I Screening of Children Study: Evaluation of Tests of Suppression

Screening of Children Study: Evaluation of Tests of Suppression

THESIS

Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University

Lauren Janelle Pallet

Graduate Program in Vision Science

The Ohio State University

2017

Master's Examination Committee:

Marjean Taylor Kulp, O.D., M.S., Adviser

Andrew Toole, O.D., Ph.D.

Catherine McDaniel, O.D., M.S.

Lauren Janelle Pallet

2017

Abstract

Background: Suppression is a phenomenon whereby an individual develops the ability to ignore a part of their binocular visual field. This condition is associated with binocular vision conditions such as amblyopia and anisometropia. Current commercial methods of testing suppression measure only foveal or central suppression at one test distance.

Purpose: The purpose of our study was to assess a new suppression target on an iPad that provides consistent luminance and assesses foveal and central suppression at one testing distance.

Methods: Subjects aged 3 and older that presented for a routine eye examination at The

Ohio State College of Optometry were invited to participate in our study. Routine testing including visual acuity, dry and wet refraction/retinoscopy, stereopsis and cover test were performed by the doctor and recorded by the examiner. Each of the suppression tests were then performed by the examiner in a random order, and repeated with the colored filters reversed. The results for each test were recorded. Cross-tabulation and McNemar chi-square analysis was used to compare the suppression testing devices.

Results: Fifty subjects were enrolled (mean age = 17.5). Twelve subjects reported suppression and one reported diplopia. Testability was excellent for all tests. There was no significant difference between tests in reported suppression, with all p values equal to

.22 or greater. No difference in reported suppression was observed with change

ii in orientation of the anaglyphic filters. Six subjects reported foveal suppression alone at near which was not identified with Worth 4 dot.

Conclusion: The iPad test of suppression provided high testability and excellent agreement with commonly used tests of suppression.

iii

Dedication

This document is dedicated to my family.

Acknowledgments

I would like to thank Dr. Kulp for her encouragement and support over the last three years. The time and effort she spent teaching me about research, binocular vision and editing the many papers I sent her way has allowed me to complete this project. Her role as my advisor has taught me an incredible amount about research and her guidance has been highly valued.

Thank you to Lynn Mitchell for her invaluable help with the statistical analysis.

Thank you to my other committee members, Dr. Toole and Dr. McDaniel, for all of their helpful insights during the development of the project and during the defense discussion.

Thank you to G-labs and Dr. Simonson for collaborating with us on this project and all the time they spent modifying the suppression target.

Vita

2009...... Southwest Senior High

2013...... B.S. Biology, University of Florida

2017...... Doctor of Optometry, Ohio State

Fields of Study

Major Field: Vision Science

TABLE OF CONTENTS

Abstract ...... ii

Vita ...... vi

List of Tables ...... ix

List of Figures ...... x

LITERATURE REVIEW ...... 1

Definition and Characteristics ...... 1

Binocular Rivalry versus Suppression ...... 2

Area of Retinal Suppression ...... 4

Binocular Vision Conditions Associated with Suppression ...... 8

Importance of Treating Suppression ...... 10

Treatment Options for Suppression...... 12

Current Methods of Suppression Testing ...... 13

METHODS ...... 22

Subjects ...... 22

Procedures ...... 22

iPad Suppression Test Design and procedure ...... 24 vii

Statistical Analysis ...... 27

RESULTS ...... 28

Subjects with Suppression ...... 28

Agreement between Suppression Tests ...... 32

Comparing Stereopsis Findings with Suppression ...... 35

Subjects with Amblyopia or Strabismus who did not report Suppression ...... 36

DISCUSSION ...... 37

Strengths and Limitations...... 39

Considerations for Future Testing ...... 39

CITATIONS ...... 40

viii

List of Tables

Table 1: Subjects with Suppression and Diplopia…...... ……………………..…….……………..30

Table 2: iPad Compared to Combined Worth Tests ...... 33

Table 3: iPad Comapred to Worth Four Dot ...... 34

Table 4: Worth Four Compared to iPad Central Suppression ...... 35

Table 5: Subjects with Amblyopia, Anisometropia and Strabismus who did not report

Suppression…………………………………………………………………………………………..……………..36

List of Figures

Figure 1: Normal Response on Four Prism Base Out Test……………………..…….…………….15

Figure 2: Worth Four Dot 1 ...... 17

Figure 3: Polarized four dot 1 ...... 18

Figure 4: Worth Test with Letters…………………………………………………………………………..20

Figure 5: iPad Suppression Target……………………………………………….…………………………25

Figure 6: Filter Comparison……………………………………………….……………………………...…. 26

LITERATURE REVIEW

Definition and Characteristics

Adler defined suppression as an inability to perceive images in all or a part of the visual field.1 Jampolsky defined suppression as an ability to inhibit the part of the binocular field that is confusing to our visual orientation.2 He described it “as an active internal inhibition and, like other sensory inhibitions, a type of conditioned reflex” that is only present in conditions of binocular vision.2 The need for the mechanism of suppression can arise from problems with binocularity such as strabismus (an eye turn) and interocular differences between the eyes, such as differences in visual acuity and/or refractive error. When the eye turns in or out the macula is now fixating on a different object from that of the other eye which causes two different images to be cast onto corresponding points on the retina. Thus, confusion in our visual field occurs due to the perception of two separate images as superimposed because each macula is viewing a different object.3 Diplopia is when we have double vision, seeing the same image in two locations. This confusion and potential diplopia is difficult for the brain to interpret and eventually the deviated eye’s image is ignored.1 Jampolsky investigated characteristics of suppression in amblyopic subjects in a 1950 paper. Amblyopia is a reduction of vision 1 that is not correctable with refractive means and is not secondary to pathological or structural defects.3 He evaluated the area of the retina being suppressed to determine if the suppressed area was consistently in one area or if it varied with the subject’s position of gaze. He found that amblyopic suppression was always specific to a retinal region and he theorized that this was because it is used to relieve discomfort in a certain area or position of gaze. Jampolsky also identified factors that can affect result of fusion status testing and are, therefore, important to keep constant when testing subjects for suppression scotomas:

A) Viewing conditions: Assessment should be performed with the subject fixating with the better eye and with minimal or no dissociation. B) Peripheral fusion C) Training: Repeat testing should be avoided if possible because the subject may become aware of the correct responses

Binocular Rivalry versus Suppression

It was suspected that suppression, in amblyopes, was related to binocular rivalry due to the similarity in functional vision loss. Binocular rivalry is a response to non-fusible contours, images projected onto each retina that are too different to be seen as one by the observer. When two images cannot be fused because of dissimilar contours, the eyes will alternate seeing the image, in other words one image is temporarily suppressed. Images can be non-fusible for several reasons, including shape, color and brightness. Binocular rivalry allows us to avoid both confusion and diplopia. The mechanism of suppression was first thought to be an exaggerated response to the normal binocular rivalry

2 phenomenon. More recent studies, however, have demonstrated differences between these two mechanisms. Smith et al showed that those with normal vision selectively inhibit low wavelength light more than other color stimuli during binocular rivalry and that rivalry is a selective inhibitory process.4 Smith et al then compared binocular rivalry and suppression in different chromatic and luminance conditions in normal and esotropic subjects.5 Specifically, they compared binocular rivalry, strabismic suppression and strabismic rivalry suppression in subjects with normal binocular vision (N=10) versus esotropia (N=5). Normal binocular vision subjects had vision equal to or better than

20/20, stereopsis equal to or better than 40 seconds. Esotropic subjects had unilateral esotropia with mild amblyopia, eccentric fixation, and harmonious anomalous correspondence. All subjects had normal color vision. Targets were presented under monocular conditions with the gratings at 45 degrees to determine the threshold values.

Square-wave gratings were presented to each eye in a mirror stereoscope to evaluate normal rivalry, strabismic suppression and strabismic rivalry suppression. In order to evaluate normal rivalry and strabismic rivalry suppression, orthogonal patterns were presented. A vertical square-wave grating was presented to one eye and a horizontal to the other eye to induce rivalry. In order to evaluate strabismic suppression, a vertical square-wave grating was presented to each eye of the strabismic amblyopes because similar contours are most likely to induce suppression in subjects. In each presentation, the method of ascending limits was used to determine the lowest stimulus intensity grating stimuli that the subject could detect. An increase in threshold would suggest less sensitivity and a decrease in threshold would suggest more sensitivity. In order to

3 determine the effects of chromatic and luminance mechanisms on rivalry and suppression wavelengths were varied between 480 nanometers and 620 nanometers. Duration, size and brightness of the targets were all varied because the function was dependent on the spatio-temporal frequencies of the targets presented. Smith et al compared the results between each of the testing conditions between the normal and strabismic subjects as well as the results between the strabismic subjects’ rivalry and suppression to determine whether rivalry and suppression were different mechanisms. The authors confirmed that normal observers showed a difference in the rivalry suppression between various wavelength stimuli, with the sensitivity being much lower for the lower wavelengths. In contrast, they observed lower sensitivity (increased threshold) in both the chromatic and luminance mechanisms in the esotropic subjects during the strabismic suppression and strabismic rivalry suppression test conditions. The decreased sensitivity was independent of the wavelength and therefore varied from the normal subjects results. They concluded that there is a difference in the mechanism between binocular rivalry of normal controls and the general decrease in sensitivity of binocular suppression in esotropes. It does not however determine the role binocular rivalry has in the development of suppression.

Area of Retinal Suppression

Areas of retinal suppression have been defined , as foveal (within 1 degree), central (between 1 and 5 degrees), and peripheral (5 degrees or greater)(referenced from the macula).1 Jampolsky studied the area of retinal suppression and mapped the scotoma in amblyopic subjects. The area of the retina where the projected image was cast onto the 4 retina was noted as the “zero measure point”. The suppression scotomas were mapped using a handheld colorless risley prism. Jampolsky considered this testing method to be most comparable to daily viewing conditions Jampolsky found an “egg shaped” suppression scotoma with esotropes demonstrating nasal suppression and exotropes demonstrating temporal suppression, with the scotoma in both being bound by the

“vertical meridian” of the macula. This became known as “hemi-retinal suppression”.2

Jampolsky also found that the scotoma was measured to be larger when beginning within the suppression zone at the zero measure point as compared to when measured from the diplopic region inward. The size, however, was not directly related to the depth of the scotoma. Large or small suppression areas could have profound suppression.2

Pratt-Johnson and Tillson6,7 conducted a study to determine if Jampolsky’s theory of hemiretinal suppression was correct or if the suppression scotoma was the same in different types of strabismus (esotropia versus exotropia). They measured the binocular field of view, the field of diplopia, and the presence of fusion versus suppression. The binocular field of view was measured as the area with both eyes open, regardless of ocular alignment and fusion status. The area was composed of a central field that is binocular and two peripheral zones that are only seen by either eye, called the monocular temporal crescents. The study included both normal and strabismic subjects from 9 to 55 years of age. Normal binocular vision was defined as visual acuity 6/6 or better, stereoacuity of at least 40 seconds with the Wirt circles and bifoveal fixation at distance and near. The binocular field of vison was mapped with an Airmark perimeter without filters or other devices between the subject and the target. This was believed to be the

5 most natural viewing condition, compared to the risley and other testing methods. The subject was instructed to fixate on a target on the Airmark perimeter while a separate 1 mm target was moved out from the center of the screen in eight different meridians, horizontal, vertical and diagonal. The borders of the binocular visual field areas were defined by the locations where the 1 mm target was no longer perceived. The monocular crescents were determined by briefly occluding the eye on the same side as the target’s direction of movement (i.e when moving the target to the right, the right eye was temporarily occluded). If the target was visible prior to occlusion but not visible when the right eye was occluded then it was assumed to be within the right eyes monocular crescent. The monocular crescent could not be determined in the strabismic eye due to the re-fixation necessary with the occlusion. Because the authors believed that suppression developed to eliminate diplopia, they also measured the field over which diplopia was perceived in normal subjects or strabismic subjects without suppression.

Diplopia was induced with a 6 prism diopter dissociating lens in front of one eye in subjects with normal binocular vision. Subjects indicated when they saw double and when they saw single. Pratt-Johnson and Tillson determined the areas that would need to be suppressed in a person with abnormal binocular function. Pratt-Johnson and Tillson also used a modified Lees screen to investigate the suppression zone. The Lees screens are two illuminated blank screens 90⁰ apart with a mirror 45⁰ between them. Second degree, 3 cm targets were presented to each eye. Eye position was monitored with after image testing. The results of the study showed the total area of vision (both binocular and monocular crescent) was smaller for esotropes and slightly larger for exotropes compared

6 to those with normal vision. Strabismic subjects with monofixation syndrome showed foveal suppression with peripheral fusion. Subjects with strabismus without fusion showed suppression involving both nasal and temporal areas of the visual field. Diplopia was reported in both nasal and temporal areas. They concluded that the trigger for suppression was hemiretinal (e.g. diplopia experienced in the nasal visual field in esotropia), however once suppression was triggered the entire visual field of the deviated eye was suppressed (with the exception of the monocular crescent) and that suppression was not limited to a hemiretinal area. This contradicted Jampolsky’s conclusion that suppression scotomas are restricted to a certain half of the retina.

Cooper and Record8 also evaluated suppression and correspondence in intermittent exotropes. They evaluated six subjects with intermittent exotropia using an

Atari screen at a test distance of 40 centimeters away. The subjects wore Keystone red – green glasses and fixated a red target on a black background while the examiner moved a green target to various locations. An infrared system was used to monitor fixation of the eyes and both an auditory and visual indicator let the subject and examiner know of any changes in fixation. The red target was seen by the fixating eye and only was visible by the eye behind the red lens. The green target was either a square or triangle seen behind the green lens and was varied in size to determine any effects of target size on suppression scotomas. The subject indicated when he/she could no longer see the green target. They found that five of the six subjects did not exhibit suppression even with the smallest target size but rather exhibited anomalous correspondence. One subject with suppression suppressed all target sizes. They concluded that patients did not suppress as

7 easily when looking at a target on a black background. Suppression and correspondence seemed to vary with the background and stimuli. These findings are specific and limited to the intermittent exotrope of the divergence excess type.8

Binocular Vision Conditions Associated with Suppression

Suppression and Amblyopia

Suppression and amblyopia have a high comorbidity in patients. There has been controversy regarding whether suppression is a result of amblyopia or if it is the cause of the amblyopia. Holopigan et al9 have commented that if suppression is the result of amblyopia then it will be inversely related to the degree of the amblyopia, so deep suppression would be associated with mild amblyopia and mild suppression would be associated with deep amblyopia.1 More recent studies, however, have suggested suppression develops first as a result of visual disruption, such as strabismus or anisometropia, and it is this chronic suppression that causes amblyopia.10,11 Li10 studied the relationship between suppression and amblyopia and conducted a study to determine if there is a direct relationship between the two. If they were directly related it would support recent research that they are separate entities and suppression is the cause of amblyopia. Whereas an indirect relationship implies less suppression is necessary with deep amblyopia because suppression only follows as needed as a result of the amblyopia.

Forty three amblyopic and 10 normal observers watched random dot kinetograms and indicated the direction of the motion. Signal and noise was presented to each eye, with 8 constant contrast to the amblyopic eye and variable contrast to the fellow. The suppression depth was measured based on the changes in contrast needed for binocular function of the patient. The lower the contrast needed to be in the fellow eye in order to provide binocular function, the greater the suppression. They revealed a larger imbalance between the eyes of amblyopic subjects as compared to eyes of normal observers. Once balanced, however the binocular function across both groups was comparable.

Furthermore, the degree of imbalance was related to the depth of suppression as determined with standard clinical tests. The authors concluded that amblyopia and suppression are two separate conditions and amblyopia is likely the result of suppression.

Suppression and Anisometropia

Anisometropia is a difference in refractive error between the two eyes that causes a distortion in size, clarity and focus between the two eyes. Brooks12 demonstrated a relationship between induced anisometropia and suppression and stereopsis. She assessed binocular function using tests of fusion status and stereopsis in patients with normal binocular vision before and after inducing anisometropia. Her study included 19 subjects ranging from 26 to 59 years of age with normal binocular vision and 20/20 corrected visual acuity. Normal binocular vision was defined as normal bagolini response, stereopsis of at least 40 seconds of arc on Titmus test, and a normal Worth response at 33 centimeters and 6 meter test distances. Hyperopic, myopic and astigmatic anisometropia was induced in each of the subjects by placing a spherical or cylindrical lens randomly

9 over the right eye of each subject with a power ranging from 1 D to 3 D, plus lenses simulating myopia, minus simulating hyperopia and cylindrical lenses simulating regular and oblique astigmatism at 90 and 45 degrees. She evaluated fusion status with each of the lenses using Worth Four dot and demonstrated a highly significant positive correlation between increasing anisometropia and suppression zone size. Induced spherical anisometropia resulted in a larger suppression zone than the induced astigmatic anisometropia. Results of the study showed none of the subjects were able to fuse the

Worth Four dot with 2 diopters of induced spherical anisometropia at 6 meters, and only

1 of the 19 could fuse the Worth Four dot at 6 m with 1 diopter of anisometropia.

Stereopsis also was reduced in most patients with small amounts of anisometropia and was decreased in all as the amount of anisometropia introduced increased. The authors demonstrated a relationship between induced anisometropia and suppression and stereopsis. One limitation of the study is that it was conducted on adults and the results cannot be extrapolated to children. Further research is needed to assess if children are more or less susceptible to changes in binocular vision status with anisometropia.12

Importance of Treating Suppression

As mentioned above, recent studies are now showing suppression may be the first development in patients with abnormal binocular vision. This indicates the importance of treating the underlying suppression.10,11 A study by Mansouri11 has shown the important role suppression plays in affecting the binocular function of amblyopes. The purpose of their study was to determine how different the stimuli to each eye needed to be in order to 10 allow binocular fusion in amblyopia and, therefore, the influence of suppression. The researchers recruited 11 amblyopes, all esotropic subjects, and 8 normal observers. All subjects wore any necessary refractive error correction. Two experiments were conducted on each subject, one with global motion and one with still form images to assess potential differences between the dorsal and ventral pathway. Random kinetic dot stimuli were produced with a McIntosh G4 screen. Targets were presented binocularly using a

Wheatstone stereoscope at an effective viewing distance of about 1 meter. The first experiment with global motion was performed both monocular and binocular. The monocular condition was first with the signal and noise being introduced to one eye and mean luminance to the other, so the subject was not aware of the eye viewing the targets.

The binocular condition presented the noise to one eye and the signal to the other eye. In the binocular experimental condition the contrast of the stimuli were varied to try and normalize the visual input between the amblyopic and fellow eye. The second experiment with still-form Gabor targets was then performed. The results of the study were that when the signal between the two eyes was equalized by decreasing the contrast in the fellow eye, amblyopic patients were able to use both eyes binocularly like the normal viewers.

The results of the study were the same for both the motion and form targets. The authors concluded that the suppression mechanism was the same in the dorsal and ventral cortical processing pathway and present in the area of the V1. This suggests that suppression may lead the development of amblyopia and treating the interocular suppression could lead to the treatment of amblyopia because there is an intact binocular summation present in amblyopes which can be achieved by changing the input to the eyes.11

Treatment Options for Suppression

There are several treatment options for suppression. Vision therapy is the mainstay of eliminating suppression in patients. During the anti-suppression therapy it is important to consider the environment to ensure the patient’s best chance at fusion and success during treatment. Factors to consider include selecting appropriate room lighting. Dim lighting may help those with deep suppression. Changing the conditions of the target used during therapy can also aid in decreasing suppression and include13:

1. Changing target illumination 2. Changing target contrast 3. Moving the target 4. Flashing the target 5. Beginning therapy with large peripheral targets 6. Begin under unnatural testing conditions and move toward a natural seeing condition

One therapy instrument often used to eliminate suppression is a cheiroscope. The cheiroscope is designed with a binocular viewing condition, where one eye is seeing an image projected off of a mirror and the other eye is looking directly at a blank sheet of paper. The patient is then supposed to draw or trace the design on the blank sheet of paper. The dominant eye fixates on the picture presented and fellow eye views the image being traced on the blank sheet. This method involves corresponding images and ensures both eyes are involved. By involving the hand and incorporating movement suppression can slowly be decreased over time.3 The criticism around any dissociating instruments is

12 the lack of natural viewing conditions, therefore the fusion status the patient experiences during such therapy may vary from everyday characteristics of suppression.14

Hess et al created a therapy device that can be used to both quantify suppression and treat the suppression in amblyopia. The patient watches a screen with a random array of moving dots. The subject clicks an arrow indicating the direction he/she sees the dots moving. The average of the findings on that task is used to determine the average number of moving dots that were necessary, out of 100, to determine the overall direction of movement. After determining the average number of moving dots, the dots are presented at high contrast to the amblyopic eye and varying contrast to the non-amblyopic eye to determine the level of contrast imbalance necessary for binocular function. Once the contrast imbalance necessary for binocular fusion is determined, the subject views the random dot movements binocularly at the indicated contrast level to engage both eyes in the task. As the amblyopic eye improves in function the contrast imbalance can be adjusted to keep both eyes engaged at the minimum imbalance necessary. The program can be connected and performed on portable devices such as an iPad. These techniques can be applied to other more engaging programs to ensure successful therapy in patients.15 16,17

Current Methods of Suppression Testing

There are currently several options available commercially for assessing suppression. The four base out prism test is often used to indicate whether suppression is present, although anomalous findings have been reported with this test.3 Flashlight tests

13 such as the Worth Four dot, polarized four dot test and the Worth test with letters are also commonly used because they can provide information regarding the presence of suppression, fusion or diplopia and the extent of any suppression (central or peripheral).14

Four Prism Base Out Test

During the four base out test (see figure 1), the examiner places a 4 prism diopter base out prism in front of one eye while the patient views a small light. The prism shifts the image of the fixation light being viewed in the direction of the apex. In a patient without suppression, the examiner should observe a version movement of both eyes (in the direction of the apex of the prism) followed by a fusional vergence movement of the other eye (not behind the prism). A small amount of base out prism is used because it is enough prism for most patients to detect the change but have enough fusional vergence to bring the image back to one. The procedure is then repeated by placing the prism in front of the other eye, and the examiner observes the resultant eye movements. In patients with suppression, only a version movement will be observed when the prism is placed in front of the non-suppressing eye because the patient will perceive the change in the image’s position but will not perceive diplopia due to the suppression in the other eye and therefore will not make a fusional vergence movement. No eye movements will be observed when the prism is placed in front of the suppressing eye because the patient will not perceived that the image shifted or that there is double vision.3,18

Figure 1: Normal Response on Four Prism Base Out Test

http://www.slideshare.net/Dottoretpchhangte/sensory-evaluation-of-squint

Worth Four Dot

The Worth Four dot displays four equidistant dots, two red, one green and one white (see figure 2). The patient wears red and green filter glasses and is shown the

Worth Four dot target (after the glasses have been placed on the patient). The examiner asks the patient how many dots are seen and what colors of dots are seen. A normal

15 fusion response is indicated by a report of seeing four dots. Seeing only three red dots means the patient is suppressing the eye behind the green filter. Seeing two green dots indicates suppression of the eye behind the red filter. Seeing 5 dots indicates double vision (crossed diplopia indicates exo projection, uncrossed diplopia indicates eso projection). The measured angle can be found in degrees by taking the arctan of the distance between two targets seen by each eye and the distance of the target from the patient. Therefore, the smallest area of suppression detectable with this instrument is approximately 4 degrees at 40 cm and 1.25 degrees at 6 meters.19

Variable responses have also been reported with the Worth Four dot test.

According to a study conducted by Simons20, the light transmission of the red and green filters in the anaglyphic glasses differed. The light transmission of the green filter was almost double the red filter. The increased light transmission can artificially improve the performance in the eye behind the green lens, and the reduced transmission of the red filter could artificially induce suppression. Performing Worth Four Dot twice, with the glasses reversed can prevent misinterpretation. Also ensuring the red-green glasses perfectly cancel ensures there is not “leak” of the other target. Leak would provide monocular cues to the correct responses because it would be visible through either filter, instead of only being visible in the absence of suppression.

Figure 2: Worth Four Dot 1

Polarized Four Dot

The polarized four dot subtends the same suppression angles as the original Worth

Four dot but has three polarized circles and one non polarized that is perceived with both eyes. The polarized four dot (see figure 3) method removes the dissociated component since the glasses are polarized instead of dichoptic (red-green). Some researchers believe a non-dissociated state leads to more accurate results than the dichoptic glasses. This method allows the examiner to determine if the patient has crossed or uncrossed diplopia by asking the subject the number of dots seen on the left side and right side of the target.14

Figure 3: Polarized four dot 1

A study conducted by Arthur et al21 compared the Worth Four dot and the polarized four dot. He evaluated the interpretable response rate, response time and age of test failure between the Worth Four dot and the polarized four dot test. The interpretable response was “percent of sensible responses”; this indicates how many people were able to understand and complete the test. The age of test failure was the age at which subjects could no longer understand and perform the test. The targets were each presented by two different examiners during routine examination at the clinic, one test at the start of the visit and another at the end of the visit. The tests were completed in a random order and were not performed sequentially to avoid repetition bias. Response time was recorded, with a maximum allowance of 60 seconds. The study recruited 107 patients with a mean

18 age of 7.5 years. The results showed 58% of patients reported fusion in the Worth Four dot compared to 72% for the polarized four dot. The polarized four dot had a higher interpretable response rate with 91% versus 73%, and a lower age of average failure, 3.5 versus 5.1 years. This suggested the polarized four dot could be more suitable for children due to the easy interpretation and lack of dissociation with anaglyphic glasses, however it is no longer commercially available.

Worth Test with Letters

The Worth test with letters can be used to assess foveal suppression at 40 cm by having the patient identify a single vertical row of 20/50 letters on the right side of the target. The suppression zone measure with this target was .7 degrees (5 millimeter distance between the red and green targets). The target (see figure 4) also provides a single vertical row of 20/120 letters in the center column and three pictures on the left side of the target.22 The smallest target on the right side of the flashlight is a simple task for children who know their letters and adults to perform. However, it is difficult for young children who do not know their letters. Because this target is flashlight based, contrast and luminance may vary.

Figure 4: Worth test with Letters

Current Market

The current market for suppression evaluation does not offer a stable luminance target with the ability to assess more than one retinal zone of suppression at a set distance. Current targets can assess a smaller retinal suppression scotoma when the testing distance increases. Eye alignment and suppression can change at different testing locations.

The purpose of the study is to assess a new suppression target with high luminance that tests foveal and central suppression at one testing distance as compared to other commonly used tests of suppression.

METHODS

Subjects

Patients aged 3 and older were recruited during routine examination from the

Binocular Vision and Pediatrics service at The Ohio State College of Optometry. All patients and parents were fluent English speakers. Both patients with normal binocular vision and those with binocular vision disorders were invited to participate. Verbal consent (subjects over the age of 18) or verbal parental permission with assent (subjects under 18) was obtained prior to performing any study-related procedures. All subjects received a copy of The Ohio State University College of Optometry’s Notice of Privacy

Practices.

Procedures

The Ohio State University Institutional Review Board (IRB) reviewed and approved the study protocol, advertisements, informed consent documents and Health

Insurance Portability and Accountability Act authorization form.

Testing of suppression included Worth Four dot (Bernell, Mishawaka, IN

46545), a foveal Worth test with letters (Bernell, Mishawaka, IN 46545), the polarized four dot test (Jim's Instrument manufacturing Inc., Iowa City, IA), and a target presented on an iPad Air with the OptoLab application, created with G Labs in Boulder,

Colorado.

Patients were tested during routine examination at the College of Optometry

Pediatrics and Binocular Vision Clinic. After entrance testing of the eye exam was complete, the examiner entered the room and read the verbal consent to the potential participant and parent in the case of a child. After receiving consent and/or parental permission and assent, the research testing of suppression was conducted. All testing was performed by the same examiner (LP) prior to any instillation of dilating drops.

Findings from the vision examination were also recorded including visual acuity, wet and dry retinoscopy, manifest refraction, cover test, visual acuity and stereopsis. These findings were recorded on our data form without any health protected information, along with the suppression testing data. The order of the four tests performed was randomized for each subject, as was the order of the orientation of the dichoptic glasses worn. All tests with the anaglyphic filter glasses were repeated with the glasses reversed to investigate any potential differences induced by unequal light transmission.

Suppression was evaluated at a distance of forty centimeters for each test. A non- stretch string was tied to the device and measured to be 40 centimeters to ensure proper testing distance. In order to detect intermittent suppression, subjects were asked if the target ever seemed to disappear and then reappear or blink on and off. This was done to

23 gain more information into the fusion status and determine if the patient was constantly suppressing or if it was intermittent. Each testing procedure is described below:

iPad Suppression Test Design and Procedure: The iPad suppression test was

three rings of targets and was designed to assess foveal and central fusion or

suppression (see figure 5). The center ring had four dots similar to the Worth Four

dot test and subtended an area of approximately 0.6 degrees (0.4 cm at 40 cm) to

evaluate foveal suppression. The second ring contained a rocket, moon, star and

sun at approximately 2 degrees (16 mm at 40 cm) to identify central fusion or

suppression. The last ring contained pictures of animals at 5 degrees (35 mm at 40

cm). A white ring separated the two outer rings of targets to provide a fusion lock.

The center ring was black but had a white dot as the fusion lock. Pictures and

shapes were used to provide high testability.23 The anaglyphic targets were red

and cyan, so each subject wore red cyan filter glasses with similar light

transmission between the red and cyan blue filters (American Paper Optics, LLC,

Bartlett, TN). The examiner ensured that there was proper cancellation to avoid

leak between the red and cyan blue targets. Paper filter glasses were worn to

allow the filter colors to be quickly and easily reversed by reversing the glasses.

Presentation on the iPad Air provided maximum brightness of 415 nits with

minimal variability in luminance.

Figure 5: iPad Suppression Target

The examiner asked the subject the following questions:

1) “what do you see at the center inside the first white ring?”

2) “what do you see inside the second white ring?”

3) “what do you see inside the very outside circle?”

Subjects could respond by naming the colors and objects.

Worth Four Dot: The test was administered with the patient wearing red-green

glasses. In order to facilitate reversing the red and green filters and to provide

more similar light transmission between the red and green filters (see figure 6),

paper red green filter glasses (American Paper Optics, LLC, Bartlett, TN) were 25

used rather than the black frame red-green glasses. The examiner asked the

subject how many dots he/she saw on the flashlight.

Figure 6: Filter Comparison

Polarized Four Dot: The subject wore circularly polarized glasses. The

examiner asked the subject how many dots he/she saw on the flashlight. The

procedure was not repeated with the filters reversed because both lenses were

polarized and provided equal light transmission.

Worth Test with Letters: The subject wore red green filter glasses (American

Paper Optics, LLC, Bartlett, TN). The examiner asked the subject the number of

letters seen in the smallest right hand column.

Statistical Analysis

All of the screening data were entered into a secure database on a password protected computer. The data were then evaluated and checked against the original documents to ensure accuracy of information transferred. All data analyses were performed using SPSS (version 15). Unless specifically stated otherwise, an alpha level of 0.05 was used to assess statistical significance. Chi square analysis (McNemar-

Bowker test) was used to determine the consistency between testing methods to detect suppression. A p-value of 0.05 or less was considered significant.

RESULTS

A total of 51 subjects participated in the study. Of the 51, 1 was not included in the study due to lack of corrective eyeglasses and inability to complete testing. The mean age of the subjects was 17.5 years of age, with a range from 5 to 72 years old. Of the 50 analyzed, one subject was not able to complete the polarized four dot and was not included in the data analysis for the polarized four dot test. There were no differences found in subjects’ reported fusion or suppression status based on orientation of the filters (results not shown).

Subjects with Suppression

Twelve subjects presented with suppression and one presented with double vision. Two subjects showed intermittent suppression with blinking foveal dots. Five subjects reported intermittent foveal suppression only. Suppression was generally associated with the presence of a strabismus (n=8), amblyopia (four strabismic, one refractive) and/or anisometropia (n=2). Amblyopic subjects who reported suppression had vision in the amblyopic eye ranging from 20/30 to 20/50 and the vision in the better eye of 20/20 or 20/25. Findings for these subjects can be seen in table 1. One subject

28 with a significant phoria (8 exophoria with 2pd hypophoria) also reported foveal suppression.

Table 1: Subjects with Suppression and Diplopia

Near Cover Refractive Error Suppression Age Visual Stereopsis Other Test Acuity

10 XP OD: +4.00-2.50x180 Foveal on 23 OD: 20/30 Global: 500” Refractive OS: plano iPad; central OS:20/20 Local: 200” Amblyope and Worth Letter was faded

16 XP OD:+0.75 Foveal 51 OD: 20/20 Global:250” TBI OS: -1.00-0.50x168 suppression OS: 20/25 Local: 40” on Worth Letter and iPad

15 IXT, 4 OD: -0.75-1.00x010 Foveal 12 OD: 20/25 Global:250” Strabismic Hypertropia OS: -0.50-2.50x157 suppression OS: 20/50 Local: 40” Amblyope on Worth Letter and iPad

16 IET OD: +0.50-0.25x180 Foveal 6 OD: 20/25 Global:250” s/p strabismic OS: +0.50-0.25x180 suppression OS: 20/20 Local: 40” surgery on Worth Strabismic Letter and Amblyope iPad

8 Exophoria OD: -2.75-0.75x167 Intermittent 37 OD: 20/20 Global:250” with 2 OS:-2.00-0.75x159 foveal OS: 20/20 Local: 25” Hypophoria suppression on Worth Letter and iPad

6 OD: +0.50-0.25x005 Intermittent 19 OD: 20/20 Global:250” Exophoria OS: +0.50-0.50x175 foveal OS: 20/20 Local: 30”

(12 ILXT at suppression distance) on Worth Letter and iPad

Continued

Table 1 Continued: Subjects with Suppression and Diplopia

15 No correction Double vision 9 OD: 20/20 Global:250” Presented with Intermittent on all testing OS: 20/20 Local: 70” double vision to Exotropia devices exam

20 IXT OD: +1.00 Foveal and 8 OD 20/20 Global:250” 10% OS: +0.75 central on OS 20/20 Local: 25” Worth Tests and iPad

35 CET OD: -5.00-0.75x017 Foveal and 20 OD: 20/20 None OS: -4.75-1.00x160 central on all OS: 20/20 devices

60 CAXT, 6 OD: -2.75-0.50x015 Foveal and 19 OD: 20/20 None Hypertropia OS: -2.25-0.25x170 central on all OS: 20/20 tests

20 CXT , 10 OD: -0.50-0.50x128 Foveal and 16 OD: 20/20 None s/p strabismic Hypophoria OS: Plano-0.75x150 central on all OS: 20/25 surgery devices Strabismic Amblyope

40 CXT, 3 OD: +0.50-2.50x082 Foveal and 37 OD: 20/20 None Strabismic Hyperphoria OS:Plano-0.75x110 central on OS: 20/50 Amblyope Worth tests and iPad. Unable to see polarized four dot

6 IXT OD: +0.75-1.00x142 Central 72 OD: 20/25 Global:250” Decompensated OS: +1.00-1.75x180 suppression OS: 20/40 Local: 40” phoria with polarized Worth Four only

Agreement between Suppression Tests

Responses on the tests of suppression were compared to determine the level of agreement. In the analysis of agreement between the iPad and Worth tests, the results from the Worth Four dot and Worth test with letters were combined so as to determine agreement regarding assessment of foveal and central suppression. McNemar analysis showed agreement between the tests for detection of central and foveal suppression.

Reported fusion or suppression agreed in all cases with the exception of one subject who was found to have foveal suppression on the iPad test but not on the Worth letters.

This subject presented with anisometropia and mild amblyopia of her right eye. The subjects current spectacle prescription was +4.00-2.00x180 in the right eye and plano in the left eye, with a best corrected visual acuity of 20/30 and 20/20, respectively. This subject reported that the Worth letters were fading and difficult to see at times but was able to detect all the letters. McNemar p-value value was .32, so we accepted the null hypothesis that the tests are not different. Results can be found in table 2.

Table 2: iPad Compared to Combined Worth Tests

In order to determine whether differences in light transmission between the anaglyphic filters may have altered the fusion status of subjects, analysis was performed to determine agreement between the results on the iPad and polarized four dot test for detection of fusion versus central suppression. (Foveal suppression was not included in this analysis because the polarized 4 dot is not able to detect foveal suppression.)

Crosstabulation results are below (table 3). Reported suppression or fusion agreed for all subjects with the exception of one subject with intermittent strabismus who reported suppression only on polarized four dot. McNemar analysis showed no significant difference between the methods (p= 0.22).

Table 3: iPad Compared to Worth Four Dot

Analysis was also performed to determine agreement between Worth 4 dot and polarized 4 dot, see table 4 below, for detection of fusion versus central suppression.

Reported suppression or fusion agreed for all subjects with the exception of one subject with intermittent strabismus who reported suppression only on polarized four dot and one subject with intermittent strabismus who reported suppression only on Worth 4 dot and iPad. The McNemar analysis showed no significant difference between tests (p =

0.99).

Table 4: Worth Four Compared to iPad Central Suppression

Comparing Stereopsis Findings with Suppression

Stereopsis values were markedly reduced for subjects with constant suppression, as seen in table 2 above. Four subjects with constant strabismus presented with suppression and no local or global stereopsis. Two subjects presented with foveal suppression and reduced stereopsis. One was a refractive amblyope and the other had a hyperphoria. Stereopsis varied in the five subjects who presented with intermittent strabismus at near. All subjects with intermittent suppression had measurable global stereopsis; local stereopsis ranged from 25 seconds of arc to 70 seconds of arc.

Subjects with Amblyopia or Strabismus who did not report Suppression

Five subjects with refractive amblyopia and one subject with intermittent

strabismus did not report suppression, seen below in table 5. All amblyopic subjects were

wearing correction and four of the five had a one line interocular difference. One

amblyopic subject had a three line interocular difference.

Table 5: Subjects with Amblyopia, Anisometropia and Strabismus who did not report Suppression Near Cover Refractive Error Stereopsis Diagnosis Age Visual Acuity Other Test 4 exophoria OD: +2.00-1.75x173 Global: 250” Refractive 5 20/25 OD In VT OS: +2.00-1.00x173 Local: 60” amblyope 20/20 OS

8 exophoria OD: Plano-0.50x077 No Global Refractive 11 20/25 OD Struggled to read OS: +4.75-0.75x006 30” Local amblyope 20/50 OS letters on Worth letters. Not blinking

Orthophoria OD: +2.50-1.50x010 Global: 250” Refractive 5 20/30 OD Wet Retinoscopy OS: +2.50-1.00x001 Local: 70” amblyope 20/25 OS OD: +4.25-2.25x009 OS: +3.50-1.25x178

12 Exophoria OD: -0.75-3.50x180 Global: 250” Refractive 10 20/25 OD OS: Plano-4.50x003 Local: 20” amblyope 20/30 OS

4 Exophoria OD: +3.00-2.00x180 Global: 250” Refractive 5 20/25 OD Wet Retinoscopy OS: +3.75-2.75x180 Local: 40” amblyope 20/30 OS OD: +4.75-2.00x005 OS: +5.50-3.50x180

6 IAXT OD: +3.00-0.50x180 None 15 20/25 In VT OS: +1.75-0.50x174 20/25

DISCUSSION

In the study thirteen out of fifty subjects recruited from this clinic population,

24%, presented with suppression or diplopia. This percentage of suppression is elevated from the general population due to the location of data collection. Suppression was associated with amblyopia, strabismus, anisometropia or significant phoria. All subjects were wearing any needed refractive correction. Those with constant strabismus and/or strabismic amblyopia consistently reported suppression. Suppression was not consistently found in those with refractive amblyopia or intermittent strabismus. Six of the thirteen subjects, 46%, presented with foveal suppression alone. The findings of the study show that foveal suppression can be present independent of central suppression and would potentially be missed by examiners only using Worth Four dot or polarized four dot.

The new iPad test showed 100% testability within a large age range of subjects, from 5 to 72 years old. It also had good agreement with common tests of suppression.

Although all subjects were also testable on the Worth tests, some young children had difficulty reading the Worth letters. Some had to point to or count how many they saw and describe the colors. It also was difficult for some subjects to identify the small letters when acuity was reduced. On the other hand, children appeared to be able to easily

37 identify the shapes on the iPad suppression test. Higher testability has been shown previously when children are tested with shapes.23

As reported we performed our methods with the filters reversed to determine any effects of filter light transmission on fusion status. Our study did not find the same results as Simons20 when evaluating the potential for induced suppression secondary to unequal transmission of light between colored filters. We found no differences in patient fusion status when comparing responses with the filters reversed (red filter over right eye and cyan/green filter over left versus cyan/green filter over right eye and red filter over left).

The difference in findings may be due to the limited sample size of subjects with suppression in the current study. Simons reported that 20% of the strabismic subjects revealed different responses of fusion status when the glasses were reversed. We may not have evaluated enough subjects to observe this phenomenon. Another cause for the differences between the studies is the consecutive testing of the devices which can cause response bias. Simons’ study was retrospective of the tests performed routinely and was not consecutively performed with the filters reversed. On the other hand, the difference between the studies could also be attributable to the more similar light transmission between the filter glasses used in our study as compared to the traditional red green filter glasses used in Simons study. These results suggest a benefit to use of filters with similar light transmission and the need for further research.

Strengths and Limitations

A strength of this study was the wide range of binocular vision disorders and age of subjects included. The main limitation to our study is the limited number of subjects enrolled with suppression. Another limitation to our study was that no children younger than five years of age were enrolled in our study.

Considerations for Future Testing

Future testing is needed on children under the age of five years. Another consideration for future testing would be moving the targets in third zone out to 7 degrees to assess peripheral suppression. Five degrees, which was assessed in the current study is the cutoff between central and peripheral. None of the methods used in the study assess peripheral but it may useful to determine the extent of suppression and suppression pattern for subjects.

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