AACE Biomarker Protocol: Identifying Subclinical Oculomotor and Electrophysiological Predictors of Acute Acquired Concomitant Esotropia
This detailed experimental protocol is designed to identify baseline biomarkers for the future development of Acute Acquired Concomitant Esotropia (AACE). It integrates high-resolution oculomotor tracking with cortical electrophysiology to detect subclinical imbalances in fusion and motor control.
I. Study Overview
- Primary Objective: To identify subclinical biomarkers (detectable before symptom onset) that predict AACE development and distinguish it from other forms of esotropia.
- Target Population: High-risk individuals (adolescents/young adults with moderate myopia and heavy digital device use, >4-5 hours/day) and age-matched controls.
- Primary Modality: EyeLink Eye Tracker (downstream oculomotor imbalance).
- Auxiliary Modality: 32-channel EEG (intermediate neural/fusion mechanisms).
II. Task Designs
Tasks programmed in MATLAB using Psychtoolbox (PTB) and Opticka, employing a dichoptic display (polarized or shutter glasses) to isolate eye-specific responses.
Task 1: Resting State (Baseline Cortical Network)
- Design: 5 minutes eyes-closed + 5 minutes eyes-open resting state.
- Biomarker Focus:
- Alpha-Band PSD: Baseline cortical “idling” or inhibition.
- IHD-PSD: Interhemispheric power differences, particularly in superior frontal gyrus and anterior cingulate — regions linked to AACE functional connectivity deficits.
Task 2: Precision Fixation Stability
- Design: Central Gaussian spot (0.5°) fixation for 60 seconds.
- Biomarker Focus:
- Fixation Instability: Quantifying microsaccades and slow drift. AACE is characterized by a “dominant deviating eye,” which may show subtle instability even before manifest deviation.
Task 3: Oculomotor Dynamics (Saccades & Smooth Pursuit)
- Saccade Design: Target jumps randomly to ±18.3° horizontally; rapid refixation.
- Smooth Pursuit Design: Step-ramp target at ±6.1°/s horizontal. Step-ramp prevents early saccades at pursuit onset.
- Biomarker Focus:
- Saccade Gain Asymmetry: Difference in amplitude/velocity between adduction and abduction. Binocular coordination of saccades is significantly poorer in AACE even after clinical “recovery.”
- Smooth Pursuit Gain: Tracking accuracy. Reduced gain reflects breakdown in the feedback loop for binocular coordination.
Task 4: Dichoptic SSVEP & Perceptual Eye Position (PEP)
- PEP Calibration: Move a dichoptic symbol (”+”) into a fixed circle (”○”) until perceived as perfectly overlapping. Records subjective strabismus angle (Perceptual Eye Position).
- SSVEP Design: Circular flickering targets (8° × 8°) presented dichoptically. Left eye: f₁ = 13 Hz; Right eye: f₂ = 15 Hz.
- Biomarker Focus:
- Intermodulation Frequency (f₁ ± f₂): Direct measure of binocular integration. Lower responses correlate strongly with larger perceptual deviations in AACE.
- SSVEP Asymmetry Index: Comparing SNR between the two eyes to quantify subclinical suppression.
III. Measurement & Analysis Plan
| Category | Measure | Significance for AACE Biomarker |
|---|---|---|
| Eye-Tracking | Binocular Coordination | Difference in gain between dominant and non-dominant eye. Poor coordination is a core AACE signature. |
| EEG | α-Band PSD (8-13 Hz) | Lower alpha power in parietal/occipital regions associated with visual stress and compensatory processing. |
| EEG | IHD-PSD | Reflected by voxel-mirrored homotopic connectivity (VMHC) deficits found in AACE patients’ frontal lobes. |
| EEG | SSVEP IM SNR | Intermodulation SNR reflects “fusion strength” of the cortical network. Reductions predict failure of binocularity. |
IV. Clinical Justification
AACE incidence is rising due to excessive near-work and digital device use, which increases medial rectus muscle tension and disrupts fusion.
- Eye tracking is the primary modality because it captures the most direct downstream motor manifestations of this tension, such as asymmetric saccade gain.
- EEG is a critical auxiliary because AACE involves functional deficits in the visual cortex and dorsal pathway. These neural signals (especially SSVEP and alpha PSD) may change before the oculomotor system completely decompensates into manifest esotropia.
Verification Note: The use of Opticka enables high-precision temporal syncing between the EyeLink and EEG amplifiers, essential for calculating smooth pursuit gain during specific EEG oscillation windows.