Abstract
Purpose
To evaluate accommodation-induced changes in the ciliary muscle (CM), Schlemm’s canal (SC), and trabecular meshwork (TM) in eyes with and without high myopia, and to assess the associations among these structures during accommodation.
Methods
116 eyes from 57 healthy control (HC) and 59 high myopia (HM) were assessed across two experiments. In the first experiment, pilocarpine-induced accommodation was applied to 78 eyes, while in the second, a -5 diopter (D) accommodative stimulus was used on 38 eyes. Anterior segment images were captured via swept-source optical coherence tomography before and after each accommodation stimulus. Measurements included the maximum thickness of CM and the anterior length of CM, the length of TM, and the area of SC. Statistical analyses evaluated group differences and correlations.
Results
Drug-induced and − 5D stimulation increased the maximum thickness of CM and the area of SC’s levels while decreasing the anterior length of CM’s levels. In the HC group, the length of TM was larger in the accommodative state, mediating the relationship between changes in the maximum thickness of CM and the area of SC. Conversely, these changes and correlations in the length of TM were insignificant in HM eyes. The length of TM increased with axial length and elongation in the anterior length of CM across all subjects; however, accommodation-related changes diminished as axial length (AL) and the anterior length of CM increased. Causal mediation analysis demonstrated that the anterior length of CM mediated the relationship between AL and the length of TM elongation.
Conclusions
In two trials, accommodation-induced changes in the CM, TM, and SC were observed in eyes with or without HM, with reduced TM and SC response in HM. Differences in CM, TM, and SC behavior during accommodation between the HC and HM groups suggest that CM contraction may reshape the aqueous humor outflow channels.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12886-026-04926-2.
Keywords: Accommodation, Ciliary muscle, Trabecular meshwork, High myopia, Optical coherence tomography
Key points
1. In normal eyes, ciliary muscle contraction enlarges Schlemm’s canal via trabecular meshwork elongation.
2. Ciliary contraction fails to deform trabecular meshwork and Schlemm’s canal in high myopia.
3. Axial elongation stretches ciliary muscle but limits its ability to lengthen trabecular meshwork.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12886-026-04926-2.
Introduction
Myopia is one of the most prevalent eye diseases globally, which significantly increases the risk of visual impairment and blindness [1]. By 2050, it is estimated that 49.8% of the global population will be affected by myopia, with 9.8% developing high myopia (HM) [2], defined in this study as spherical equivalent ≤ -6.0 D or axial length ≥ 26.5 mm. HM is associated with a markedly increased axial length (AL) of the eye, leading to potentially severe ocular complications, including elevated intraocular pressure (IOP) [3–7]. Studies indicate that patients with high myopia and ocular hypertension are about 4.3 times more likely to develop open-angle glaucoma [8–10]. Moreover, IOP-lowering interventions, such as trabeculotomy, are less effective in patients with HM [11]. Despite the clinical importance of these findings, the mechanism underlying IOP elevation in HM remains poorly understood, posing a significant challenge to the effective management of high myopia-associated open-angle glaucoma.
Documented evidence indicates that the morphology of trabecular meshwork (TM) and Schlemm’s canal (SC) plays a key role in regulating IOP, particularly during accommodation. For instance, Xiang et al. demonstrated that accommodation could induce an increase in the extension of the TM and the size of SC in children with myopia [12]. Ex vivo experiments have further revealed a structural connection between the ciliary muscle (CM), TM and SC through elastic fibers [13, 14]. These observations suggest the existence of a functional complex where CM contraction drives TM and SC expansion and deformation. Morphological differences in the CM between emmetropic and myopic eyes, particularly during accommodation, have been documented in multiple studies [15–17]. However, little is known about how this intricate interaction among CM, TM, and SC differs in high myopic eyes compared to those in emmetropic eyes.
In our previous studies, optical coherence tomography (OCT) enabled the segmentation and analysis of inward and forward CM movement during accommodation [18, 19]. In addition, TM and SC biometrics were successfully quantified with swept-source OCT (SS-OCT) [20]. The present study was designed to test the hypothesis that accommodation-induced ciliary muscle contraction is associated with deformation of the trabecular meshwork and expansion of Schlemm’s canal, and that this biomechanical coupling is reduced in eyes with high myopia. Based on previous anatomical evidence of structural links among these tissues and OCT-based observations of accommodation-related changes, we evaluated the biometric changes in these structures before and after accommodation and analyzed their associations in eyes with and without high myopia. This approach was intended to clarify whether the coordination among these anterior segment tissues differs in high myopia and may thereby influence the aqueous humor outflow pathway.
Methods
Figure 1A illustrates the experimental flow. The study enrolled 116 subjects, including 57 healthy controls (HC) and 59 subjects with HM. Participants were assigned to either the drug-induced or physiological accommodation experiment according to their preference. This design allowed us to compare pharmacologic and physiologic stimulation while avoiding an overly long protocol and possible carryover effects within the same session. In the first experiment, 78 participants received pilocarpine-induced accommodation, while the second experiment involved 38 subjects who experienced a -5 diopter (D) physiological accommodative stimulus via a visual target. OCT imaging was conducted before and after each accommodation to assess anterior segment parameters, detailed in subsequent sections.
Fig. 1.
A, Experimental flow. B, Schematic of the customized experimental setup used for SS-OCT during physical accommodation. The mirror and the visual target on the display are both attached to a single removable component. The mirror was placed in front of the right eye with the distance of 5 cm, and target-mirror distance plus the eye-mirror distance (meter as unit) were set in accordance with the formula: Distance (a + b) = -1/(RE + A). The iridocorneal angle at the nasal side of the right eye was imaged using SS-OCT, which was aligned by the live view of the build-in camera to ensure that the same cross-sectional position was scanned. a: the eye-mirror distance (set as 5 cm); b: the distance between the mirror and the LED
Subjects
The study included adults aged 20–50, divided into two groups: (1) HC group with a spherical equivalent (SE; spherical dioptric power plus half of the cylindrical dioptric power) of + 0.50 D to -3.00 D; and (2) HM group, defined the SE ≤ -6.0 D or AL of ≥ 26.5 mm. All participants had corrected visual acuity of at least 20/20. Exclusion criteria included the use of at least contact lenses within one week before the experimental testing; history of ocular disease, intraocular surgery, or relevant systemic diseases; allergy to pilocarpine and related drugs; significant complications of high myopia; and diffuse or more severe choroidal atrophy (pathological myopia per the International Meta-Analysis for Pathological Myopia classification system [21]). As a result, only individuals with simple high myopia were enrolled.
The Ethics Committee of Wenzhou Medical University approved this study, which complied with the principles of the Declaration of Helsinki. All participants provided written informed consent.
Basic clinical examinations
All subjects underwent comprehensive ophthalmologic examinations, assessing refractive error, best-corrected visual acuity (BCVA), AL, IOP, slit lamp, and fundus evaluations. BCVA was recorded as the logarithm of the minimum angle of resolution (logMAR). AL measurements were acquired using IOLMaster 700 (Carl Zeiss, Meditec, Germany). IOP was measured with a non-contact method using the full autotonometer TX-20 (Canon, Tokyo, Japan). Digital 45° color fundus photographs were captured with a retinal camera (Canon EOS 10D SLR Backing, Canon, Tokyo, Japan).
Experimental flow protocol
In this study, participants selected drug-induced or physical accommodation based on their preferences and willingness to receive pilocarpine, to improve compliance and minimize unnecessary drug exposure or discomfort. The procedure for the accommodation experiment was as follows.
For the drug stimulation experiment (EXP I), one drop of pilocarpine eye drops (Zhenrui, 5 ml:0.1 g, Shandong Dr. Leng Fruida Pharmaceutical Co. Ltd.) was instilled, followed by an additional drop after 5 min. Participants were instructed to rest with their eyes closed for 30–40 min after the first drop to ensure stable contraction of the CM [22]. OCT imaging and IOP measurements (Goldmann applanation tonometry; HAAG-STREIT, Switzerland) were obtained before and after pilocarpine-induced CM contraction. Thirty participants from both groups consented to undergo measurements of changes in IOP before and after accommodation.
The physiological stimulation experiment (EXP II) induced stimulation through near and distant stimuli. As illustrated in Fig. 1B, participants turned their heads to the right without rotating their eyes. A mirror placed 5 cm in front of the right eye reflected the target stimulus, which appeared on an LED display and was applied as the stimulus target by showing a letter “E” with the size of 0.4 logMAR in the visual chart. The display and the mirror were mounted on a single, movable unit to allow coordinated positioning. The distance between the target and the mirror, plus the distance between the eye and the mirror (in meters; denoted [a + b] in Fig. 1B), was calculated using the formula: Distance = -1/(RE + A), where RE represents the refractive error in spherical equivalents, and A represents accommodative stimuli. An initial OCT image was captured when subjects were relaxed by positioning the target at the eye’s far point. A second OCT image was taken after applying a -5D stimulus by moving the target closer. For instance, in a -5.0D myopic eye, the target was placed 15 cm from the mirror in a relaxed state and repositioned to 5 cm in an accommodative state. The nasal side of the right eye was selected for imaging. Participants were instructed to turn their heads while avoiding eye rotation, maintaining fixation on the built-in right fixation lights in Experiment I or on the mirror-reflected target in Experiment II. The examiner adjusted the OCT probe to ensure that the same cross-sectional position was scanned in each condition.
All subjects underwent SS-OCT (CASIA 2; Tomey, Nagoya, Japan), an imaging system specifically designed for anterior segment imaging. This SS-OCT utilizes a swept light source with a wavelength of 1,310 nm, a scan speed of 50,000 A-scans per second, and an axial resolution of under ten µm. All eyes were imaged in darkness by a single examiner (ZL). The nasal side of the right eye was selected for imaging, following a protocol outlined in previous studies [18–20]. Participants were instructed to turn their heads while avoiding eye rotation, maintaining fixation on the built-in right fixation lights (EXP I) or the mirror target (EXP II). The examiner adjusted the OCT probe to center the iridocorneal angle within the field of view. Once aligned, each eye was scanned in the two-dimensional mode using angle analysis with an auto-light function. Each scan consisted of one frame with 1200 A-line in 1.66 s and overlaid 64 times. Scans were reviewed to ensure image quality, with participants asked to fixate steadily and refrain from blinking. Alignment was monitored in real-time using the live camera view, and the probe was adjusted to ensure that the same cross-sectional position was scanned, as indicated by the specular reflex (a vertical high-reflectivity line in Figs. 2A and B).
Fig. 2.
OCT images under the relaxed state of emmetropia show the boundaries and the parameters of the ciliary muscle (A, B). C and D are magnified images that show the trabecular meshwork and Schlemm’s canal and their biometric parameters, respectively. OCT, optical coherence tomography; CM, ciliary muscle; TM, trabecular meshwork. Scale bars: 0.5 mm
A blinded examiner analyzed the OCT images to quantify the morphological parameters of the CM, TM, and SC. Using a custom-developed semi-automated algorithm, boundaries for the CM (air-conjunctiva, sclera-ciliary muscle, and ciliary muscle-ciliary body) were segmented as previously described [18, 19, 23]. The maximum thickness of the CM and the anterior length of the CM were calculated after segmentation and correction for optical distortion (Fig. 2A and B). The anterior length of CM was defined as the distance from the scleral spur to the region of maximum thickness.
Analyses of TM and SC parameters were conducted using ImageJ software (Figs. 2C and D; http://imagej.nih.gov/ij/; provided in the public domain by the National Institutes of Health, Bethesda, MD, USA), following the protocol in our previous studies [20]. Manual tracing of the SC and TM was performed by adjusting the contrast and magnification to optimize the visibility of both structures, as described previously [20, 24, 25]. Optical correction for image distortion was performed before segmentation based on Snell’s principle [19]. The area of SC was defined by its enclosed contour of SC, and the length of TM was measured from Schwalbe’s line to the scleral spur. The scleral spur is a high-reflectivity point between the TM and the ciliary body. At the same time, Schwalbe’s line is defined as the boundary between the highly reflective inner corneal layer and the low-reflective TM.
Statistical analyses
All statistical analyses were conducted using SPSS (version 22.0; IBM Corp., Armonk, NY, USA). Reproducibility and repeatability were assessed via the Intraclass Correlation Coefficient (ICC) and Coefficient of Repeatability (CoR%). CoR% was defined as the standard deviation of the difference between two measurements divided by their mean. For reproducibility and repeatability analyses, 20 OCT images per group were randomly selected from the image pool obtained in each experiment, including scans from both the non-accommodative and accommodative states. The same observers evaluated the images for consistency. Reproducibility was measured by analyzing two images from the same position during the same imaging session, while repeatability was assessed by reanalyzing the same image after two weeks. Reproducibility was evaluated using two consecutively acquired images from the same eye at the same position during the same imaging session, provided that both scans had acceptable quality and clearly identifiable landmarks. This approach provided a thorough and reliable evaluation.
A one-way analysis of variance (ANOVA) was applied across the two experimental sets to analyze group differences. χ2 tests were used to assess sex distribution differences between groups. Paired t-tests evaluated biometric CM, TM, and SC changes during accommodation. Pearson’s correlation analyses examined the relationships between CM, TM, and SC biometric parameters under accommodative conditions. Additionally, causal mediation analyses assessed the potential mediating effects of these associations.
Results
Basic characteristics, repeatability and reproducibility of measurements
A total of 116 participants were included in this study. The drug-induced accommodation experiment comprised 39 HC eyes and 39 eyes with HM. The physiological accommodation experiment involved an additional 18 HC and 20 eyes with HM (Table 1). No significant differences were observed between the HC and HM groups in terms of age, sex ratio, or IOP. Myopia severity and AL were both greater in the HM group compared to the HC group. For both the HC and HM groups, no significant differences were found in age, sex ratio, or IOP among participants in the two experiments. Objective measurement confirmed that pilocarpine induced a substantial accommodative response in both groups (control group: 7.67 ± 1.57 D; high myopia group: 8.59 ± 0.87 D), indicating that the pharmacological stimulus was effective in both cohorts.
Table 1.
Basic characteristics of the four groups
| Subject | Healthy Control | High Myopia | P3 | ||||
|---|---|---|---|---|---|---|---|
| EXPT I | EXPT II | P1 | EXPT I | EXPT II | P2 | ||
| Number, eyes | 39 | 18 | - | 39 | 20 | - | - |
| Age, years |
27.64 ± 7.38 (20 ~ 50) |
25.17 ± 3.88 (20 ~ 35) |
0.67 |
26.31 ± 4.35 (22 ~ 46) |
25.35 ± 1.73 (23 ~ 30) |
0.35 | 0.51 |
| Sex, Male: Female | 16:23 | 7:11 | 0.79 | 15:24 | 9:11 | 0.52 | 1.00 |
| SE, D |
-0.31 ± 0.29 (-0.875 ~ 0.75) |
-1.15 ± 0.89 (-2.50 ~ 0) |
< 0.01 |
-7.38 ± 1.20 (-11.25 ~ -6.00) |
-6.50 ± 1.59 (-9.75 ~ -4.00) |
0.02 | < 0.01 |
| Axial Length, mm |
23.70 ± 0.70 (22.14 ~ 25) |
24.32 ± 0.86 (23.23 ~ 25) |
0.01 |
26.26 ± 0.76 (24.56 ~ 27.79) |
26.59 ± 0.63 (25.19 ~ 27.59) |
0.10 | < 0.01 |
| IOP, mmHg |
14.70 ± 2.70 (10 ~ 22.3) |
14.04 ± 2.57 (9.5 ~ 18.3) |
0.39 |
14.82 ± 2.85 (12 ~ 20) |
15.40 ± 2.39 (9.6 ~ 18.3) |
0.53 | 0.29 |
mean ± SD; SE, spherical equivalent; IOP, intraocular pressure; -, not performed
P1, P value between the 5D stimulus and pilocarpine stimulus in healthy control group; P2, P value between the 5D stimulus and pilocarpine stimulus in high myopia group; P3, P value between the healthy control and high myopia groups
The ICC and CoR% were used to check the consistency of all the measurements. Between the two groups in the repeated measurements across two experiments (pre- and post-accommodation), the ICC ranged from 0.679 to 0.988 and the CoR% ranged from 2.017 to 7.680 (See Supplementary Table S1). In addition, the ICC of these parameters, which were analyzed twice at 2 different times for 2 weeks varied from 0.708 to 0.993, and the CoR% varied from 2.06 to 6.31 (Supplementary Table S2).
Comparisons of CM, TM, and SC biometrics and their changes during accommodation between high myopia and healthy control groups
Significant differences in CM, TM, and SC biometrics were observed between the HC and HM groups. No significant differences were noted among the participants in the different experiments (Tables 2 and 3). In the non-accommodative state, the anterior length of CM and the length of TM were longer in the HM group than in the HC group. Under accommodation, the anterior length of CM was also longer in highly myopic eyes, but the length of TM showed no significant difference between the groups. The area of SC did not differ significantly during non-accommodation, but was smaller in the HM group during accommodation. However, this finding should be interpreted cautiously because the larger variance in the area of SC in Experiment I may have reduced the power to detect true differences.
Table 2.
Biometrics of the Ciliary Muscle, Trabecular Meshwork, and Schlemm’s Canal in Non-accommodative State
| the maximum thickness of CM (µm) | the anterior length of CM (µm) | the length of TM (µm) | the area of SC (µm2) | ||
|---|---|---|---|---|---|
| EXPT Ⅰ | HC |
597.56 ± 70.88 (427.17 ~ 750.34) |
844.83 ± 179.50 (433.71 ~ 985.93) |
608.14 ± 68.55 (460.98 ~ 785.32) |
2732.67 ± 1283.83 (1291.87 ~ 5448.31) |
| HM |
601.15 ± 64.76 (442.38 ~ 731.96) |
1096.72 ± 150.33 (767.62 ~ 1349.86) |
666.22 ± 72.43 (485.99 ~ 832.03) |
3122.37 ± 1653.25 (2235.7 ~ 6908.69) |
|
| P1 | 0.91 | < 0.01 | < 0.01 | 0.96 | |
| EXPT Ⅱ | HC |
608.54 ± 33.76 (517.89 ~ 651.02) |
899.49 ± 84.37 (787.50 ~ 1078.50) |
595.04 ± 48.48 (512.78 ~ 695.02) |
3307.28 ± 458.97 (2475.78 ~ 3994.99) |
| HM |
606.36 ± 39.29 (522.49 ~ 668.97) |
1164.98 ± 125.22 (942.68 ~ 1396.04) |
662.00 ± 26.12 (615.09 ~ 712.02) |
3286.65 ± 163.85 (2982.18 ~ 3544.86) |
|
| P2 | 0.79 | < 0.01 | < 0.01 | 0.17 | |
| P3 | 0.52 | 0.20 | 0.46 | 0.11 | |
| P4 | 0.75 | 0.10 | 0.81 | 0.63 |
HC, healthy control group; HM, high myopia group; CM, ciliary muscle; TM, trabecular meshwork; SC, Schlemm’s canal
P1, P value between the two groups in Experiment Ⅰ; P2, P value between the two groups in Experiment Ⅱ; P3, P value of HC subjects between the two experiments; P4, P value of HM subjects between the two experiments. Comparisons were performed using One-way ANOVA and post-hoc multiple tests
Table 3.
Biometrics of the Ciliary Muscle, Trabecular Meshwork, and Schlemm’s Canal in Accommodative State
| the maximum thickness of CM (µm) | the anterior length of CM (µm) | the length of TM (µm) | the area of SC (µm2) | ||
|---|---|---|---|---|---|
| EXPT Ⅰ | HC | 696.02 ± 69.77 | 678.16 ± 120.27 | 714.07 ± 75.40 | 4477.84 ± 1772.53 |
| HM | 656.13 ± 79.09 | 929.65 ± 133.99 | 683.14 ± 68.71 | 3828.33 ± 1724.21 | |
| P1 | 0.24 | < 0.01 | 0.42 | 0.01 | |
| EXPT Ⅱ | HC | 686.26 ± 31.73 | 750.36 ± 77.92 | 696.06 ± 21.40 | 4970.63 ± 351.06 |
| HM | 661.16 ± 44.65 | 976.64 ± 44.65 | 679.87 ± 30.39 | 3723.13 ± 184.64 | |
| P2 | 0.01 | < 0.01 | 0.03* | < 0.05 | |
| P3 | 0.60 | 0.05 | 0.31 | 0.24 | |
| P4 | 0.78 | 0.17 | 0.85 | 0.79 |
HC, healthy control group; HM, high myopia group; CM, ciliary muscle; TM, trabecular meshwork; SC, Schlemm’s canal
P1, P value between the two groups in Experiment Ⅰ; P2, P value between the two groups in Experiment Ⅱ; P3, P value of HC subjects between the two experiments; P4, P value of HM subjects between the two experiments. Comparisons were performed using One-way ANOVA and post-hoc multiple tests
*P value of ANOVA was 0.10, suggesting no significant difference
Similar changes in the ocular anterior segment biometrics were observed during accommodation between the two groups and two trials, including a decrease in the anterior length of CM and increase in the maximum thickness of the CM and the area of SC after accommodation (Fig. 3), except for the area of SC in the HM group in EXPT (I) The length of TM shortening was observed in the HC group, but not in the HM group. Moreover, the magnitudes of the biometric changes were comparable across experiments. In the HC group, changes in the maximum thickness of the CM, the length of TM, and the area of SC were greater than in the HM group (Fig. 4), except for the maximum thickness of the CM in EXPT (II) No significant difference was found in the anterior length of CM changes between the groups.
Fig. 3.
Box and whisker plots of the biometry among the ciliary muscle, trabecular meshwork, and Schlemm’s canal in the non-accommodative and accommodative states in the healthy control (blue boxes) and high myopia (grey boxes) groups during pilocarpine-induced accommodation (filled boxes, A-D) and physical accommodation (unfilled boxes, E-H). The median is represented by the middle line within each box. The second and third quartiles are represented by the lower and upper segments of the box, respectively. The whiskers of the plot represent the minimum (bottom whisker) and the maximum (top whisker). CM, ciliary muscle; TM, trabecular meshwork; SC, Schlemm’s canal. HC: healthy control group; HM: high myopia group. Non-ACC, non-accommodation state; ACC, Accommodation state
Fig. 4.
Comparisons in the changes among the ciliary muscle, trabecular meshwork, and Schlemm’s canal in the healthy control (blue, HC) and high myopia (grey, HM) groups during pilocarpine (filled boxes, EXPT I) and physical (unfilled boxes, EXPT II) accommodation. (A) The change in the maximum thickness of CM; (B) The change in the anterior length of CM; (C) The change in the length of TM; (D) The change in the area of SC. CM, ciliary muscle; TM, trabecular meshwork; SC, Schlemm’s canal
A significant decrease in IOP was observed during pilocarpine-induced accommodation (HC group: 14.65 ± 2.95 mmHg vs. 13.55 ± 2.68 mmHg, P = 0.03; HM group: 15.91 ± 2.27 mmHg vs. 14.26 ± 2.09 mmHg, P < 0.01). The IOP reduction magnitude was comparable between the two groups (-1.11 ± 1.86 mmHg vs. -1.65 ± 1.26 mmHg, P = 0.36).
Associations of the changes in CM, TM, and SC parameters during accommodation
Positive correlations were observed between changes in the maximum thickness of the CM and increases in the length of TM and the area of SC in the HC groups during pilocarpine-induced or target-stimulated accommodation. In contrast, no significant correlations were observed in the HM groups (Fig. 5A-D). Changes in the anterior length of CM showed no significant relationship with biometric changes in the TM or SC (Fig. 5E-H). The the length of TM changes was positively correlated with the area of SC in the HC group; however, no such association was observed in the HM group (Fig. 6A and B).
Fig. 5.
The correlations between the changes in the length of TM and the area of SC with the maximum thickness of CM (A-D) and the anterior length of CM (E-H) during pilocarpine stimulus (filled circle, A, B, E, F) and physical stimulus (unfilled circle, C, D, G, H) accommodation. Subjects in healthy control group were represented as blue circle, while high myopia group as black circle. CM, ciliary muscle; TM, trabecular meshwork; SC, Schlemm’s canal
Fig. 6.
The correlations between the changes in the area of SC with the length of TM in the HC and HM groups during pilocarpine stimulus (A) and physical accommodation (B). Causal mediated analysis showing the association between the maximum thickness of CM change with the area of SC change was mediated by the change in the length of TM (C): a, the effect of change in the maximum thickness of CM on the mediator (change in the length of TM); b, the effect of the mediator (change in the length of TM) on the outcome variable (change in the area of SC); c’, direct effect; c, total effect. CM, ciliary muscle; TM, trabecular meshwork; SC, Schlemm’s canal; HC, healthy control; HM, high myopia
Consequently, causal mediation analyses assessed whether the association between the maximum thickness of the CM and the area of SC changes was mediated by the length of TM changes in HC subjects. Following Baron and Kenny approach [26], weakening of the association between changes in the maximum thickness of the CM and the area of SC was found when the length of TM (mediator) was included in the regression model (Fig. 6C). This suggests that thickened the maximum thickness of the CM influenced the area of SC through the length of TM elongation during accommodation in the HC group.
Associations of axial length with the anterior length of CM, the length of TM, and their changes during accommodation
Positive correlations were found among AL, the anterior length of CM, and the length of TM in all subjects under non-accommodative state, indicating that the anterior length of CM and the length of TM increased with ocular axial elongation (Fig. 7A-C). Causal mediation analyses showed that AL elongation stretched the length of TM, a process mediated by an increase in the anterior length of CM (Fig. 8A).
Fig. 7.
Associations of axial length with the anterior length of CM, the length of TM and their changes during accommodation. Scatterplot showing AL versus the anterior length of CM (A) and the length of TM (B), and the anterior length of CM versus the length of TM (C) in non-accommodation state. The relationships between the accommodation related change in the length of TM with the anterior length of CM and the length of TM in non-accommodation state were shown in scatterplot D and E. Filled circle represent pilocarpine-induced accommodation, and unfilled circle represent physical accommodation. CM, ciliary muscle; TM, trabecular meshwork; AL, axial length
Fig. 8.
(A) Causal mediated analysis showing the association between the AL variability with the length of TM at non-accommodation was mediated by the anterior length of CM variability: a, the effect of AL variability on mediator, (the anterior length of CM) variable; b, the effect of mediator on the outcome, (the length of TM) variable; c’, direct effect; c, total effect., (B) The association between the the anterior length of CM variability with the accommodation related change in the length of TM was mediated by the length of TM at non-accommodation: a, the effect of the anterior length of CM variability on mediator, (the length of TM) variable; b, the effect of mediator on the outcome, (change in the length of TM) variable; c’, direct effect; c, total effect. CM, ciliary muscle; TM, trabecular meshwork; AL, axial length
In addition, accommodation-induced changes in TM length correlated with increases in the anterior length of CM, and TM length changed in both experiments (Fig. 7D and E). Causal mediation analysis showed that the association between the anterior length of CM and changes in the length of TM were mediated by elongation of the length of TM (Fig. 8B).
Discussion
SS-OCT was used to assess biometric changes in the CM, TM, and SC during in vivo accommodation. Results revealed that all subjects exhibited forward and inward CM movement as well as SC enlargement. Notably, significant the length of TM during accommodation was observed exclusively in the non-high myopic groups. Previous studies [27, 28] have demonstrated variations in TM and SC between emmetropia and high myopia eyes, potentially influencing HM-related open-angle glaucoma risk. This study investigated the associations between accommodation-induced changes in CM, TM, and SC. In non-high myopic eyes, CM contraction was correlated with TM elongation and SC enlargement, indicating accommodation-induced regulation of the aqueous humor outflow channel. However, these correlations were not statistically significant in high myopic eyes. These findings indicate the heightened risk of open-angle glaucoma in high myopic patients, enabling earlier and more accurate diagnosis.
The human eye typically responds to a near stimulus by inducing neural signals that cause CM contraction. Pilocarpine-induced accommodation, however, directly alters CM function through receptor interaction [29]. Despite differences in mechanism and duration of action between drug-induced and physiological accommodation, our study revealed similar morphological changes in the CM, TM, and SC following both types of accommodation. These findings suggest that while the underlying mechanisms differ, the resulting patterns of muscle contraction are comparable.
This study showed that changes in CM, TM, and SC biometrics during accommodation differed between eyes with high myopia and those without. The changes in the maximum thickness of the CM correlated with changes in the length of TM and the area of SC among HC subjects. Additionally, causal mediation analysis showed that an increase in the length of TM may mediate the relationship between CM contraction and SC enlargement. An in vitro histological study [30] revealed that CM elastic fibers are positioned parallel to the sclera near Schwalbe’s line, run through the TM, and align perpendicularly to the tissue near the SC. Furthermore, the highest density of CM tendons was located in the juxtacanalicular region of the TM, where the CM elastic fiber network connects to the SC’s endothelial membrane. The findings of this study indicate that these structural connections may facilitate a functional relationship in which CM contraction leads to TM stretching and, consequently, SC expansion during accommodation. These anatomical and functional links may play a role in the regulation of aqueous outflow, warranting further investigation.
The amplitude of biometric changes in the CM, TM, and SC were significantly smaller during accommodation in eyes with HM, with no significant correlation among these parameters. This observation may suggest a cause related to the CM. Specifically, the accommodative contraction of the CM mainly involves its anterior portion, which may undergo less thickening in high myopic eyes due to the gradual replacement of muscle fibers with fibrous connective tissue [15, 17, 31, 32]. Histological studies indicate that disrupted potassium ion homeostasis within the CM can impair contraction in high myopia [33]. Additionally, in vivo studies have shown that different regions of the CM vary in thickness, with the posterior segment being thicker and the anterior segment thinner in high myopia, indicating a posterior shift of the CM [16, 34]. Consequently, the posterior tendon of CM may restrict contraction during accommodation, reducing TM and SC expansion.
Conversely, extraciliary muscle-related factors may also play a role. Previous studies [27, 28] have shown that the anterior sclera in highly myopic eyes is thinner than in HC, reducing its ability to provide adequate support under tension. This lack of support may weaken the structural integrity among the CM, TM, and SC. In addition, HM has been associated with alterations in collagen fiber structure [35], including reduced fiber plasticity and altered collagen stiffness [36, 37], which could impair the tissue’s functional deformability.
Further analysis revealed that the length of TM increased with AL elongation, driven by anterior elongation of the CM. This finding suggests that the TM may be stretched by the elongated CM in high myopia. In a non-accommodative state, TM was longer in highly myopic eyes than in HC. Supporting this, Li [27] and Chen [28] reported that the TM is thinner in high myopia, suggesting that it may undergo compression and elongation. Additionally, the accommodative change in the length of TM was not significant in the HM subjects and was much lower than that in the HC subjects, suggesting that the TM in high myopic subjects may not undergo further stretching by CM contractions (Fig. 9). The reduced deformability of the TM and SC could contribute to aqueous outflow reduction and increased IOP, warranting further investigation in highly myopic patients with POAG. Furthermore, the identification of structural weaknesses in the TM and SC could lead to targeted therapeutic strategies aimed at enhancing aqueous humor outflow, thereby mitigating the risk of elevated IOP and subsequent glaucomatous damage.
Fig. 9.
Schematic diagram shows the morphologic changes in the ciliary muscle (blue), trabecular meshwork (orange) and Schlemm’s canal (green) during accommodation in healthy control (A) and high myopia (B). The ciliary muscle and trabecular meshwork were longer, while the elongation of trabecular meshwork were smaller in high myopia
This study revealed that although both HC and highly myopic eyes experienced changes in IOP following accommodation, the difference in the magnitude of these changes between the two groups was not significant. Potential explanations for this include the thinning of the scleral wall in highly myopic, which may influence IOP measurements due to reduced scleral rigidity. This could complicate the early diagnosis of open-angle glaucoma in individuals with HM. Additionally, given the young and healthy nature of the participants, coupled with the absence of pathological changes in the aqueous outflow structures, it is speculated that structural changes related to CM regulation may precede functional alterations.
This study has several limitations. First, only morphological changes in the CM, TM, and SC in the nasal orientation were measured. Evaluating other meridians is recommended for future studies. Second, although IOP was measured during pharmacological accommodation and showed significant changes, future studies could also assess IOP before and after physiological accommodation to validate these findings. Third, the relatively large variability in Schlemm’s canal area in Experiment 1 may have reduced statistical power and obscured true differences; therefore, the nonsignificant findings related to Schlemm’s canal area should be interpreted with caution. Fourth, participants were not randomized to the two accommodation paradigms, and accommodative response amplitude was not objectively measured, particularly in the physiological stimulation experiment. Accordingly, selection bias and between-group differences in actual accommodative response may have affected the comparability between the two experiments. Future studies using randomized or crossover designs with objective accommodation measurements are needed. This approach could further clarify the effects of CM contraction as well as TM and SC deformation, on aqueous outflow in patients with HM and open-angle glaucoma.
Conclusion
In conclusion, CM contraction during accommodation was observed in the HC and HM groups, but TM elongation was only observed in HC. Correlations among CM thickening, TM elongation, and SC enlargement were observed in the HC group but not in the HM group. The relationship between the changes in CM and SC was mediated by an increase in TM. The length of TM became longer with AL and was mediated by an increase in the anterior length of CM. The change in the length of TM during accommodation decreased with increasing the anterior length of CM, which was mediated by TM elongation. Therefore, the morphology and contraction ability of the CM play a role in the deformation of aqueous outflow channels, that is, the TM and SC, during accommodation.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Acknowledgements
We would like to thank Editage (www.editage.cn) for English language editing.
Abbreviations
- CM
Ciliary muscle
- SC
Schlemm’s canal
- TM
Trabecular meshwork
- HC
Healthy control
- HM
High myopia
- D
Diopter
- AL
Axial length
- IOP
Intraocular pressure
- OCT
Optical coherence tomography
- SS-OCT
Swept-source OCT
- BCVA
Best-corrected visual acuity
- EXP I
The drug stimulation experiment
- EXP II
The physiological stimulation experiment
- ICC
Intraclass Correlation Coefficient
- ANOVA
A one-way analysis of variance
Author contributions
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Funding
This study was supported by research grants from the National Nature Science Foundation of China (Grant Nos.82101177, 82471119, and U22A201722), the National Key Research and Development Program of China (2020YFC2008200), and the Natural Science Foundation of Zhejiang Province (Grant No. LQ20H120002 and LQ21H120007), the Basic Scientific Research Projects in Wenzhou (Grant No.Y20220145), the Zhejiang Province Medical and Health Science and Technology Plan (Grant No.2023KY913).
Data availability
The data supporting the findings of this study are available from the corresponding author upon reasonable request. Because the dataset contains clinical information of pediatric patients and is subject to institutional and ethical restrictions, it cannot be made openly available. De-identified data may be shared for non-commercial academic purposes after review and approval by the corresponding author and the institution.
Declarations
Ethics approval and consent to participate
Study approval statement: This study protocol was reviewed and approved by the Ethics Committee of Wenzhou Medical University, Wenzhou, China (approval number: 2022-028-K-20), and the study was conducted in accordance with the principles of the Declaration of Helsinki.
Consent to participate
Written informed consent was obtained from all participants, or from their parents/legal guardians in the case of minor patients, after they were informed of the purpose of the study, the procedures involved, potential benefits, and possible risks.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Yilei Shao and Zixuan Li contributed equally to the work presented here and should therefore be regarded as equivalent authors.
Contributor Information
Fan Lu, Email: lufan62@mail.eye.ac.cn.
Zhangliang Li, Email: 13968832833@eye.ac.cn.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data supporting the findings of this study are available from the corresponding author upon reasonable request. Because the dataset contains clinical information of pediatric patients and is subject to institutional and ethical restrictions, it cannot be made openly available. De-identified data may be shared for non-commercial academic purposes after review and approval by the corresponding author and the institution.