This work was supported in part by NIH grant R44EY025902 and by the Mass Eye &#38; Ear Curing Kids Grant.

This study was conducted in accordance with the tenets of the Declaration of Helsinki, at Schepens Eye Research Institute (Boston, MA) and Spaulding Rehabilitation Hospital (Boston, MA). Informed consent was obtained from all the participants. The study was approved by the local institutional review boards of Mass Eye and Ear (Boston, MA).
NOTE: Patient inclusion criteria were prior diagnosis of horizontal strabismus (constant or intermittent exotropia or esotropia) and no other visual impairments. This study was a part of a larger one reported previously12. Data for 14 patients recruited in the US in the larger study12 are reported here with permission. An optometrist specialized in vision rehabilitation who routinely evaluate strabismus in clinic performed prism and alternate cover test, following by measurement with the app to prevent bias of the cover test results by the objective app measurement.
1. Prepare the test
NOTE: Testing can be performed in any environment; however, the following controls are likely to aid in successful testing.
<ol>
	<li>Conduct the test in a well-lit environment. Let the patients face in a direction such that corneal reflections from windows and ceiling lights are not located in the center of the eyes. Try to avoid strong background light, such as windows. 
	NOTE: Usually it helps to have a ceiling light right above the head, or a window on one side of the patient. Sometimes, asking the patient to hold their hand above their brow or using a visor can help shield the eyes from strong light sources which create additional reflections on the cornea, as needed. Turning off point light sources such as canister lights or gooseneck lamps will decrease the intensity of extra corneal reflections, making it easier for the software to detect the reflection from the camera flash as intended. If point light source is needed it may be diffused by pointing it at the wall or using a diffuser (i.e., lamp shade).</li>
</ol>
2. Measure tropia (manifest strabismus) with single snapshot&#8722;near fixation
<ol>
	<li>Launch the app and set the mode to No Cover (button at upper right corner).</li>
	<li>Select near fixation (button at lower right corner).</li>
	<li>Hold the phone in landscape orientation about 40 cm from the patient at eye level with the rear-camera facing the patient to be measured. 
	NOTE: The distance does not have to be accurately controlled. The app can automatically compensate for different distances.</li>
	<li>Instruct the patient to fixate on the flash light, which is off at this point. For tests requiring precise accommodation such as when screening for accommodative esotropia, paste a fixation target (such as a letter) on the back of the phone, directly below or above the flashlight.</li>
	<li>While the patient confirms he/she is fixating, press the round button to take a snapshot, which will be analyzed by the app.</li>
	<li>When the analysis is completed, the app will show detected eye features: limbus (iris outer) boundary indicated by a large circle (green), the center of the eye indicated by a cross (green), and the location of the corneal reflection indicated by a small circle (red). Verify these features are detected without obvious errors (such as incorrect limbus fitting, or incorrect location or missing corneal reflection).</li>
	<li>On the same screen, under the captured picture, the app will show the measurements related to the eye alignment. If satisfied with the results, press the save button to save the current test in the phone. Otherwise, press the back-arrow button to retest.</li>
</ol>
3. Measure tropia (manifest strabismus) with snapshot&#8722;far fixation
NOTE: To measure tropia for far fixation, the angle kappa for each eye needs to be measured at least once. The app will automatically choose the latest measurement of angle kappa in the history. If it is not available for either eye, the app will give a reminder to first obtain this measurement (see section 6 for details of angle kappa measurement).
<ol>
	<li>Launch the app and set the mode to No Cover (button at upper right corner).</li>
	<li>Select far fixation mode (button at lower right corner).</li>
	<li>Hold the phone in landscape orientation about 40 cm from the patient at eye level with the rear face of the phone facing the patient. 
	NOTE: The distance does not have to be accurately controlled. The app can automatically compensate for different distances.</li>
	<li>Place the phone slightly below two eyes so that the patient can look above the phone and fixate a target in the distance (typically 5 m away). Make sure the camera is in approximately between the two eyes, not too far to the side of either eye.</li>
	<li>While making sure the patient is fixating properly, press the round button to take a snapshot.</li>
	<li>When the analysis is completed, the app will show detected eye features: limbus boundary indicated by a large circle (green), the center of the eye indicated by a cross (green), and the location of the corneal reflection indicated by a small circle (red). Verify these features are detected without obvious errors (such as incorrect limbus fitting, or incorrect location or missing corneal reflection).</li>
	<li>Under the picture there are measurement outcomes for eye alignment including prism diopters. If satisfied with the results, press the save button to save the test in the phone. Otherwise, press the back-arrow button to retest.</li>
</ol>
4. Measure intermittent strabismus or phoria with cover test&#8722;near fixation
<ol>
	<li>Launch the app and toggle on the cover test mode (button at upper right corner), and select near fixation (button at lower right corner).</li>
	<li>Hold the phone in landscape orientation about 40 cm from the patient. 
	NOTE: The distance does not have to be accurately controlled. The app can automatically compensate for different distances.</li>
	<li>Instruct the patient to fixate the flash light, which is turned off at this point. For tests requiring precise accommodation, paste a fixation target on the back of the phone, directly below or above the flashlight.</li>
	<li>Use an occluder to cover one of the eyes.</li>
	<li>Press the round button. The app will start to monitor the status of the two eyes (whether one eye is covered).</li>
	<li>While making sure the patient is fixating properly, remove the occluder quickly (i.e., cover-uncover test), or first move the occluder between the two eyes to perform alternate covering a few times and then take the occluder away quickly. The app will automatically take a picture as soon as the occlude is taken away from eyes.</li>
	<li>When the analysis is completed, the app will show detected eye features: iris indicated by a large green circle, the center of the eye indicated by a green cross, and corneal reflection from flash indicated by a small red circle. Verify these features are detected without obvious errors.</li>
	<li>Under the picture there are measurement outcomes for eye alignment in prism diopters. If satisfied with the results, press the save button to save the test in the phone. Otherwise, press the back-arrow button to retest.</li>
</ol>
5. Measure intermittent strabismus or phoria with cover test&#8722;far fixation
NOTE: To measure intermittent ocular misalignment for far fixation, the angle kappa for each eye needs to be measured at least once. The app will automatically choose the latest angle kappa measure. If it is not available for either eye, the app will give a reminder to first obtain this measurement (see section 6 for details of angle kappa measurement).
<ol>
	<li>Launch the app and set the mode to cover test (button at upper right corner).</li>
	<li>Select far fixation (button at lower right corner).</li>
	<li>Hold the phone in landscape orientation about 40 cm from the patient at eye level. 
	NOTE: The distance does not have to be accurately controlled. The app can automatically compensate for different distances. It is best if the flash light/camera is between the eyes. Since the camera and flash are off to one corner in most phone models, this means the phone display itself will be slightly off-center.</li>
	<li>Instruct the patient to look just above the phone and to fixate the target in distance (typically 6 m away).</li>
	<li>Use an occluder to cover an eye.</li>
	<li>Press the round button. The app will start to detect the uncovering of the eye.</li>
	<li>While making sure the patient is fixating properly, remove the occluder quickly (i.e., cover-uncover test), or first move the occluder between the two eyes to perform alternate covering a few times and then take the occluder away quickly. The app will automatically take a picture as soon as the occluder is taken away from eyes.</li>
	<li>When the analysis is completed, the app will show detected eye features: limbus boundary indicated by a large circle (green), the center of the eye indicated by a cross (green), and the location of the corneal reflection indicated by a small circle (red). Verify these features are detected without obvious errors (such as incorrect limbus fitting, or incorrect location or missing corneal reflection).</li>
	<li>Under the picture there are measurement outcomes for eye alignment in prism diopters. If satisfied with the results, press the save button to save the test in the phone. Otherwise, press the back-arrow button to retest.</li>
</ol>
6. Measure angle kappa
<ol>
	<li>Launch the app.</li>
	<li>Select Measure angle kappa.</li>
	<li>Hold the phone in landscape orientation about 40 cm from the patient at eye level. 
	NOTE: The distance does not have to be accurately controlled. The app can automatically compensate for different distances.</li>
	<li>Instruct the patient to use the eye to be tested (either eye) to fixate on the flash light, which is off at this point. Have the other covered by hand or an occluder.</li>
	<li>While making sure the patient is fixating properly, tap the round button to take a snapshot, which will be analyzed by the app.</li>
	<li>When the analysis is completed, the app will show the detected eye features: limbus boundary indicated by a large circle (green), the center of the eye indicated by a cross (green), and the location of the corneal reflection indicated by a small circle (red). Verify these features are detected without obvious errors (such as incorrect limbus fitting, or incorrect location or missing corneal reflection). Under the picture there are measurement outcomes for angle kappa (in degrees).</li>
</ol>

<ol>
	<li>Kemper, A. R., Clark, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preschool+vision+screening+in+pediatric+practices.">Preschool vision screening in pediatric practices.</a> Clinical Pediatrics. 45 (3), 263-266 (2006).</li><li>Rowe, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+profile+of+strabismus+in+stroke+survivors.">The profile of strabismus in stroke survivors.</a> Eye. 24 (4), 682-685 (2010).</li><li>Black, K., McCarus, C., Collins, M. L. Z., Jensen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ocular+Manifestations+of+Autism+in+Ophthalmology.">Ocular Manifestations of Autism in Ophthalmology.</a> Strabismus. 21 (2), 98-102 (2013).</li><li>Taylor, K., Elliott, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interventions+for+strabismic+amblyopia.">Interventions for strabismic amblyopia.</a> Cochrane Database of Systematic Reviews. 10 (8), (2011).</li><li>Cotter, S. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fixation+preference+and+visual+acuity+testing+in+a+population-based+cohort+of+preschool+children+with+amblyopia+risk+factors.">Fixation preference and visual acuity testing in a population-based cohort of preschool children with amblyopia risk factors.</a> Ophthalmology. 116 (1), 145-153 (2009).</li><li>Robaei, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+Associated+with+Childhood+Strabismus:+Findings+from+a+Population-Based+Study.">Factors Associated with Childhood Strabismus: Findings from a Population-Based Study.</a> Ophthalmology. 113 (7), 1146-1153 (2006).</li><li>Tarczy-Hornoch, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+factors+for+decreased+visual+acuity+in+preschool+children:+the+multi-ethnic+pediatric+eye+disease+and+Baltimore+pediatric+eye+disease+studies.">Risk factors for decreased visual acuity in preschool children: the multi-ethnic pediatric eye disease and Baltimore pediatric eye disease studies.</a> Ophthalmology. 118 (11), 2262-2273 (2011).</li><li>Chan, K. W., Deng, L., Weissberg, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+Strabismus+by+Non-Health+Care+Professionals+in+an+Ethnically+Diverse+Set+of+Images.">Detection of Strabismus by Non-Health Care Professionals in an Ethnically Diverse Set of Images.</a> JAMA Ophthalmology. 134 (1), 30-36 (2016).</li><li>Hunter, D. G., Guyton, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vertical+location+of+the+corneal+light+reflex+in+strabismus+photography.">Vertical location of the corneal light reflex in strabismus photography.</a> Archives of Ophthalmology. 116 (6), 767-771 (1998).</li><li>Eskridge, J. B., Wick, B., Perrigin, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Hirschberg+test:+a+double-masked+clinical+evaluation.">The Hirschberg test: a double-masked clinical evaluation.</a> American Journal of Optometry and Physiological Optics. 65 (9), 745-750 (1988).</li><li>Hasebe, S., Ohtsuki, H., Tadokoro, Y., Okano, M., Furuse, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+reliability+of+a+video-enhanced+Hirschberg+test+under+clinical+conditions.">The reliability of a video-enhanced Hirschberg test under clinical conditions.</a> Investigative Ophthalmology &amp; Visual Science. 36 (13), 2678-2685 (1995).</li><li>Pundlik, S., Tomasi, M., Liu, R., Houston, K., Luo, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+Preliminary+Evaluation+of+a+Smartphone+App+for+Measuring+Eye+Alignment.">Development and Preliminary Evaluation of a Smartphone App for Measuring Eye Alignment.</a> Translational Vision Science &amp; Technology. 8 (1), 19 (2019).</li><li>Cheng, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+EyeTurn+App+for+School+Vision+Screening.">The EyeTurn App for School Vision Screening.</a> American Academy of Optometry Annual Meeting. , (2018).</li><li>Committee on Practice and Ambulatory Medicine and Section on Ophthalmology. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+Photoscreening+for+Children's+Vision+Screening.">Use of Photoscreening for Children's Vision Screening.</a> Pediatrics. 109 (3), 524-525 (2002).</li><li>Simons, B. D., Siatkowski, R. M., Schiffman, J. C., Berry, B. E., Flynn, J. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pediatric+photoscreening+for+strabismus+and+refractive+errors+in+a+high-risk+population.">Pediatric photoscreening for strabismus and refractive errors in a high-risk population.</a> Ophthalmology. 106 (6), 1073-1080 (1999).</li><li>Kerr, N. C., Somes, G., Enzenauer, R. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+developmentally-at-risk+status+on+the+reliability+of+the+iScreen(R)+photorefractive+device+in+young+children.">The effect of developmentally-at-risk status on the reliability of the iScreen(R) photorefractive device in young children.</a> The American Journal of Orthopedics. 61, 117-123 (2011).</li><li>Arnold, R. W., O'Neil, J. W., Cooper, K. L., Silbert, D. I., Donahue, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+a+smartphone+photoscreening+app+to+detect+refractive+amblyopia+risk+factors+in+children+aged+1-6+years.">Evaluation of a smartphone photoscreening app to detect refractive amblyopia risk factors in children aged 1-6 years.</a> Clinical Ophthalmology. 12, 1533-1537 (2018).</li></ol>

All authors have a pending patent application on a method of measuring strabismus using a smartphone camera. The technology is being commercialized by EyeNexo LLC, which was founded by authors GL, PS, MT and KH, under a license from Mass Eye and Ear.

A person without professional training can use the EyeTurn app to capture pictures of the eyes and obtain ocular alignment measurements, which might be interpreted by an eye care specialist onsite or remotely. The app only provides magnitude of the misalignment, rather than any interpretation or diagnosis. Eye care professionals such as optometrists or ophthalmologists should determine if the misalignment is significant or not, and make a diagnosis after considering other factors including the conditions under which the measurement was taken.
Taking good quality pictures is essential for the measurement. The camera should be placed at a position between two eyes. Being too far away from the midline can cause a difference in the image size between two eyes, and consequently result in measurement inaccuracy.
The limbus boundary is one of the key features that the app uses for locating eye position. Verifying the limbus boundary fitting (the green circle in results) is a crucial step. If the fitting appears to be inaccurate, the measurement will be subject to errors and the eye care professional will not be able to correctly interpret the test. Usually for patients with larger eye fissures, i.e., iris area being more revealed, the fitting will be robust and accurate. On the other hand, for patients with smaller eye fissures, which have only a small portion of the left and right boundaries revealed, the fitting may be prone to inaccuracies. In this situation, operators can ask the patients to open their eyes widely, or gently lift the eyelid wide open. The current version does not provide measurement of vertical misalignment, which will be implemented in future versions.
In addition to the promise for use in strabismus clinics, another potential application of the app is in vision screening. For prevention of amblyopia, the American Academy of Pediatrics strongly endorsed the development of cost-effective image-based screening as a means to extend screening to all children14. Red reflex method, which compares the brightness of the &#34;red eye&#34; flash artifact with the strabismus eye being a lighter or brighter red color, can detect both refractive error and strabismus, but cannot quantify the magnitude of the strabismus. Devices implementing the red flex method include Photoscreener and Vision Screener15,16. These photoscreeners have not been widely adopted by school districts, likely due to cost. Compared to standalone systems, modern smartphone cameras provide better value, improved accessibility, and rapidly improved and higher resolution cameras. Recently, there is an app that implements the red reflex method, GCK app17. The GCK app has some limitations in that it does not give a quantitative measurement of strabismus and requires more control of ambient lighting than the Hirschberg methods. The app presented in this article can be potentially an alternative or complementary solution for vision screening, because of its ease of use and equivalent accuracy with standard clinical measurement using prisms.

Measurement of eye alignment is frequently performed in vision care clinics. Cover test with prism neutralization is the commonly used clinical method for quantifying the degree of eye misalignment (strabismus). This method requires a high degree of training and experience. Accurate measurement becomes more challenging when patients cannot fully engage in the exam such as young children1, individuals with brain injuries or stroke2, or developmental disabilities3. Furthermore, there is a need for ocular alignment testing in school screening, because strabismus develops during childhood in an estimated 5&#8722;8% of the US population4, and is a substantial risk factor for amblyopia with about 30&#8722;40% of cases of amblyopia attributed to strabismus5,6,7. However, school nurses are normally not trained to conduct the standard cover test with prism neutralization for such screening. For non-eye care professionals, an additional challenge in strabismus screening is that intermittent strabismus (misalignment is not always manifested) and smaller magnitudes of misalignment are not visually obvious (&#60;15 prism diopters [&#916;])8.
In an attempt to address the challenges in the detection and measurement of strabismus, we have developed a smartphone app (EyeTurn) that implements and automates the photographic Hirschberg method9 by comparing the displacement of corneal reflections between the eyes. While conventional photographic Hirschberg method has been shown to have good reproducibility in clinics10,11, the cost for dedicated, standalone devices is a barrier for wide adoption. By providing an easy-to-use tool to measure eye alignment with standard smartphones, we hypothesize it will be widely adopted in school vision screening and used by non-eye care professionals. Our previous evaluation studies have shown that the app measurement is consistent with the current clinical standard of prism and alternate cover test12, for strabismus magnitudes of esotropia and exotropia up to 60&#916;. In a pilot school screening study, we also showed that the app can help the school nurse detect children with intermittent exotropia who were missed by standard school vision screening protocols13.
The iOS version of the app is currently available to researchers and clinicians upon request for research purposes. The requesters have thus far included school nurses, pediatric ophthalmologists, optometrists, neuro-ophthalmologists, and strabismus specialists. The purpose of this article is to share the detailed app protocols for using the app to evaluate ocular alignment under different viewing conditions, namely, near and far fixation distance; with and without eye covering to break binocular fusion.

<table><tbody><tr><td>EyeTurn</td><td>EyeNexo</td><td></td><td>Smartphone app for measureing eye misalignment</td></tr></tbody></table>

using an automated hirschberg test app to evaluate ocular alignment

A smartphone app has been developed to perform the automated photographic Hirschberg test for objective measurement of ocular misalignment. By computing the difference in corneal reflection generated by the phone camera flash relative to the iris center based on high resolution images, the app can measure misalignment with a much higher precision than the naked eye performing the Hirschberg test. It has been validated in a previous clinical evaluation study by comparing to the clinical gold standard-prism and alternate cover test. The goal of this article is to describe the testing techniques regarding how to use the app to measure ocular alignment for different fixation distances, without or with cover to break fusion, as well as angle kappa, so that users can use the app to perform equivalent tests typically done in clinic using prisms.

In this work, we describe the protocols to evaluate ocular alignment using a smartphone app that performs the photographic Hirschberg test. The interface of the app is shown in Figure 1. The users can choose to perform cover test or measure a patient with both eyes fixating at a target simultaneously, either at near or far fixation distances. Once the viewing conditions are determined depending on the test purposes, the users can follow the protocols and take a photo of the patient. After image processing, the app will show the analysis results to the users. As an example shown in Figure 2, the limbus boundaries (green circles) of the two eyes as well as the corneal reflection of the flash light (red dots) were detected correctly. This suggests that the ocular alignment measure (18.5&#916;) shown below the image is not subject to image analysis error. In this particular case, the patient had left exotropia, which is obvious from the image as the corneal reflection offset was much larger in the left eye. However, the app does not report which eye is deviated, because in cases of small strabismus angle and unknown angle kappa, it would be unreliable for the app to determine the deviated eye. For comparison, an example without strabismus is shown in Figure 3. Figure 4 shows an example of erroneous limbus detection. While the detection of corneal reflection (small red circle) is correct, the green circle apparently does not match the limbus boundary. The test should be redone.
According to cover test on those patients, the range of strabismus angle was between 25&#916; esotropia to 50&#916; exotropia, with the smallest magnitude of strabismus angle being 6&#916;. There were 10 patients with exotropia and 4 patients with esotropia. As the linear regression analysis showed (slope = 1.02, R2 = 0.94, p &#60; 0.001), the app measurements of strabismus angles were consistent with clinical cover test measurements (Figure 5).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/60908/60908fig1.jpg" /> 
Figure 1: User interface of the strabismus testing app. Users can toggle on cover test and fixation distance. Under different conditions, the instructions given to the patient may be different, as described in the protocol. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60908/60908fig1large.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/60908/60908fig2.jpg" /> 
Figure 2: A case of left exptropia. This is the results shown to the users, who should verify the detection of limbus boundary and corneal reflection before reading the strabismus angle. If those image features are not detected correctly, the users should redo the test. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60908/60908fig2large.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/60908/60908fig3.jpg" /> 
Figure 3: An example under near fixation without cover test. The corneal reflection and eye center were aligned well in both eyes. Therefore the horizontal (HOR) ocular misalignment was almost zero, as the app reported. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60908/60908fig3large.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/60908/60908fig4.jpg" /> 
Figure 4: An example of erroneous limbus detection. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60908/60908fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/60908/60908fig5.jpg" /> 
Figure 5: Comparison of strabismus angle measurement using the app with clinical measurements done with covert testing (n = 14). Negative values indicate exotropic deviations, positive values indicate esotropic deviations. Overall, measurements with the app were consistent with the clinical measurements of strabismus. This figure has been modified from our previous publication12. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/60908/60908fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Using an Automated Hirschberg Test App to Evaluate Ocular Alignment at JoVE.com

Using an Automated Hirschberg Test App to Evaluate Ocular Alignment

We present a protocol of using a smartphone app to perform Hirschberg test for measuring manifest and intermittent ocular misalignment (strabismus) under near and far fixation conditions.

A smartphone app has been developed to perform the automated photographic Hirschberg test for objective measurement of ocular misalignment. By computing ...

using-an-automated-hirschberg-test-app-to-evaluate-ocular-alignment

Universidad San Sebastian

Research

JoVE Journal

Medicine

11.4K Views.  Harvard Medical School. We present a protocol of using a smartphone app to perform Hirschberg test for measuring manifest and intermittent ocular misalignment (strabismus) under near and far fixation conditions.

Video: Using an Automated Hirschberg Test App to Evaluate Ocular Alignment

Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to progressive loss of motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. To evaluate these potential deficits in severely physically impaired ALS patients, eye-tracking is a promising means to conduct cognitive tests. The present article focuses on how eye movements, an indirect means of communication for physically disabled patients, can be utilized to allow for detailed neuropsychological assessment. The requirements, in terms of oculomotor parameters that have to be met for sufficient eye-tracking in ALS patients are presented. The properties of stimuli, including type of neuropsychological tests and style of presentation, best suited to successfully assess cognitive functioning, are also described. Furthermore, recommendations regarding procedural requirements are provided. Overall, this methodology provides a reliable, easy to administer and fast approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS. The only confounding factor might be deficits in voluntary eye movement control in a subset of ALS patients.

Cognitive deficits are common in about one third of patients with amyotrophic lateral sclerosis, a neurological condition leading to progressive impairments in speech and movement abilities. To conduct cognitive tests in patients unable to speak or write a reliable and easy to administer eye-tracking paradigm was developed.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with pathological involvement of upper and lower motoneurons, subsequently leading to ...

Behavior

Scanning Light Scattering Profiler (SLPS) Based Methodology to Quantitatively Evaluate Forward and Backward Light Scattering from Intraocular Lenses

The scanning light scattering profiler (SLSP) methodology has been developed for the full-angle quantitative evaluation of forward and backward light scattering from intraocular lenses (IOLs) using goniophotometer principles. This protocol describes the SLSP platform and how it employs a 360&#176; rotational photodetector sensor that is scanned around an IOL sample while recording the intensity and location of scattered light as it passes through the IOL medium. The SLSP platform can be used to predict, non-clinically, the propensity for current and novel IOL designs and materials to induce light scatter. Non-clinical evaluation of light scattering properties of IOLs can significantly reduce the number of patient complaints related to unwanted glare, glistening, optical defects, poor image quality, and other phenomena associated with the unintended light scattering. Future studies should be conducted to correlate SLSP data with clinical results to help identify which measured light scatter is most problematic for patients that have undergone cataract surgery subsequent to IOL implantation.

Scanning Light Scattering Profiler SLPS Based Methodology to Quantitatively Evaluate Forward and Backward Light Scattering from Intraocular Lenses

This protocol describes the scanning light scattering profiler (SLSP) that enables the full-angle quantitative evaluation of forward and backward scattering of light from intraocular lenses (IOLs) using goniophotometer principles.

The scanning light scattering profiler (SLSP) methodology has been developed for the full-angle quantitative evaluation of forward and backward light ...

Engineering

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 ...

Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells In Vivo

Structural changes in the retina are common manifestations of ophthalmic diseases. Optical coherence tomography (OCT) enables their identification in vivo&#8212;rapidly, repetitively, and at a high resolution. This protocol describes OCT imaging in the mouse retina as a powerful tool to study optic neuropathies (OPN). The OCT system is an interferometry-based, non-invasive alternative to common post mortem histological assays. It provides a fast and accurate assessment of retinal thickness, allowing the possibility to track changes, such as retinal thinning or thickening. We present the imaging process and analysis with the example of the Opa1delTTAG mouse line. Three types of scans are proposed, with two quantification methods: standard and homemade calipers. The latter is best for use on the peripapillary retina during radial scans; being more precise, is preferable for analyzing thinner structures. All approaches described here are designed for retinal ganglion cells (RGC) but are easily adaptable to other cell populations. In conclusion, OCT is efficient in mouse model phenotyping and has the potential to be used for the reliable evaluation of therapeutic interventions.

Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells In Vivo

This manuscript describes a protocol for the in vivo imaging of the mouse retina with high-resolution spectral domain optical coherence tomography (SD-OCT). It focuses on retinal ganglion cells (RGC) in the peripapillary region, with several scanning and quantifying approaches described.

Structural changes in the retina are common manifestations of ophthalmic diseases. Optical coherence tomography (OCT) enables their identification in ...

Neuroscience

Quantification of Oculomotor Responses and Accommodation Through Instrumentation and Analysis Toolboxes

Through the purposeful stimulation and recording of eye movements, the fundamental characteristics of the underlying neural mechanisms of eye movements can be observed. VisualEyes2020 (VE2020) was developed based on the lack of customizable software-based visual stimulation available for researchers that does not rely on motors or actuators within a traditional haploscope. This new instrument and methodology have been developed for a novel haploscope configuration utilizing both eye tracking and autorefractor systems. Analysis software that enables the synchronized analysis of eye movement and accommodative responses provides vision researchers and clinicians with a reproducible environment and shareable tool. The Vision and Neural Engineering Laboratory&#39;s (VNEL) Eye Movement Analysis Program (VEMAP) was established to process recordings produced by VE2020&#39;s eye trackers, while the Accommodative Movement Analysis Program (AMAP) was created to process the recording outputs from the corresponding autorefractor system. The VNEL studies three primary stimuli: accommodation (blur-driven changes in the convexity of the intraocular lens), vergence (inward, convergent rotation and outward, divergent rotation of the eyes), and saccades (conjugate eye movements). The VEMAP and AMAP utilize similar data flow processes, manual operator interactions, and interventions where necessary; however, these analysis platforms advance the establishment of an objective software suite that minimizes operator reliance. The utility of a graphical interface and its corresponding algorithms allow for a broad range of visual experiments to be conducted with minimal required prior coding experience from its operator(s).

VisualEyes2020 (VE2020) is a custom scripting language that presents, records, and synchronizes visual eye movement stimuli. VE2020 provides stimuli for conjugate eye movements (saccades and smooth pursuit), disconjugate eye movements (vergence), accommodation, and combinations of each. Two analysis programs unify the data processing from the eye tracking and accommodation recording systems.

Through the purposeful stimulation and recording of eye movements, the fundamental characteristics of the underlying neural mechanisms of eye movements ...

Bioengineering

Assessing Early Stage Open-Angle Glaucoma in Patients by Isolated-Check Visual Evoked Potential

Recently, the isolated-check visual evoked potential (icVEP) technique was designed and has been reported to detect glaucomatous damage earlier and faster. It creates low spatial frequency/high temporal frequency bright stimuli and records cortical activity initiated primarily by afferents in the magnocellular ON pathway. This pathway contains neurons with larger volumes and axonal diameters, and it is preferentially damaged in early glaucoma, which can result in visual field loss. The study presented here uses standard operative procedures (SOP) of icVEP to obtain reliable results. It can detect visual function loss using a signal-to-noise ratio (SNR) corresponding to the defects of retinal nerve fiber layer (RNFL) in early stage open-angle glaucoma (OAG). A setting of 10 Hz and condition of 15% positive-contrast (bright) are selected to differentiate OAG patients and control subjects, with each check containing eight runs. Each run persists for 2 s (for 20 total cycles). A flowchart is constructed, which consists of pupil size and intraocular pressure over a 30 min rest period before each examination. Additionally, the testing order of eyes is performed to obtain reliable electroencephalographic signals. VEPs are recorded and analyzed automatically by software, and SNRs are derived based on a multivariate statistic. An SNR of &#8804; 1 is considered abnormal. A receiver-operating-characteristic (ROC) curve is applied to analyze the accuracy of group classification. Then, the SOP is applied in a cross-sectional study, showing that icVEP can detect glaucomatous visual function abnormality in the central visual field in the form of SNR. This value also correlates with the thickness thinning of RNFL and produces high classification accuracy for early stage OAG. Thus, it serves as a useful and objective diagnostic technology for the early detection of glaucoma.

The isolated-check visual evoked potential (icVEP) method is implemented here to assess the magnocellular ON pathway that is initially damaged in glaucoma. The study shows standard operative procedures using icVEP to obtain reliable results. It is proved to serve as a useful objective diagnosing technology for the early detection of glaucoma.

Recently, the isolated-check visual evoked potential (icVEP) technique was designed and has been reported to detect glaucomatous damage earlier and ...

Testing of all Six Semicircular Canals with Video Head Impulse Test Systems

Throughout the last decade, there has been a rapid development of existing test procedures and methods evaluating the human vestibular system. In 2009 and 2013, commercially available video Head Impulse Testing (vHIT) has enabled clinicians to examine the function of all three paired semicircular canals within the vestibular system. The vHIT test has revolutionized vestibular testing and, at many clinics and hospitals around the world, this test is now considered the most important initial test of vertiginous patients. There are several manufacturers of vHIT systems around the world. A test protocol for two of the most widespread vHIT systems, EyeSeeCam and ICS Impulse, will be presented. Included in this protocol is a description of the two different test methods termed 2D vHIT testing and 3D vHIT testing. The vHIT system includes a lightweight goggle with accompanying software. The test is fast (5-10 min) and can be done with minimal discomfort to the person being examined. However, there are many steps of the test, and each of these steps may alter the final test results, if the individual steps of the test are not performed correctly. It is therefore of paramount importance that the examiner is familiar with the potential noise and/or artifact triggers. Systematic training of future examiners before performing vHIT in a clinical setting and compliance with this protocol may minimize these challenges of the test. The vHIT test is not just a &#8220;plug and play&#8221; test. However, if carried out correctly, this test offers excellent objective assessment of the function of the high frequency domain of the vestibular system. It has a very high positive predictive value and offers a specificity very close to one hundred percent.

This protocol describes how to correctly perform the video head impulse test with two separate test systems commonly used worldwide. Both the 2D and 3D video head impulse test methods are described.

Throughout the last decade, there has been a rapid development of existing test procedures and methods evaluating the human vestibular system. In 2009 and ...

Biomechanical Characterization of Porcine Ocular Lens with Automated Compression

Automated Compression Testing of the Ocular Lens

The biomechanical properties of the ocular lens are essential to its function as a variable power optical element. These properties change dramatically with age in the human lens, resulting in a loss of near vision called presbyopia. However, the mechanisms of these changes remain unknown. Lens compression offers a relatively simple method for assessing the lens' biomechanical stiffness in a qualitative sense and, when coupled with appropriate analytical techniques, can help quantify biomechanical properties. A variety of lens compression tests have been performed to date, including both manual and automated, but these methods inconsistently apply key aspects of biomechanical testing such as preconditioning, loading rates, and time between measurements. This paper describes a fully automated lens compression test wherein a motorized stage is synchronized with a camera to capture the force, displacement, and shape of the lens throughout a preprogrammed loading protocol. A characteristic elastic modulus may then be calculated from these data. While demonstrated here using porcine lenses, the approach is appropriate for the compression of lenses of any species.

Author Spotlight: Advancing Understanding of Age-Related Lens Stiffness Changes 

We present an automated method for characterizing the effective elastic modulus of an ocular lens using a compression test.

The biomechanical properties of the ocular lens are essential to its function as a variable power optical element. These properties change dramatically ...

Binocular Dynamic Visual Acuity in Eyeglass-Corrected Myopic Patients

Current clinical visual assessment mainly focuses on static vision. However, static vision may not sufficiently reflect real-life visual function as moving optotypes are frequently observed daily. Dynamic visual acuity (DVA) might reflect real-life situations better, especially when objects are moving at high speeds. Myopia impacts static uncorrected distance visual acuity, conveniently corrected with eyeglasses. However, due to peripheral defocus and prism effects, eyeglass correction might affect DVA. The present research demonstrates a standard method to examine eyeglass-corrected DVA in myopia patients, and aimed to explore the influence of eyeglass correction on DVA. 
Initially, standard subjective refraction was performed to provide the eyeglass prescription to correct the refractive error. Then, binocular distance vision-corrected DVA was examined using the object-moving DVA protocol. Software was designed to display the moving optotypes according to the preset velocity and size on a screen. The optotype was the standard logarithmic visual chart letter E and moves from the middle of the left to the right side horizontally during the test. Moving optotypes with randomized opening direction for each size are displayed. The subjects were required to identify the opening direction of the optotype, and the DVA is defined as the minimum optotype that subjects could recognize, calculated according to the algorithm of logarithmic visual acuity.
Then, the method was applied in 181 young myopic subjects with eyeglass-corrected-to-normal static visual acuity. Dominant eye, cycloplegic subjective refraction (sphere and cylinder), accommodation function (negative and positive relative accommodation, binocular cross-cylinder), and binocular DVA at 40 and 80 degrees per second (dps) were examined. The results showed that with increasing age, DVA first increased and then decreased. When myopia was fully corrected with eyeglasses, a worse binocular DVA was associated with more significant myopic refractive error. There was no correlation between the dominant eye, accommodation function, and binocular DVA.

The present research demonstrates a method to accurately examine dynamic visual acuity (DVA) in myopic subjects with eyeglass correction. Further analysis indicated that the closer the refraction state to emmetropia, the better the eyeglass-corrected binocular DVA is at both 40 and 80 degrees per second.

Current clinical visual assessment mainly focuses on static vision. However, static vision may not sufficiently reflect real-life visual function as ...

Using an Automated Hirschberg Test App to Evaluate Ocular Alignment

Summary

Explore More Videos

Chapters in this video

Eye-Tracking Control to Assess Cognitive Functions in Patients with Amyotrophic Lateral Sclerosis

Scanning Light Scattering Profiler (SLPS) Based Methodology to Quantitatively Evaluate Forward and Backward Light Scattering from Intraocular Lenses

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

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

Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells In Vivo

Quantification of Oculomotor Responses and Accommodation Through Instrumentation and Analysis Toolboxes

Assessing Early Stage Open-Angle Glaucoma in Patients by Isolated-Check Visual Evoked Potential

Testing of all Six Semicircular Canals with Video Head Impulse Test Systems

Automated Compression Testing of the Ocular Lens

Binocular Dynamic Visual Acuity in Eyeglass-Corrected Myopic Patients