Clinical optometric exam measures.

Best-corrected visual acuity will be assessed for each eye at a distance using the Snellen eye chart. Subjective refraction will be performed to ensure that participants meet the refractive error inclusion criteria. The cover-uncover (unilateral cover) test and prism and alternate cover test (PACT) will be performed at distance (4 m) and near (40 cm) to objectively determine the direction and magnitude of the deviation. Participants will wear their refractive correction (if prescribed) and be asked to keep a 20/30 isolated letter clear during testing. For PACT testing, a prism will be added until the direction of movement is reversed (e.g., exophoric becomes esophoric). The magnitude will be recorded as the largest prism that results in neutrality (before the first reversal movements, i.e., high neutral). The Randot Stereo test (Stereo Optical, Chicago, IL, USA) will assess local and global stereopsis. A local stereopsis of 70 seconds of arc or better and a global stereopsis of 500 seconds of arc or better are required to enroll. Assessments are summarized in Fig 2.

Other oculomotor testing will include the following conventional optometric exam parameters. The Astron Accommodative Rule (Bernell, Mishawaka, IN, USA item GR50, Bernell) will be used to measure the NPC. The device consists of a rod with a movable slide, and a single column of letters (20/30 equivalent at 40 cm) will be used as a target. PFV and negative fusional vergence (NFV) will be measured using the step vergence procedure with a handheld horizontal prism bar (Gulden Ophthalmics Elkins Park, PA, USA, Product Number 11112). Negative fusional vergence will be measured before positive fusional vergence. The participant will view a 20/30 size column of letters (Gulden Ophthalmics Elkins Park, PA, USA, Product Number: 15302) held on the participant’s midline at 40 cm. The examiner will move the prism bar to achieve a change at a rate of ~2 Δ /sec. The participant will report when the target is blurry or double and when they can regain fusion. The vergence facility will be assessed with a 12BO / 3BIΔ prism (Gulden Ophthalmics Elkins Park, PA, USA, Product Number: 11107) and the Gulden Fixi-Tic (Gulden Ophthalmics Elkins Park, PA, USA, Product Number: 15112) at near (40 cm) and repeated at far (4 m). The 12BO / 3BIΔ prism will be placed before the right eye (base-out first), and when the participant experiences single, clear vision, they will say "now." The base-in prism is then placed before the right eye, and once the participant experiences single and clear vision, they again say "now." The procedure is repeated for one minute. The examiner will record the number of times a participant can see the target as single and clear in one minute.

Accommodation will be assessed using the following methods. The monocular amplitude of accommodation will be evaluated for both the right and left eye with the Astron Accommodative Rule using a vertical column of 20/30 letters placed initially at 40 cm and slowly moving towards the participant at a rate of 1cm/sec until it blurs. The participant will be instructed to keep the letters clear and tell the examiner when the letters first blur (first sustained blur). The monocular accommodative facility will be assessed using a ±2D lens flipper (Gulden Ophthalmics Elkins Park, PA, USA, Product Number: 11132) and the Gulden Fixi-Tic target for the right eye only. The participant will view the Gulden fixation target at 40 cm. The examiner will alternate between each lens when the participant states the visual target is clear. The number of lens flips will be counted within one minute.

Visual and concussion symptoms.

Symptoms surveys include the Convergence Insufficiency Symptoms Survey (CISS) and VisQual-T [71]. CISS is a 15-question survey to assess visual comfort while reading. The greater the score, the more symptomatic the participant. A participant is classified as symptomatic using a threshold score of ≥21 for adults or ≥16 for children. The CISS has a sensitivity of 97.8%, a specificity of 87%, and an interclass correlation coefficient of 0.89 [72,73]. The Vision Quality of Life with Time (VisQuaL-T) is a series of 10 questions about daily activities inquiring about the duration of time when visual symptoms become apparent. VisQuaL-T has an ICC = 0.83 within normative data [71]. All participants will be asked to complete the CISS and VisQual-T surveys two times at enrollment, once recalling their symptoms pre-injury, and a second time based on how they felt in the past few days. At Outcome 1, Outcome 2, and the one-year follow-up assessment, these surveys will only be administered once.

OculoMotor Assessment Tool (OMAT).

The OculoMotor Assessment Tool (OMAT) (Gulden Ophthalmics Elkins Park, PA, USA, Product Number: 18009 and the OMAT smartphone application) will be used to assess horizontal saccades, vertical saccades and vergence jumps [74]. Each of these tests lasts one minute. The OMAT app, available for a smartphone, enables the user to count and time the number of eye movements for the initial and later 30 seconds of the one-minute test. The OMAT provides data that can be used to assess oculomotor endurance. Before using the OMAT, participants will be asked to rate the following symptoms: headache, dizziness, nausea, and fogginess on a Likert Scale from 0 to 10 (zero is no symptoms, and ten is highly symptomatic). The symptoms will be rated again after each of the OMAT subtests.

The OMAT will be placed on the participant’s nasion for horizontal and vertical saccades. The participant will be asked to look from one “X” placed 25 cm along the midline and move their eyes from 25⁰ in the left visual field to 25⁰ in the right visual field (50⁰ horizontal saccade). The participant will be asked to make as many saccades as possible in one minute and to slow down or even stop if symptoms become too overwhelming. For vertical saccades, the OMAT will then be rotated for the participant to initiate 50⁰ vertical saccades. For vergence jumps, two targets (vertical lines) will be added to the OMAT bar placed along the midline at 9 cm and another at 24 cm to stimulate a symmetrical vergence step stimulus of 20° (35 Δ). For each task, the number of eye movements will be counted using the OMAT application and recorded in REDCap.

Objective eye movement recordings.

An Oculus DK2 virtual reality headset integrated with ISCAN (Woburn, MA, U.S.A.) infrared (λ = 950nm) video-based eye tracker with a sampling rate of 240 Hz and a manufacturer-reported resolution of 0.1⁰ will be utilized. Hygiene masks will be used so the virtual reality headset does not touch any participants. The visual stimulus will be a Distribution of Gaussian with a 2⁰ eccentricity for mostly foveal stimulation.

The objective eye movement recordings will comprise two tests: an oculomotor battery and an oculomotor endurance test with a break between tests. The battery will contain eight monocular calibrations (four for each eye) located at known angles of 1⁰, 3⁰, 5⁰, and 7⁰ inward rotation, encompassing the visual field of the eye movements to be recorded. Then, convergence and divergence symmetrical steps of 4⁰ and 6⁰ magnitude changes after a delay of up to 0.5 sec to reduce predictive cues [75] known to stimulate the dorsal lateral prefrontal cortex [76] will be presented over a 5-minute duration. There will be 30 convergent steps starting at an initial vergence demand of 4⁰ and ending at a vergence demand of 8⁰ and 30 divergent steps beginning at an initial vergence demand of 8⁰ and ending at a vergence demand of 4⁰. There will be ten convergence and divergence 4⁰ steps between the vergence demands of 6⁰ and 10⁰. There will be ten convergence and divergence 6⁰ steps between the vergence demands of 4⁰ and 10⁰. All vergence steps will be recorded for a 5-second duration. Then, slow (1⁰/sec) and fast (4⁰/sec) convergence and divergence ramps will be presented randomly for a 5-minute total duration. There will be 15 observations of each ramp type between the vergence demand range of 4⁰ to 10⁰. The last 2.5 minutes of the test will be 5⁰ and 10⁰ leftward and rightward saccades presented pseudo-randomly over the range of 5⁰ into the left visual field from midline to 5⁰ into the right visual field from midline. Saccades will be presented for 2 seconds for each observation, where there will be 30 observations of saccades of 5⁰ magnitude and 20 observations of saccades with a 10⁰ magnitude. Participants will be given breaks between vergence steps, vergence ramps, and saccades. The duration of each break will be participant-dependent due to potential concussion-related symptoms. There will be a total of 12.5 minutes of eye movement recording for the oculomotor battery test.

Oculomotor endurance, or the ability to sustain performance, has been suggested to be an independent risk factor post-concussion [70]. Hence, the second test is an oculomotor endurance test. It will have the same eight monocular calibrations of four per eye at the same positions as the oculomotor battery test. Then, there will be 2.5 minutes of only 4⁰ convergence and 4⁰ divergence symmetrical steps between a vergence demand of 4⁰ to 8⁰ for a 3-second duration. There will be 25 observations of convergence and 25 divergence steps for a total of 50 vergence movements. Then, the oculomotor battery described above will be repeated: 5 minutes of vergence steps, 5 minutes of vergence ramps, and 2.5 minutes of saccades. The vergence endurance test (VET) is 15 minutes of eye movement testing. The break between each movement type will be participant-dependent based on how symptomatic they may feel. It is also anticipated that not all participants will be able to complete testing due to symptoms.

Functional Magnetic Resonance Imaging (fMRI).

A 3 Tesla Siemens Prisma with a 64-channel head coil (Siemens Medical Solutions, Parkway Malvern, PA, U.S.A.) will be used at the Rutgers University Brain Imaging Center (RUBIC) for the participants within the NJ site. An Eyelink-1000 system (SR Research, Canada) will record the right-eye movements at 250 Hz to ensure that the participant performs the requested oculomotor tasks and is calibrated before image acquisition using a 9-point calibration. A mirror on the head coil, angled in front of the eyes and situated 15 cm away from the participant’s nasion, will allow the participant to view a 1920 by 1080-pixel resolution screen 80 cm from the mirror. Participants needing eyeglasses will use fMRI-compatible glasses to the closest 0.5 D of their refractive prescription throughout the session, calculated as the mean sphere plus half of the cylinder, or wear their contacts which is preferred for refractive correction. The details of the tasks and what will occur while being scanned will be explained to each participant before starting the experiment. All females who have the possibility of being pregnant will take a pregnancy test or sign a waiver confirming that they are not pregnant. No pregnant females will be scanned. A detailed screening form will be administered to all participants before every scan to ensure that no ferrous metal, implants, or conditions that can lead to an adverse reaction will occur while being imaged. An emergency squeeze ball is also available to alert the MRI technician if the participant is distressed and needs to stop the experiment.

After the localizer scan of 14 seconds and gradient field map recording of 1 minute 18 seconds, three task-induced fMRI recordings will be conducted. First, a 15-second echo planar imaging (EPI) scan will be done so participants are less startled by the sounds of the fMRI machine. The tasks include a vergence-motor task (VM), a vergence-sensory task (VS), and a saccadic task. All stimulus tasks will be 25 seconds per block, with eleven rest blocks and ten blocks of task. The stimulus-induced tasks will be 8 minutes and 45 seconds in length each. A magnetization-prepared rapid acquisition gradient echo (MP-RAGE) will be next, which will take 4 minutes and 26 seconds. Then, a resting state scan (rs-fMRI) will be conducted for 7 minutes 12 seconds, and arterial spin labeling (ASL) scans for 7 minutes 26 seconds. The total imaging time is 54 minutes, and if participants need more of a break between tasks, the ASL scan will be dropped.

Due to the symptomatic behavior of the CONC-CI participants, the three stimulus-induced tasks (VM, VS, and saccade) that need more visual attention from the participants are planned for the beginning of the fMRI scanning queue to reduce any probable effects of fatigue on the expected brain activations and blood-oxygen-level-dependent (BOLD) signals. Functional imaging experiments for the three stimulus-induced and the resting state will be acquired using an echo planar imaging (EPI) sequence with the following parameters: 720 ms for TR, 33 ms for TE, 90° flip angle, 192 mm FOV, 3.0x3.0x3.0 mm³ spatial resolution, and 56 slices in an axial configuration. The disparity vergence step experiment evokes the afferent and efferent portions of the vergence motor (VM) system. It will use a set of eccentric squares that stimulate 4° and 6° symmetrical disparity vergence step responses analogous to the quantitative eye movement experiment. The procedure is analogous to a clinician asking a patient to look between two targets along the participant’s midline. The stimulus target extends 2° by 2° in stimulus eccentricity. The vergence step stimuli will be presented for a duration between 1.8 to 2.8 seconds per eye movement using the following order: 3° Convergent (Con), 3° Con, 3° Divergent (Div), 4° Con, 2° Div, 3° Con, 2° Div, 3° Div, and 3° Div steps. The vergence sensory (VS) experiment will be the same as the VM experiment, with a dot in the center of the screen added, but the participants will be asked not to move their eyes while the eccentric squares move on the screen. This task would exclude the motor response associated with the vergence motor and stimulate the BOLD signals related to the sensory vergence system. The VM protocol has a good intraclass correlation (ICC>0.4) coefficient for stimulating the vergence neural substrates [77]. The protocol will be repeated for saccades where the rest block is a small square target that is stationary on the participant’s midline for 25 seconds, followed by 5° or 10° saccades into the left or right visual field and be a square target similar to prior studies [78,79].

The MPRAGE sequence will be used to acquire a high-resolution anatomical reference with the following parameters: 1900 ms for time repetition (TR), 2.52 ms for time echo (TE), 900 ms for longitudinal relaxation time (T1), 9° flip angle, 256 mm field of view (FOV), 1.0x1.0x1.0 mm³ spatial resolution, and 176 slices within an axial orientation. During the rs-fMRI scan, participants will be asked to keep their eyes open and not think about or concentrate on any particular thoughts using the same EPI sequence parameters used during the stimulus-induced tasks. The last scan will be the ASL, which will have the following parameters: a TR of 4600 ms, TE of 16.18 ms, 46 slices, a FOV of 192 mm, a flip angle of 180° a slice thickness of 3 mm. Each participant will be asked to close their eyes in the ASL scanning.

Statistical model.

A priori sample size calculation was performed using paired t-tests with equal variance for TYP-CI patients from both placebo/sham therapy and OBVAT. The CITT defined the clinically relevant true mean difference for CISS, NPC, and PFV as 10 points, 4 cm, and 10Δ with a standard deviation of 12, 4.5, and 11.3, respectively. The previous pilot data had an estimated correlation of -0.3, 0.9, -0.4, and -0.3 for CISS, NPC, PFV, and beta weight from oculomotor vermis for functional, respectively [81]. Hence, the resultant standard deviation of the difference (OBVAT–placebo/sham therapy) is 19, 2, 19, and 27. Assuming 80% power, Alpha = 0.05, and adjusting for an 80% retention rate and 15% data loss due to motion artifacts during fMRI experiments results in the number of participants needed to be 37, 6, 37, 46, respectively. Using the maximum sample size for all conditions to be satisfied yields a group size of 46 per arm. To round up, the number of participants for a statistically powered study would be 50 CONC-CI for each arm (i.e., 50 CONC-CI into OBVAM+SCC and 50 CONC-CI into SCC only for six weeks).

In the unlikely event that the sample size power analysis is not valid during post hoc analyses computation, an additional 20 participants will be recruited where each group would be about 60 participants for a total of 120 total participants. This group size is substantially greater than the 25-participant arm size in other typical convergence insufficiency randomized clinical trials assessing the same primary measures of optometric signs and symptoms used within this current study [82]. Hence, it is highly likely that the proposed 50-participant arm size will be sufficient; however, the contingency is to increase the arm size to 60 participants if needed or 120 total participants. Furthermore, if the post hoc test supports insufficient statistical power, then methods to decrease variance within the dataset will be applied. The following methods will be explored for the objective assessment measurements. If for the imaging analyses, the power analysis is not sufficient then rather than performing whole-brain analyses, a region of interest (ROI) based analysis will be employed. If power analysis is insufficient for eye movement analyses, then additional filtering of eye movement data will be employed, and further averaging will be done.

The CONCUSS randomized clinical trial’s primary aim is to investigate the longitudinal changes for the immediate compared to delayed OBVAM arms. To assess the effects of time, group, and their interaction on clinical measures, a mixed model analysis will be employed [83]. This model will include fixed effects for Time (baseline, outcome 1, outcome 2), Group (immediate OBVAM therapy, delayed OBVAM therapy), and their interaction (Time × Group), with random intercepts for participants to account for the repeated measures within participants. The formula for the mixed model is the following:

Dep ~ 1 + Time + Group + Time:Group + (1 | Participants)

Where:

• Dep is the dependent variable for PFV, NPC, CISS, and secondary measures including imaging parameters, metrics for eye movement assessments, other clinical signs, and additional participant symptom surveys.
• Time is an independent variable for baseline, outcome 1, and outcome 2.
• Group is an independent variable for immediate OBVAM treatment and delayed OBVAM treatment.
• Time: Group is the interaction between Time measurements and Group measurements.
• (1 | Participants) is the random intercept accounting for within-participant variability.

The mixed effects model accounts for the correlation between repeated measures by including random intercepts for participants. This approach models within-participant correlation appropriately. Interaction effects between Time and Group will be examined, and post-hoc tests will be conducted to explore the within-group and between-group differences over time. Bonferroni correction will be applied to post-hoc comparisons to control for Type I errors. Since a mixed model will be employed, the normality of the residuals of the mixed-effects model after accounting for fixed and random effects will be checked [84]. Standard checks to assess the assumptions of the mixed-effects model will be conducted. These include checking the residuals’ normality via diagnostic tools such as the Shapiro-Wilks test, Q-Q plots, and residual distribution histograms. These steps will ensure the robustness of our model’s assumptions. However, if the residuals continue to deviate significantly, then a generalized linear mixed model (GLMM) to account for non-normal distributions will be employed.

For the secondary analysis, the same mixed-effects model framework as applied in the analysis for the primary outcomes for the secondary outcomes will be used. Specifically, models will be fit to account for fixed effects of time, group, and their interaction (Time × Group), with random intercepts for participants. Post-hoc tests will be performed to further explore the main effects and interactions. Subgroup analyses to explore whether the effects of time and group differ by key demographic or clinical variables, such as age and sex will be conducted. For these analyses, the mixed-effects models including interactions between the subgroup variables and the fixed effects (e.g., Time × Group × Sex or Time × Group × Age) will be performed. These analyses will allow the investigation of whether the observed effects are moderated by specific participant characteristics. For all exploratory secondary analyses, additional covariates, such as time since injury, number of concussions, mechanism of injury, sex, and age to understand the impact of these covariates on the outcome measures will be investigated. In addition, for imaging statistical analyses, average framewise displacements will be included as a participant-level covariate. Analyses will explore whether including these covariates in the mixed-effects models changes the primary results. Non-linear models will be considered if the relationship between predictors and outcomes appears to deviate from linearity.

Objective eye movement data analysis.

Eye movement data will first be calibrated from voltage values to degrees of rotation. Vergence eye movement data will be filtered with a 4^th-order Butterworth low pass filter with a cutoff frequency of 40 Hz, and saccades will be filtered using a cutoff frequency of 100 Hz. Blinks are easily identified because the signal will saturate, and eye movement responses that blink during the transient or dynamically moving portion of the eye movement trace will be omitted. Latency will be assessed as the time when the eye moves towards the new visual target quantified as a 5% change in the intended vergence demand. Peak vergence velocity will be computed by taking the difference in the left and right eye movement traces and applying a two-point central difference algorithm to compute the derivative of the position trace. Convergence will be plotted as positive and divergence as negative. Peak saccadic velocity will be calculated by averaging the left and right eye movement traces and applying a two-point central difference algorithm to compute the derivative. The number of saccades, the magnitude of saccades, and whether the saccade(s) generated more or less error in attaining the final vergence position will be assessed as done in prior research [85].

Rightward saccadic movements will be positive, and leftward will be negative. The final amplitude will be the average of the last 0.5 seconds of the positional traces, where blinks will be omitted from the trace. For vergence steps and saccades, latency, peak velocity, and final amplitude will be assessed for all the eye movement response types. The absolute difference between the stimulus target and oculomotor response will be evaluated for vergence ramps to determine how much error is present for slow (1⁰/sec) and fast (4⁰/sec) convergence and divergence ramps. For the endurance analysis, the peak velocity of the 4⁰ convergence steps will be assessed during the battery and the endurance tests as a function of experimental time. A linear regression will be performed for all the responses where a downward linear slope will show a decrease in performance, a flat line will show no substantial change in performance, and an upward line slope will show a performance improvement. This analysis will be repeated for divergence and saccadic eye movements.

Advanced imaging data analysis.

The following toolboxes will be used to analyze the imaging datasets: Statistical Parametric Mapping (SPM) (https://www.fil.ion.ucl.ac.uk/spm/software/) in MATLAB, FMRIB’s Software Library (FSL) [86] (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/) and Analysis of Functional Neuroimages toolbox (AFNI) [87] (http://afni.nimh.nih.gov/afni/). For each of the software packages, the same software version for each data processing platform will be maintained throughout the study analysis. The first five time points will be removed for each fMRI dataset to reduce T1-relaxation effects. A general linear model (GLM)—based activation analysis will be performed for the stimulus-induced tasks to derive participant-specific functional activation maps. Group-level analyses will be performed to study differences between the task-induced functional activity in both arms between Outcome 1 and between the enrollment and Outcome 2 measurements. Functional connectivity methods, including Independent Component Analysis (ICA) [88], Region of Interest (ROI) analysis, seed-to-seed and seed-to-voxel approaches [89], Amplitude of Low-Frequency Fluctuations (ALFF) [90], and regions of Homogeneity (ReHO) [91], will be performed on the rs-fMRI dataset. For the ASL data analysis, statistical models will be performed to investigate cerebral blood flow (CBF) changes and how cerebral perfusion changes in response to different interventions in CONC-CI participants. Correction for multiple comparisons will be used at p<0.05. A mixed model analysis will be used to study the time by group interaction with the statistical package R using the Jamovi Software [92]. The significance level will be set at p < 0.05.

Finally, the objective is to implement robust statistical methods that can elucidate potential connections between brain physiology and oculomotor function during the task and rest and in CONC-CI participants. This analytical approach will enable us to investigate disparities in the effectiveness of immediate OBVAM compared to delayed OBVAM while also exploring the influence of time and dosage on this population. To this end, comprehensive correlation analysis will be performed between all our measurements, including the clinical measures, oculomotor test, and task-induced and rsfMRI scans. For significant results in the group-level fMRI analysis, functional brain activation (beta weights) and other functional brain measures will be extracted for each participant. These functional brain measures will be used in a linear regression framework as dependent variables, along with clinical and oculomotor measures as independent factors to quantify the relationship between brain physiology and oculomotor function in CONC-CI participants and the impact of OBVAM on these relationships.

Data management plans.

A database will be set up for all collected data from each participant. Data related to each participant’s name would be coded by participant ID. Matched names and participant IDs will only be shared with the research coordinator and Project Principal Investigator (TLA). All collected data will be visually checked for data quality. Participants in both treatment groups will be monitored weekly during the treatment sessions and follow-up visits for any adverse event(s) or unanticipated problem(s). The Office for Human Research Protections (OHRP) definitions of a serious adverse event, unexpected event, definitely-related, probably-related, possibly-related, and unrelated will be used [93]. Upon the occurrence of an unanticipated problem, the Adverse Event Form will be completed by the Principal Investigator (PI) and faxed to the IRB within 7 days. The PI will also inform participants of any important new information that might affect their willingness to continue participating in the research. If an adverse event necessitates changes to the consent/assent form(s) and/or protocol, that notification will be given to currently or previously enrolled participants, an amendment request will be submitted in conjunction with the adverse event report. The IRB will decide whether any new findings, new knowledge, or adverse events should be communicated to participants.

The research team will thoroughly discuss all discrepancies to achieve a group consensus. In cases where necessary, consultations with experts in clinical trials will be pursued for additional insights. Imaging data will be uploaded to NIH CDE https://cde.nlm.nih.gov/home and NIH FITBIR (Federal Interagency Traumatic Brain Injury Research Informatics System) (https://fitbir.nih.gov) using the Brain Imaging Data Structure (BIDS) format (neuroimaging.io) with the clinical signs, symptoms, and eye movements raw data and summary metrics.

Ethical considerations.

This study is registered at ClinicalTrials.gov (Identifier: NCT05262361; March 2, 2022, https://clinicaltrials.gov/study/NCT05262361). The protocol of this study is approved by the ethical committee of the New Jersey Institute of Technology, Rutgers University-Newark, Children’s Hospital of Philadelphia, and Salus University. An alliance agreement was reached between institutions using the SMART IRB platform. NJIT is the IRB of record. Annual progress reports are required. All participants or their legal guardians will give written informed consent before enrolling in the study, and written assent will be required if the participant is a child. The nature and all steps of the study will be explained to the participants and their legal guardians, if the participant is a minor, before giving consent to the study inclusion, and all their questions will be addressed during the study. All participants will be made aware that they can withdraw from the study at any time of the study without any consequences and will still have care administered by their principal physician. The matched participant IDs and identifiable information of all participants will not be shared with the research team other than the research coordinators and the Project Principal Investigator (TLA). An online database and survey platform (REDCap) will be used during the clinical data collection and treatment sessions to record all the dataset inputs (redcap.research.chop.edu). All oculomotor and imaging data will be anonymized and only have participant IDs. Authorized research team members who need to access the data for further analysis will only have access to the anonymized final datasets. Due to the non-invasive nature of all assessments and interventions, health risks are not anticipated during the study using objective measurements beyond the provocation of concussive symptoms that the participant is already experiencing.

Status of study.

The NIH funding was received on September 1, 2021. Recruitment began on February 21, 2022, for both NJIT and CHOP clinical sites and is estimated to continue until September 1, 2025. The project is planned to be completed on August 28, 2026. Instrumentation has been installed [94] and all study personnel have been trained and certified. Vision therapists will be recertified annually to ensure a consistent administration of OBVAM.

Dissemination plans.

The results of this study will be published in peer-reviewed scientific journals. Current models describing vergence [95] will be modified to consider the impact of concussion on the convergence system. The study findings will also be disseminated at major national and international scientific conferences. This study’s findings can be broadly disseminated to test the effectiveness of other therapies in visual neuroscience, studying motor learning and rehabilitation (applications ranging from basic science to neurological injury/disease) in conditions such as neurodegenerative diseases. The results of the objective and clinical evaluations will be provided in an easy-to-understand report format for all participants who would like to receive their results. OBVAM will be taught in interactive workshops at the American Academy of Optometry and other clinical professional societies.

Amendments to the study.

The PI (TLA) and the lead clinicians (MS and AG) will discuss any study amendments. If an unexpected change is needed, an amendment will be submitted to the IRB, and the protocol will be revised in clinicaltrials.gov. Since all participants will be under the care of a physician, any unanticipated symptoms or events will be discussed in consultation with the participant’s physician. If any subsequent injuries occur while a participant is undergoing OBVAM, then the physician will decide whether OBVAM needs to be suspended or reduced from the dosage of twice per week. The physician will be responsible for terminating treatment if any complications arise, and the IRB will be notified.

Risk management.

OBVAM is considered a low-risk therapeutic intervention. If a participant begins to show regression of progress or other complications arise, the primary physician will be consulted immediately to determine the next steps of treatment. The primary physician has the right to withdraw any participant from the trial if unexpected worsening of symptoms occurs. After a participant finishes the 16 sessions of OBVAM, if they have not remediated the primary care physician will determine what type of other therapeutic intervention(s) including additional vision therapy sessions may be prescribed to further improve function and reduce symptoms.