Non-Visual Components of Anomalous Head Posturing (AHP) In Patients with Infantile Nystagmus Syndrome (INS)

AuthorBlock: Richard W. Hertle1, Cecily Kelleher1, David Bruckman2, Neil McNinch1, Isabel Alvim Ricker1, Rachida Bouhenni1 1Children's Hosp Medical Ctr of Akron, Hudson, Ohio, United States; 2Cleveland Clinic, Ohio, United States;

DisclosureBlock: Richard W. Hertle, None; Cecily Kelleher, None; David Bruckman, None; Neil McNinch, None; Isabel Alvim Ricker, None; Rachida Bouhenni, None;

Purpose To investigate the visual and non-visual etiologies of anomalous head posturing in patients with INS.Methods This is a prospective, cohort analysis of clinical and AHP data in 34 patients with INS. Data collected included routine demography and surgical procedure. Main outcome measures included: 1) binocular, best-corrected, LogMAR visual acuity in the null position (BVA), 2) AHP in degrees while measuring best-corrected binocular acuity, 3) AHP in degrees while being prompted to position their head in “the most comfortable position.” 4) response to question regarding their subjective sense of straight in their AHP and 5) with their head straight. Paired t-test was used to determine significance in objective vs. subjective AHP.Results Age ranged from 10-51 yrs (mean 16.5 yrs). 56% were male. 53% had BVA > 20/40. Associated systemic or ocular system deficits were present in 88%, including; developmental delay (12%), neuropsychiatric disease (29%), albinism (50%), (32%), (24%), optic nerve and/or retinal disease (44%) and refractive error (94%), 74% (25 pts) had eye movement recording confirmed eccentric null position and a > 10 degree AHP, 15% (5 pts) had a periodic or aperiodic component. Mean AHP of all patients during BVA testing was (-0.88 roll, -3.35 pitch, -4.18 yaw). Mean AHP for patients with a > +/-10 degree AHP was (-10.50 roll, -13.15 pitch, -27.30 yaw). There was a significant non-congruous response during subjective response to head posturing with most sensing their head as straight when physically not and vice-versa (p=0.00011,table).Conclusions Clinical AHP in patients with INS exists in all 3 dimensions of roll (lateral flexion), pitch (chin lift), and yaw (cervical rotation). Although the visual system may be causally related to the onset of an AHP in patients with INS due to an eccentric null zone, its persistence over time or after surgical intervention is likely due to a combination of visual (e.g. nystagmus, strabismus) and non-visual( e.g. abnormal egocentric localization and/or musculo-skeletal symmetry) factors.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Utility of a cheiroscope to test simultaneous perception and fusion

AuthorBlock: Ken Kakeue1, Miharu Mihara1, Atsushi Hayashi1 1Ophthalmology, University of Toyama, Toyama, Japan;

DisclosureBlock: Ken Kakeue, None; Miharu Mihara, None; Atsushi Hayashi, None;

Purpose The examinations of simultaneous perception and fusion using a synoptophore are often difficult in patients with strabismus, particularly young children, despite their importance before a strabismus surgery. Cheiroscopic tracing, which requires fusion and simultaneous perception, is used in young children for training of function. The aim of this study was to investigate the utility of cheiroscopic tracing to test simultaneous perception and fusion.Methods The participants had a visual acuity of over 0.0 logarithm of the minimum angle of resolution (logMAR), and no history of amblyopia or neurological or musculoskeletal diseases. The study included 33 patients with strabismus, who could perform cheiroscopic tracing. Square line drawings of two sizes (20° and 6°) were used for cheiroscopic tracing. Patients were required to trace two pictures with each eye. We determined that patients had no simultaneous perception or fusion when they could not trace the pictures. Patients were categorized under two groups: intermittent exotropia (XT; n = 19; mean age, 9.8 ± 5.6) and esotropia (ET; n = 14; mean age, 10.2 ± 6.0). In addition, all patients were examined for simultaneous perception and fusion using a synoptophore. We compared the results of cheiroscopic tracing with those of synoptophore testing for simultaneous perception and fusion.Results Using a synoptophore, simultaneous perception was detected in 89.5% and 85.7% cases of the XT and ET groups, respectively, and fusion was detected in 73.7% and 71.4% cases of the XT and ET groups, respectively. Simultaneous perception or fusion did not differ significantly between the two groups. Seven patients with XT and four patients with ET had no simultaneous perception or fusion in the synoptophore test. Among those patients, six with XT were associated with and two with ET were four years of age.Conclusions Eleven patients, who were detected with no simultaneous perception or fusion using a synoptophore, were included in this study. Cheiroscopic tracing was useful for checking the presence of simultaneous perception and fusion in these patients.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Changes in the binocular coordination of saccadic eye movement and smooth pursuit in patients with acute acquired comitant esotropia after strabismus surgery

AuthorBlock: Miharu Mihara1, Atsushi Hayashi1, Ken Kakeue1, Ryoi Tamura2 1Ophthalmology, University of Toyama, Toyama, TOYAMA, Japan; 2Integrative Neuroscience, University of Toyama, Toyama, Japan;

DisclosureBlock: Miharu Mihara, None; Atsushi Hayashi, None; Ken Kakeue, None; Ryoi Tamura, None;

Purpose Changes in saccadic eye movement (SEM) and smooth pursuit (SP) in patients with esotropia (ET) after strabismus surgery are largely unknown, because of few relevant reports. In previous reports, patients with early-onset ET are described with greater asymmetry in the gain in SP between temporal to nasal and nasal to temporal than that of patients with late-onset ET. We investigated the change in horizontal SP and SEM in patients with late-onset ET, particularly acquired comitant esotropia (ACE), comparing pre- to post-surgical data using an eye-tracker.Methods Horizontal SEM and SP of ten patients (mean age: 21.9 ± 8.4 years) with AACE were recorded using a video eye-tracker under binocular viewing before and after strabismus surgery in the non-dominant- eye. To study SEM, the participants were instructed to fixate their gaze on a target located in the center at the beginning of the test trial, and to fixate on a new target as rapidly as possible when it randomly appeared at either 18.3°-rightward or 18.3°-leftward. To study SP, the participants were asked to track a step-ramp target moving at ±6.1°/s horizontally as accurately as possible. The asymmetry in the adduction−abduction gain of each SEM and SP and the differences in the gain in each SEM and SP between the right and left eyes, that is, binocular coordination, were compared between the pre- and post-surgical data.Results After the surgery, the gain in SEM of the adduction in the both eyes and the abduction in the dominant-eye decreased. The asymmetry of adduction−abduction gain of SEM in each eye after surgery was significantly larger than that before surgery. The differences in the gain of SEM between both eyes in rightward and leftward decreased after surgery, but not significantly. The asymmetry of adduction−abduction after surgery in the gain in SP in each eye was smaller than that before surgery, but not significantly. After surgery, the left-right eye difference in gain of SP in the non-dominant eye direction decreased significantly.Conclusions Ocular alignment correction by strabismus surgery in patients with ACE results in an improvement in the binocular coordination of SP, not SEM, because SP needs visual feedback.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Changes in saccadic eye movement (SEM) and smooth pursuit (SP) in patients with esotropia (ET) after strabismus surgery are largely unknown, because of few relevant reports. We investigated the change in the gain of horizontal SP and SEM in ten patients with acquired comitant esotropia (ACE), comparing pre- to post-surgical data using an eye-tracker. After the surgery, the gain in SEM was not significantly change. However, the left-right eye difference in gain of SP decreased significantly. That is, ocular alignment correction by strabismus surgery in patients with ACE results in an improvement in the binocular coordination of SP, because SP needs visual feedback. Measurement of Contrast Sensitivity using Vertical Vergence Eye Movements

AuthorBlock: Deepa Dhungel1, Scott Stevenson1 1Optometry, University of Houston, Houston, Texas, United States;

DisclosureBlock: Deepa Dhungel, None; Scott Stevenson, None;

Purpose The current psychophysical methods for measuring the spatial contrast sensitivity function (CSF) require subject compliance, attention and active participation of the subject in the task. This poses a challenge for subjects with compromised communication or comprehension ability. Measuring vertical vergence, a reflex eye movement can be used as an alternative method for determining contrast sensitivity in such cases. The purpose of the study was to measure contrast sensitivity using vertical vergence eye movements and compare with the results from a psychophysical method.Methods Subjects were 3 adults with normal vision. A Dual Purkinje image eye tracker was used for eye tracking. Vertical vergence was measured in response to full screen vertical disparity modulation of horizontal sine wave gratings modulated sinusoidally at a frequency of 0.25 Hz with amplitude of 0.5 degrees. Each trial was 16 seconds long. A block of trials comprised combinations of 8 contrasts [0%, 1%, 2%,4%,8%,16%,32%,64%] and 8 spatial frequencies [0.125, 0.25, 0.50, 1, 2, 4, 8 and 16cycle per degree] presented in shuffled order. Oculometric contrast thresholds were determined by interpolating the contrast values at which the mean response curves cross a criterion line. The criterion was defined as the upper 95% CI above the mean for responses to 0% contrast. The psychophysical CSF was obtained with a 2AFC staircase method for the same spatial frequencies.Results Vertical vergence responses were robust for middle spatial frequencies (0.5 to 4 cpd) with contrast thresholds close to or better than 1% in all three subjects (sensitivities at or above 100). The responses for lower and higher spatial frequencies were less reliable showing lower contrast sensitivities. The shape of the oculometric CSF was similar to that of psychometric CSF. The thresholds obtained from the two methods for middle ranged spatial frequencies were also comparable.Conclusions The results of this study suggests that vertical vergence can be used as a reliable method for measuring contrast sensitivity. Refining the number of trials will possibly make it feasible to use it as an efficient way of measuring CSF.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. This study aims to measure a form of vision that determines the subject's ability to discern low contrast patterns objectively by measuring eye movements. This method requires minimal subject response, attention and task participation. Thus, it can be useful in measuring visio especially in cases with compromised comprehension or communication ability. Eyetracking-enhanced VEP for nystagmus

AuthorBlock: Matt J. Dunn1, Perry Carter2, Fatima Shawkat2, Daniel Osborne2, Jay Self2 1School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom; 2University Hospital Southampton, Southampton, United Kingdom;

DisclosureBlock: Matt J. Dunn, None; Perry Carter, None; Fatima Shawkat, None; Daniel Osborne, None; Jay Self, None;

Purpose Visual evoked potential (VEP) testing is an essential first stage in the diagnostic workup of patients with infantile nystagmus (IN). VEPs are an important factor in the diagnosis of albinism, which accompanies IN in ~28% of cases, as well as chiasmal, optic nerve and neurometabolic disease that can all present with IN. VEPs are also used to assess prognostic visual ability in cases of retinal dystrophy and optic nerve disease. Despite being used regularly in those with IN, VEP testing requires patients to keep the eyes still; something that people with IN naturally cannot do. Fixation instability during VEP testing is believed to reduce VEP signal amplitude, and as a result, the reliability of VEP may be reduced in one of the patient groups that needs it the most. This study investigates whether VEP signal quality (amplitude) can be improved in people with IN, by triggering acquisition only during the foveating (slow) periods of the nystagmus waveform.Methods A novel method of VEP triggering was developed, by recording live eye movements from individuals with IN (using an EyeLink 1000+), and triggering VEP acquisition (with an Espion device) only during foveating periods of the nystagmus waveform (i.e., low velocity). VEP amplitude as acquired using this method was compared to VEPs triggered using continuous (regular, non-gaze-contingent) acquisition. Data were collected in six patients with IN (pattern onset/offset in all participants, and pattern reversal in four). Further data collection is underway and will be reported in full at the meeting.Results VEP signal amplitude is significantly increased by gaze-contingent VEP triggering (mean = 12 µV, as compared to 9 µV under continuous acquisition; p = 0.03).Conclusions Triggering VEP acquisition during foveation periods significantly increases the VEP amplitude and therefore has the potential to improve prognostic reliability in people with IN.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Nystagmus is a condition causing constant involuntary eye movements. Many people with nystagmus also have an underlying visual disorder, such as albinism, retinal dystrophy or nerve disease. “Visual evoked potential” (VEP) – a technique that records brain signals while the patient looks at patterns shown on a screen – aids with both diagnosis and prognosis of these disorders. Accurate VEP testing requires the patient to keep their eyes still, which people with nystagmus cannot do. Therefore, VEPs may be unreliable in one of the patient groups that need it the most.

Fortunately, in most people with nystagmus, there are regular brief periods in which the eyes move more slowly. By connecting a VEP device to an eye tracker, we are able to trigger VEP measurements at the exact moment of these slower periods. Results in six patients show a significant improvement in VEP signal quality, suggesting greater diagnostic and prognostic reliability. Effect of alternating flicker occlusion of different frequencies on vergence eye movements.

AuthorBlock: Bhavatharini Ramakrishnan1, Scott Stevenson1 1Optometry, University of Houston, Houston, Texas, United States;

DisclosureBlock: Bhavatharini Ramakrishnan, None; Scott Stevenson, None;

Purpose Alternate occlusion therapy has been reported to improve stereoacuity and visual acuity in some amblyopic subjects. We wondered how alternate occlusion flicker affects binocular function during the therapy. Here we tested the effects of alternate occlusion flicker on symmetrical vergence responses to disparity steps.Methods Vergence eye movements were measured using a dual Purkinje image eye tracker. The stimulus used for the testing was a filtered noise pattern of spatial frequency 0.25 or 2 c/deg with a bandwith of 1 octave and variable contrast. Trials were 2 seconds long, with a near or far disparity step at either 250 or 350 msec into the trial. Data were collected in blocks of 120 trials (6 contrast x 5 flickers x 2 directions x 2 onset times) in shuffled order. Ten blocks were collected at 2 c/deg and 4 at .25 c/deg.Results Vergence latency was measured as the time taken by the subject to reach half of the total vergence demand (1 deg). At the lowest flicker rates tested, 2 and 4 Hz, vergence responses were absent or very slow. At 8 hertz flicker, vergence was present but delayed for all contrast levels. At the highest flicker rates, 16 and 32 Hz, responses were robust and rapid for all but the lowest contrasts.Conclusions Alternate occlusion flicker at 2 and 4 Hz abolished responses to disparity steps in our stimuli. Flicker at 8 Hz, similar to that used previously for therapy, delayed and disrupted vergence in our normal subjects but did not abolish it.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Finite Element Model (FEM) of Active Rectus Extraocular Muscle (EOM) Contraction to Rotate the Eye

AuthorBlock: Somaye Jafari1, Yong Tao Lu2, Joseph Park1, Joseph Demer1,3 1Stein Eye Institute, University of California, Los Angeles, Los Angeles, California, United States; 2Department of Engineering Mechanics, Department of Engineering Mechanics, Dalian University of Technology, Dalian, China; 3Department of Neurology, University of California, Los Angeles, Los Angeles, California, United States;

DisclosureBlock: Somaye Jafari, None; Yong Tao Lu, None; Joseph Park, None; Joseph Demer, None;

Purpose There is lacking a complete FEM of active EOMs suitable for simulation of eye rotation by physiological forces. The rectus EOMs exhibit highly complex nonlinear, incompressible, active, fiber-reinforced & hyperelastic mechanical behavior. This study sought to implement a complete rectus EOM contraction model to study mechanics of eye rotation.Methods Rectus EOM geometries were obtained from high resolution, surface coil magnetic resonance images of right eyes of 5 normal human adults. The constitutive model here is based on the 3D muscle model of Tang et al. (J Biomech 42, 865-872, 2009) and Lu et al. (Methods Biomech Biomed Engin 14,1079-1088, 2011) capable of simulating both active & passive behavior during lengthening & shortening. The strain energy defined in the current model consists of 3 portions: isotropic part of the EOM, EOM fiber structures (including the active function), & volume change using material properties of rectus EOMs of cows and humans. To implement active EOM behavior, a VUMAT subroutine in the software environment ABAQUS (Dassault Systemes) was implemented to define the constitutive properties of EOM & initial fiber directions along it. In this analysis the globe is rigid, & all deformation is caused by the EOM twitch activation function implemented within the VUMAT. Each muscle consists of 20,000 tetrahedral elements for with the approximate size of 0.8mm. Using this approach, the medial rectus muscle was commanded to contract and the lateral rectus to relax, aiming for 6° adduction.Results The model was stable, & implemented 6° rotation and 0.7mm translation of the globe center occurring over a 450ms period. The simulation required about 30 minutes of multiprocessor computer time by considering a mass scale factor of 1000. Maximum strain and stress during adduction were ~11% and 0.03 MPa respectively observed within the lateral rectus muscle.Conclusions Realistic EOM contraction can be implemented for ocular rotation using a widely-available software platform for FEM. This method of EOM activation allows us to build a realistic model of biomechanical behavior of all of the active & passive tissues in the orbit to clarify mechanisms ocular disorders such as strabismus & optic nerve traction.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Contraction of the eye muscles is responsible for rotation of the eye. Therefore, that would be important to understand how the muscles contract. In this study we were able to implement a complete muscle contraction Finite element model for eye muscles in order to study the mechanics of the orbit. Geometries of the rectus muscles were obtained by MRI of the right eye for 5 patients. We implemented a code into the finite element software based on a 3D muscle model using material properties of the cows and human. Initial fiber directions along the muscle were defined in the code. In this analysis all deformation occurred through the muscles is caused by the twitch activation function implemented within the code. In this study the medial rectus muscle contracts while the lateral rectus muscle relaxes until we achieve a 6 degree of globe rotation. During the movement of the globe, we observed the 6 degree and 0.7 mm of globe rotation and translation respectively occurred over 450ms of the time period. This method of muscle activation allows us to understand some of the eye diseases such as strabismus and optic nerve traction. Effect of Small Vessel Ischemia on Horizontal Saccades

AuthorBlock: Paul A. Wetzel1, George T. Gitchel1,2, Mark S. Baron2,3 1Dept. of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia, United States; 2Southeast Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, United States; 3Neurology, Virginia Commonwealth University, Virginia, United States;

DisclosureBlock: Paul A. Wetzel, None; George T. Gitchel, None; Mark S. Baron, None;

Purpose Small vessel ischemia (SVI), also commonly called “white matter disease” is a common phenomenon in elderly individuals. Often, these small strokes in the cerebral white matter can manifest symptoms that mimic Parkinson’s disease, and are often referred to a Movement Disorder clinic for diagnosis. Some small strokes are expected with advanced age, and may add to difficulty in differentiating idiopathic Parkinson’s Disease from small vessel ischemia. This study examines the effects of small vessel strokes during horizontal tracking as an objective measure to assist in clinical diagnosis of SVI.Methods In an ongoing study, the eye movements of 100 veterans diagnosed with MRI-confirmed SVI and 100 controls were recorded binocularly at 500 Hz (SR Research, EyeLink II). Participants were instructed to track spatially and temporally randomized step changes in target position along the horizontal axis. Data were analyzed for response latency, saccadic amplitude, duration, velocity and acceleration, including position accuracy and fixation stability. Statistical analysis was performed on all eye measurement parameters using ANOVA.Results While the eye movements for controls were within normal ranges, specific abnormalities were found in subjects with SVI. Most notably, main sequence analysis showed almost twice as much variability in saccadic peak velocity for a given amplitude compared to controls. While saccadic peak velocity for controls exhibited a spread of ~75°/s at 20° amplitude, SVI subjects had an increased spread of almost 130°/s. Additionally, the saccadic waveform tends to be distorted in SVI, with 85% of subjects exhibiting small peaked dynamic overshoots (typically <5% of total saccadic amplitude), along with post-saccadic ringing that dampened into stable fixations. The latency of saccades between controls and SVIs were not significant. Fixation RMS velocity among controls was slightly less, implying more stable fixation compared to SVIs.Conclusions SVI produces significant alteration of consistency within saccadic main sequence, as well as altering saccadic termination behavior. Fixation stability may also be an important indicator of SVI status. The present combined findings suggest that eye movement parameters could be a sensitive clinical means to differentiate SVI and, as such, provide a valuable tool to clinicians.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Disparity-defined letter test: A new tool for evaluating stereo deficits

AuthorBlock: Wei Hau Lew1, Daniel R. Coates1 1University of Houston College of Optometry, Houston, Texas, United States;

DisclosureBlock: Wei Hau Lew, None; Daniel R. Coates, None;

Purpose Random Dot-Stereograms (RDS), used to test global stereopsis, have been proposed to be more sensitive in detecting stereo deficits in amblyopes, since local stereopsis tests (e.g. Wirt Circle) may exhibit monocular cues. These clinical tests only assess stereo acuity at a certain size, primarily at higher spatial frequencies (SFs) with small targets. Amblyopes are often diagnosed with a stereo deficit when assessed with these tests. It is unclear if the deficits occur across the entire spectrum of SFs, or only at high SFs, due to their reduced visual acuity (VA). We designed an RDS with disparity- defined optotypes to assess stereo in a range of SFs and contrast levels in normal and stereo deficient groups.Methods We generated Sloan optotypes of various sizes (0.25-3.75cpd) with crossed disparity embedded in RDS. On each trial, a random optotype was presented for 1sec with a haploscope and LCD screens. Subjects (5 normal observers, 1 intermittent exotropia-IXT, 2 strabismic amblyopes) identified the letter. A staircase method was used to determine the minimum disparity needed to identify letters at each size. Stimuli were tested at 100%, 50% and 25% contrast. To simulate ocular imbalance, subjects also performed the task with an interocular contrast ratio (ICR) of 50% and 25%, with a lower contrast in the dominant eye.Results The disparity-defined letter sensitivity function had a bandpass curve peaking at 1-2cpd and intersected the x-axis at a cut-off frequency of ~5cpd (disparity-defined VA, “dVA”=20/120). As the overall contrast decreased, the peak shifted downwards with a cut-off at lower SFs. However, only the middle and high SFs were affected, sparing the low SFs. Surprisingly, results for 50% and 25% ICR were similar to the outcome for binocular contrast reductions of 50% and 25%, respectively. The curve for the IXT subject with 100% contrast was even lower (dVA=20/300) than that of normal observers at 25% contrast, with greater loss at high SFs than low SFs. The strabismic observers were not able to perform the task even with the largest letters.Conclusions We found that thresholds for identifying disparity-defined letters vary with the size of optotypes in a bandpass-shaped pattern. With a range of SFs, this test can help determine selective losses of stereo deficits at particular SFs, as well as identifying the high SF cut-off (dVA). Strabismic observers may need larger dots and longer duration.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Binocular Vision Characteristics in Patients before and after Cataract Surgery

AuthorBlock: Qing-Qing Tan1,2, James S. Lewis3, Mitchell Scheiman4 1Biomedicine , Salus University, Elkins Park, Pennsylvania, United States; 2Department of Ophthalmology, Affiliated Hospital of North Sichuan Medical College, , China; 3LewisLASIK, Pennsylvania, United States; 4Pennsylvania College of Optometry, Salus University, Elkins Park, Pennsylvania, United States;

DisclosureBlock: Qing-Qing Tan, None; James S. Lewis, None; Mitchell Scheiman, None;

Purpose To compare the binocular vision status of patients 50 years of age and above pre- and post-cataract surgery, and to investigate the risk factors for patients who develop binocular vision anomalies after cataract surgery.Methods In this prospective study, we enrolled patients (50 years or older) who were scheduled for bilateral cataract surgery from January to November 2019. A comprehensive binocular vision test battery was administered including measurement of eye alignment using the cover test, assessment of positive and negative fusional vergence (step vergence testing), vergence facility testing using 3BI/12BO prism, and the near point of convergence before the first surgery and the third visit after the second surgery. A detailed diagnostic classification protocol was applied to identify the presence of binocular vision anomalies pre- and post-surgery.Results Seventy-three participants were included at baseline and 51 completed the postoperative evaluation. The mean age at baseline was 70.2±6.7 years and the mean follow-up time was 57.3±29.8 days after the second surgery. At baseline, 46 of 73 (63%) patients were diagnosed with non-strabismic binocular vision anomalies (NSBVA), including 40 (54.8%) with convergence insufficiency, 3 (4.1%) with basic exophoria , 2 (2.7%) with convergence excess, and 1 (1.4%) with fusional vergence dysfunction. One participant with convergence insufficiency also had a vertical phoria. Of the 51 participants who completed the postoperative evaluation, 60.8% had binocular vision disorders. There were a number of conversions from NSBVA to normal binocular vision and vice-versa (Table 1). Logistic regression showed that the adjusted odds ratio of preexisting NSBVA diagnosis for predicting risk of postoperative NSBVA was 8.8 (P<0.01).Conclusions Binocular vision problems, especially convergence insufficiency, are prevalent in the elderly population with cataract. Cataract surgery does not seem to be a significant risk factor for the development of new binocular vision problems. The main risk factor for predicting a postoperative binocular vision problem is preexisting NSBVA. A limitation of the study is a lack of normative binocular vision data for the elderly population. This study suggests that normative data should be developed for patients 50 years of age and above.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Comparison of stereopsis at ages 4½ and 10½ in the Infant Aphakia Treatment Study

AuthorBlock: E Eugenie Hartmann2,3, Carolyn Drews-Botsch1, Lindreth DuBois4, George Cotsonis5, Scott R. Lambert6 1Epidemiology, Emory University, Birmingham, Alabama, United States; 2Vision Center, Akron Children's Hospital, Akron, Ohio, United States; 3Research Institute, Akron Children's Hospital, Akron, Ohio, United States; 4Ophthalmology, Emory University, Atlanta, Georgia, United States; 5Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia, United States; 6Ophthalmology, Stanford University, Palo Alto, California, United States;

DisclosureBlock: E Eugenie Hartmann, None; Carolyn Drews-Botsch, None; Lindreth DuBois, None; George Cotsonis, None; Scott R. Lambert, None;

Purpose Stereopsis is the hallmark of binocular vision but is generally believed to be unachievable in patients who undergo treatment for unilateral congenital cataracts. We have demonstrated some level of stereopsis at age 4½ in our study and have reevaluated this population at age 10½.Methods Infants between the ages of 4 weeks and 7 months with a visually significant unilateral cataract were randomly assigned to be left aphakic or have an IOL implanted at the time of the initial cataract extraction. A total of 114 infants were enrolled in the study between December 23, 2004 and January 16, 2009 at 12 clinical sites. Patients were followed on a regular basis until age 5 years. One additional assessment was obtained at age 10½ to measure long-term outcomes after the sensitive period for visual development. The Randot Preschool Stereotest was used at age 4½ by a traveling tester and at age 10½ by a study certified tester at each site. Monocular visual acuity at age 10½ was evaluated using the E-ETDRS protocol.Results Only 11 of the 107 patients tested on the Preschool Randot at age 10½ demonstrated some level of stereopsis, defined as identifying at least two of the three images viewed through polarizing lenses. E- ETDRS visual acuity in the treated eyes for these patients varied from 20/40 or better to 20/200 or worse (Table 1). Six of the original 114 did not provide VA data at age 10½ and one patient had been lost to follow-up before the 4½ year testing, hence the total number for this report was limited to 107. Comparing stereopsis measures between the two ages indicated that only three of the patients who had demonstrated stereopsis on this test at age 4½ also showed stereopsis at the later age (Table 2). It should be noted that all three of the individuals who had positive findings at both ages had E-ETDRS VA of 20/40 or better (Kappa = 0.473 (95% CI 0.12,0.83)).Conclusions These findings demonstrate that, while rare, it is possible for patients with unilateral congenital cataracts to achieve some degree of stereopsis measured by randot stimuli. However, the static nature of these tests may under-represent the extent to which an individual uses both eyes together in the real world.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. We enrolled a total of 114 infants between the ages of 4 weeks and 7 months who had a visually significant unilateral cataract. Infants were recruited between December 23, 2004 and January 16, 2009 from 12 clinical centers across the country. All infants had surgery to remove the cataract and were randomly assigned to being left aphakic (no lens and treated with a contact lens) or had an intra-ocular-lens (IOL) implanted at the time of surgery. Patients were followed on a regular basis until age 5 years. One additional assessment was obtained at age 10½. We were interested in determining the extent to which any of these patients might demonstrate the ability to perceive depth based on the disparity between images presented to each eye separately – stereopsis. We measured stereoacuity at both 4½ and 10½ years of age. We found that approximately 10% of the patients demonstrated some level of stereoacuity using a standardized static test at age 10½. This suggests that these individuals may be able to use both eyes together and appreciate depth as illustrated in 3-D movies. Development of Nystagmus in MyoD Knockout Mice

AuthorBlock: Laura Johnson1,2, Rachel Kueppers1, Linda K. McLoon1,3 1Ophthalmology and Visual Neurosciences, University of Minnesota-Twin Cities, Minneapolis, Minnesota, United States; 2Molecular, Cellular, Developmental Biology & Genetics Graduate Program, University of Minnesota-Twin Cities, Minnesota, United States; 3Neuroscience, University of Minnesota- Twin Cities, Minnesota, United States;

DisclosureBlock: Laura Johnson, None; Rachel Kueppers, None; Linda K. McLoon, None;

Purpose Extraocular muscles (EOM) maintain a large population of activated satellite cells that provide for continuous remodeling throughout life. While limb skeletal muscles have some myonuclear turnover, it is much more limited than seen in the EOM and other craniofacial muscles. MyoD is a myogenic regulatory factor that activates genes required for muscle differentiation. Its expression results in exit from the cell cycle and stable terminal differentiation. In muscles derived from the paraxial head mesoderm MyoD is downstream of expression of Pax7 and Pitx2, both markers of myogenic precursor cells in EOM. We hypothesized that knocking out MyoD would prevent or slow the progression toward integration into existing muscle fibers, reducing the ability of EOM to remodel continuously.Methods We used a MyoD knockout mouse to determine the effects of MyoD on EOM and eye movements. Eye tracking using optokinetic nystagmus of MyoD knockouts and their wild type (WT) litter mate controls was performed on an ISCAN device and analyzed using R. Optokinetic nystagmus responses were recorded for each animal. Animals were tested with no stimuli in light and dark conditions, and with rotating bars at a spatial frequency of 0.12cpd and high contrast (100) between light and dark bars.Results Of the WT mice tested, before one year of age the optokinetic nystagmus reflex was normal. In the older WT mice, pendular nystagmus and jerk nystagmus were present. In the oldest WT mice, no eye movements were generated. Of the MyoD KO mice tested, only one had a somewhat normal optokinetic nystagmus reflex. Of the others, 5 had pendular nystagmus, 3 had no detectable eye movements, 3 had bouts of jerk and pseudo-pendular jerk nystagmus. In some of the mice, these abnormal movements were followed by bouts of over 10 seconds duration with no eye movements.Conclusions In the absence of MyoD expression over time, normal control of the optokinetic nystagmus reflex was significantly impaired. Lack of MyoD led to an increase in abnormal nystagmic eye movements in the knockout mice tested compared to the wild-type mice. We hypothesize that it is likely due to reduced ability of the myofiber to remodel over time. We are currently testing this hypothesis.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Eye movements are controlled by eye muscles (EOM) which are continuously remodeling throughout life. MyoD is a gene required for muscle differentiation and is downstream of expression of satellite cell markers Pax7 and Pitx2. We hypothesized that knocking out MyoD expression would prevent or slow down muscle precursor cell integration into existing muscle fibers, which would reduce the ability of the EOM to remodel continuously. We knocked out MyoD in mice and tracked their eye movements using the optokinetic nystagmus reflex. Lack of MyoD led to an increase in abnormal eye movements in the knockout mice tested compared to the wild-type mice. Role of Superior Colliculus in fixation preference during a delayed saccade task in strabismic non-human primates

AuthorBlock: Santoshi Ramachandran1, Vallabh E. Das1 1College of Optometry, University of Houston, Houston, Texas, United States;

DisclosureBlock: Santoshi Ramachandran, None; Vallabh E. Das, None;

Purpose Strabismic patients and non-human primates often develop the ability to saccade to and fixate on a target with either eye depending on the targets’ spatial location. Spatial fixation preference in strabismus could possibly be accounted for in a competitive decision framework wherein the brain chooses between two retinal errors (since eyes are pointing in different directions) to prepare a saccade. We tested this framework by recording from visuo-motor neurons in the superior colliculus (SC), a structure critical in target selection and saccade generation, during spatial fixation preference behavior.Methods Single cell neural recordings from the intermediate/deep SC were obtained while a head-fixed strabismic [M1, ~30° XT] monkey performed a delayed saccade task under binocular viewing conditions. Once the neuronal receptive field was localized, visual targets were presented at one of two locations corresponding to the receptive field location of either the viewing or deviated eye, and resulted in fixation-switch or no fixation-switch saccades. Amplitude and direction were matched (Exp 1 – two target condition). For certain target locations, fixation-switch and no fixation-switch saccades were in opposite directions (different colliculi) (Exp 2 – single target condition). Paired t-tests were performed to compare firing rates of visual, buildup and saccade related response in fixation-switch and no fixation-switch trials.Results Exp 1 (n=10): Robust visual sensory responses were observed when targets were presented to either the viewing or deviated eye with evidence of only small interocular suppression. As expected, motor responses for fixation-switch and no-fixation switch trials were not significantly different since the saccade parameters are matched. Additionally, the mean build-up responses showed no difference in these trials since the cell corresponds to the ‘winning’ saccade. Exp 2 (n=11): For the single target condition, both visual and mean build-up responses were reduced for trials in which the cell did not correspond to the ‘winning’ eye, suggesting that the build-up activity may be used to facilitate eye choice. Analysis of more cells from M1 and data acquisition from a second animal is ongoing.Conclusions Analysis of neural data from SC visuo-motor cells suggests that this structure plays an important role in eye choice for visual stimuli in strabismus.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. Strabismic patients and animals can sometimes develop the ability to look at a target with either of their eyes and can spontaneously change which eye they are using depending on where the target is. The neural mechanism driving fixation-switch behavior is unknown. In this study we examined firing rates of neurons in the superior colliculus (SC) which is critical in target selection and saccade generation. We found that a robust sensory response was elicited when a visual target was presented to the viewing or the deviated eye. We also found that the build-up period, which is in-between when the brain senses a target and when it sends the command to move the eye may be facilitating the eye choice. This investigation could provide insight on how the brains of strabismic patients and animals work in converting a sensation, as sight, to an action such as a saccade. Spatial localization during monocular and dichoptic viewing

AuthorBlock: Apoorva Karsolia1, Scott Stevenson1, Vallabh E. Das1 1University of Houston, Houston, Texas, United States;

DisclosureBlock: Apoorva Karsolia, None; Scott Stevenson, None; Vallabh E. Das, None;

Purpose To investigate the accuracy and precision of localization under monocular and dichoptic viewing conditions in individuals with normal ocular alignment, to ultimately evaluate the role of eye position signals in spatial localization in individuals with strabismus.Methods Stimuli were rear projected onto a curved screen (field of view 180° x 90°), with a dynamic noise background. A target disc (1.5°) was flashed for 1 sec, followed after a delay (0.25, 0.5, 1, 1.5, 2, 5, or 7 secs) by a response disc. Subjects fixated on the response disc, and used a mouse to move it to the remembered location of the target. The experiments were performed under monocular viewing and dichoptic viewing with red-green glasses. Under dichoptic viewing, four conditions [green target – green response cue (GG), green-red (GR), red-green (RG), and red-red (RR)] were tested. Errors in localization were calculated as the difference between the estimated and real positions of the target cue. For each subject, ~30 trials with same time intervals were pooled, and localization error was quantified as the area of the 68th percentile bivariate contour ellipse (BCEA).Results Under monocular viewing (n=8), the mean monocular horizontal localization error was close to 0° and was not different between 0.5 and 7 seconds (p>0.05, ANOVA) in all subjects. BCEA increased linearly with time under monocular viewing in all subjects. During dichoptic testing (n=3), mean horizontal error from same eye trials was close to 0° (mean GG: 0.30°, mean RR: 0.46°). For alternate eye trials, there was a shift in horizontal localization error (mean GR: -3.68°, mean RG: -5.27°) that corresponded to the mean phoria (mean GR: -2.78°, mean: RG -2.68°) recorded during the testing procedure; however trial-by-trial correlation between phoria and localization error was weak. For same eye trials, the BCEA increased linearly with time, but for alternate eye trials, the BCEA reached saturation for larger time intervals in 2/3 subjects.Conclusions Spatial localization becomes progressively worse with time. Under dichoptic viewing, subjects are unable to compensate for their phoria during spatial localization. An interpretation is that oculomotor proprioception may not provide the required feedback of eye position. Testing strabismus subjects could add insight into the relationship between eye position feedback and spatial localization.Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. In our day to day lives we are constantly surrounded with visual stimuli. To keep track of objects in our environment, an internal representation of space is essential. Our study shows that under monocular conditions, our ability to accurately localize a previously fixated target is independent of the time since last fixation, but the precision worsens with time. Moreover, under conditions of binocular competition (dichoptic viewing), subjects are unable to compensate for their transient misalignment, and make greater errors as compared to monocular viewing conditions. The study provides insight into the relationship between eye position feedback and spatial localization.