Zonular Tension Research Articles

Model of zonular forces on the lens capsule during accommodation

How the human eye focuses for near; i.e. accommodates, is still being evaluated after more than 165 years. The mechanism of accommodation is essential for understanding the etiology and potential treatments for myopia, glaucoma and presbyopia. Presbyopia affects 100% of the population in the fifth decade of life. The lens is encased in a semi-elastic capsule with attached ligaments called zonules that mediate ciliary muscle forces to alter lens shape. The zonules are attached at the lens capsule equator. The fundamental issue is whether during accommodation all the zonules relax causing the central and peripheral lens surfaces to steepen, or the equatorial zonules are under increased tension while the anterior and posterior zonules relax causing the lens surface to peripherally flatten and centrally steepen while maintaining lens stability. Here we show with a balloon capsule zonular force model that increased equatorial zonular tension with relaxation of the anterior and posterior zonules replicates the topographical changes observed during in vivo rhesus and human accommodation of the lens capsule without lens stroma. The zonular forces required to simulate lens capsule configuration during in vivo accommodation are inconsistent with the general belief that all the zonules relax during accommodation.

A method for generating zonular tension in the murine eye by embedding and compressing the globe in a hydrogel

The ocular lens is the primary organ within the eye responsible for accommodation. During accommodation, the lens is subject to biomechanical forces. We previously demonstrated that stretching the porcine lens can increase lens epithelial cell proliferation. Although murine lenses are commonly employed in lens research, murine lens stretching has remained unexplored. Murine lens stretching thus represents a novel source of potential discovery in lens research. In the present study, we describe a method for stretching the murine lens by compressing the murine globe embedded in a hydrogel. We hypothesized that, as the eye is compressed along the optic axis, the lens would stretch through zonular tension due to the equatorial region of the eye bulging outward. Our results showed that this led to a compression-dependent increase in murine lens epithelial cell proliferation, suggesting that compression of the embedded murine globe is a viable technique for studying the mechanobiology of the lens epithelium.

The major influence of anterior and equatorial zonular fibres on the far-to-near accommodation revealed by a 3D pre-stressed model of the anterior eye

PurposeTo explore the synergistic function of the ligaments in eye, the zonular fibres, that mediate change in eye lens shape to allow for focussing over different distances. MethodsA set of 3D Finite Element models of the anterior eye together with a custom developed pre-stress modelling approach was proposed to simulate vision for distant objects (the unaccommodated state) to vision for near objects (accommodation). One of the five zonular groups was cut off in sequence creating five models with different zonular arrangements, the contribution of each zonular group was analysed by comparing results of each specific zonular-cut model with those from the all-zonules model in terms of lens shape and zonular tensions. ResultsIn the all-zonular model, the anterior and equatorial zonules carry the highest tensions. In the anterior zonular-cut model, the equatorial zonular tension increases while the posterior zonular tension decreases, resulting in an increase in the change in Central Optical Power (COP). In the equatorial zonular-cut model, both the anterior and posterior zonular tensions increase, causing a decreasing change in COP. The change in COP decreases only slightly in the other models. For vitreous zonular-cut models, little change was seen in either the zonular tension or the change in COP. ConclusionsThe anterior and the equatorial zonular fibres have the major influence on the change in lens optical power, with the anterior zonules having a negative effect and the equatorial zonules contributing a positive effect. The contribution to variations in optical power by the equatorial zonules is much larger than by the posterior zonules.

Modulation of Membrane Trafficking of AQP5 in the Lens in Response to Changes in Zonular Tension Is Mediated by the Mechanosensitive Channel TRPV1.

In mice, the contraction of the ciliary muscle via the administration of pilocarpine reduces the zonular tension applied to the lens and activates the TRPV1-mediated arm of a dual feedback system that regulates the lens' hydrostatic pressure gradient. In the rat lens, this pilocarpine-induced reduction in zonular tension also causes the water channel AQP5 to be removed from the membranes of fiber cells located in the anterior influx and equatorial efflux zones. Here, we determined whether this pilocarpine-induced membrane trafficking of AQP5 is also regulated by the activation of TRPV1. Using microelectrode-based methods to measure surface pressure, we found that pilocarpine also increased pressure in the rat lenses via the activation of TRPV1, while pilocarpine-induced removal of AQP5 from the membrane observed using immunolabelling was abolished by pre-incubation of the lenses with a TRPV1 inhibitor. In contrast, mimicking the actions of pilocarpine by blocking TRPV4 and then activating TRPV1 resulted in sustained increase in pressure and the removal of AQP5 from the anterior influx and equatorial efflux zones. These results show that the removal of AQP5 in response to a decrease in zonular tension is mediated by TRPV1 and suggest that regional changes to PH2O contribute to lens hydrostatic pressure gradient regulation.

Simulated zonular tension analysis in the presence of zonular disinsertion

Purpose: To analyze and understand the zonular tension and distribution of forces in the presence of zonular disinsertion in a model simulation with and without a capsular tension ring (CTR). Methods: This study was conducted at Complejo Hospitalario Universitario Albacete, University of Castilla La Mancha, Spain. Twelve load cells were arranged in a circular fashion to simulate the 360 degrees of zonulae in the eye. An elastic band was prestretched in a uniform and radial manner in 12 directions. Force measurements were taken using 12 load cells, uniformly arranged at 30° spacing around the elastic band. Tension was measured at each cell, before and after the simulated zonulardisinsertion. Every clock hour of zonular disinsertion was cycled through all 12 load cells. The tension was evaluated for zonular disinsertion ranging from 0 to 5 clock hours (0° to 150°) with and without a CTR. Results: An increase in zonular tension was recorded in the load cells adjacent to the segments of zonular disinsertion. As the zonular disinsertion progressed, opposing forces could no longer cancel each other out, leading to a displacement of thecomplex. The use of a CTR redistributed the forces, providing better centration in the presence of zonulolysis. Conclusion: This study visualizes the distribution of forces and displacement of the capsular bag complex in the presence of zonular disinsertion and demonstrates a significant increase in zonular tension in the areas adjacent to the segment of zonular disinsertion. The use of a CTR managed to redistribute the tension over the remaining zonulae, maintaining better centration in the presence of zonulolysis. The knowledge of this behavior can help surgeons tackle clinically significant zonular disinsertion.

Evaluation of a Novel Zonular Tension Restoring Accommodating Silicone IOL Design: Pilocarpine and Cyclopentolate-Induced Effect 20 Months after Implantation.

Purpose To investigate a novel zonular-stress restoring accommodating 1-piece silicone IOL. Setting. Angeles City, Philippines. Design Prospective randomized bilateral study. Methods Each patient received a study IOL (ActaLens™, Emmetrope, La Canada, CA) in one eye and a control IOL (CrystaLens® AO, B&L, USA, or an AcrySof IQ®, Alcon, USA) in the contralateral eye to allow for intraindividual comparison. At the 20-month follow-up, two measurement days were set to measure all eyes before and after instilling 2% pilocarpine on the first day and 1% cyclopentolate on the second measurement day using an optical biometry device (Lenstar, Haag-Streit AG, Switzerland), respectively. PCO was graded by two examiners independently at the slit lamp. Results In total, 16 eyes of 8 patients were included. In the study group and the control group, the pilocarpine-induced ACD shift was 0.32 mm (SD: 0.12) (p=0.014) and 0.04 mm (SD: 0.16) (p=0.854), respectively. In the study group and the control group, the mean cyclopentolate-induced ACD shift was 0.14 (SD: 0.06) (p=0.014) and 0.03 mm (SD: 0.03) (p=0.181), respectively. PCO and Nd : YAG rates were higher in the study group, but differences were not found to be significant (AcrySof vs. ActaLens p=0.100 and CrystaLens vs. ActaLens p=0.174). Conclusion The investigated IOL is a novel concept for an accommodating IOL, and results showed a moderate pilocarpine-induced forward shift of the IOL 20 months following implantation. For all patients, the investigated IOL seems to have a higher PCO rate compared to standard monofocal IOLs.

Regulation of the Membrane Trafficking of the Mechanosensitive Ion Channels TRPV1 and TRPV4 by Zonular Tension, Osmotic Stress and Activators in the Mouse Lens.

Lens water transport generates a hydrostatic pressure gradient that is regulated by a dual-feedback system that utilizes the mechanosensitive transient receptor potential vanilloid (TRPV) channels, TRPV1 and TRPV4, to sense changes in mechanical tension and extracellular osmolarity. Here, we investigate whether the modulation of TRPV1 or TRPV4 activity dynamically affects their membrane trafficking. Mouse lenses were incubated in either pilocarpine or tropicamide to alter zonular tension, exposed to osmotic stress, or the TRPV1 and TRPV4 activators capsaicin andGSK1016790A (GSK101), and the effect on the TRPV1 and TRPV4 membrane trafficking in peripheral fiber cells visualized using confocal microscopy. Decreases in zonular tension caused the removal of TRPV4 from the membrane of peripheral fiber cells. Hypotonic challenge had no effect on TRPV1, but increased the membrane localization of TRPV4. Hypertonic challenge caused the insertion of TRPV1 and the removal of TRPV4 from the membranes of peripheral fiber cells. Capsaicin caused an increase in TRPV4 membrane localization, but had no effect on TRPV1; while GSK101 decreased the membrane localization of TRPV4 and increased the membrane localization of TRPV1. These reciprocal changes in TRPV1/4 membrane localization are consistent with the channels acting as mechanosensitive transducers of a dual-feedback pathway that regulates lens water transport.

A validated finite element model to reproduce Helmholtz's theory of accommodation: a powerful tool to investigate presbyopia.

To reproduce human in vivo accommodation numerically. For that purpose, a finite element model specific for a 29-year-old subject was designed. Once the proposed numerical model was validated, the decrease in accommodative amplitude with age was simulated according to data available in the literature. In contrast with previous studies, the non-accommodated eye condition was the reference configuration. Consequently, two aspects were specifically highlighted: contraction of the ciliary muscle, which was simulated by a continuum electro-mechanical model and incorporation of initial lens capsule stresses, which allowed the lens to become accommodated after releasing the resting zonular tension. The morphological changes and contraction of the ciliary muscle were calibrated accurately according to the experimental data from the literature. All dynamic optical and biometric lens measurements validated the model. With the proposed numerical model, presbyopia was successfully simulated. The most widespread theory of accommodation, proposed by Helmholtz, was simulated accurately. Assuming the same initial stresses in the lens capsule over time, stiffening of the lens nucleus is the main cause of presbyopia.

Principles of Accommodation and Technology Update of Presbyopia Corrections using IR and UV Lasers

Purpose: To update and review the technology and principles of laser presbyopia reversal (LAPR) via sclera ablation and thermal shrinkage using infrared and UV lasers. Recent clinical data and new methods are also summarized.
 Study Design: LAPR using laser sclera ablation for increased accommodation of presbyopic eyes.
 Place and Duration of Study: New Taipei City, Taiwan, between June, 2021 and July, 2021.
 Methodology: Accommodation gain was obtained by laser scleral ablation of an eye using Er:YAG laser (at 2.94 um) using either line-pattern or dots-pattern outside the limbus in the oblique quadrants of an eye. The principles of accommodation and the key factors influencing the outcomes are discussed. The accommodation gain (AG) after the surgery is mainly due the change in anterior curvature and anterior shift of the lens. The effectiveness of ciliary body contraction for lens relaxation (or accommodation) may be influenced by the combined aging factors, including lens property changes (index, size, thickness and curvature), tissue elastic changes (in sclera and ciliary) and the zonular tension change. Classical theories of accommodation include Helmholtz and Schachar hypothesis. The key issues and new directions to overcome the drawbacks of the existing LAPR procedure (based on scleral ablation) are proposed. Clinical outcomes from two major groups, SurgiLight and Ace Vision, with two years follow are summarized.
 Results: Clinical outcomes during 2000 to 2020 are summarized showing an average Accommodation gain about 2.0 D, and postoperative egression about 0.25 D (after two years).
 Conclusion: Laser presbyopia reversal (LAPR) via sclera ablation using infrared laser is safe and effective, but suffers drawbacks of being invasive and procedures are too slow. New directions are required for improved outcomes.

Comparative Analisys of Cataract Phakoemulsification, Complicated with the Zonular Weakness

Purpose: To assess the iridocrystalline complex status in patients with cataract, complicated by zonular weakness, before and after surgical treatment. Patients and Methods. The study enrolled 28 patients (29 eyes) with cataract, complicated by zonular weakness (8 women, 20 men, 74.13 ± 8.48 years old). All patients undergone phacoemulsification with IOL implantation and a capsular tension ring (CTR) if it was necessary. In each case optical biometry, ultrasound biomicroscopy and applanation tonometry were provided. After 1, 3 and 6 months postoperatively refractometry, visual acuity measurement, optical biometry, ultrasound biomicroscopy and OCT of the anterior segment were carried out. Results . Patients were divided into 2 groups. In I group (17 eyes) standard phacoemulsification was provided. In II group (11 eyes) it was necessary to implant CTR. 1 patient was excluded due to the extracapsular cataract extraction. Preoperatively angle of the crystalline lens tilt (3.62 ± 0.34° and 1.78 ± 0.27°, p = 0,00) and IOP were higher in group II. 6 months postoperatively UCVA was significantly higher in group II (0.59 ± 0.09 and 0.39 ± 0.21, p = 0.09), upright angle of IOL tilt (0.28 ± 0.35° and 1.40 ± 1.46°, p = 0.10), total zonnular length (14.28 ± 1.00 and 18.93 ± 0.86 mm, p = 0.00) and the value of IOL decentration (0.80 ± 0.17 and 0.20 ± 0.22 mm, p = 0.04) were significantly less in group II. Conclusion . The angle of crystalline lens tilt according to ultrasound biomicroscopy could be considered as an important diagnostic criterion for the CTR implantation necessity during phacoemulsification. CTR implantation provided decrease of IOL tilt and decentration due to a more regular distribution of zonular tension that increases the UCVA postoperatively in complicated cases. OCT of the anterior segment of the eye and ultrasound biomicroscopy application after phacoemulsification gives a great capacity in IOL-capsular complex visualization and measurement.

Changes to Zonular Tension Alters the Subcellular Distribution of AQP5 in Regions of Influx and Efflux of Water in the Rat Lens.

PurposeThe lens uses circulating fluxes of ions and water that enter the lens at both poles and exit at the equator to maintain its optical properties. We have mapped the subcellular distribution of the lens aquaporins (AQP0, AQP1, and AQP5) in these water influx and efflux zones and investigated how their membrane location is affected by changes in tension applied to the lens by the zonules.MethodsImmunohistochemistry using AQP antibodies was performed on axial sections obtained from rat lenses that had been removed from the eye and then fixed or were fixed in situ to maintain zonular tension. Zonular tension was pharmacologically modulated by applying either tropicamide (increased) or pilocarpine (decreased). AQP labeling was visualized using confocal microscopy.ResultsModulation of zonular tension had no effect on AQP1 or AQP0 labeling in either the water efflux or influx zones. In contrast, AQP5 labeling changed from membranous to cytoplasmic in response to both mechanical and pharmacologically induced reductions in zonular tension in both the efflux zone and anterior (but not posterior) influx zone associated with the lens sutures.ConclusionsAltering zonular tension dynamically regulates the membrane trafficking of AQP5 in the efflux and anterior influx zones to potentially change the magnitude of circulating water fluxes in the lens.

A NEW METHOD OF ASSESSMENT ZONULAR LENS

Purpose. To compare the wave front aberrations and their changes under the action of cycloplegia in eyes with myopia and hyperopia. Material and methods. We examined 46 patients: 20 (39 eyes) with myopic (average -5.2±1.5 D) and 26 patients (53 eyes) with hyperopic refraction (mean refraction +3,1±1,15 D) aged 5 - 17 years (average 11.6±0.6 years). All the patients underwent aberrometry in a darkened room before and after medical cycloplegia (instillations of 1% cyclopentolate dihydrochloride twice, with an interval of 10 minutes, aberrometry in 40 minutes after the first instillation) with the aberrometer divice OPD-ScanIII, Nidek. Result. Significant differences: horizontal trefoil (C8) and horizontal coma (C7) before cycloplegia in myopia was significantly higher, and their changes under cycloplegia significantly lower or absent. The difference of these aberrations, with are associated with the dislocation of the crystalline lens, decentration of the optical elements of the eye, provides the evidence of weak zonular tension in the eyes with myopia. The method of assessing zonular on the dynamics of the polynomias C8 and C7 in the background of cycloplegia was developed. Conclusion. The developed method of indirect assessment of the condition of the zonular lens according to the comparative aberrometry before and after cycloplegia recommended for prognosis of postnatal refraktogenesis and evaluation of progressive myopia treatment effectiveness.

Uveitis-Glaucoma-Hyphaema Syndrome. General review.

Uveitis-Glaucoma-Hyphaema Syndrome (UGH syndrome, or "Ellingson" Syndrome) is a rare condition caused by the mechanical trauma of an intraocular lens malpositioned over adjacent structures (iris, ciliary body, iridocorneal angle), leading to a spectrum of iris transillumination defects, microhyphaemas and pigmentary dispersion, concomitant with elevated intraocular pressure (IOP). UGH Syndrome can also be characterized by chronic inflammation, secondary iris neovascularization, cystoid macular edema (CME). The fundamental step in the pathogenesis of UGH syndrome appears to arise from repetitive mechanical iris trauma by a malpositioned or subluxed IOL. These patients have uncomplicated cataract implants and return for episodes of blurry vision weeks to months after surgery. This may be accompanied by pain, photophobia, erythropsia, anterior uveitis, hyphaema along with raised intraocular pressure. A careful history and examination, as well as appropriate investigations can confirm the diagnostic. Treatment options are IOL Explantation exchange, topical and systemic medication, and cyclophotocoagulation, the placement of a Capsular Tension Ring to redistribute zonular tension and Anti-vascular endothelial growth factor (anti-VEGF) Therapy.

Lens zonular tension may promote cortical cataractogenesis.

Lens zonular tension may promote cortical cataractogenesis.

Welcome to clinical ophthalmology.

Purpose: Cortical cataracts commonly occur in people with presbyopia and may be due to age-related loss of accommodation. Wedge-shaped or spoke-like opacities develop underneath insertion points of lens zonules, suggesting a possible link between lens zonular tension and cortical cataracts. Previous studies have suggested an association between accommodative stress and formation of cortical cataracts. We tested the hypothesis that increasing the tension of lens zonules by paralyzing ciliary muscles with cycloplegic drugs may promote cortical cataractogenesis. Methods: Diabetic rats were treated with cycloplegic eye drops (atropine or cyclopentolate) to paralyze the ciliary muscles and produce lens zonular tension. Lens opacification, diffusion of fluorescein into the lenses, and protein leakage into aqueous humor, were assessed at various time points. For human comparison, visual accommodative amplitude data from patients with cortical cataracts as well as agematched normal controls were collected and analyzed. Results: Atropine and cyclopentolate-treated diabetic rats developed lens opacities earlier and with greater severity than diabetic control rats. Fluorescein diffusion into the lens, and leakage of proteins in the aqueous in atropine-treated diabetic eyes was significantly higher than in diabetic controls, and undetectable in nondiabetic controls. Clinical data showed significantly lower visual accommodative amplitude in cortical cataract patients than in normal controls. Conclusion: Chronic use of cycloplegic drugs that paralyze ciliary muscles and increase lens zonular tension can accelerate lens leakage and opacification, contributing to formation of cortical cataracts. Clinical and experimental data support the hypothesis that increased lens zonular tension, which can be associated with presbyopia and clinical pupillary dilation, may promote cortical cataractogenesis.

The zonules selectively alter the shape of the lens during accommodation based on the location of their anchorage points.

To determine the role of anterior and posterior zonular tension on the optomechanical lens response during accommodation simulation. Ten eyes from nine hamadryas baboons (4.9 ± 0.7 years) and 20 eyes from 18 cynomolgus monkeys (5.4 ± 0.3 years) were dissected, leaving the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a segmented scleral rim intact. The lens preparation was mounted in a lens stretcher, and the outer scleral shell was displaced radially in a stepwise fashion. The load, lens, and ciliary body diameters, lens power, lens thickness, and the anterior and posterior radius of curvature were measured during stretching. The zonular fibers attached to either the posterior or anterior lens surface were then carefully transected and the experiment was repeated. Zonular transection was confirmed in four eyes via laser scanning confocal microscopy after immunostaining. The effect of zonular transection on the tissue response to stretching was quantified. Without anterior zonules, 48% and 97% of the changes in anterior and posterior radii are retained. Without posterior zonules, 81% and 67% of the changes in anterior and posterior radii are retained. The changes in lens shape were reduced after transecting either the anterior or posterior zonules; however, both surfaces still changed shape. While either the anterior or posterior zonules alone are capable of changing the shape of both lens surfaces, the anterior zonules have a greater effect on the anterior lens surface, and the posterior zonules have a greater effect on the posterior lens surface.

Saccadic lens instability increases with accommodative stimulus in presbyopes.

An SRI dual Purkinje image (dPi) eye tracker was used to measure lens wobble following saccades with increasing accommodative effort as an indirect measure of ciliary muscle function in presbyopes. Ten presbyopic subjects executed 32 four-degree saccades at 1-s intervals between targets arranged in a cross on illuminated cards at each of 9 viewing distances ranging from 0.5- to 8-D accommodative demands. Post-saccadic lens wobble artifacts were extracted by subtraction of P1 (H(1)/V(1)) position signals from P4 signals (Theta(H)/Theta(V)), both of which were sampled by the eye tracker at 100 Hz. A ray tracing eye model was also employed to model the fourth Purkinje image shifts for a range of lens translations and tilts. Combining all saccades from all subjects showed a significant positive relationship between lens wobble artifact amplitude and accommodative demand. Eye model simulations indicated that artifacts of the amplitude measured could arise from either lens tilts (in the range of 2-4 degrees) or lens translations (in the range of 0.1 to 0.2 mm). Saccadic lens wobble artifacts increase with accommodative effort in presbyopes, indicating preserved ciliary muscle function and greater relaxation of zonular tension with accommodative effort. Variation across subjects may reflect differences in accommodative effort, ciliary muscle function for a given effort, and/or in intraocular anatomy.

Effect of Anterior Zonule Transection on the Change in Lens Diameter and Power in Cynomolgus Monkeys during Simulated Accommodation

To quantify the role of anterior zonular tension on the optomechanical lens response during simulation of accommodation in primates. Postmortem cynomolgus monkey eyes (n = 14; age range, 3.0-11.5 years) were dissected leaving intact the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a scleral rim. The lens was mounted in a lens-stretching system and stretched radially in step-wise fashion. The load, and the lens diameter and power were measured at each step and the diameter- and power-load relationships were quantified. The anterior zonular fibers were then transected, and the experiment was repeated. The equatorial lens diameter and lens optical power before and after zonular transection were compared. Stretching increased the lens diameter by 0.25 +/- 0.09 mm (median +/- interquartile range) before and 0.25 +/- 0.19 mm after zonular transection. Stretching decreased the lens power by 13.0 +/- 6.5 D before and 10.6 +/- 8.0 D after zonular transection. The load required to change the diameter of the lens by 1 mm decreased from 18.8 +/- 10.7 g before to 15.0 +/- 7.8 g after zonular transection. The absolute change in power per gram of loading decreased from 2.5 +/- 1.1 before to 2.0 +/- 1.2 D after zonular transection. The cynomolgus monkey lens retains a significant fraction of its accommodative ability after transection of the anterior zonules in simulated accommodation experiments.

Accommodation and presbyopia

Accommodation is a dynamic change in the dioptric power of the eye. According to the widely accepted and experimentally confirmed theory of Helmholtz, it is achieved by release of zonular tension with contraction of the ciliary muscle and consecutive modelling of the shape of the crystalline lens by the elastic lens capsule. The ability to accommodate is gradually lost with age (presbyopia). Because of difficulties in examining the accommodative apparatus in vivo, many theories, in part contradictory, about the mechanism of accommodation and the origin of presbyopia have been developed. In recent years experimental studies have greatly increased the knowledge about the acommodative apparatus and suggest a multifactorial aetiology of presbyopia. A better understanding of the physiology of accommodation and presbyopia can contribute to the development of effective treatments.

The stress on the anterior lens surface during human in vivo accommodation

Purpose:To determine the qualitative change in stress on the lens capsule during in vivo human accommodation.Methods:Nine subjects (mean age: 30 years; range: 25–38 years) were studied, each of whom had...