Objective assessment of eye alignment and disparity-driven vergence in Parkinson's disease

Abstract

Background: Self-reported diplopia is described in up to one-third of Parkinson's disease (PD) patients.

Objective: The purpose of our study was to expand our understanding of the mechanistic underpinnings of diplopia in PD. We hypothesize that the time-based control of eye alignment and increased eye deviation under binocular viewing will be related to the fusion-initiating and fusion-maintaining component deficits of disparity-driven vergence in PD.

Methods: We used high-resolution video-oculography to measure eye alignment under binocular and monocular viewing and disparity-driven vergence in 33 PD and 10 age-matched healthy participants. We computed eye deviation and time-based control of eye alignment, occurrence of conjugate saccadic eye movements, latency and gain of vergence (fusion initiation), and variance of eye position at the end of dynamic vergence (fusion maintenance).

Results: We categorized PD subjects into three groups, considering their time-based control of eye alignment as compared to healthy controls in binocular viewing. Group 1 = 45% had good control and spent >80% of the time when the eyes were well-aligned, Group 2 = 26% had intermediate control and spent <80% but greater >5% of the time when the eyes were well-aligned, and Group 3 = 29% had very poor control with increased eye deviation majority of the times (<5% of the time when the eyes were well-aligned). All three groups exhibited greater eye deviation under monocular viewing than controls. PD subjects exhibited fusion-initiating and fusion-maintaining vergence deficits (prolonged latencies, reduced vergence gain, increased variance of fusion-maintaining component) with a greater probability of saccadic movements than controls. Group 2 and Group 3 subjects were more likely to exhibit failure to initiate vergence (>20%) than Group 1 (13%) and controls (0%) trials. No significant difference was found in the Unified Parkinson's Disease Rating Scale (UPDRS-a tool to measure the severity of PD) values between the three PD groups (Group 1 = 33.69 ± 14.22, Group 2 = 38.43 ± 22.61, and Group 3 = 23.44 ± 1, p > 0.05).

Conclusion: The majority of PD subjects within our cohort had binocular dysfunction with increased eye deviation under monocular viewing and disparity-driven vergence deficits. PD subjects with intermediate or poor control of eye deviation under binocular viewing had greater fusion-initiating and fusion-maintaining vergence deficits. The study highlights the importance of assessing binocular dysfunction in PD subjects independent of the severity of motor symptoms.

Keywords: Parkinson’s disease; basal ganglia; density-based clustering; strabismus; supra-oculomotor area; vergence.

Figure 1

Methodology of eye deviation analysis: (A,B) show the time series of right and left eye horizontal and vertical eye position data from a Parkinson’s disease subject collected under right (A) and left (B) eye viewing conditions while viewing a target in primary position for 20 s. Notice that in right eye viewing condition (A), the left eye is deviated to the left and during left eye viewing (B), the right eye is deviated to the right indicative of an exodeviation. The viewing eye data obtained under monocular viewing is designated as the expected eye position – i.e., the right eye position data [blue trace in (A)] under right eye viewing is designated as right eye expected eye position data and vice versa whereas the non-viewing eye data obtained under monocular viewing is the actual eye position data, i.e., non-viewing right eye data [cyan trace in (B)] obtained under left eye viewing is designated as actual eye position data of the right eye and vice versa. (C,D) show the respective “expected” (dark blue and dark red traces) and “actual” eye position traces (light blue and light red) for the right (C) and left eye (D). Annotations on the side show median values for expected horizontal and expected vertical eye positions to use in the calculation of the angle of deviation. The eye deviation was measured by comparing the position of each eye with itself when it was viewing vs. non-viewing (i.e., expected and actual eye positions, respectively). (E,F) show the computed difference in horizontal and vertical planes between the “expected” and “actual” eye positions for the right (E) and left eyes (F).

Figure 2

Application of DBSCAN: (A–C) shows the time series [x-axis: time(s); y-axis: eye deviation (deg)]; (A) shows the computed difference between expected and actual eye positions in horizontal and vertical planes; (B) shows the Initial application of DBSCAN resulting in 5 well-aligned and 8 misaligned clusters. Inset shows the instance of filtering out rapid eye movements, in this case, an SWJ; (C) shows a single well-aligned super-cluster. Misaligned clusters with horizontal means <2° and vertical means <1° apart are combined. End result: 1 super-cluster of good binocular alignment and 3 misaligned super-clusters.

Figure 3

Examples of horizontal and vertical eye positions obtained from the right eye during a 30-s epoch under left eye viewing (monocular) and binocular viewing conditions: From a Control subject in BV [(A)-left top panel)] and MV [(A)-right top panel)], eye positions maintained fairly close together under BV with minimal increase in difference (exodeviation) between actual and expected eye positions observed under MV; (A) (middle panel): eye deviation, i.e., difference in eye positions for BV (right) and MV (left) in horizontal and vertical planes in control subject; (A) (bottom panel): histogram of difference of horizontal eye positions (95% lower and upper bounds with span in parenthesis) showing less spread in BV than MV with the majority of data points falling within the threshold window of 3.5°). PDG1 subject: (B) (left top panel): BV—eye positions maintained close together, (B) (right top panel): MV—significant difference (7–9.25° horizontal) between actual and expected eye position; (B) (middle panel): minimal difference in eye positions for BV (right) and a significantly larger difference in MV (left) in horizontal and vertical planes in PDG1; (B) (bottom panel): histogram of difference of horizontal eye positions showing constrained spread in BV and relatively larger spread in MV. PDG2 subject: (C) (left top panel): BV—eye positions maintained close together initially with right eye deviating up to 8° starting around the halfway point, (C) (right top panel): MV—gradually increasing rightward deviation in horizontal plane; (C) (middle panel): difference in eye positions for BV (right) and MV (left) in horizontal and vertical planes in PDG2 showing significantly higher deviation; (C) (bottom panel): histogram of difference of eye positions showing large spread in both BV and MV with increased span under BV. PDG3 subject: (D) (left top panel): BV—large difference in eye positions throughout, (D) (right top panel): MV—large angle deviation in horizontal between actual and expected eye position; (D) (middle panel): difference in eye positions for BV (right) and MV (left) in horizontal and vertical planes and horizontal eye deviation in PDG3; (D) (bottom panel): histogram of the horizontal difference of eye positions showing extremely large spread in both BV and MV with increased span under both BV and MV.

Figure 4

(A,B) Scatter plot of the log of cluster means generated using the DBSCAN algorithm for each participant in BV (A) and MV (B) in horizontal (x-axis) and vertical (y-axis) planes. Marker size is indicative of time spent in that region. Controls (black squares) are very well-controlled in BV with the majority of points within the threshold window in MV (i.e., within or near gray box depicting threshold for well-aligned clusters—3.5° horizontal; 2° vertical) than PD subjects. PDG1 subjects (green diamonds) are comparable to controls in BV but show significant deviation in MV. PDG2 subjects (blue circles) show some increase in eye deviation in BV with a large increase in eye deviation in MV. PDG3 subjects (red triangles) show significantly worse eye alignment with extremely large eye deviation reflected as the majority of red symbols being outside the threshold window, particularly in MV.

Figure 5

Examples of vergence initiation strategies and their distribution by group: (A–D) show vergence strategies seen across four groups of participants. Black solid circle denotes peak velocity. Gray lines define the start and end of fusion initiation/gaze shift. Dashed green trace defines the fusion maintenance component. Notice that in the pure vergence strategy (A), the left eye moves to the right and the right eye moves to the left with a net purely disconjugate component (green trace—positive excursion suggestive of convergence response). In the pure saccade strategy (B), the right and left eyes move to the right with a net conjugate movement (cyan trace) and there is a minimal change in the disconjugate component (green trace). For the vergence saccade (VS) strategy (C), there is an initial pure vergence movement that is followed by a saccade whereas in the saccade vergence (SV) strategy (D), there is a saccadic component (arrow) that precedes the pure vergence component. For the strategies incorporating conjugate shift (B–D) notice that the saccades are asymmetric resulting in a net disconjugate component that contributes to the vergence gain (dark green section in Re_actual, LE_actual, and Vergence traces emphasized with black arrows). The resultant conjugate shift (cyan trace) is emphasized with red arrows.

Figure 6

(A–D) depict the distribution of different strategies recruited to perform gaze shift in BV—pure vergence “PV”, vergence-saccade—“VS”, saccade-vergence—“SV”, and pure saccade—“PS”. In (A), control subjects were successful in performing vergence-leading eye movements (PV or VS) 95% of the time whereas, PDG1 subjects (B) were successful in performing vergence-leading eye movements 44% of the time. PDG2 subjects (C) had significant difficulty in executing any appreciable gaze shift (33%) and could only perform vergence-leading eye movements 35% of the time. PDG3 subjects (D) also had significant difficulty in executing any appreciable gaze shift (21%) and executed a much higher percentage of saccade-leading eye movements 14% of the time and divergence (wrong direction) movements 10% of the time. Notice that minimal movement, wrong direction (divergence movement), and pure saccade strategies were seen only in PD subjects with a greater % of patients in PDG2 and PDG3 that exhibited minimal movement strategy.

Figure 7

(A) Summary box plot of vergence gaze shift gain with respect to the strategy used. Controls have the highest overall gain compared to the PD groups across all strategies with the ability to initiate movement for all trials. PD Groups had lower overall gains and trials with pure saccades and minimal movement. Gains in conjugate segments of gaze shifts (PS, VS, and SV) are computed from asymmetric saccades giving rise to a net disconjugacy. (B) Logarithmic plot of latencies found during each trial broken down into the latency of vergence (disconjugate) movement (x-axis) and saccade (conjugate) movement (y-axis) across different groups. In the case of pure vergence (missing ordinate) or pure saccade (missing abscissa), a constant but arbitrary value was assigned in place of the missing value to plot against combination strategies (alternate strategies involving both vergence and saccade). Most controls (black squares) utilized vergence-leading strategies (PV or VS) (values are above the equality line). PDG1 (green diamonds), PDG2 (blue circles), and PDG3 (red triangles) subjects had several trials with saccade-leading (SV or PS) strategies.