Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis.

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.

Ciliary muscle and anterior segment characteristics in pre-presbyopic adults with Down syndrome.

PURPOSE: Previous research has shown that accommodation deficits are common in individuals with Down syndrome (DS), but the origin and mechanisms behind these deficits are still unknown. The aim of this study was to investigate the characteristics of different ocular structures involved in accommodation, in particular the ciliary muscle (CM), in a population of individuals with DS to further understand this deficit and its mechanisms. METHODS: Thirty-two volunteer participants of pre-presbyopic age with (n = 16) and without DS (n = 16) were recruited. Temporal and nasal images of the CM were acquired using anterior segment optical coherence tomography (AS-OCT) while participants fixated an eccentrically located target. Analysis of CM parameters was undertaken using validated semi-automated software. Axial length, anterior chamber depth, lens thickness and corneal curvature were obtained with the Topcon Aladdin Optical Biometer and Corneal Topographer. Non-cycloplegic refractive error and accommodative ability were obtained with an open-field autorefractor and dynamic retinoscopy, respectively. Independent t-tests were conducted to determine differences in CM and other anterior segment parameters between participants with and without DS. RESULTS: No significant differences were found in the CM parameters studied between participants with and without DS (p > 0.05). In contrast, significant differences were found in visual acuity (p < 0.001), accommodative response (p < 0.001) and corneal curvature (K1 p = 0.003 and K2 p < 0.001) between participants with and without DS. CONCLUSIONS: Despite having poorer accommodation, pre-presbyopic adults with DS do not have a different CM morphology to that found in typically developing adults. These findings suggest that the accommodative deficit found in this population is not due to a mechanical deficit of the CM.

Monocular transcorneal electrical stimulation induces ciliary muscle thickening in contralateral eye.

Transcorneal electrical stimulation (TES) is used as therapy for retinal diseases such as retinitis pigmentosa (RP) and was suggested for assessing retinal sensitivity by determining phosphene thresholds, subjective luminance impressions caused by retinal stimulation. Further applications concerned the accommodation process, revealing an improved accommodative amplitude in presbyopic eyes after TES treatment. The respective changes of the ciliary muscle (CM), the structure most important for near vision, during TES are yet unknown. In a pilot study, we aimed to assess whether monocular TES leads to morphological and functional CM changes and whether central accommodation control is affected. Ten healthy, near-emmetropic adults participated in the trial (4 females, age 26.3 ± 3.6 years). Using a wavefront and a stimulus generator, a biphasic square-wave stimulus (2 s positive and 6 s negative amplitude) of 0 µA average current was produced and transferred to the eye by means of a Dawson-Trick & Litzkow electrode. Prior to the stimulation, an individual determination of phosphene thresholds served to define individual TES current amplitudes, which ranged between 60 and 100 µA. Optical coherence tomography (OCT) imaging of the right eye's temporal ciliary muscle was performed before and during ipsi- as well as contralateral monocular TES in randomized order in the morning and afternoon of the same day. During imaging, subjects fixated a target at 4 m distance and refraction was simultaneously recorded via eccentric infrared photorefraction. OCT images were assessed using previously published custom-developed software, allowing the definition of selective CM thickness (CMT) readings, and plotting of continuous CMT profiles along the muscle border. CMT profiles revealed that both stimulations, on the ipsi- and contralateral eye, induced a thickening of the CM compared to the non-stimulated state. The selective CMT readings confirmed a significant increase with ipsi- (31 ± 30 µm; p = 0.010) and contralateral (25 ± 16 µm; p = 0.001) TES. However, refraction during far vision was not significantly affected by either stimulation (ipsilateral [n = 5]: median Δw/-w/o = 0 D; contralateral [n = 7]: Δw/-w/o = 0.13 D). Pupil size on average increased during TES, but without reaching significance (ipsilateral [n = 5] median Δw/-w/o = 0.23 mm, contralateral [n = 7] Δw/-w/o = 0.39 mm). Ipsilateral CM thickening could be explained by local changes within the stimulated ciliary muscle, such as increased blood flow or interstitial fluid rise induced by TES. However, the CMT increase in the right eye when TES was performed contralaterally, on the left eye, indicates an involvement of the central control circuit of accommodation. Further possible explanations for this finding are a synchronization of neuronal activities in the visual pathway, the release of vasoactive neuropeptides, or effects on the central blood pressure regulation. Given a neuromodulation effect on the CM function, TES might have implications for children with accommodation insufficiencies and as additional therapy in myopia control management, e.g. in combination with multifocal contact lens treatment. Our study is important for the clinical application of TES, and the outcome might add crucial knowledge to the current understanding of the accommodation process and inform research and treatment of both myopia and presbyopia.

A single-cell transcriptomic atlas of the human ciliary body.

The ciliary body critically contributes to the ocular physiology with multiple responsibilities in the production of aqueous humor, vision accommodation and intraocular immunity. Comparatively little work, however, has revealed the single-cell molecular taxonomy of the human ciliary body required for studying these functionalities. In this study, we report a comprehensive atlas of the cellular and molecular components of human ciliary body as well as their interactions using single-cell RNA sequencing (scRNAseq). Cluster analysis of the transcriptome of 14,563 individual ciliary cells from the eyes of 3 human donors identified 14 distinct cell types, including the ciliary epithelium, smooth muscle, vascular endothelial cell, immune cell and other stromal cell populations. Cell-type discriminative gene markers were also revealed. Unique gene expression patterns essential for ciliary epithelium-mediated aqueous humor inflow and ciliary smooth muscle contractility were identified. Importantly, we discovered the transitional states that probably contribute to the transition of ciliary macrophage into retina microglia and verified no lymphatics in the ciliary body. Moreover, the utilization of CellPhoneDB allowed us to systemically infer cell-cell interactions among diverse ciliary cells including those that potentially participate in the pathogenesis of glaucoma and uveitis. Altogether, these new findings provide insights into the regulation of intraocular pressure, accommodation reflex and immune homeostasis under physiological and pathological conditions.

The evolution of mechanism of accommodation and a novel hypothesis.

Myopia and presbyopia are two major optometry problems facing the whole society. The mechanism of accommodation is strongly related to the treatments of myopia and presbyopia. However, the key mechanism of accommodation has puzzled us for over 400 years and is still not clear at present, leading to the stagnation of prevention and treatment of myopia and presbyopia. With the continued development of experimental technologies and equipment, the approaches to elucidate accommodation's intricacies have become more methodological and sophisticated. Fortunately, some significant progress has been made. This article is to review the evolution of the mechanism of accommodation. Helmholtz proposed a classical theory of "zonules relax during accommodation." In contrast, Schachar put forward a theory of "zonules taut during accommodation." Those hypotheses are relatively complete, but either do not fully explain everything about the accommodation mechanism or lack sufficient experimental and clinical evidence to support them. Then, some contentious issues are discussed in detail to find the truth. Finally, we proposed our hypothesis about accommodation based on the anatomy of the accommodative apparatus.

Impact of accommodative insufficiency and accommodative/vergence therapy on ciliary muscle thickness in the eye.

PURPOSE: Recent evidence suggests that the ciliary muscle apical fibres are most responsive to accommodative load; however, the structure of the ciliary muscle in individuals with accommodative insufficiency is unknown. This study examined ciliary muscle structure in individuals with accommodative insufficiency (AI). We also determined the response of the ciliary muscle to accommodative/vergence therapy and increasing accommodative demands to investigate the muscle's responsiveness to workload. METHODS: Subjects with AI were enrolled and matched by age and refractive error with subjects enrolled in another ciliary muscle study as controls. Anterior segment optical coherence tomography was used to measure the ciliary muscle thickness (CMT) at rest (0D), maximum thickness (CMTMAX) and over the area from 0.75 mm (CMT0.75) to 3 mm (CMT3) posterior to the scleral spur of the right eye. For those with AI, the ciliary muscle was also measured at increasing levels of accommodative demand (2D, 4D and 6D), both before and after accommodative/vergence therapy. RESULTS: Sixteen subjects with AI (mean age = 17.4 years, SD = 8.0) were matched with 48 controls (mean age = 17.8 years, SD = 8.2). On average, the controls had 52-72 µm thicker ciliary muscles in the apical region at 0D than those with AI (p = 0.03 for both CMTMAX and CMT 0.75). Differences in thickness between the groups in other regions of the muscle were not statistically significant. After 8 weeks of accommodative/vergence therapy, the CMT increased by an average of 22-42 µm (p ≤ 0.04 for all), while AA increased by 7D (p < 0.001). CONCLUSIONS: This study demonstrated significantly thinner apical ciliary muscle thickness in those with AI and that the ciliary muscle can thicken in response to increased workload. This may explain the mechanism for improvement in signs and symptoms with accommodative/vergence therapy.

Cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis.

Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From ∼24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), pig (Sus scrofa), and mouse (Mus musculus). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.

Comparison in conjunctival-Tenon's capsule thickness, anterior scleral thickness and ciliary muscle dimensions between Caucasians and Hispanic by optical coherence tomography.

PURPOSE: To investigate the differences in the dimensions of the anterior ocular segment, and specifically in conjunctival-Tenon's capsule thickness (CTT), anterior scleral thickness (AST) and ciliary muscle thickness (CMT), between Caucasian and Hispanic subjects using swept-source optical coherence tomography (SS-OCT). METHODS: Cross-sectional study including 53 Hispanic and 60 Caucasian healthy participants, matched by age, sex and refractive error, who underwent a complete ophthalmological examination. CTT, AST and CMT were manually measured in the temporal and nasal quadrants at 0, 1, 2 and 3 mm from the scleral spur using SS-OCT. RESULTS: Mean age and refractive error were 38.7 ± 12.3 years and -1.05 ± 2.6 diopters, and 41.8 ± 11.7 years and -0.50 ± 2.6 diopters for the Hispanic and Caucasians, respectively (p = 0.165 and p = 0.244). The CTT was increased in the temporal quadrant in the Hispanic group in the three studied regions (CTT1, CTT2 and CTT3; being the means 223.0 ± 68.4, 215.3 ± 66.4 and 203.8 ± 67.1 µm versus 190.8 ± 51.0, 189.4 ± 53.2 and 187.4 ± 55.3 µm respectively; p < 0.001). Larger AST values were observed in the temporal quadrant in the Hispanic group (AST2: 559.8 ± 80.8 µm and AST3: 591.6 ± 83.0 µm) compared to the Caucasian group (520.7 ± 50.1 and 558.9 ± 54.7 respectively; p ≤ 0.022). No differences were observed in the nasal quadrant for CTT, AST1 and AST3 (p ≥ 0.076). No differences emerged in the CM dimensions (p ≥ 0.055). CONCLUSION: CTT and AST measurements were thicker in the temporal quadrant of Hispanic patients compared to Caucasians. This could have implications for the pathogenesis of different ocular diseases.

Ciliary muscle thickness in adults with Down syndrome.

PURPOSE: The relationship between ciliary muscle thickness (CMT), age and refractive error was investigated to determine if CMT, like other anterior ocular anatomy, differs in adults with Down syndrome (DS). METHODS: The CMT of 33 adults with DS was imaged using anterior segment optical coherence tomography. Images from the right eye obtained 45 minutes after cycloplegia (1% tropicamide, 2.5% phenylephrine) were analysed to calculate thickness at 1, 2 and 3 mm posterior to the scleral spur (CMT1, CMT2, CMT3), maximum thickness (CMTMAX) and apical thickness (AT = CMT1 - CMT2). Spherical equivalent refractive error was determined by clinical refraction using both non-dilated and dilated measures. Multivariate regression analysis evaluated the relationship between CMT and refractive error while controlling for subject age. RESULTS: Images were analysed from 26 subjects (mean age (SD) 29 years; mean refractive error (SD): -0.90 (5.03) D, range: -15.75 to +5.13D). Mean (SD) CMT decreased with posterior position (CMT1: 804 (83) µm; CMT2: 543 (131) µm; CMT3: 312 (100) µm). Mean (SD) CMTMAX and AT was 869 (57) µm and 260 (84) µm, respectively. There was a significant linear correlation indicating thinning CMT with increasing age for CMT1 and CMT2 (p ≤0.05). CMT2 and CMT3 had a significant negative correlation (thicker muscle with increasing myopic refractive error) (p ≤0.01). AT had a significant positive correlation (thicker muscle with increasing hyperopic refractive error) (p <0.01). CONCLUSIONS: Ciliary muscle thickness in participants with DS was found to be in a similar range with similar refractive error trends to previous reports of individuals without DS. However, it is important to note that the refractive error trends were driven by individuals with moderate to high levels of myopia.

In vivo analysis of ciliary muscle in myopic Chinese young adults using ArcScan Insight® 100.

OBJECTIVE: To analyse the morphological characteristics of the ciliary muscle (CM) and to explore its relationship with different ocular biometric parameters in myopic young Chinese adults. METHODS: This observational, cross-sectional study included 50 right eyes from 50 myopic adults. The CM area (CMA), CM thickness (CMT) and CM length (CML) were measured using the ArcScan Insight® 100. CMT was determined at three points: 1.0 mm (CMT-1), 2.0 mm (CMT-2) and 3.0 mm (CMT-3) posterior to the scleral spur. CML was measured on the scleral (CMLs) and vitreous (CMLv) aspects. The spherical equivalent refraction (SER), axial length (AL) and subfoveal choroidal thickness (SFCT) were examined to determine their associations with CM parameters (CMA, CML and CMT). RESULTS: The mean SER and AL were -4.39 ± 2.29 D and 25.61 ± 1.15 mm, respectively. Compared with the nasal CMA, CML and CMT (CMT-1, CMT-2 and CMT-3) findings, the temporal CM parameters (CMA, CMLs, CMLv, CMT-1, CMT-2 and CMT-3) were found to be significantly thicker (all p < 0.001, except CMLv and CMT-1; p < 0.01). The nasal CMA was associated with the average corneal curvature (r = 0.30, p = 0.03) and SER (r = -0.30, p = 0.04). Nasal and temporal CMT-2 were negatively correlated with SER (r = -0.33 and -0.32, respectively, both p < 0.05). There was no correlation between CM parameters (except nasal CMLs, r = 0.31, p = 0.03) and SFCT, or between CM parameters and either the AL or anterior chamber depth (all p > 0.05). CONCLUSION: These results suggest that there is temporal versus nasal asymmetry of the CM. CMA, CMT or CML did not vary with axial growth of the eye. The CM is not simply stretched as the eye elongates in myopic young adults.

Pseudomyopia with paradoxical accommodation: a case report.

BACKGROUND: Pseudomyopia is caused by increased refractive power by ciliary muscle spasm. Most patients cannot overcome pseudomyopia spontaneously; therefore, treatment of pseudomyopia is fastidious and needs a multidisciplinary approach. We report a case of unusual pseudomyopia with paradoxical accommodation, straining eyes to induce emmetropia at far distance and relaxing eyes to focus at near objects, contrary to physiological accommodation. CASE PRESENTATION: A 33-year-old woman experienced intermittent distant vision discomfort. This occurred at least a few hundred times daily. She could see near objects clearly; however, distant objects could be seen clearly only when she strained her eyes. Uncorrected distance visual acuity was 20/20 and manifest refraction (MR) in both eyes in the relaxed state was approximately - 2.5 D. MR changed to approximately - 0.5 D when she grimaced and strained her eyes when attempting to focus on distant letters. Her response was contrary to the physiological accommodative response. Cycloplegic refraction was approximately 0.0 D. Binocular autorefractor/keratometer was used to objectively evaluate her refractive response and pupil reaction according to accommodative stimulation. The IOL Master was used to evaluate the anterior chamber depth (ACD), lens thickness (LT), and pupil diameter with relaxed and strained eyes. For stepwise static accommodative stimuli (1-5 D), the refractive responses were correspondingly stepwise, similar to those elicited by healthy individuals. However, contrary to physiological accommodation, she strained her eyes to see distant objects and relaxed them to see near objects. There was no change in pupil diameter despite the accommodative stimuli being maximum. Biometry results showed that ACD deepened and LT flattened with eye strain, which were contrary to those during physiological accommodation. CONCLUSIONS: We report a rare case with reverse of physiological accommodative response. When patients complain of unusual distant visual discomfort, pseudomyopia with paradoxical accommodation should be considered.

[Internal ophthalmoplegia after retinal laser photocoagulation]. / Vnutrennyaya oftal'moplegiya kak oslozhnenie lazernoi koagulyatsii setchatki.

Laser photocoagulation of the retina is a highly effective technique for preventing visual loss in patients with a wide range of eye fundus diseases. The procedure involves creating thermal burns in the eye fundus accompanied by tissue coagulation, but unfortunately it can lead to possible side-effects and potential complications in the future. Some of the rare complications following retinal laser photocoagulation discussed in this article are accommodative weakness and pupil dilation with eventual transitory myopia and corneal sensitivity impairment. This literature review aims to provide an objective summary of global scientific literature on the issue of internal ophthalmoplegia developing after retinal laser photocoagulation, and describes in detail the current state of the problem including reported occurrences, inciting factors and underlying pathophysiology.

Disrupted potassium ion homeostasis in ciliary muscle in negative lens-induced myopia in Guinea pigs.

Myopia is a main cause of preventable or treatable visual impairment, it has become a major public health issue due to its increasingly high prevalence worldwide. Currently, it is confirmed that the development of myopia is associated with the disorders of accommodation. As a dominant factor for accommodation, ciliary muscle contraction/relaxation can regulate the physiological state of the lens and play a crucial role in the development of myopia. To investigate the relationship between myopia and ciliary muscle, the guinea pigs were randomly divided into a normal control (NC) group and a negative lens-induced myopia (LIM) group, and the animals in each group were further randomly assigned into 2-week (n = 18) and 4-week (n = 21) subgroups in accordance with the duration of myopic induction of 2 and 4 weeks, respectively. In the present study, right eyes of the animals in LIM group were covered with -6.0 D lenses to induce myopia. Next, we performed the haematoxylin and eosin (H&E) staining to observe the pathological change of ciliary muscle, determined the contents of adenosine triphosphate (ATP) and lactate acid (LA), and measured the Na+/K+-ATPase expression and activity in ciliary muscles in both NC and LIM groups. Moreover, we also analyzed the potassium ion (K+) flux in ciliary muscles from 4-week NC and LIM guinea pigs. As a result, we found that the arrangements of ciliary muscles in LIM guinea pigs were broken, dissolved or disorganized; the content of ATP decreased, whereas the content of LA increased in ciliary muscles from LIM guinea pigs. Monitoring of K+ flux in ciliary muscles from LIM guinea pigs demonstrated myopia-triggered K+ influx. Moreover, we also noted a decreased expression of Na+/K+-ATPase (Atp1a1) at both mRNA and protein levels and reduced activity in ciliary muscles from LIM guinea pigs. Overall, our results will facilitate the understanding of the mechanism associated with inhibitory Na+/K+-ATPase in lens-induced myopia and which consequently lead to the disorder of microenvironment within ciliary muscles from LIM guinea pigs, paving the way for a promising adjuvant approach in treating myopia in clinical practice.

Morphological ciliary muscle changes associated with form deprivation-induced myopia.

Myopic children have larger ciliary muscles than non-myopic children, suggesting that the ciliary muscle may have an impact on or be affected by refractive error development. The guinea pig represents an attractive model organism for myopia development research. The purpose of the study was to investigate whether form deprivation-induced myopia in one or more strains of guinea pig causes thickening of the ciliary muscle as seen in human myopia. Thirty-nine guinea pigs were bred from in-house progenitors obtained from Cincinnati Children's Hospital (Cincinnati) and the United States Army (Strain 13). At 2-4 days of age the right eyes of animals were exposed to form deprivation for 7 days while the fellow eyes served as controls. Refractive error was determined with retinoscopy while vitreous chamber depth (VCD) and axial length (AL) were determined with A-scan ultrasound. Ciliary muscle characteristics (ciliary muscle length, cross-sectional area, volume, cell number, cell size, and smooth muscle actin concentration) were determined histologically with antibody labeling and analyzed according to whether the animal developed axial myopia (anisometropia > -2.00 D with VCD and/or AL differences > 0.1 mm) or was unresponsive. This analysis method yielded four groups with Group 1 having no induced myopia but with axial elongation (n = 11), Group 2 having myopia without vitreous or axial elongation (n = 8), Group 3 having myopia with either vitreous or axial elongation (n = 11), and Group 4 having myopia with both vitreous and axial elongation (n = 8). There were no post-treatment inter-ocular differences between strains or for the overall group of animals for any ciliary muscle variable; however, a higher response group number in multivariate ordinal regression was related to having a treated compared to fellow eye that had a lower smooth muscle actin concentration (p = 0.006), with a shorter ciliary muscle length (p = 0.042), and a less oblate eye shape (p = 0.010). Guinea pig ciliary muscle length and smooth muscle actin concentration were significantly less in the treated eyes of axially myopic animals suggesting that 7 days of form deprivation induced ciliary muscle cellular atrophy or inhibited ciliary muscle growth. Form deprivation myopia in the guinea pig does not result in the increase in ciliary muscle thickness associated with human juvenile and adult myopia.

Does anisometropia affect the ciliary muscle thickness? An ultrasound biomicroscopy study.

PURPOSE: To compare the ciliary muscle thickness (CMT) of the normal fellow eye to that of the amblyopic eye using ultrasound biomicroscopy (UBM) in patients with unilateral anisometropic amblyopia. METHODS: Thirty patients with unilateral anisometropic amblyopia were involved. The patients were divided into two groups: 19 hyperopic and 11 myopic. Axial length (AL) was measured with optic biometry and anterior chamber depth (ACD), iris area, and CMT were measured with UBM. RESULTS: The mean age was 34.10 ± 6.61 years. The mean spherical difference between two eyes was 2.59 diopter (D) in hyperopic patients and 3.77D in myopic patients. In the hyperopic patients, nasal CMT1(nCMT), temporal CMT1(tCMT), tCMT2, and tCMT3 values were statistically thinner in amblyopic eyes than healthy eyes (p = 0.036, p = 0.003, p = 0.023, p = 0.005, respectively). ACD values were statistically lower in amblyopic eyes (2.78 ± 0.26 mm) than healthy eyes (2.90 ± 0.21 mm) (p < 0.001). In the myopic patients, nCMT1, nCMT2, nCMT3, tCMT1, tCMT2, and tCMT3 values were statistically thicker in amblyopic eyes than healthy eyes (p = 0.003, p = 0.003, p = 0.005, p = 0.003, p = 0.003, p = 0.019, respectively). ACD values were statistically higher in amblyopic eyes (3.20 ± 0.30 mm) than healthy eyes (3.06 ± 0.29 mm) (p = 0.004). Also, there was no significant difference in the iris area between the amblyopic and normal eyes of the myopic and hyperopic patients (p > 0.05). CONCLUSIONS: Amblyopic eyes in patients with unilateral myopic anisometropia have thicker CMT and deeper ACD than healthy eyes. Conversely, amblyopic eyes in patients with unilateral hyperopic anisometropia have thinner CMT and shorter ACD than healthy eyes. There is a positive correlation between AL and CMT.

Ciliary muscle morphology and accommodative lag in hyperopic anisometropic children.

PURPOSE: To investigate the cross-sectional area (CSA) and thickness of the ciliary muscle and their correlation with accommodative lag in hyperopic anisometropic children. METHODS: Forty children aged between 6 and 10 years with hyperopic anisometropia were recruited. The more hyperopic eye (mean refractive power of 3.51 ± 1.70 D) was compared with the less hyperopic eye (mean refractive power of 0.78 ± 1.41 D). The thickness and CSA of the ciliary muscle were measured with anterior segment optical coherence tomography (OCT) images at four meridians. The differences between the eyes and the correlations between CSA, thickness, axial length and accommodative lag were accessed. RESULTS: There was no statistically significant difference in CSA between the two groups at any meridian, except at the inferior meridian (P < 0.05). There was no statistically significant difference in ciliary muscle thickness between eyes at any meridian, except on the temporal and the nasal meridians (P < 0.05). There was a significant difference in the ratio of CSA to axial length at all meridians between the two groups (all P < 0.05). Accommodative lag was 1.65 ± 0.55 D and 0.93 ± 0.45 D in the more and less hyperopic eyes, respectively, which was a statistically significant difference (P < 0.05). There was no significant correlation between the CSA with the axial length and the accommodative lag. CONCLUSIONS: This study demonstrated a greater degree of accommodative lag in the more hyperopic eye of anisometropic children. There was no correlation among accommodative lag, axial length and CSA of the ciliary muscle with the degree of hyperopia.

Ciliary muscle dimensions measured by swept-source optical coherence tomography in eyes with primary open-angle glaucoma and healthy eyes.

PURPOSE: To compare in vivo swept-source optical coherence tomography (SS-OCT) measurements of the ciliary muscle (CM) in patients with primary open-angle glaucoma (POAG) and healthy subjects, and examine correlations between CM dimensions and several covariates. METHODS: This was a cross-sectional study of the right eyes of 181 subjects: 89 POAG patients and 92 healthy subjects. Using the Triton SS-OCT device (Topcon, Tokyo, Japan), CM length (CML), area (CMA) and thickness measured 1000 µm (CMT1), 2000 µm (CMT2) and 3000 µm (CMT3) from the scleral spur were determined in the temporal and nasal quadrants. POAG patients were subjected to visual field (VF) and peripapillary retinal nerve fiber layer (RNFL) assessment. CM dimensions were then assessed for correlation with VF mean defect (MD), mean RNFL thickness and intraocular pressure (IOP). RESULTS: Mean CMLs were 4325 ± 340 µm and 4195 ± 843 µm for the healthy subjects and POAG patients, respectively (p = 0.17). Mean CM thicknesses were CMT1 = 546 ± 56 µm, CMT2 = 326 ± 44 µm and CMT3 = 174 ± 16 µm in the healthy eyes versus CMT1 = 534 ± 108, CMT2 = 332 ± 99 and CMT3 = 183 ± 74 in the POAG eyes, with no significant differences detected (all p ≥ 0.25). In the temporal quadrant, mean CMA was 1.12 ± 0.29 mm2 and 1.15 ± 0.24 mm2 for the healthy and POAG subjects, respectively (p = 0.45). No correlations were observed between CM measurements and RNFL thickness (p ≥ 0.15), IOP or VF MD (p ≥ 0.14) in POAG subjects irrespective of glaucoma severity (p ≥ 0.19). CONCLUSIONS: While SS-OCT proved useful to measure CM dimensions in vivo, these dimensions did not differ between healthy individuals and POAG subjects. In the patients with POAG, no correlations were detected between CM dimensions and VF, RNFL or IOP.

Prolonged nearwork affects the ciliary muscle morphology.

There is evidence for a possible link between myopia development and near vision. We investigated the effect of prolonged nearwork on ciliary muscle (CM) morphology and accommodation in 18 myopic and 17 emmetropic subjects (age 19 to 25). The CM was imaged during far (0.25 D) and near vision (4 D) using optical coherence tomography (OCT), and accommodation to a step pulse (0.25 D - 4 D - 0.25 D, 15 s each) was assessed by eccentric infrared photorefraction before and after a 30-min reading task at 25 cm. OCT images were analyzed using a custom-developed semi-automatic segmentation algorithm to determine CM thickness (CMT) profiles and selective CMT readings. Accommodation was assessed using a non-linear model. On average, the CM got thinner after nearwork, predominantly at 0.0-1.4 mm posterior to the scleral spur in emmetropes, and at 1.0-1.9 mm in myopes. Selective CMT readings confirmed a significant thinning after nearwork (univariate ANOVA F1,66 = 26.313, p < 0.001), without any influence of the subjects' refractive state (F1,66 = 1.887, p = 0.174) or the target distance (F1,66 = 0.014, p = 0.907). The mean accommodation response for targets at infinity was significantly increased after nearwork (F1,32 = 7.775, p = 0.009), with a larger myopic shift in myopes (F1,32 = 11.310, p = 0.002). No change in velocity of accommodation was found. Sharing properties of striated muscles, the CM was expected to increase its thickness, but the opposite was found. Previous studies suggesting sustained nearwork to result in a CM spasm cannot be confirmed by the data presented here. Further research exploring the possible impact of sympathetic innervation is necessary as it is activated during intense nearwork.

Effect of ciliary-muscle contraction force on trapezius muscle activity during computer mouse work.

The present study aimed to identify whether or not an increase in ciliary-muscle contraction force, when the eye-lens is adjusted for viewing at a near distance, results in an increase in trapezius muscle activity, while performing a natural work task. Twelve participants, ranging in age from 21 to 32 years, performed a computer-mouse work task during free gaze conditions. A moving visual target was tracked with a computer mouse on a screen placed at two different distances from the eyes, 25 cm and 50 cm. Tracking performance, eye accommodation, and bilateral trapezius muscle activity were measured continuously. Ciliary-muscle contraction force was computed according to a formula which takes into account the age-dependent, non-linear relationship between the contraction force of the ciliary muscle and the produced level of eye accommodation. Generalized estimating equations analyses were performed. On the dominant hand side and for the nearest screen distance, there was a significant effect of ciliary-muscle contraction force on the trapezius muscle activity (p < 0.001). No other effects were significant (p > 0.05). The results support the hypothesis that high visual demands, during computer mouse work, increase ciliary muscle contraction force and contribute to a raise of the sustained level of trapezius muscle activity. The current study specifically clarifies the validity of the relationship between ciliary-muscle contraction force and trapezius muscle activity and demonstrates that this relationship is not due to a general personality trait. We conclude that a high level of ciliary muscle contraction force can contribute to a development of musculoskeletal complaints in the neck-shoulder area.

Therapeutic Effects of Anthocyanins for Vision and Eye Health.

Anthocyanin (AC) is widely used as supplement of eye health in Europe and in East Asia. In this review, I describe AC effects to clarify the mechanism is important in order to understand the effects of AC on vision health. The bioavailability of AC is quite low but, reported as intact form and many kinds of metabolite. And AC passes through the blood-aqueous fluid barrier and blood-retinal barrier. In vitro study, AC had a relaxing effect on ciliary muscle which is important to treat both myopia and glaucoma. And AC stimulate the regeneration of rhodopsin in frog rod outer segment. Furthermore, AC could inhibit the axial length and ocular length elongation in a negative lens-induced chick myopia model. In addition, we summarized clinical studies of AC intake improved dark adaptation and transient myopic shift and the improvement on retinal blood circulation in normal tension glaucoma patients.