Foveolar Drusen Decrease Fixation Stability in Pre-Symptomatic AMD.

Purpose: This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD). Methods: We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO. Results: FEM were measured with high precision (RMS-S2S = 0.0015 degrees on human eyes) and small foveal drusen (median diameter = 60 µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea. Conclusions: A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

Multi-modal and multi-scale clinical retinal imaging system with pupil and retinal tracking.

We present a compact multi-modal and multi-scale retinal imaging instrument with an angiographic functional extension for clinical use. The system integrates scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT) and OCT angiography (OCTA) imaging modalities and provides multi-scale fields of view. For high resolution, and high lateral resolution in particular, cellular imaging correction of aberrations by adaptive optics (AO) is employed. The entire instrument has a compact design and the scanning head is mounted on motorized translation stages that enable 3D self-alignment with respect to the subject's eye by tracking the pupil position. Retinal tracking, based on the information provided by SLO, is incorporated in the instrument to compensate for retinal motion during OCT imaging. The imaging capabilities of the multi-modal and multi-scale instrument were tested by imaging healthy volunteers and patients.

A New Method for Visualizing Drusen and Their Progression in Flood-Illumination Adaptive Optics Ophthalmoscopy.

Purpose: Drusen are dynamic sub-RPE deposits that are risk factors for late-stage age-related macular degeneration (AMD). Here we show a new imaging method using flood-illumination adaptive optics (FIAO) that reveal drusen with high contrast and resolution. Methods: A fovea-centered 4° × 4° FIAO image and eight surrounding images with gaze displaced by ±2° vertically and horizontally were acquired. Clinical color fundus and spectral-domain optical coherence tomography were acquired for clinical grading and comparison. Custom software registered overlapping FIAO images and fused the data statistically to generate a fovea-centered 4° × 4° gaze-dependent image. Our dataset included 15 controls (aged 31-72) and 182 eyes from 104 AMD patients (aged 56-92), graded as either normal aging (n = 7), and early (n = 12), intermediate (n = 108) and late AMD (n = 42); 27 had subretinal drusenoid deposits (SDDs), and 83 were imaged longitudinally. Results: No gaze varying structures were detected in young eyes. In aging eyes with no evidence of age-related changes, putative drusen <20 µm in diameter were visible. Gaze-dependent images revealed more drusen and many smaller drusen than visible in color fundus images. Longitudinal images showed expansion and fusion of drusen. SDDs were lower contrast, and RPE atrophy did not yield a consistent signal. Conclusions: Gaze-dependent imaging in a commercially available FIAO fundus camera combined with image registration and postprocessing permits visualization of drusen and their progression with high contrast and resolution. Translational Relevance: This new technique offers promise as a robust and sensitive method to detect, map, quantify, and monitor the dynamics of drusen in aging and AMD.

Fixational eye movements in passive versus active sustained fixation tasks.

Human fixational eye movements are so small and precise that high-speed, accurate tools are needed to fully reveal their properties and functional roles. Where the fixated image lands on the retina and how it moves for different levels of visually demanding tasks is the subject of the current study. An Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) was used to image, track and present a variety of fixation targets (Maltese cross, disk, concentric circles, Vernier and tumbling-E letter) to healthy subjects. During these different passive (static) or active (discriminating) tasks under natural eye motion, the landing position of the target on the retina was tracked in space and time over the retinal image directly with high spatial (<1 arcmin) and temporal (960 Hz) resolution. We computed both the eye motion and the exact trajectory of the fixated target's motion over the retina. We confirmed that compared to passive tasks, active tasks elicited a partial inhibition of microsaccades, leading to longer drift periods compensated by larger corrective saccades. Consequently, the overall fixation stability during active tasks was on average 57% larger than during passive tasks. The preferred retinal locus of fixation was the same for each task and did not coincide with the location of the peak cone density.

Laser Doppler holography of the anterior segment for blood flow imaging, eye tracking, and transparency assessment.

Laser Doppler holography (LDH) is a full-field blood flow imaging technique able to reveal human retinal and choroidal blood flow with high temporal resolution. We here report on using LDH in the anterior segment of the eye without making changes to the instrument. Blood flow in the bulbar conjunctiva and episclera as well as in corneal neovascularization can be effectively imaged. We additionally demonstrate simultaneous holographic imaging of the anterior and posterior segments by simply adapting the numerical propagation distance to the plane of interest. We used this feature to track the movements of the retina and pupil with high temporal resolution. Finally, we show that the light backscattered by the retina can be used for retro-illumination of the anterior segment. Hence digital holography can reveal opacities caused by absorption or diffusion in the cornea and eye lens.

Characteristics of saccades during the near point of convergence test.

The near point of convergence test is widely used to evaluate binocular vision. It assesses the ability of the eyes to converge at short distances. Although the test consists of a pure symmetrical vergence task, small involuntary saccades occur concurrently. The main goal of this study was to analyze saccadic characteristics as a function of vergence demand when testing the near point of convergence. To this purpose, the eye movements of 11 participants were registered with an eye-tracker while they performed the near point of convergence test by following a target that traveled forward and backward on a motorized bench. Saccade amplitude increased and, on average, saccade rate decreased with vergence demand. In general, the direction of the concurrent vergence movement had no significant effect on saccade characteristics. However, each individual subject showed idiosyncratic behavior. Most saccades tended to be corrective in terms of both binocular disparity and individual fixation position errors. In particular, most participants tended to correct the fixation position error of the dominant eye.

An automated and objective cover test to measure heterophoria.

Heterophoria is the relative deviation of the eyes in absence of fusional vergence. Fusional vergence can be deprived by, for example, occluding one eye while the other fixates a visual target. Then, the occluded eye will presumably deviate from its initial position by an amount that corresponds to the heterophoria. Its assessment in clinical practice is crucial for the diagnosis of non-strabismic binocular dysfunctions such as convergence insufficiency. Traditional clinical methods, like the cover test or the modified Thorington test, suffer from practitioner's subjectivity, impossibility to observe the occluding eye or unusual viewing conditions. These limitations could be overcome by using eye tracking systems to measure objectively the heterophoria. The main purpose of this study was to compare the performance of an automated and objective method to measure near heterophoria using an eye-tracker with two conventional methods: the cover-uncover test and the modified Thorington test. The eye tracking method gave us the possibility to measure the heterophoria as the deviation of the occluded eye (mimicking the cover test) or as the deviations of the occluded and fixating eyes (adhering to the theoretical definition of heterophoria). The latter method provided smaller results than the former, although on average the differences might not be clinically relevant. The proposed objective method exhibited considerably better repeatability than the two conventional clinical methods. It showed better agreement with the modified Thorington test than with the cover-uncover test, and a similar level of agreement was obtained between the two clinical methods. To conclude, the use of eye-trackers to measure heterophoria provides objective and more repeatable measures. As eye-trackers become common tools in clinical settings, their use to measure heterophoria should be the new gold standard.

Robust eye tracking based on multiple corneal reflections for clinical applications.

A set of methods in terms of both image processing and gaze estimation for accurate eye tracking is proposed. The eye-tracker used in this study relies on the dark-pupil method with up to 12 corneal reflections and offers an unprecedented high resolution imaging of the pupil and the cornea. The potential benefits of a higher number of glints and their optimum arrangement are analyzed considering distinct light sources configurations with 12, 8, 6, 4, and 2 corneal reflections. Moreover, a normalization factor of the pupil-glint vector is proposed for each configuration. There is a tendency for increasing accuracy with the number of glints, especially vertically (0.47 deg for 12 glints configuration versus 0.65 deg for 2 glints configuration). Besides the number of corneal reflections, their arrangement seems to have a stronger effect. A configuration that minimizes the interference of the eyelids with the corneal reflections is desired. Finally, the normalization of the pupil-glint vectors improves the vertical eye tracking accuracy up to 43.2%. In addition, the normalization also limits the need for a higher number of light sources to achieve better spatial accuracy.

Monocular microsaccades are visual-task related.

During visual fixation, we constantly move our eyes. These microscopic eye movements are composed of tremor, drift, and microsaccades. Early studies concluded that microsaccades, like larger saccades, are binocular and conjugate, as expected from Hering's law of equal innervation. Here, we document the existence of monocular microsaccades during both fixation and a discrimination task, reporting the location of the gap in a foveal, low-contrast letter C. Monocular microsaccades differ in frequency, amplitude, and peak velocity from binocular microsaccades. Our analyses show that these differences are robust to different velocity and duration criteria that have been used previously to identify microsaccades. Also, the frequency of monocular microsaccades differs systematically according to the task: monocular microsaccades occur more frequently during fixation than discrimination, the opposite of their binocular equivalents. However, during discrimination, monocular microsaccades occur more often around the discrimination threshold, particularly for each subject's dominant eye and in case of successful discrimination. We suggest that monocular microsaccades play a functional role in the production of fine corrections of eye position and vergence during demanding visual tasks.