Our study used FE analysis to understand how horizontal eye movements can influence the biomechanical environment of peripapillary tissues. Our models demonstrated that, during eye movements, the ONH was sheared in the transverse plane through the pulling action of the optic nerve and its meninges. The traction forces of the optic nerve sheath were large, which resulted in stresses within the peripapillary tissues localized in the nasal and temporal quadrants. These stresses also were highly influenced by the stiffness of the surrounding connective tissue structures (sclera, dura, pia, but not LC).
Our model predicted a shearing deformation of peripapillary tissues during horizontal eye movements, which was characterized by opposite displacements of nasal and temporal peripapillary tissues (
Fig. 2). This deformation pattern is in agreement with that observed in three recent OCT studies.
13–15 Furthermore, LC strains (see
Supplementary Material SC) in this study were on the same order of magnitude as those measured in vivo.
14 Additionally, the deformed and undeformed geometries of this model matched well with MRI observations.
16 This suggests that our FE model, although simplified, may be useful to provide a first but preliminary understanding of the stress levels exhibited by peripapillary tissues following eye movements.
For a horizontal eye rotation of 13°, the estimated traction forces generated by the pulling action of the optic nerve sheath were 90 mN in abduction and 150 mN in adduction. These forces are of the same order of magnitude as those exerted on the globe by the rectus extraocular muscles. Collins et al.
33 demonstrated that, for horizontal eye movements of 50°, the maximum forces that could be developed by the lateral and medial muscles were on average 580 and 730 mN (measured from 29 healthy subjects), respectively. The corresponding muscle forces for eye rotations of 13° would be less than 151 and 190 mN because of the nonlinear relationship between eye rotation amplitude and active force level.
33 Interestingly, the predicted optic nerve sheath traction force in adduction was larger than that in abduction, suggesting that rectus muscles must overcome a larger resistance force in adduction. This is consistent with the fact that the force generated by the medial muscle is typically higher than that of the lateral muscle during horizontal eye movements.
33 Furthermore, the large optic nerve traction force has been demonstrated to be able to retract the eye globe within its orbit in highly myopic eyes with staphyloma.
17 Future studies on eye motility may consider including the non-negligible effects of optic nerve traction.
Previous studies on the structural changes of the ONH region mainly focused on the effects of IOP. Wang et al.
9 observed a folding of the RPE and a sliding of the end of RPE on BM under acute IOP elevation, which was associated with a transient enlargement of the peripapillary beta zone. Moreover, Panda-Jonas et al.
34 observed changes in areas of peripapillary gamma zone in young glaucoma patients after marked surgical reduction of IOP. Our model showed that ONH deformations induced by eye movements are comparable or larger than those induced by a transient IOP
35 or CSFP increases
36 (see
Supplementary Material SC), indicating a potential role for ocular movements in the development and progression of peripapillary zones. It could be possible that both the peripapillary beta zone and peripapillary gamma zone are caused partially by abnormal stretching of the ONH region by the optic nerve and its sheaths during eye movements. Note that the links between mechanical stress/strain and peripapillary zones are speculative; further experimental or clinical studies may aid in understanding their potential relationships. In our previous study using in vivo OCT imaging,
14 we observed on average larger gaze-induced ONH deformations in subjects with peripapillary zones. That study was, however, limited to a small sample size (5 eyes without peripapillary zones versus 11 eyes with peripapillary zones), and repeating such work with a larger sample size may provide a better understanding of the correlation between eye movements and peripapillary zones.
Eye movements might partly contribute to axial elongation in myopia. A few studies have reported small axial elongations as a result of either a shift in gaze direction
18,37 or accommodation.
38,39 It has been hypothesized that the change in axial length might be due to mechanical forces generated by the ciliary muscles or extraocular muscles,
40 noting that the extraocular muscle forces are not acting on the axial direction and their effects on globe geometry might be complex and limited. Because our work predicts an optic nerve sheath traction force of the same order of magnitude as extraocular muscle forces, and this traction force directly pulls the globe along its anterior-posterior direction, it would be plausible to suggest that optic nerve traction may have a role to play in axial elongation. If this hypothesis were to be proven correct, optic nerve traction in convergence, such as during prolonged near-reading in myopes, may stretch the globe significantly and accelerate myopic progression. Moreover, axial elongation itself might be able to cause peripapillary zones through the sliding of BM and stretching of the scleral canal border tissues,
1,41 supporting the hypothesis that peripapillary zones might be correlated with eye movements.
It has been reported that, in incipient myopia, peripapillary zone enlargements were associated with the development of tilted discs, mainly the development and enlargement of peripapillary gamma zone in association with a rotation of the optic disc around its vertical axis.
41 The shearing deformation observed in this study (
Fig. 2) and other OCT observations
13–15 might be able to explain the optic disc rotation about the vertical axis (axis along the superior-inferior direction) observed in myopic eyes.
42 It is plausible that continuous stretching of peripapillary tissues following repeated eye movements might contribute to the development of rotated optic discs and peripapillary zones simultaneously through a tissue remodeling process. Note that our model simulated only horizontal eye movements and was symmetric about a transverse plane, which can only yield disc tilting about the vertical axis. The complexity of physiological eye movements (e.g., combination of adduction and depression) in association with variations in eye and orbit anatomy (e.g., axial length or location of the optic nerve origin in the nasal upper region of the orbit) may contribute to the variety of tilting directions seen in patients with tilted optic discs.
43 Additionally, Sibony et al.
44 reported that patients with myopic tilted discs may spontaneously develop peripapillary subretinal hemorrhages. The authors speculated that these were caused by gaze-evoked shearing of blood vessels at the ONH site. Our simulation results support their hypothesis, and future studies are needed to explore the effects of eye movements on the hemodynamics of the ONH region.
Following eye movements, the average ppBM stresses in adduction and abduction did not differ significantly (4.5% difference). However, the difference in ppS stresses was relatively large (ppS stress in adduction was 16% higher than in abduction). This trend was similar to our previous studies,
14,16 in which LC strains in adduction were higher than those in abduction. Other independent studies also concluded that ONH deformation was more affected by adduction.
13,15 Additionally, a higher ppS stress in adduction also was consistent with a larger optic nerve sheath traction force predicted in this study. We speculated that the overall higher stresses in ppS and higher traction forces in adduction were because of a more elongated optic nerve in adduction than in abduction for the same magnitude of eye rotation. A detailed geometric analysis was performed to explain our hypothesis, which can be found in a separate study.
14
Quadrant-wise stress predictions showed that, in adduction, stress in the temporal ppS was 96% higher than that in the nasal ppS (0.25 vs. 0.13 MPa). In abduction, nasal ppS stress was 64% higher than that in the temporal ppS (0.20 vs. 0.12 MPa). On the contrary, the stress differences in temporal and nasal ppBM were small (5% for adduction and 8% for abduction). Because the traction force exerted by the optic nerve sheaths was not evenly applied on the ppS, it is logical that the ppS stresses would be different in nasal and temporal quadrants. Furthermore, as the ppS is structurally stronger than ppBM (ppS is 100 times thicker than ppBM with an elastic modulus of the same order of magnitude) and the dura sheath directly anchors to the border between the posterior sclera and the peripapillary scleral flange, it is reasonable that traction forces mainly affect the uniformity of stress distribution in the outer part of the ppS and not in the ppBM (
Fig. 3). Considering both adduction and abduction models, the average stress experienced by the temporal ppS (which was highest in adduction; 0.25 MPa) was 27% higher than that in the nasal quadrant (which was highest in abduction; 0.20 MPa), whereas the corresponding differences for ppBM were within 5%. The higher stress experienced by the temporal ppS may explain why peripapillary zones are more commonly found on the temporal side,
3 although this would need to be further investigated. It is worth mentioning that adduction-evoked phosphenes
13,45–47 are normally greater on the temporal side of the blind spot, suggesting that nasal peripapillary tissues may be more affected. This is in contradiction with our prediction of higher temporal stresses in adduction. We speculate that it is because retinal cell function is not only affected by the magnitude of stress but also its type (e.g., compression, tension, shearing, or their combinations). Generally, in adduction, the optic nerve sheath pulls the temporal tissues and compresses the nasal tissues, resulting in different stress patterns in nasal and temporal tissues. However, the links between stress/strain patterns to retinal cell functions have not yet been established.
Our sensitivity study showed that a stiffer sclera reduced the overall BM stress following eye movements. This finding is relatively intuitive, as a stiffer sclera will tend to limit the deformations of the whole ONH, thus shielding ppBM from further stress. We also found that the stiffer the dura mater, the higher the ppBM stresses following eye movements. This is not surprising, as a stiffer dura will tend to restrict eye movements by exerting a larger pulling force on the globe.
Our eyes exhibit frequent movements in daily activities (approximately 170,000 saccades per day
48) and the magnitudes are typically within 15°.
49 Large shifts of gaze are usually accomplished by a combination of head and eye movements. For example, reading text from an A4 size page (width: 170 mm) and from a normal distance will result in an eye rotation angle (eccentricity) of approximately 11° and a head rotation angle of approximately 0.65°.
50 However, reading text from a larger document (width: 535 mm) can result in a head rotation angle of approximately 15.5° and an eye rotation angle that is increased to only approximately 23°.
50 Note that the eye rotation angle used in our simulations was 13°, which is within the normal range of the eye rotation in daily activities. We speculated that if gaze-induced stresses were to exceed a safe threshold over a significant period, tissue growth and remodeling of the peripapillary connective tissues should be expected. However, it should be noted that peripapillary tissue stresses induced by eye movements are transient, as opposed to chronic increases in IOP or CSFP. It is still unclear whether these transient stresses could be harmful to peripapillary tissues.