No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Influence of Ocular Rigidity and Ocular Biomechanics on the Pathogenesis of Age-Related Presbyopia
Abstract
This chapter discusses ocular rigidity and ocular biomechanical dysfunction as they relate to the age-related pathogenesis of presbyopia. The major factors associated with presbyopia as they relate to ocular rigidity and ocular biomechanical dysfunction are highlighted. Furthermore, specific reference is made to modifying the biomechanical properties and structural stiffness of the scleral outer coat utilizing laser scleral therapies. Recent literature has illuminated that the loss of accommodative ability in presbyopes has many contributing lenticular, as well as extralenticular and physiological factors which are affected by increasing age. There is evidence that the progressive increase in ocular rigidity which occurs with age produces stress and strain on the delicate ocular structures within the globe. This affects not only the anatomy and physiology of the eye but most specifically the capabilities of the accommodative mechanism of the eye. Examining the impact of ocular biomechanics, ocular rigidity, and age-related loss of accommodation could not only illuminate our understanding of how the accommodative mechanism works but the interrelationships which contribute to understanding how the visual focusing system works as a whole. A unique outcome to biomechanical analysis gives a more comprehensive static and dynamic understanding which could lead to new ophthalmic treatment paradigms for various approaches to address presbyopia. Scleral therapies which aim to decrease ocular rigidity may play an increasingly important role for treating biomechanical dysfunction in presbyopes by providing at least one means of addressing the true etiology of the clinical manifestation and pathophysiology of the loss of accommodation, depth of focus, and quality of vision seen with age. This material casts new light on the development of these therapies and progress in the biomechanical approaches to presbyopia as well as translation of ocular biomechanics into surgical and clinical practice.
Purpose: The aim of this paper is to outline the various corneal approaches to the treatment of presbyopia and discuss their effectiveness Method: Most corneal surgical procedures involve LASIK. Supracor uses a progressive ablation profile to provide an aberration optimized smooth transition from distance to near correction. In presbyLASIK a hyper positive area is created at the centre of the cornea for near vision and the periphery provides a focus for distance. The Intracor procedure is an intra-stromal treatment using a femto-second laser. It creates concentric rings with the stroma. These bring about central steepening of the cornea. Monovision corrects one eye for distance and the less dominant eye for near. Conductive keratoplasty uses heat generated by high radio frequency current to alter the corneal stroma. Corneal small aperture implants or inlays are inserted into the cornea through a pocket created by femto-second laser to improve the near and intermediate vision. Results: Supracor offers the best prospect but the high retreatment rate is a major drawback. Intracor and corneal inlays offer the best hope for elimination of reading glasses but reduction of distance vision, loss of binocularity and reduction of the effect overtime limit their use. Monovision for a selective group of patient is still the best alternative. Conclusions: There is no ideal corneal surgical approach to presbyopia. The future may involve more than one approach, perhaps a corneal approach for patients under 50 and a lens solution for older patient. The ideal procedure and best outcome is still some way off.
Purpose
To determine the long-term visual outcomes of six eyes of 3 patients up to 13 years following the Laser Anterior Ciliary Excision (LaserACE) procedure.
Methods
Three male patients of ages 59, 59, and 60 presented for evaluation at Storm Eye Institute, Medical University of South Carolina at 8, 10, and 13 years after the LaserACE procedure for presbyopia, respectively. All 3 patients had a history of laser vision correction (LVC) prior to LaserACE treatment. Visual performance was evaluated using ray-tracing aberrometry, specifically higher-order aberrations, visual Strehl of the optical transfer function (VSOTF), depth of focus (DoF), and effective range of focus (EROF). VSOTF was computed as a function of defocus using a through-focus curve. Subjective DoF was overlaid on the VSOTF through-focus curve to establish the best image quality metric threshold value for correlation between subjective and objective DoF. EROF was determined by measuring the difference in diopters between the near and distance DoF curves, at 50% of VSOTF.
Results
Distance-corrected visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity for all patients remained at 20/20 or better up to 13 years postoperatively. EROF averaged 1.56 ± 0.36 (D) for all eyes.
Conclusions and Importance
LaserACE provided improvement in near vision functionality in these LVC patients with long-term stability. The LaserACE procedure is not on the visual axis, therefore these patients could still receive correction to their hyperopic regression.
Background
To evaluate the effects on near and intermediate visual performance after bilateral Laser Anterior Ciliary Excision (LaserACE) procedure.
Methods
LaserACE surgery was performed using the VisioLite 2.94 μm erbium: yttrium–aluminum–garnet (Er:YAG) ophthalmic laser system in 4 oblique quadrants on the sclera over the ciliary muscle in 3 critical zones of physiological importance (over the ciliary muscles and posterior zonules) with the aim to improve natural dynamic accommodative forces. LaserACE was performed on 26 patients (52 eyes). Outcomes were analyzed using visual acuity testing, Randot stereopsis, and the CatQuest 9SF patient survey.
Results
Binocular uncorrected near visual acuity (UNVA) improved from +0.20 ± 0.16 logMAR preoperatively, to +0.12 ± 0.14 logMAR at 24 months postoperatively (p = 0.0014). There was no statistically significant loss in distance corrected near visual acuity (DCNVA). Binocular DCNVA improved from +0.21 ± 0.17 logMAR preoperatively, to +0.11 ± 0.12 logMAR at 24 months postoperatively (p = 0.00026). Stereoacuity improved from 74.8 ± 30.3 s of arc preoperatively, to 58.8 ± 22.9 s of arc at 24 months postoperatively (p = 0.012). There were no complications such as persistent hypotony, cystoid macular edema, or loss of best-corrected visual acuity (BCVA). Patients surveyed indicated reduced difficulty in areas of near vision, and were overall satisfied with the procedure.
Conclusions
Preliminary results of the LaserACE procedure show promising results for restoring visual performance for near and intermediate visual tasks without compromising distance vision and without touching the visual axis. The visual function and visual acuity improvements had clinical significance. Patient satisfaction was high postoperatively and sustained over 24 months.
Trial registration
NCT01491360 (https://clinicaltrials.gov/ct2/show/NCT01491360). Registered 22 November 2011.
Purpose:
To quantify changes in ocular dimensions associated with age, refractive error, and accommodative response, in vivo, in 30- to 50-year-old human subjects.
Methods:
The right eyes of 91 adults were examined using ultrasonography, phakometry, keratometry, pachymetry, interferometry, anterior segment optical coherence tomography, and high-resolution magnetic resonance imaging. Accommodation was measured subjectively with a push-up test and objectively using open-field autorefraction. Regression analyses were used to assess differences in ocular parameters with age, refractive error, and accommodation.
Results:
With age, crystalline lens thickness increased (0.03 mm/yr), anterior lens curvature steepened (0.11 mm/yr), anterior chamber depth decreased (0.02 mm/yr), and lens equivalent refractive index decreased (0.001/yr) (all p < 0.01). With increasing myopia, there were significant increases in axial length (0.37 mm/D), vitreous chamber depth (0.34 mm/D), vitreous chamber height (0.09 mm/D), and ciliary muscle ring diameter (0.10 mm/D) (all p < 0.05). Increasing myopia was also associated with steepening of both the cornea (0.16 mm/D) and anterior lens surface (0.011 mm/D) (both p < 0.04). With accommodation, the ciliary muscle ring diameter decreased (0.08 mm/D) and the muscle thinned posteriorly (0.008 mm/D), allowing the lens to shorten equatorially (0.07 mm/D) and thicken axially (0.06 mm/D) (all p < 0.03).
Conclusions:
Refractive error is significantly correlated with not only the axial dimensions but also the anterior equatorial dimension of the adult eye. Further testing and development of accommodating intraocular lenses should account for differences in patients' preoperative refractive error.
Purpose:
To describe an anteriorly located system of zonular fibres that could be involved in fine-tuning of accommodation.
Methods:
Forty-six human and 28 rhesus monkey eyes were dissected and special preparations were processed for scanning electron microscopy and reflected-light microscopy. Additional series of frontal and sagittal histological and ultrathin sections were analysed in respect to the origin and insertion of anteriorly located zonules. The presence of sensory terminals at the site of the originating zonules within the connective tissue of the ciliary body was studied by immunohistochemistry. For in-vivo visualization ultrasound biomicroscopy (UBM) was performed on 12 human subjects.
Results:
Fine zonular fibres originated from the valleys and lateral walls of the most anterior pars plicata that covers the anterior and inner circular ciliary muscle portion. These most anterior zonules (MAZ) showed attachments either to the anterior or posterior tines or they inserted directly onto the surface of the lens. At the site of origin, the course of the MAZ merged into the connective tissue fibres connecting the adjacent pigmented epithelium to the ciliary muscle. Numerous afferent terminals directly at the site of this MAZ-origin were connected to the intrinsic nervous network of the ciliary muscle.
Conclusions:
A newly described set of zonular fibres features the capabilities to register the tensions of the zonular fork and lens capsule. The close location and neural connection towards the circular ciliary muscle portion could provide the basis for stabilization and readjustment of focusing that serves fast and fine-tuned accommodation and disaccommodation.
Purpose:
To profile accommodative biometric changes longitudinally and to determine the influence of age-related ocular structural changes on the accommodative response prior to the onset of presbyopia.
Methods:
Twenty participants (aged 34-41 years) were reviewed at six-monthly intervals over two and a half years. At each visit, ocular biometry was measured with the LenStar biometer (www.Haag-Streit.com) in response to 0.00, 3.00 and 4.50 D stimuli. Accommodative responses were measured by the WAM 5500 Auto Ref/Keratometer (www.grandseiko.com).
Results:
During accommodation, anterior chamber depth reduced (F = 29, p < 0.001), whereas crystalline lens thickness (F = 39, p < 0.001) and axial length (F = 5.4, p = 0.009) increased. The accommodative response (F = 5.5, p = 0.001) and the change in anterior chamber depth (F = 3.1, p = 0.039), crystalline lens thickness (F = 3.0, p = 0.042) and axial length (F = 2.5, p = 0.038) in response to the 4.50 D accommodative target reduced after 2.5 years. However, the change in anterior chamber depth (F = 2.2, p = 0.097), crystalline lens thickness (F = 1.7, p = 0.18) and axial length (F = 1.0, p = 0.40) per dioptre of accommodation exerted remained invariant after 2.5 years. The increase in disaccommodated crystalline lens thickness with age was not significantly associated with the reduction in accommodative response (R = 0.32, p = 0.17).
Conclusion:
Despite significant age-related structural changes in disaccommodated biometry, the change in biometry per dioptre of accommodation exerted remained invariant with age. The present study supports the Helmholtz theory of accommodation and suggests an increase in lenticular stiffness is primarily responsible for the onset of presbyopia.
Purpose:
We tested the hypothesis that there are age- and race-related differences in posterior scleral material properties, using eyes from human donors of European (20-90 years old, n = 40 eyes) and African (23-74 years old, n = 22 eyes) descent.
Methods:
Inflation tests on posterior scleral shells were performed while full-field, three-dimensional displacements were recorded using laser speckle interferometry. Scleral material properties were fit to each eye using a microstructure-based constitutive formulation that incorporates the collagen fibril crimp and the local anisotropic collagen architecture. The effects of age and race were estimated using Generalized Estimating Equations, while accounting for intradonor correlations.
Results:
The shear modulus significantly increased (P = 0.038) and collagen fibril crimp angle significantly decreased with age (P = 0.002). Donors of African descent exhibited a significantly higher shear modulus (P = 0.019) and showed evidence of a smaller collagen fibril crimp angle (P = 0.057) compared to donors of European descent. The in-plane strains in the peripapillary sclera were significantly lower with age (P < 0.015) and African ancestry (P < 0.015).
Conclusions:
The age- and race-related differences in scleral material properties result in a loss of scleral compliance due to a higher shear stiffness and a lower level of stretch at which the collagen fibrils uncrimp. The loss of compliance should lead to larger high frequency IOP fluctuations and changes in the optic nerve head (ONH) biomechanical response in the elderly and in persons of African ancestry, and may contribute to the higher susceptibility to glaucoma in these at-risk populations.
Purpose:
We report, for the first time to our knowledge, dynamic movements of the vitreous membrane and peripheral choroid during accommodation, and age-related changes in the anterior sclera.
Methods:
We studied 11 rhesus monkeys (ages 6-27 years) and 12 human subjects (ages 19-65 years). Accommodation was induced pharmacologically in human subjects and by central electrical stimulation in the monkeys. Ultrasound biomicroscopy, endoscopy, and contrast agents were used to image various intraocular structures.
Results:
In the monkey, the anterior hyaloid membrane bows backward during accommodation in proportion to accommodative amplitude and lens thickening. A cleft exists between the pars plicata region and the anterior hyaloid membrane, and the cleft width increases during accommodation from 0.79 ± 0.01 mm to 1.01 ± 0.02 mm in young eyes (n = 2, P < 0.005), as fluid from the anterior chamber flows around the lens equator toward the cleft. In the older eyes the cleft width was 0.30 ± 0.19 mm, which during accommodation increased to 0.45 ± 0.20 mm (n = 2). During accommodation the ciliary muscle moved forward by approximately 1.0 mm, pulling forward the choroid, retina, vitreous zonule, and the neighboring vitreous interconnected with the vitreous zonule. Among the humans, in the older eyes the scleral contour bowed inward in the region of the limbus, compared to the young eyes.
Conclusions:
The monkey anterior hyaloid bends posteriorly during accommodation in proportion to accommodative amplitude and the sclera bows inward with increasing age in both species. Future descriptions of the accommodative mechanism, and approaches to presbyopia therapy, may need to incorporate these findings.
Purpose:
To determine if the accommodative forward movements of the vitreous zonule and lens equator occur in the human eye, as they do in the rhesus monkey eye; to investigate the connection between the vitreous zonule posterior insertion zone and the posterior lens equator; and to determine which components-muscle apex width, lens thickness, lens equator position, vitreous zonule, circumlental space, and/or other intraocular dimensions, including those stated in the objectives above-are most important in predicting accommodative amplitude and presbyopia.
Methods:
Accommodation was induced pharmacologically in 12 visually normal human subjects (ages 19-65 years) and by midbrain electrical stimulation in 11 rhesus monkeys (ages 6-27 years). Ultrasound biomicroscopy imaged the entire ciliary body, anterior and posterior lens surfaces, and the zonule. Relevant distances were measured in the resting and accommodated eyes. Stepwise regression analysis determined which variables were the most important predictors.
Results:
The human vitreous zonule and lens equator move forward (anteriorly) during accommodation, and their movements decline with age, as in the monkey. Over all ages studied, age could explain accommodative amplitude, but not as well as accommodative lens thickening and resting muscle apex thickness did together. Accommodative change in distances between the vitreous zonule insertion zone and the posterior lens equator or muscle apex were important for predicting accommodative lens thickening.
Conclusions:
Our findings quantify the movements of the zonule and ciliary muscle during accommodation, and identify their age-related changes that could impact the optical change that occurs during accommodation and IOL function.
Purpose:
To calculate age-related and per diopter (D) accommodative changes in crystalline lens and ciliary muscle dimensions in vivo in a single cohort of emmetropic human adults ages 30 to 50 years.
Methods:
The right eyes of 26 emmetropic adults were examined using ultrasonography, phakometry, anterior segment optical coherence tomography, and high resolution magnetic resonance imaging. Accommodation was measured both subjectively and objectively.
Results:
In agreement with previous research, older age was linearly correlated with a thicker lens, steeper anterior lens curvature, shallower anterior chamber, and lower lens equivalent refractive index (all P < 0.01). Age was not related to ciliary muscle ring diameter (CMRD) or lens equatorial diameter (LED). With accommodation, lens thickness increased (+0.064 mm/D, P < 0.001), LED decreased (-0.075 mm/D, P < 0.001), CMRD decreased (-0.105 mm/D, P < 0.001), and the ciliary muscle thickened anteriorly (+0.013 to +0.026 mm/D, P < 0.001) and thinned posteriorly (-0.011 to -0.015, P < 0.01). The changes per diopter of accommodation in LED, CMRD, and ciliary muscle thickness were not related to subject age.
Conclusions:
The per diopter ciliary muscle contraction is age independent, even as total accommodative amplitude declines. Quantifying normal biometric dimensions of the accommodative structures and changes with age and accommodative effort will further the development of new IOLs designed to harness ciliary muscle forces.
To explore the attachments of the posterior zonule and vitreous in relation to accommodation and presbyopia in monkeys and humans.
Novel scanning electron microscopy (SEM) and ultrasound biomicroscopy (UBM) techniques were used to visualize the anterior, intermediate, and posterior vitreous zonule and their connections to the ciliary body, vitreous membrane, lens capsule, and ora serrata, and to characterize their age-related changes and correlate them with loss of accommodative forward movement of the ciliary body. alpha-Chymotrypsin was used focally to lyse the vitreous zonule and determine the effect on movement of the accommodative apparatus in monkeys.
The vitreous attached to the peripheral lens capsule and the ora serrata directly. The pars plana zonule and the posterior tines of the anterior zonule were separated from the vitreous membrane except for strategically placed attachments, collectively termed the vitreous zonule, that may modulate and smooth the forward and backward movements of the entire system. Age-dependent changes in these relationships correlated significantly with loss of accommodative amplitude. Lysis of the intermediate vitreous zonule partially restored accommodative movement.
The vitreous zonule system may help to smoothly translate to the lens the driving forces of accommodation and disaccommodation generated by the ciliary muscle, while maintaining visual focus and protecting the lens capsule and ora serrata from acute tractional forces. Stiffening of the vitreous zonular system may contribute to age-related loss of accommodation and offer a therapeutic target for presbyopia.
The purpose of this study was to characterize the pressure-volume relation in the living human eye, measure the ocular pulse amplitude (OPA), and calculate the corresponding pulsatile ocular blood flow (POBF) in a range of clinically relevant IOP levels.
Fifty patients with cataract (50 eyes) were enrolled in the study. After cannulation of the anterior chamber, a computer-controlled device for the intraoperative measurement and control of IOP was used to artificially increase the IOP in a stepping procedure from 15 to 40 mm Hg. The IOP was continuously recorded for 2 seconds after each infusion step. The pressure-volume relation was approximated with an exponential fit, and the ocular rigidity coefficient was computed. OPA, pulse volume (PV), and POBF were measured from the continuous IOP recordings.
The average rigidity coefficient was 0.0224 microL(-1) (SD 0.0049). OPA increased by 91% and PV and POBF decreased by 29% and 30%, respectively, when increasing the IOP from 15 to 40 mm Hg. The OPA is positively correlated with the coefficient of ocular rigidity (r = 0.65, P < 0.01).
The present results suggest a nonlinear pressure-volume relation in the living human eye characterized by an increase in rigidity at higher IOP levels. The increased OPA and decreased pulse volume relate to the decreased POBF and the increased mechanical resistance of the ocular wall at high IOP levels.
To investigate the age-related differences in the inhomogeneous, anisotropic, nonlinear biomechanical properties of posterior sclera from old (22.9 +/- 5.3 years) and young (1.5 +/- 0.7 years) rhesus monkeys.
The posterior scleral shell of each eye was mounted on a custom-built pressurization apparatus, then intraocular pressure (IOP) was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured with speckle interferometry. Each scleral shell's geometry was digitally reconstructed from data generated by a 3-D digitizer (topography) and 20-MHz ultrasound (thickness). An inverse finite element (FE) method incorporating a fiber-reinforced constitutive model was used to extract a unique set of biomechanical properties for each eye. Displacements, thickness, stress, strain, tangent modulus, structural stiffness, and preferred collagen fiber orientation were mapped for each posterior sclera.
The model yielded 3-D deformations of posterior sclera that matched well with those observed experimentally. The posterior sclera exhibited inhomogeneous, anisotropic, nonlinear mechanical behavior. The sclera was significantly thinner (P = 0.038) and tangent modulus and structural stiffness were significantly higher in old monkeys (P < 0.0001). On average, scleral collagen fibers were circumferentially oriented around the optic nerve head (ONH). No difference was found in the preferred collagen fiber orientation and fiber concentration factor between age groups.
Posterior sclera of old monkeys is significantly stiffer than that of young monkeys and is therefore subject to higher stresses but lower strains at all levels of IOP. Age-related stiffening of the sclera may significantly influence ONH biomechanics and potentially contribute to age-related susceptibility to glaucomatous vision loss.
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.
To utilize time-domain optical coherence tomography (OCT) to measure changes in the crystalline lens with age and accommodation.
A cross-sectional study of pre-presbyopic and presbyopic subjects was conducted. Amplitude of accommodation was measured with the push-up test. Objective accommodation was measured with the Grand Seiko auto-refractor and a Badal lens system. Lens thickness was measured with the Zeiss Visante OCT and an internal optometer. The data were analysed using correlation coefficients, linear regression, and by calculating the average change in lens thickness per diopter change in objective accommodation.
Twenty-two subjects between the ages of 36 and 50 years completed the study. Subjective amplitude of accommodation ranged from 2.17 to 6.38 D. Objective accommodation ranged from 0.22 to 4.56 D. The mean lens thickness was 4.05+/-0.20 mm. The mean change in lens thickness for up to a 5-D accommodative stimulus ranged from 0.01 to 0.26 mm. The correlation coefficients were: age and subjective accommodation, r= -0.74; age and objective accommodation, r= -0.84; change in lens thickness and age, r= -0.65; change in lens thickness and subjective accommodation, r=0.74; change in lens thickness and objective accommodation, r=0.64; objective and subjective accommodation, r=0.82 (all p<0.01). An increase in lens thickness of 21 microm per year of age was determined by linear regression. For the subjects who showed at least 1 D of accommodative response on the Grand Seiko auto-refractor, there was an increase of 51+/-19 microm per dioptre of accommodation.
Optical coherence tomography is a non-invasive technique that can be used to quantify changes in the thickness of the crystalline lens. Subjective and objective measurements of accommodation, as well as age, were robustly correlated with the measured changes in lens thickness. Lens thickness changes with age and accommodation as measured with the Visante OCT compare well with previous findings using Scheimpflug photography and ultrasound.
Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells (RGC), resulting in gradual and progressive permanent loss of vision. Reducing intraocular pressure (IOP) remains the only proven method for preventing and delaying the progression of glaucomatous visual impairment. However, the specific role of IOP in optic nerve injury remains controversial, and little is known about the biomechanical mechanism by which elevated IOP leads to the loss of RGC. Published studies suggest that the biomechanical properties of the sclera and scleral lamina cribrosa determine the biomechanical changes of optic nerve head, and play an important role in the pathologic process of loss of RGC and optic nerve damage. This review focuses on the current understanding of biomechanics of sclera in glaucoma and provides an overview of the possible interactions between the sclera and IOP. Treatments and interventions aimed at the sclera are also discussed.
The ciliary muscle plays a major role in controlling both accommodation and outflow facility in primates. The ciliary muscle and the choroid functionally form an elastic network that extends from the trabecular meshwork all the way to the back of the eye and ultimately attaches to the elastic fiber ring that surrounds the optic nerve and to the lamina cribrosa through which the nerve passes. The ciliary muscle governs the accommodative movement of the elastic network. With age ciliary muscle mobility is restricted by progressively inelastic posterior attachments and the posterior restriction makes the contraction progressively isometric; placing increased tension on the optic nerve region. In addition, outflow facility also declines with age and limbal corneoscleral contour bows inward. Age-related loss in muscle movement and altered limbal corneoscleral contour could both compromise the basal function of the trabecular meshwork. Further, recent studies in non-human primates show that the central vitreous moves posteriorly all the way back to the optic nerve region, suggesting a fluid current and a pressure gradient toward the optic nerve. Thus, there may be pressure and tension spikes on the optic nerve region during accommodation and these pressure and tension spikes may increase with age. This constellation of events could be relevant to glaucomatous optic neuropathy. In summary, our hypothesis is that glaucoma and presbyopia may be literally linked to each other, via the choroid, and that damage to the optic nerve may be inflicted by accommodative intraocular pressure and choroidal tension "spikes", which may increase with age.
Purpose:
To elucidate the dynamic accommodative movements of the lens capsule, posterior lens and the strand that attaches to the posterior vitreous zonule insertion zone and posterior lens equator (PVZ INS-LE), and their age-related changes.
Methods:
Twelve human subjects (ages 19-65 years) and 12 rhesus monkeys (ages 6-27 years) were studied. Accommodation was induced pharmacologically (humans) or by central electrical stimulation (monkeys). Ultrasound biomicroscopy was used to image intraocular structures in both species. Surgical procedures and contrast agents were utilized in the monkey eyes to elucidate function and allow visualization of the intraocular accommodative structures.
Results:
Human: The posterior pole of the lens moves posteriorly during accommodation in proportion to accommodative amplitude and ciliary muscle movement. Monkey: Similar accommodative movements of the posterior lens pole were seen in the monkey eyes. Following extracapsular lens extraction (ECLE), the central capsule bows backward during accommodation in proportion to accommodative amplitude and ciliary muscle movement, while the peripheral capsule moves forward. During accommodation the ciliary muscle moved forward by ~1.0 mm, pulling forward the vitreous zonule and the PVZ INS-LE structure. During the accommodative response the PVZ INS-LE structure moved forward when the lens was intact and when the lens substance and capsule were removed. In both the monkey and the human eyes these movements declined with age.
Conclusions:
The accommodative shape change of the central capsule may be due to the elastic properties of the capsule itself. For these capsule/lens accommodative posterior movements to occur, the vitreous face must either allow for it or facilitate it. The PVZ INS-LE structure may act as a 'strut' to the posterior lens equator (pushing the lens equator forward) and thereby facilitate accommodative forward lens equator movement and lens thickening. The age-related posterior restriction of the ciliary muscle, vitreous zonule and the PVZ-INS LE structure dampens the accommodative lens shape change. Future descriptions of the accommodative mechanism, and approaches to presbyopia therapy, may need to incorporate these findings.
Intraocular pressure (IOP) induced strains in the peripapillary sclera may play a role in glaucoma progression. Using inflation testing and ultrasound speckle tracking, the 3D strains in the peripapillary sclera of human donor globes were measured. Our results showed that the peripapillary sclera experiences through-thickness compression and meridional stretch during inflation. Minimal circumferential dilation was observed, while the out-of-plane shear was significant and almost twice in magnitude of the largest principal. These 3D strain characteristics provide a more complete delineation of the biomechanical responses of the peripapillary sclera to physiological increases in IOP and their potential role in ocular diseases.
Presbyopia is an age-related eye condition where one of the signs is the reduction in the amplitude of accommodation, resulting in the loss of ability to change the eye's focus from far to near. It is the most common age-related ailments affecting everyone around their mid-40s. Methods for the correction of presbyopia include contact lens and spectacle options but the surgical correction of presbyopia still remains a significant challenge for refractive surgeons. Surgical strategies for dealing with presbyopia may be extraocular (corneal or scleral) or intraocular (removal and replacement of the crystalline lens or some type of treatment on the crystalline lens itself). There are however a number of limitations and considerations that have limited the widespread acceptance of surgical correction of presbyopia. Each surgical strategy presents its own unique set of advantages and disadvantages. For example, lens removal and replacement with an intraocular lens may not be preferable in a young patient with presbyopia without a refractive error. Similarly treatment on the crystalline lens may not be a suitable choice for a patient with early signs of cataract. This article is a review of the options available and those that are in development stages and are likely to be available in the near future for the surgical correction of presbyopia.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
To understand, demonstrate, and further research the mechanisms of accommodation and presbyopia.
Private practice, Little Silver, New Jersey, USA.
Experimental study.
The CAMA 2.0 computer-animated model of accommodation and presbyopia was produced in collaboration with an experienced medical animator using Autodesk Maya animation software and Adobe After Effects.
The computer-animated model demonstrates the configuration and synchronous movements of all accommodative elements. A new classification of the zonular apparatus based on structure and function is proposed. There are 3 divisions of zonular fibers; that is, anterior, crossing, and posterior. The crossing zonular fibers form a scaffolding to support the lens; the anterior and posterior zonular fibers work reciprocally to achieve focused vision. The model demonstrates the important support function of Weiger ligament. Dynamic movement of the ora serrata demonstrates that the forces of ciliary muscle contraction store energy for disaccommodation in the elastic choroid. The flow of aqueous and vitreous provides strong evidence for our understanding of the hydrodynamic interactions during the accommodative cycle. The interaction may result from the elastic stretch in the choroid transmitted to the vitreous rather than from vitreous pressue. The model supports the concept that presbyopia results from loss of elasticity and increasing ocular rigidity in both the lenticular and extralenticular structures.
The computer-animated model demonstrates the structures of accommodation moving in synchrony and might enhance understanding of the mechanisms of accommodation and presbyopia.
Dr. Goldberg is a consultant to Acevision, Inc., and Bausch & Lomb.
Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
• Twice daily topical application of 50 μg of prostaglandin F2α tromethamine to cynomolgus monkey eyes produced significant ocular hypotension lasting at least six hours, with the intraocular pressure (IOP) falling between 35% and 50%, ie, to about 8 to 10 mm Hg, following the seventh dose. A single topical application of 1 mg of pilocarpine hydrochloride produced a much smaller IOP reduction and strong, probably maximal accommodation, both of which lasted at least eight hours. When prostaglandin F2α-treated eyes were given pilocarpine before the seventh dose of prostaglandin F2α, accommodation and IOP responded as in eyes receiving pilocarpine only. Atropine sulfate pretreatment of eyes receiving pilocarpine and prostaglandin F2α completely prevented pilocarpine-induced accommodation and inhibition of ocular hypotension induced by prostaglandin F2α. We hypothesize that (1) prostaglandin F2α reduces IOP by increasing uveoscleral drainage of aqueous humor, and (2) pilocarpine pretreatment contracts the ciliary muscle, obliterating the intramuscular spaces and closing off the uveoscleral drainage pathway and thus physiologically blocking the effect.
Purpose To determine the chromatic coordinates of different human crystalline lenses to analyze the age‐induced change in the color of the crystalline.
Methods The spectral transmission of nine human crystalline lenses of different ages were measured by using a Perkin‐Elmer 800 UV/VIS spectrophotometer. Using these data we calculated the chromatic coordinates of each crystalline lens for both solar and incandescent illumination. The study adheres to the tenets of the Declaration of Helsinki for Research Including Human Subjects and was approved by the Institutional Review Board.
Results The results show a greater saturation of color with the increase of age. In principle, the change tends towards yellow, although for ages of over 70 years it veers more towards orange colors. All the crystalline lenses were more yellow and saturated under incandescent illumination.
Conclusion At the beginning, a young crystalline lens is transparent and its chromatic coordinates practically coincide with those corresponding to solar light. As age increases, the crystalline lens yellows. On the basis of the results obtained, it cannot be claimed that the more yellow a crystalline lens is, the older it is. Our results show that between 40 and 67 years the chromatic coordinates are quite similar, especially under incandescent illumination. However, total transmission of light is more important for vision than the color of the lens and we have found that the age‐induced changes in these two parameters do not always coincide. All this shows that the different factors that influence yellowing of the crystalline lens do not act in the same way on everyone and that crystalline opacification does not depend solely on aging.
Abstract Biomechanics is the study of the relationship between forces and function in living organisms and is thought to play a critical role in a significant number of ophthalmic disorders. This is not surprising, as the eye is a pressure vessel that requires a delicate balance of forces to maintain its homeostasis. Over the past few decades, basic science research in ophthalmology mostly confirmed that ocular biomechanics could explain in part the mechanisms involved in almost all major ophthalmic disorders such as optic nerve head neuropathies, angle closure, ametropia, presbyopia, cataract, corneal pathologies, retinal detachment and macular degeneration. Translational biomechanics in ophthalmology, however, is still in its infancy. It is believed that its use could make significant advances in diagnosis and treatment. Several translational biomechanics strategies are already emerging, such as corneal stiffening for the treatment of keratoconus, and more are likely to follow. This review aims to cultivate the idea that biomechanics plays a major role in ophthalmology and that the clinical translation, lead by collaborative teams of clinicians and biomedical engineers, will benefit our patients. Specifically, recent advances and future prospects in corneal, iris, trabecular meshwork, crystalline lens, scleral and lamina cribrosa biomechanics are discussed.
PurposeTo discuss the various static and dynamic surgical approaches which attempt to give presbyopes good vision at far, intermediate and near viewing distances.ContentStatic methods broadly adopt the same optical techniques as those used in presbyopic contact lens correction and aim to satisfy the needs of the presbyope by increasing binocular depth-of-focus, often using monovision as well as simultaneous-imagery. Dynamic methods generally attempt to make use of at least some of the still-active elements of the accommodation system. They include procedures which are supposed to modify the relative geometry of the ciliary muscle and lens, or which reduce the stiffness of the presbyopic lens either by replacing it with other natural or man-made material or by subjecting it to femtosecond laser treatment. Alternatively the natural lens may be replaced by some form of intraocular lens which changes power as a result of forces derived from the still-active ciliary muscle, zonule and capsule, or other sources.Conclusions
At present, multifocal intraocular lenses appear to offer the most consistent and reliable surgical approach to surgical presbyopic correction. They have obvious advantages in convenience and stability over optically-similar, simultaneous-image presbyopic contact lenses but this must be balanced against their relative inflexibility in cases of patient dissatisfaction. Dynamic methods remain largely experimental. Although some approaches show promise, as yet no method has demonstrated a reliable, long-term ability to correct distance refractive error and to appropriately change ocular power in response to changes in viewing distance over the normal range of interest.
To outline the refractive problems associated with presbyopia and to review the basis and relative merits of currently-available methods for their correction, with detailed consideration of spectacle and contact lens approaches.
In the developed world, most of the present population will spend roughly half their lives as presbyopes. The well-known presbyopic changes with age in amplitude of accommodation and required near addition are briefly reviewed, together with the less widely acknowledged slow drifts that occur in distance refraction. The desirability of restoring to presbyopes clear vision for objects at any distance, ideally corresponding to vergences within the range of at least 0 to -5 D, in any viewing direction, is stressed. A general outline is given of possible corrective methods. Methods which satisfy the needs of a 50 year-old may not be suitable for the 80 year-old. Corrections may involve both fixed- and variable-focus lens systems, and surgical methods which modify the optics of the cornea, replace the crystalline lens with different fixed optics, or attempt to at least partially restore active accommodation. Some more recent methods of spectacle and contact lens correction are described in more detail. Particular attention is given to recent commercially-developed spectacles in which the corrective power can be varied actively by either mechanical (liquid-filled deformable lenses or Alvarez lenses) or electrical (liquid crystal lenses) means to allow objects at different distances to be seen clearly. Contact lens corrections show less progress and are still preferred only by a minority of older patients, most of whom are early presbyopes.
The rising proportion of presbyopes in the population, covering an age span of around 40 years, represents both a problem for those concerned with giving their patients the best vision possible at both far and near viewing distances and a commercial opportunity. Traditional single-vision distance and near, bifocal, and progressive spectacle lens solutions, together with contact lens modalities for presbyopic correction, are being challenged by a variety of new approaches. It remains to be seen whether the latter will receive wide acceptance in practice.
Purpose:
To compare ocular rigidity (OR) and outflow facility (C) coefficients in medically treated open-angle glaucoma (OAG) patients and controls, and to investigate differences in ocular pulse amplitude (OPA) and pulsatile ocular blood flow (POBF) between the two groups.
Methods:
Twenty-one OAG patients and 21 controls undergoing cataract surgery were enrolled. Patients with early or moderate primary or pseudoexfoliative OAG participated in the glaucoma group. A computer-controlled system, consisting of a pressure transducer and a microstepping device was employed intraoperatively. After cannulation of the anterior chamber, IOP was increased by infusing the eye with microvolumes of saline solution. IOP was recorded after each infusion step. At an IOP of 40 mm Hg, an IOP decay curve was recorded for 4 minutes. OR coefficients, C, OPA, and POBF were estimated from IOP and volume recordings.
Results:
There were no differences in age or axial length in the two groups. The OR coefficient was 0.0220 ± 0.0053 μl(-1) in the OAG and 0.0222 ± 0.0039 μl(-1) in the control group (P = 0.868). C was 0.092 ± 0.082 μL/min/mm Hg in the glaucoma group compared with 0.149 ± 0.085 μL/min/mm Hg in the control group at an IOP of 35 mm Hg (P < 0.001) and 0.178 ± 0.133 μL/min/mm Hg vs. 0.292 ± 0.166 μL/min/mm Hg, respectively, at an IOP of 25 mm Hg (P < 0.001). There were no differences in OPA or POBF between the two groups in baseline and increased levels of IOP (P > 0.05).
Conclusions:
Manometric data reveal lower C in OAG patients and increased C with increasing IOP. There were no differences in the OR coefficient, OPA, and POBF between medically treated OAG patients and controls, failing to provide evidence of altered scleral distensibility and choroidal blood flow in OAG.
The mechanism of accommodation has been studied for at least four hundred years. The most interesting aspect of accommodation is that its time course is well in advance of other physiological functions – it begins to decline by adolescence and is lost about two-thirds of the way through the normal line span. The state of presbyopia is reached when accommodation has declined sufficiently to interfere with close tasks requiring acute vision. Presbyopia is generally considered to originate with the ‘plant’ of the accommodative system, either within the lens and its capsule or within their support structures. One of the lenticular theories, the Hess–Gullstrand theory, is distinguished from other theories by its claim that as age increases there is an increasing excess amount of ciliary muscle contraction beyond the ability of the lens and capsule to respond to it. For all other theories, the maximum possible amount of ciliary muscle contraction is always necessary to produce maximum accommodation, at least beyond the age at which it reaches its peak. From my review of the present understanding of the mechanisms of accommodation and the theories of the development of presbyopia, I conclude that there is overwhelming evidence against the Hess–Gullstrand theory and that it is unlikely that changes in the ciliary muscle contractility contribute significantly to the development of presbyopia.
A bstract
Ocular rigidity (OR) refers to the relationship between pressure and volume changes in the eyeball. Since the description of the differential tonometry method for the calculation of an OR coefficient by Friedenwald, several other methodologies have been proposed to measure OR, including the anterior chamber manometry, axial length (AL) changes, measurement of pulse amplitude and fundus pulse, ultrasound elastography and evaluation of corneal hysteresis. However, most of these methodologies suffer from deficiencies, such as invasive nature, poor accuracy or reproducibility or technical complexity. Nevertheless, it is possible that OR affects the pathogenesis and clinical course of a variety of ocular conditions, including glaucoma, age‐related macular degeneration, presbyopia, corneal changes following refractive surgery as well as the accuracy of IOP measurements by many tonometers. Thus, the future development of non‐invasive and easy‐to‐use methodologies for the accurate measurement of OR in the every‐day practice would be clinically important.
All people will be presbyopic by age 50, and we now understand something of the basis for this condition. It turns out to be a direct consequence of two features; first the design of the transparent lens and the way it must change shape to enable focussing by the human eye, and second the instability of proteins over a very long time period. The incremental changes that take place in the lens to render the central region inflexible by middle age and, as a consequence the person presbyopic, may also promote the subsequent development of cataract. Based on the most recent data, heat-induced denaturation of proteins in the lens appears to be a worthy topic for future investigation. Understanding such processes may allow us to glimpse the origin both of presbyopia and age-related nuclear cataract.
Lenses from 27 human eyes ranging in age from 10 to 87 years were used to determine how accommodation and age affect the optical properties of the lens. A scanning laser technique was used to measure focal length and spherical aberration of the lenses, while the lenses were subjected to stretching forces applied through the ciliary body/zonular complex. The focal length of all unstretched lenses increased linearly with increasing age. Younger lenses were able to undergo significant changes in focal length with stretching, whereas lenses older than 60 years of age showed no changes in focal length with stretching. These data provide additional evidence for predominantly lens-based theories of presbyopia. Further, these results show that there are substantial optical changes in the human lens with increasing age and during accommodation, since both the magnitude and the sign of the spherical aberration change with age and stretching. These results show that the optical properties of the older presbyopic lens are quite different from the younger, accommodated lens.
To quantify changes in crystalline lens curvature, thickness, equatorial diameter, surface area, and volume during accommodation using a novel two-dimensional magnetic resonance imaging (MRI) paradigm to generate a complete three-dimensional crystalline lens surface model.
Nineteen volunteers, aged 19 to 30 years, were recruited. T(2)-weighted MRIs, optimized to show fluid-filled chambers of the eye, were acquired using an eight-channel radio frequency head coil. Twenty-four oblique-axial slices of 0.8 mm thickness, with no interslice gaps, were acquired to visualize the crystalline lens. Three Maltese cross-type accommodative stimuli (at 0.17, 4.0, and 8.0 D) were presented randomly to the subjects in the MRI to examine lenticular changes with accommodation. MRIs were analyzed to generate a three-dimensional surface model.
During accommodation, mean crystalline lens thickness increased (F = 33.39, P < 0.001), whereas lens equatorial diameter (F = 24.00, P < 0.001) and surface radii both decreased (anterior surface, F = 21.78, P < 0.001; posterior surface, F = 13.81, P < 0.001). Over the same stimulus range, mean crystalline lens surface area decreased (F = 7.04, P < 0.005) with a corresponding increase in lens volume (F = 6.06, P = 0.005). These biometric changes represent a 1.82% decrease and 2.30% increase in crystalline lens surface area and volume, respectively. CONCLUSIONS; The results indicate that the capsular bag undergoes elastic deformation during accommodation, causing reduced surface area, and the observed volumetric changes oppose the theory that the lens is incompressible.
The biomechanical environment of the optic nerve head (ONH), of interest in glaucoma, is strongly affected by the biomechanical properties of sclera. However, there is a paucity of information about the variation of scleral mechanical properties within eyes and between individuals. We thus used biaxial testing to measure scleral stiffness in human eyes. Ten eyes from 5 human donors (age 55.4+/-3.5 years; mean+/-SD) were obtained within 24h of death. Square scleral samples (6mm on a side) were cut from each ocular quadrant 3-9 mm from the ONH centre and were mechanically tested using a biaxial extensional tissue tester (BioTester 5000, CellScale Biomaterials Testing, Waterloo). Stress-strain data in the latitudinal (toward the poles) and longitudinal (circumferential) directions, here referred to as directions 1 and 2, were fit to the four-parameter Fung constitutive equation W=c(e(Q)-1), where Q=c(1)E(11)(2)+c(2)E(22)(2)+2c(3)E(11)E(22) and W, c's and E(ij) are the strain energy function, material parameters and Green strains, respectively. Fitted material parameters were compared between samples. The parameter c(3) ranged from 10(-7) to 10(-8), but did not contribute significantly to the accuracy of the fitting and was thus fixed at 10(-7). The products cc(1) and cc(2), measures of stiffness in the 1 and 2 directions, were 2.9+/-2.0 and 2.8+/-1.9 MPa, respectively, and were not significantly different (two-sided t-test; p=0.795). The level of anisotropy (ratio of stiffness in orthogonal directions) was 1.065+/-0.33. No statistically significant correlations between sample thickness and stiffness were found (correlation coefficients=-0.026 and -0.058 in directions 1 and 2, respectively). Human sclera showed heterogeneous, near-isotropic, nonlinear mechanical properties over the scale of our samples.
To quantify accommodative and age-related changes in the anteroposterior position and thickness of the ciliary muscle in phakic and pseudophakic eyes.
Department of Surgery/Bioengineering, UMDNJ-Robert Wood Johnson Medical School, Piscataway; Institute of Ophthalmology and Visual Science UMDNJ-New Jersey Medical School, Newark, New Jersey; MRI Research, Inc., Middleburg Heights, Ohio, USA.
Magnetic resonance images were taken of phakic and pseudophakic eyes.
The cohort comprised 32 phakic volunteers and 8 volunteers with a monocular intraocular lens (IOL) aged 22 to 91 years. No anteroposterior accommodative movement of the ciliary muscle apex occurred in either group. The muscle moved closer to the cornea with advancing age in phakic eyes; IOL implantation returned the muscle to a youthful position. An age-dependent increase in ciliary muscle anteroposterior thickness occurred that was not mitigated by IOL implantation. Muscle thickness increased with accommodation in only phakic eyes.
Presbyopia-correction strategies cannot rely on accommodative anterior movement of the ciliary muscle. Forces on the uvea by crystalline lens-pupillary margin contact may increase with accommodation and lens growth, producing accommodative and age-dependent increases in muscle thickness and significant age-dependent anterior muscle displacement. Intraocular lens implantation removed these forces, allowing choroidal elasticity to restore the muscle to a youthful position; however, the increase in thickness was permanent and likely due to an age-dependent increase in connective tissue. This supports the geometric theory of presbyopia development and that the mechanical forces in human accommodation and presbyopia are very different from those in the rhesus monkey model.
To investigate the change that occurs in intraocular pressure (IOP) and ocular pulse amplitude (OPA) with accommodation in young adult myopes and emmetropes.
Fifteen progressing myopic and 17 emmetropic young adult subjects had their IOP and OPA measured using the Pascal dynamic contour tonometer. Measurements were taken initially with accommodation relaxed, and then following 2 min of near fixation (accommodative demand 3 D). Baseline measurements of axial length and corneal thickness were also collected prior to the IOP measures.
IOP significantly decreased with accommodation in both the myopic and emmetropic subjects (mean change -1.8+/-1.1 mm Hg, p<0.0001). There was no significant difference (p>0.05) between myopes and emmetropes in terms of baseline IOP or the magnitude of change in IOP with accommodation. OPA also decreased significantly with accommodation (mean change for all subjects -0.5+/-0.5, p<0.0001). The myopic subjects (baseline OPA 2.0+/-0.7 mm Hg) exhibited a significantly lower baseline OPA (p=0.004) than the emmetropes (baseline OPA 3.2+/-1.3 mm Hg), and a significantly lower magnitude of change in OPA with accommodation.
IOP decreases significantly with accommodation, and changes similarly in progressing myopic and emmetropic subjects. However, differences found between progressing myopes and emmetropes in the mean OPA levels and the decrease in OPA associated with accommodation suggested some changes in IOP dynamics associated with myopia.
The sclera is the white outer shell and principal load-bearing tissue of the eye as it sustains the intraocular pressure. We have hypothesized that the mechanical properties of the posterior sclera play a significant role in and are altered by the development of glaucoma-an ocular disease manifested by structural damage to the optic nerve head. An anisotropic hyperelastic constitutive model is presented to simulate the mechanical behavior of the posterior sclera under acute elevations of intraocular pressure. The constitutive model is derived from fiber-reinforced composite theory, and incorporates stretch-induced stiffening of the reinforcing collagen fibers. Collagen fiber alignment was assumed to be multidirectional at local material points, confined within the plane tangent to the scleral surface, and described by the semicircular von Mises distribution. The introduction of a model parameter, namely, the fiber concentration factor, was used to control collagen fiber alignment along a preferred fiber orientation. To investigate the effects of scleral collagen fiber alignment on the overall behaviors of the posterior sclera and optic nerve head, finite element simulations of an idealized eye were performed. The four output quantities analyzed were the scleral canal expansion, the scleral canal twist, the posterior scleral canal deformation, and the posterior laminar deformation. A circumferential fiber organization in the sclera restrained scleral canal expansion but created posterior laminar deformation, whereas the opposite was observed with a meridional fiber organization. Additionally, the fiber concentration factor acted as an amplifying parameter on the considered outputs. The present model simulation suggests that the posterior sclera has a large impact on the overall behavior of the optic nerve head. It is therefore primordial to provide accurate mechanical properties for this tissue. In a companion paper (Girard, Downs, Bottlang, Burgoyne, and Suh, 2009, "Peripapillary and Posterior Scleral Mechanics--Part II: Experimental and Inverse Finite Element Characterization," ASME J. Biomech. Eng., 131, p. 051012), we present a method to measure the 3D deformations of monkey posterior sclera and extract mechanical properties based on the proposed constitutive model with an inverse finite element method.
The anterior and equatorial zonular insertions of 17 normal suspended lenses were studied with respect to age (17 to 90 years) by scanning electron microscopy. From our observations, with the normal lens growth, the distance between the lens zonular insertion and the equator (insertion-equatorial distance) increases; the distance between the insertion ring and the ciliary body (insertion-cb distance) remains relatively constant; and the circumlental space (equator-cb distance) decreases. These changes are most pronounced in the fifth decade and continue with age. Between ages 17 and 46, there are numerous equatorial zonules, while the older eyes are devoid of zonules in this region. However, in these older eyes fine zonules with the same morphology are seen anterior to the equator. Since the zonules are laid down early in development and their position on the capsule is fixed, these observations show a capsular shift resulting in a movement of zonules onto the anterior lens face. These findings show definitive changes with age in the architecture of the lens suspensory system which must be considered a factor in the failure of the lens to accommodate with advancing age (presbyopia).
1. Apparatus has been designed to alter the shape of the human lens by tensile forces applied to the zonular fibres indirectly through the ciliary body. The changes in dioptric power of the lens for monochromatic sodium light were measured at the same time. Simultaneous serial photography, and direct measurement enabled one to relate a change in shape of the lens to the change in dioptric power. Subsequently, the same lens was isolated and spun around its antero‐posterior polar axis and high speed photography recorded its changing profile.
2. By comparing the changes in lens profile due to zonular tension and centrifugal force respectively, the force developed in the zonule for a given change in the shape of the lens could be calculated. Changes in dioptric power associated with those of shape can thus be related directly to the force of contraction of the ciliary muscle necessary to reduce the initial tension of the zonule in the unaccommodated state.
3. The force of contraction of the ciliary muscle as measured by radial force exerted through the zonule and the change in dioptric power of the lens were not linearly related. The relationship is more exactly expressed by the equation [Formula: see text] where D = amplitude of accommodation in dioptres (m ⁻¹ ), F CB = force of contraction of the ciliary muscle as measured by changes in tension of the zonule (N), K df = dioptric force coefficient and is constant for a given age ( m ⁻¹ N −½ × 10 2·5 ). This coefficient is 0·41 at 15 yr and 0·07 at 45 yr of age.
4. In youth for maximum accommodation (10‐12 D) the force is approximately 1·0 × 10 ⁻² N while to produce sufficient accommodation for near vision (3·5 D) the force is less than 0·05 × 10 ⁻² N.
5. After the age of 30 yr the force of contraction of the ciliary muscle necessary to produce maximum accommodation rises steadily to about 50 yr of age and thereafter probably falls slightly. At about 50 yr of age the ciliary muscle is some 50% more powerful than in youth.
6. Even if hypertrophy of the muscle did not occur the amplitude of accommodation would be reduced at the most by only 0·8 D of that observed at the onset of presbyopia.
To understand the mechanism and cause of accommodation and presbyopia, the sclera in the region of the ciliary body of presbyopic patients was expanded. The amplitude of accommodation was increased in all presbyopic patients. A unique hypothesis of accommodation based on increased zonular tension is presented, which when applied clinically, results in a treatment for presbyopia.
The anterior lens capsule provides a thick, easily handled model system for the study of the organization of type IV collagen, the main component of basement membranes. We have used the technique of rapid freezing, deep-etch, and rotary replication to study the three-dimensional organization of the collagen skeleton in mammalian lens capsule after a variety of extraction procedures. In all cases the collagen appeared as a densely packed three-dimensional branching network of fine microfibrils. The organization of the microfibrils appears to show some regularity, with branch points approximately 40 nm apart. Most junctions are three-way and the network forms predominantly five-sided figures. This closely resembles the collagenous network described by Yurchenco and Ruben (1987, 1988) in human amniotic basement membrane and EHS tumor matrix, but extends their findings to another system for which X-ray diffraction data are available. The three-dimensional network is discussed in terms of molecular packing of type IV collagen in light of the information available from the diffraction data.
The age-related changes of the ciliary muscle of human eyes (33-87 years) were studied on histological meridional sections. Eighty-five melanoma eyes and 10 eyes of normal donors were investigated. The total area and the length of the muscle, the area of the three main portions and the distance of the inner apex of the muscle to the scleral spur were determined and correlated with age. Total area and length of the muscle show a continuous and significant decrease with age. The area of the longitudinal and reticular portion continuously decreases, whereas the area of the circular portion significantly increases with age. The decrease in area is more pronounced in the longitudinal portion than in the reticular portion of the muscle, which shows an age-related increase in connective tissue. In addition, the distance of the inner apex of the muscle to the scleral spur shortens continuously. Thus, with increasing age the ciliary muscle adopts an anterior-inward position. A similar form is seen in young eyes after ciliary muscle contraction only. There might be a functional relationship between the observed age-changes in the ciliary muscle system and the phenomenon of the so-called 'lens paradox' (steepening of the anterior and posterior curvatures of the disaccommodated lens with age).
Ocular biometric parameters and accommodative amplitude were measured by various techniques in 100 normal emmetropic human subjects age 18-70 yr. Anterior chamber depth decreased and lens thickness increased linearly over the entire age group. Accommodative amplitude declined linearly until a stable nadir was reached at about age 50 yr. The respective slopes and intercepts of the age-dependent decline in anterior chamber depth were essentially the same for measurements made independently by optical pachmetry, A-scan ultrasonography, and slit-lamp Scheimpflug photography. The age-dependent increase in lens thickness differed in slope and intercept for measurements made by photography and ultrasonography if the generally accepted lenticular sound velocity was assumed for all subjects. However, if putative lenticular sound velocity was adjusted for age, the relationships given by the two techniques were essentially identical. Total anterior segment length (defined as the distance between the anterior corneal and posterior lens surfaces), vitreous cavity length (distance between the posterior lens and anterior retinal surfaces), and total globe length were all independent of age. This constellation of findings indicates that the human lens grows throughout adult life while the globe does not, that thickening of the lens completely accounts for shallowing of the anterior chamber with age, but that the posterior surface of the lens remains fixed in position relative to the cornea and retina.
Multiple strips of choroid (56) and sclera (64) from eight pairs of human eye-bank eyes were subjected to simple tension in a test apparatus to determine the rigidity (modulus of elasticity) of these tissues. The modulus of elasticity of the chorodial complex (choroid-Bruch's membrane-pigment epithelium) was significantly greater in posteriorly located samples than in anteriorly located ones (7.5 +/- 7.0 vs. 2.2 +/- 1.5 x 10(5) N m-2, mean +/- S.D.). The modulus of elasticity for the complex averaged across all locations was 6.0 +/- 2.8 x 10(5) N m-2 and the average stress at failure was 3.3 +/- 1.3 x 10(5) N m-2. The modulus of elasticity for scleral strips also varied with location and averaged 2.9 +/- 1.4 x 10(6) N m-2 for anterior sclera and 1.8 +/- 1.1 x 10(6) N m-2 for posterior sclera at stress levels ranging from 20- to 260 x 10(4) N m-2. There was a significant correlation of scleral stiffness with age (P less than 0.05, r = 0.80). The elastic properties of the choroidal complex may be relevant to the pathogenesis of a variety of ocular diseases, including macular degeneration, angioid streaks, choroidal folds, and choroidal ruptures.
The cause of presbyopia is closely related to the force of contraction of the ciliary muscle and the resistance to deformation of the crystalline lens. Two views are currently in conflict. The view of Donders (1864) that presbyopia is caused by a decrease in the force of contraction of the ciliary muscle with age, and the opposing view of Helmholtz (1855) that the lens becomes more difficult to deform with age due to lenticular sclerosis. The present paper shows that, in fact, the ciliary muscle undergoes a compensatory hypertrophy as accommodative amplitude decreases with age. The force of contraction is about 50% greater at the onset of presbyopia than in youth. However, because of increased lenticular resistance its effect on the amplitude of accommodation is small. It is shown that the reason the lens becomes more difficult to deform is not because of lenticular sclerosis, since the lens substance does not lose water. The increased difficulty of deformation is because the capsule loses its elastic force with age and the lens fibres, particularly in the nucleus, become more compacted.