth and extent and improving binocular vision (restoring simultaneous binocular perception). In some cases, this coincides with improved stereoacuity14,15.
Some studies have proposed a different intervention approach that is focused on the direct stimulation of stereopsis through perceptual learning activities16,17. These studies are confined to a succession of cases treated under laboratory conditions. In Astle et al.&#39;s study, stereopsis was stimulated in two adult anisometropic amblyopes16 over the course of nine laboratory sessions. Treatment included binocular stimulation using a mirror stereoscope with stereogram pairs based on random-dot images. Ding and Levi stimulated stereopsis in a course of treatment conducted entirely under laboratory conditions, using a mirror stereoscope and stereograms based on Gabor patches18. Their subjects were five adults, four of which having no stereopsis and one being stereo-deficient. Subjects were required to perform between 3,000-20,000 perceptual learning training trials.
Furthermore, Xi et al. studied anisometropic amblyopes over the course of 10 -13 perceptual learning training sessions, during which 3-D anaglyph textures were used to stimulate stereopsis19. Finally, in Vedamurthy et al.&#39;s study, 11 stereo-deficient adults were engaged in visuo-motor task training (a &#34;squash-the-bug&#34; game) in a virtual reality environment17. These subjects performed 12,600 trials in 35 sessions over the course of 8-11 weeks.
Direct stimulation of stereopsis has been performed in laboratory studies, but this therapy model is time-consuming and difficult to apply in a daily clinical practice, especially with children. Thus, a feasible therapy model has been devised for which a successful proof of concept has been previously presented20. This protocol incorporates the results of a prospective, randomized, double-blind, parallel-group study based on perceptual learning treatment using random-dot stimuli in a video game format to improve stereoacuity. An in-depth explanation of the protocol followed in this study is presented.

<table><tbody><tr><td>Autorrefractometer, model TRK 1P</td><td>Topcon, Japan</td><td></td><td>Refractive error measurements by autorrefraction</td></tr><tr><td>Computerized Stereoscopic Game</td><td>University of Oviedo, Spain</td><td></td><td>The computer-based test itself was developed at the University of Oviedo by SM-G, coauthor of this manuscript. After finishing this study, a private company named VISIONARY TOOL (www.visionarytool.com) has contacted both SM-G and JAP-C to participate in the development of a computerized visual training tool. This tool includes several games and tests. The one used in this article, based on random dot hidden silhouettes, is one of them.</td></tr><tr><td>Randot Preschool Stereoacuity Test</td><td>Stereo Optical Company Inc, USA</td><td></td><td>Global stereoacuity test</td></tr><tr><td>Screen model</td><td>SIFIMAV, Italy</td><td></td><td>Logarithmic visual acuity chart ETDRS format</td></tr><tr><td>Wirt Circles Test</td><td>Stereo Optical Company Inc, USA</td><td></td><td>Local stereoacuity test</td></tr></tbody></table>

stereoacuity improvement using random-dot video games

Conventional amblyopia therapy involves occlusion or penalization of the dominant eye, though these methods enhance stereoscopic visual acuity in fewer than 30% of cases. To improve these results, we propose a treatment in the form of a video game, using random-dot stimuli and perceptual learning techniques to stimulate stereoacuity. The protocol is defined for stereo-deficient patients between 7-14 years of age who have already received treatment for amblyopia and have a monocular best corrected distance visual acuity of at least 0.1 logMAR. Patients are required to complete a perceptual learning program at home using the video game. While compliance is stored automatically in the cloud, periodic optometry center visits are used to track patient evolution and adjust the game&#39;s stereoscopic demand until the smallest detectable disparity is achieved. The protocol has proved to be successful, and effectiveness is gauged in terms of a two-level gain on a random stereoacuity test (global stereoacuity or cyclopean stereoacuity reference test). Moreover, the random-dot stimuli learning transfers to medial lateral stereoscopic acuity according to a Wirt Circles test, in which success criteria is a final stereoacuity of over 140&#34;, and the attained enhancement corresponds to no less than two levels of stereoscopic acuity. Six months later, a random-dot stereoacuity test recorded no reduction in the stereoacuity that was achieved.

As a representative example of the results that can be achieved following this protocol, we summarize the results of a recent study carried out by Portela et al.20. Figure 3 and Figure 4 show the outcomes that were obtained.
Sixteen stereo-deficient subjects aged between 7-14 years of age were included in this study, four of whom had a history of refractive amblyopia (2 anisometropic and 2 isometropic). Twelve of the subjects had a history of successfully treated strabismic amblyopia, and four of these had a history of both strabismic and anisometropic amblyopia. Eleven of the 12 subjects with a history of strabismic amblyopia presented esotropia, and one presented exotropia. All participants had previously received amblyopia therapy and achieved good levels of visual acuity but did not attain a fine level of stereoacuity (less than or equal to 200&#34;). All but one of the subjects were able to complete the 60 assigned training sessions that were 8 min each (8 h in total). Compliance was considered to be 100% when patients completed the training in less than 12 weeks and 0% when the training took more than 24 weeks. On average, subjects took 79 days to complete the 60 sessions (IQR = 66-102 days); therefore, they surpassed the minimum recommended compliance of five sessions per week. Compliance outcomes were excellent (88.36%).
Visual acuity among the subjects remained stable during and post-therapy. Stereoacuity, however, improved in a significant number of subjects (see Figure 3). The means, medians, and minimum and maximum values are presented in Table 1. When these were analyzed using the Mann-Whitney U test, stereoacuity improved significantly after treatment (Random-Dot Stereoacuity test, p = 0.019; Wirt Circles test, p = 0.014). For a better understanding, Figure 4 shows a graphic presentation of the improvement in stereoacuity between the start and end of therapy.
Stereoacuity improved by at least one level in 11 subjects when stereoacuity was measured with the random stereoacuity test. Where stereoacuity was evaluated with the Wirt Circles test, improvement of at least one level was also observed in 11 subjects. Clinically speaking, an improvement in stereoacuity measured with a random stereoacuity test is significant when the improvement reaches at least two levels (Adam&#39;s criteria)27, and this was achieved in seven subjects. Where the Wirt Circles test was used, an improvement of at least two levels and a stereoacuity equal or better than 140&#34; is considered significant (Levi&#39;s criteria)12, and this was achieved in 10 subjects. After 6 months, the outcomes were stable according to the random-dot stereoacuity test. This is the reference test to measure stereoacuity, with its main feature being its excellent test-retest reliability23.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/60236/60236fig1a.jpg" />
Figure 1: Protocol steps. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60236/60236fig1alarge.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/60236/60236fig2a.jpg" />
Figure 2: Logical process of the game. The subject must indicate which figure appears, selecting one from those shown at the bottom of the screen (left image). If the answer is correct, the software emits a high-pitched sound, and the same image appears in picture form (right image). If the subject provides three consecutive correct answers, the software generates a new screen with a random-dot image representing a finer stereopsis. If the subject provides a wrong answer, the software emits a deep sound and the random-dot image remains the same (left image). Finally, if the subject provides three consecutive wrong answers, the software will show the correct answer (right image). This figure is adapted from Portela et al.20 with permission from Optometry and Vision Science. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60236/60236fig2alarge.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/60236/60236fig3a.jpg" />
Figure 3: Measurements of basal and post-treatment levels of stereoacuity. Random-dot stereoacuity (RDS) and Wirt Circles tests were used to measure stereoacuity. Measurements are in log seconds of arc. This figure is adapted from Portela et al.20 with permission from Optometry and Vision Science. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60236/60236fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/60236/60236fig4.jpg" />
Figure 4: Medians of stereoacuity data before and immediately post treatment for each stereoacuity test. (A) Random-dot stereoacuity (RDS) test and (B) Wirt Circles test. Boxes indicate 25% and 75% quartiles. Measurements are in log seconds of arc. This figure is adapted from Portela et al.20 with permission from Optometry and Vision Science. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60236/60236fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td></td>
			<td colspan="2">Baseline Stereo</td>
			<td colspan="2">Post-Treatment Stereo</td>
		</tr>
		<tr>
			<td></td>
			<td>Wirt</td>
			<td>RST</td>
			<td>Wirt</td>
			<td>RST</td>
		</tr>
		<tr>
			<td>Mean</td>
			<td>293.13&#177;271.17</td>
			<td>475.00&#177;240.84</td>
			<td>107.50&#177;51.60</td>
			<td>305.63&#177;306.50</td>
		</tr>
		<tr>
			<td>Median</td>
			<td>200 [95 to 400] 95%</td>
			<td>400 [250 to 800] 95%</td>
			<td>100 [60 to 140] 95%</td>
			<td>150 [100 to 700] 95%</td>
		</tr>
		<tr>
			<td>Min</td>
			<td>50</td>
			<td>200</td>
			<td>40</td>
			<td>40</td>
		</tr>
		<tr>
			<td>Max</td>
			<td>800</td>
			<td>800</td>
			<td>200</td>
			<td>800</td>
		</tr>
	</tbody>
</table>
Table 1: Means, standard deviation, medians, interquartile ranges, and maximum and minimum stereoacuity values. The left columns show baseline stereoacuity data, and the right columns show post-treatment stereoacuity outcomes. Stereoacuity was measured using random-dot stereoacuity (RDS) and Wirt Circles tests. Measurements are in seconds of arc. This figure is adapted from Portela et al.20 with permission from Optometry and Vision Science.

Watch this Scientific Journal Video about Stereoacuity Improvement using Random-Dot Video Games at JoVE.com

Stereoacuity Improvement using Random-Dot Video Games

Presented here is a protocol to improve stereoacuity using gamified perceptual learning software based on random-dot stimuli. Patients are stereo-deficient subjects without strabismus. The protocol combines optometry center visits with home exercises using software. Compliance and stereoacuity evolution are stored in the cloud.

Conventional amblyopia therapy involves occlusion or penalization of the dominant eye, though these methods enhance stereoscopic visual acuity in fewer ...

stereoacuity-improvement-using-random-dot-video-games

Nanyang Technological University

Research

JoVE Journal

Behavior

14.1K Views.  University of Oviedo. Presented here is a protocol to improve stereoacuity using gamified perceptual learning software based on random-dot stimuli. Patients are stereo-deficient subjects without strabismus. The protocol combines optometry center visits with home exercises using software. Compliance and stereoacuity evolution are stored in the cloud.

Video: Stereoacuity Improvement using Random-Dot Video Games

Measuring Sensitivity to Viewpoint Change with and without Stereoscopic Cues

The speed and accuracy of object recognition is compromised by a change in viewpoint; demonstrating that human observers are sensitive to this transformation. Here we discuss a novel method for simulating the appearance of an object that has undergone a rotation-in-depth, and include an exposition of the differences between perspective and orthographic projections. Next we describe a method by which human sensitivity to rotation-in-depth can be measured. Finally we discuss an apparatus for creating a vivid percept of a 3-dimensional rotation-in-depth; the Wheatstone Eight Mirror Stereoscope. By doing so, we reveal a means by which to evaluate the role of stereoscopic cues in the discrimination of viewpoint rotated shapes and objects.

We discuss a novel method forviewpoint-rotation of visual stimuli, and demonstrate using a mirror stereoscopethe three-dimensional percept of rotation-in-depth. The technique can be used to investigate the role of stereoscopic cues in encoding viewpoint-rotated figures.

The speed and accuracy of object recognition is compromised by a change in viewpoint; demonstrating that human observers are sensitive to this ...

Combining Computer Game-Based Behavioural Experiments With High-Density EEG and Infrared Gaze Tracking

Experimental paradigms are valuable insofar as the timing and other parameters of their stimuli are well specified and controlled, and insofar as they yield data relevant to the cognitive processing that occurs under ecologically valid conditions. These two goals often are at odds, since well controlled stimuli often are too repetitive to sustain subjects' motivation. Studies employing electroencephalography (EEG) are often especially sensitive to this dilemma between ecological validity and experimental control: attaining sufficient signal-to-noise in physiological averages demands large numbers of repeated trials within lengthy recording sessions, limiting the subject pool to individuals with the ability and patience to perform a set task over and over again. This constraint severely limits researchers' ability to investigate younger populations as well as clinical populations associated with heightened anxiety or attentional abnormalities. Even adult, non-clinical subjects may not be able to achieve their typical levels of performance or cognitive engagement: an unmotivated subject for whom an experimental task is little more than a chore is not the same, behaviourally, cognitively, or neurally, as a subject who is intrinsically motivated and engaged with the task. A growing body of literature demonstrates that embedding experiments within video games may provide a way between the horns of this dilemma between experimental control and ecological validity. The narrative of a game provides a more realistic context in which tasks occur, enhancing their ecological validity (Chaytor &amp; Schmitter-Edgecombe, 2003). Moreover, this context provides motivation to complete tasks. In our game, subjects perform various missions to collect resources, fend off pirates, intercept communications or facilitate diplomatic relations. In so doing, they also perform an array of cognitive tasks, including a Posner attention-shifting paradigm (Posner, 1980), a go/no-go test of motor inhibition, a psychophysical motion coherence threshold task, the Embedded Figures Test (Witkin, 1950, 1954) and a theory-of-mind (Wimmer &amp; Perner, 1983) task. The game software automatically registers game stimuli and subjects' actions and responses in a log file, and sends event codes to synchronise with physiological data recorders. Thus the game can be combined with physiological measures such as EEG or fMRI, and with moment-to-moment tracking of gaze. Gaze tracking can verify subjects' compliance with behavioural tasks (e.g. fixation) and overt attention to experimental stimuli, and also physiological arousal as reflected in pupil dilation (Bradley et al., 2008). At great enough sampling frequencies, gaze tracking may also help assess covert attention as reflected in microsaccades - eye movements that are too small to foveate a new object, but are as rapid in onset and have the same relationship between angular distance and peak velocity as do saccades that traverse greater distances. The distribution of directions of microsaccades correlates with the (otherwise) covert direction of attention (Hafed &amp; Clark, 2002).

Procedures for recording high-density EEG and gaze data during computer game-based cognitive tasks are described. Using a video game to present cognitive tasks enhances ecological validity without sacrificing experimental control.

Experimental paradigms are valuable insofar as the timing and other parameters of their stimuli are well specified and controlled, and insofar as they ...

Neuroscience

Methods to Test Visual Attention Online

Online data collection methods have particular appeal to behavioral scientists because they offer the promise of much larger and much more representative data samples than can typically be collected on college campuses. However, before such methods can be widely adopted, a number of technological challenges must be overcome &#8211; in particular in experiments where tight control over stimulus properties is necessary. Here we present methods for collecting performance data on two tests of visual attention. Both tests require control over the visual angle of the stimuli (which in turn requires knowledge of the viewing distance, monitor size, screen resolution, etc.) and the timing of the stimuli (as the tests involve either briefly flashed stimuli or stimuli that move at specific rates). Data collected on these tests from over 1,700 online participants were consistent with data collected in laboratory-based versions of the exact same tests. These results suggest that with proper care, timing/stimulus size dependent tasks can be deployed in web-based settings.

To replicate laboratory settings, online data collection methods for visual tasks require tight control over stimulus presentation. We outline methods for the use of a web application to collect performance data on two tests of visual attention.

Online data collection methods have particular appeal to behavioral scientists because they offer the promise of much larger and much more representative ...

The Measurement and Treatment of Suppression in Amblyopia

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%1-3, the majority of cases being monocular2. Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation.
Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself4,5 . Amblyopia is characterized by both monocular and binocular deficits6,7 which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions8. Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia9,10 .
Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device11,12 . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which neither eye has a performance advantage is a measure of the "balance point" and is a direct measure of suppression. This technique has been validated psychophysically both in control13,14 and patient6,9,11 populations.
In addition to measuring suppression this technique also forms the basis of a novel form of treatment to decrease suppression over time and improve binocular and often monocular function in adult patients with amblyopia12,15,16 . This new treatment approach can be deployed either on the goggle system described above or on a specially modified iPod touch device15.

Amblyopia is a developmental disorder of the visual cortex that is often accompanied by strong suppression of one eye. We present a new technique for measuring and treating interocular suppression in patients with amblyopia that can be deployed using virtual reality goggles or a portable iPod Touch device.

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

Medicine

Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio based cues and set within the context of a video game metaphor, users gather relevant spatial information regarding a building's layout. This allows the user to develop an accurate spatial cognitive map of a large-scale three-dimensional space that can be manipulated for the purposes of a real indoor navigation task. After game play, participants are then assessed on their ability to navigate within the target physical building represented in the game. Preliminary results suggest that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building as indexed by their performance on a series of navigation tasks. These tasks included path finding through the virtual and physical building, as well as a series of drop off tasks. We find that the immersive and highly interactive nature of the AbES software appears to greatly engage the blind user to actively explore the virtual environment. Applications of this approach may extend to larger populations of visually impaired individuals.

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind.

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio ...

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.

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 ...

Assessing Binocular Central Visual Field and Binocular Eye Movements in a Dichoptic Viewing Condition

Macular degeneration typically results in heterogeneous binocular central visual defects. Currently available approaches to assess central visual field, like the microperimetry, can test only one eye at a time. Therefore, they cannot explain how the defects in each eye affect the binocular interaction and real-world function. Dichoptic stimulus presentation with a gaze-controlled system could provide a reliable measure of monocular/binocular visual fields. However, dichoptic stimulus presentation and simultaneous eye-tracking are challenging because optical devices of instruments that present stimulus dichoptically (e.g., haploscope) always interfere with eye-trackers (e.g., infrared video-based eye-trackers). Therefore, the goals were 1) to develop a method for dichoptic stimulus presentation with simultaneous eye-tracking, using 3D-shutter glasses and 3D-ready monitors, that is not affected by interference and 2) to use this method to develop a protocol for assessing central visual field in subjects with central vision loss. The results showed that this setup provides a practical solution for reliably measuring eye-movements in dichoptic viewing condition. In addition, it was also demonstrated that this method can assess gaze-controlled binocular central visual field in subjects with central vision loss.

Presented here is a protocol for assessing binocular eye movements and gaze-controlled central visual field screening in participants with central vision loss.

Macular degeneration typically results in heterogeneous binocular central visual defects. Currently available approaches to assess central visual field, ...

An Automated Assessment of Visual Acuity in Infants and Toddlers

An Automated Method for Assessing Visual Acuity in Infants and Toddlers Using an Eye-Tracking System

Visual acuity measurement is an important visual function test to perform in infancy and childhood. However, accurate visual acuity measurement in infants is difficult because of deficiencies in their communication ability. This paper presents a novel automated method to assess visual acuity in children (5-36 months old). This method, the automated acuity card procedure (AACP), uses a webcam for eye tracking and recognizes children's watching behaviors automatically. A two-choice preferential-looking test is performed when the tested child watches the visual stimuli shown on a high-resolution digital display screen. When the tested child watches the stimuli, their facial pictures are recorded by the webcam. These pictures are used by the set computer program to analyze their watching behavior. With this procedure, the child's eye movement responses to different stimuli are measured, and their visual acuity is assessed without communication. By comparing the results with grating acuity obtained by Teller Acuity Cards (TACs), AACP performance is deemed comparable to that of TACs.

Author Spotlight: An Automated Method for Assessing Visual Acuity in Infants and Toddlers Using an Eye-Tracking System  

In this paper, we present a novel automated method for assessing visual acuity in infants and toddlers by using an eye-tracking system.

Visual acuity measurement is an important visual function test to perform in infancy and childhood. However, accurate visual acuity measurement in infants ...

Assessing Vision via Shape Recognition in Random Dot Kinematograms

Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes

The standard visual acuity measurements rely on stationary stimuli, either letters (Snellen charts), vertical lines (vernier acuity) or grating charts, processed by those regions of the visual system most sensitive to the stationary stimulation, receiving visual input from the central part of the visual field. Here, an acuity measurement is proposed based on discrimination of simple shapes, that are defined by motion of the dots in the random dot kinematograms (RDK) processed by visual regions sensitive to motion stimulation and receiving input also from the peripheral visual field. In the motion-acuity test, participants are asked to distinguish between a circle and an ellipse, with matching surfaces, built from RDKs, and separated from the background RDK either by coherence, direction, or velocity of dots. The acuity measurement is based on ellipse detection, which with every correct response becomes more circular until reaching the acuity threshold. The motion-acuity test can be presented in negative contrast (black dots on white background) or in positive contrast (white dots on black background). The motion defined shapes are located centrally within 8 visual degrees and are surrounded by RDK background. To test the influence of visual peripheries on centrally measured acuity, a mechanical narrowing of the visual field to 10 degrees is proposed, using opaque goggles with centrally located holes. This easy and replicable narrowing system is suitable for MRI protocols, allowing further investigations of the functions of the peripheral visual input. Here, a simple measurement of shape and motion perception simultaneously is proposed. This straightforward test assesses vision impairments depending on the central and peripheral visual field inputs. The proposed&#160;motion-acuity test advances the capability of standard tests to reveal spare or even strengthened vision functions in patients with injured visual system, that until now remained undetected.

Author Spotlight: Assessment of Visual Acuity in Central Vision Loss Through Motion-Based Peripheral Vision Testing

A novel motion-based acuity test that allows the assessment of central and peripheral visual processing in low-vision and healthy individuals, along with goggles limiting peripheral vision compatible with MRI protocols, are described here. This method offers a comprehensive vision assessment for functional impairments and dysfunctions of the visual system.

The standard visual acuity measurements rely on stationary stimuli, either letters (Snellen charts), vertical lines (vernier acuity) or grating charts, ...

Gaze-Contingent Framework for Studying and Training in Simulated Vision Loss

A Gaze-Contingent Display Framework for Perceptual Learning Research with Simulated Central Vision Loss

Macular degeneration (MD) is one of the leading causes of vision impairment in the Western world. Patients with MD tend to develop spontaneous eye movement strategies to compensate for their vision loss, including adopting a preferred retinal locus, or PRL, a spared peripheral region that they use more frequently to replace the damaged fovea. However, not all patients are successful in developing a PRL, and even when they do, it might take them months. Currently, no gold standard rehabilitative therapy exists, and MD research is further hindered by issues of recruitment, compliance, and comorbidity. To help address these issues, a growing body of research has used eye tracking-guided, gaze-contingent displays in a simulated central vision loss paradigm in individuals with intact vision. While simulated vision loss is qualitatively different than pathological central vision loss, our framework provides for a highly controlled model through which to study compensatory eye movements and test possible rehabilitation interventions in low vision. By developing a comprehensive framework, rather than relying on isolated and disconnected tasks, we create a cohesive environment where we can test larger-scale hypotheses, allowing us to examine interactions between tasks, assess training effects across multiple measures, and establish a consistent methodology for future research. Furthermore, participants in simulated central vision loss studies show similarities in their oculomotor compensatory behaviors compared to patients with MD. Here, we present a framework for conducting gaze-contingent studies related to simulated central vision loss. We emphasize the utilization of the framework to test behavioral and oculomotor performance of healthy individuals on a wide range of perceptual tasks encompassing different levels of visual processing. We also discuss how this framework can be adapted for training MD patients.

Development of a Gaze-Contingent Display Framework Designed for Perceptual and Oculomotor Research with Simulated Central Vision Loss

We present development of a gaze-contingent display framework designed for perceptual and oculomotor research simulating central vision loss. This framework is particularly adaptable for studying compensatory behavioral and oculomotor strategies in individuals experiencing both simulated and pathological central vision loss.