Slit-lamp studies of the rhesus monkey eye: II. Changes in crystalline lens shape, thickness and position during accommodation and aging

Changes in crystalline lens shape and axial thickness, anterior chamber depth and anterior cornea-posterior lens distance during accommodation induced by corneal iontophoresis of carbachol or electrical stimulation of the Edinger-Westphal nucleus were studied in 25 living, surgically aniridic rhesus monkey eyes, aged 1-25 years. Intraocular distances and anterior and posterior lens surface curvatures were evaluated from slit-lamp Scheimpflug photographs; distances were also determined by A-scan ultrasonography. With increasing accommodation, both lens surfaces become more sharply curved, the lens thickens and the anterior chamber shallows, while the posterior lens surface remains fixed relative to the cornea. Within statistical limits, the respective curvature and distance changes are the same for a given dioptric accommodation induced by either stimulation technique. The respective intraocular distance-accommodation relationships are identical whether derived from photographic or ultrasonographic measurements. Temporal and contralateral reproducibility of all measurements is excellent. Each parameter-accommodation relationship is strikingly linear in all eyes, although above 20 D the slopes of the lens surface curvature-accommodation relationships may have decreased. The curvature change per D of accommodation averages approximately 20% more for the posterior than for the anterior lens surface. There is relatively little interindividual variation in the slope of each relationship despite the significant interindividual differences in age and accommodative amplitude, indicating that the relationships are independent of age. However, when extrapolated back to the non-accommodated resting state, the data indicate that the lens thickens, both its surfaces become more sharply curved, and the anterior chamber shallows with age in adult greater than 5 years, while opposite trends are seen in younger animals.     

Comparison of the behavior of natural and refilled porcine lenses in a robotic lens stretcher

The mechanism by which the eye dynamically changes focal distance (accommodation), and the mechanism by which this ability is lost with age (presbyopia), are still contested. Due to inherent confounding factors in vivo, in vitro measurements have been undertaken using a robotic lens stretcher to examine these mechanisms as well as the efficacy of lens refilling - a proposed treatment for presbyopia. Dynamic forces, anterior and posterior curvatures, and lens thickness are all correlated for young natural and refilled porcine lenses. Comparisons are made to lenses refilled with a homogeneous polymer system. The amplitude of accommodation of the young porcine lens is very small such that it may be a suitable model for presbyopia. The behavior of refilled lenses was highly dependent on the refill volume. The volume could be tuned to maximize accommodative amplitude in the refilled lens.     

Shapes and dimensions of in vitro human lenses

There are inconsistencies in the literature regarding lens-shape change with age. This study looks at the dimensions and curvatures of 20 human lenses varying in age from 10–84 years. All lenses were from post-mortem eyes. Large individual variations mask any indications of a trend with age. There is a suggestion that growth in sagittal width is predominantly in the anterior section, indicating that the lens shape may become more symmetrical as it ages.     

In vivo study of changes in refractive index distribution in the human crystalline lens with age and accommodation

PURPOSE: Magnetic resonance imaging (MRI) was used to map the refractive index distribution in human eye lenses in vivo and to investigate changes with age and accommodation. METHODS: Whole-eye MR images were obtained for sagittal and transverse axial planes in one eye each of 15 young (19-29 years) and 15 older (60-70 years) subjects when viewing a far ( approximately 6 m) target and at individual near points in the young subjects. Refractive index maps of the crystalline lens were calculated by using a procedure previously validated in vitro. RESULTS: A central high refractive index plateau region and sharp decline in refractive index at the periphery were seen in all three groups. The peripheral decline was steepest in the older lenses and least steep in the young accommodated lenses. Average lens thickness increased (+0.27 mm; P < 0.05) and equatorial diameter decreased (-0.35 mm; P < 0.05) with accommodation. Axial thickness (+0.96 mm; P < 0.05) and equatorial diameter (+0.28 mm; P < 0.05) increased with age. The central index (1.409 +/- 0.008) did not differ between groups. The axial thickness of the central plateau increased with age (+0.83 mm; P < 0.05) but not significantly with accommodation. The equatorial diameter of the central plateau increased with age (+0.56 mm; P < 0.01) and decreased with accommodation (-0.43 mm; P < 0.05). CONCLUSIONS: The refractive index of the central plateau region does not change significantly with accommodation or ageing, but its size increases with age and the peripheral decline in refractive index becomes steeper in older lenses.     

Changes in ocular dimensions and refraction with accommodation

The purpose of this study was to measure the changes in ocular dimensions with accom-modation, with particular reference to the radius of curvature of the posterior surface of the crystalline lens. The increase in power of the eye with accommodation is considered to arise primarily from a decrease in the radius of curvature of the anterior surface of the lens, with the role of the posterior surface somewhat unclear. We measured the axial dimensions (A-Scan ultrasonography), cornea1 radius of curvature (keratometryl, refractive error (auto-refractor) and radii of curvature of the lenticular surfaces (video phakometryl for 11 subjects, mean age 21.2 + 2.6 years, for five levels of ocular accommodation up to 8.00D. At maximum accommodation the mean changes were a decrease in anterior chamber depth of 0.24 mm. an increase in lens thickness of 0.28 mm. a decrease in radius of curvature of the anterior surface of the lens of 4.95 mm and 1.34 mm for the posterior surface. The corres-pondtng increase in power of the lenticular surfaces for an equivalent refractive index of 1.422 for the lens was 5.53 D and 3.10 D for the anterior and posterior surfaces respectively. No significant changes were recorded in axial length or vitreous chamber depth. We conclude that when crystalline lens power is calculated on the basis of an equivalent refractive index, changes in the posterior surface of the lens contribute around one third of the Increase in lens power associated with 8.00 D of ocular accommodation.     

Objective evaluation of the changes in the crystalline lens during accommodation in young and presbyopic populations using Pentacam HR system

AIM: To quantify the changes in the lens profile with accommodation in different age groups. METHODS: The Pentacam HR system was used to obtain the images of the anterior eye segment from 23 young and 15 presbyopic emmetropic subjects in unaccommodated (with an accommodation stimulus of 0.0D) and accommodated (with an accommodation stimulus of 5.0D for the young group and 1.0D for the presbyopic group) states. The phakic crystalline lens shape, including curvature of crystalline lens and central lens thickness (CLT), and the measurements of anterior segment length (ASL), central anterior chamber depth (CACD) were investigated. The anterior chamber volume (ACV) was also measured. RESULTS: The reduction of CACD and ACV were significant in both groups after accommodation stimulus. From the profile of anterior eye segment, a significant decrease in anterior crystalline lens radii of curvature (-2.52mm) and a mean increase in CLT (0.222mm) and ASL (0.108mm) were found in the young group with an accommodation stimulus of 5.0D. However, no statistically significant changes of CLT, ASL, or crystalline lens radii of curvature were found in the presbyopic group. CONCLUSION: Our data showed that the shallowing of anterior chamber during accommodation was caused by the forward bulging of the anterior lens surface, rather than by anterior shifting of lens position in either young or presbyopic subjects.     

Biometry of the crystalline lens in early-onset diabetes.

Lenticular biometry on non-cataractous lenses has been studied by means of Scheimpflug photography and digital image analysis in 153 patients with early-onset insulin-dependent diabetes and 153 non-diabetic controls. Anteroposterior axial lens thickness, cortical thickness, nuclear thickness, anterior and posterior lenticular curvatures, and anterior chamber depth were assessed. Highly significant differences between the lenses of the diabetic subjects and non-diabetic controls were found. After the effect of age had been accounted for within the diabetic subgroup, diabetic duration was found to be a highly significant determinant of lens dimensions, such that age-related dimensional changes for various biometric parameters were accelerated by between 52% and 121% after the onset of diabetes. Because the diabetic duration of the early-onset diabetic subjects studied in this work was accurately known, this report is the first in which a precise assessment of the effect of 'true' diabetic duration on lens biometry has been possible.     

Contribution of the crystalline lens gradient refractive index to the accommodation amplitude in non-human primates: in vitro studies

The purpose of this study was to determine the contribution of the gradient refractive index to the change in lens power in hamadryas baboon and cynomolgus monkey lenses during simulated accommodation in a lens stretcher. Thirty-six monkey lenses (1.4-14.1 years) and twenty-five baboon lenses (1.8-28.0 years) were stretched in discrete steps. At each stretching step, the lens back vertex power was measured and the lens cross-section was imaged with optical coherence tomography. The radii of curvature for the lens anterior and posterior surfaces were calculated for each step. The power of each lens surface was determined using refractive indices of 1.365 for the outer cortex and 1.336 for the aqueous. The gradient contribution was calculated by subtracting the power of the surfaces from the measured lens power. In all lenses, the contribution of the surfaces and gradient increased linearly with the amplitude of accommodation. The gradient contributes on average 65 ± 3% for monkeys and 66 ± 3% for baboons to the total power change during accommodation. When expressed in percent of the total power change, the relative contribution of the gradient remains constant with accommodation and age in both species. These findings are consistent with Gullstrand's intracapsular theory of accommodation.     

A quantitative analysis of sutural contributions to variability in back vertex distance and transmittance in rabbit lenses as a function of development, growth, and age.

PURPOSE: To correlate specific parameters of lens structure (anterior and posterior suture branch length and planar area) with variability in back vertex distance (BVD) and scatter in rabbit lenses as a function of development, growth, and age. METHODS: Lenses from juvenile (n = 9), adult (n = 9), and aged (n = 10) New Zealand White rabbits were utilized in this study. After sacrifice, lens suture patterns were photographed using a stereo surgical dissecting microscope. Within 5 min of sacrifice, average BVD, variability in BVD, and scatter were assessed with a Scantox In Vitro Assay System. Laser beams were passed incrementally along anterior and posterior suture planes through right eye (oculus dexter, OD) lenses, and between suture planes through left eye (oculus sinister, OS) lenses. After fixation, lens axial dimensions and suture branch lengths were assessed and used to create scaled, 3-dimensional computer assisted drawings (3-D CADs) depicting gross lens shape and sutural changes throughout life. RESULTS: Whereas average BVD only increased significantly as a function of growth, variability in BVD only increased significantly as a function of aging. However, anterior sutures exerted a greater influence on variability of BVD than posterior sutures throughout growth and aging. This difference is consistent with anterior suture branches being longer, or extending farther peripherally, than posterior sutures. Scatter was essentially unchanged between juvenile and adult lenses but significantly increased in aged lenses. Notably, posterior sutures effected a greater age-related increase in scatter than anterior sutures. This difference was consistent with the formation of numerous small, posterior subbranches and subplanes later in life. Structural analysis also suggested that asymmetric age-related lens compaction had occurred, predominantly affecting posterior lens dimensions. CONCLUSIONS: Lens sutures significantly influence average BVD throughout development and growth, and variability in BVD throughout aging. In addition, even though the rabbit lenses appeared transparent throughout growth and aging, unequal length and area of anterior vs. posterior suture branches and planes respectively, as well as a greater degree of age-related posterior lens compaction, were factors contributing to increased scatter.     

Deformations and Ruptures in Human Lenses With Cortical Cataract Subjected to Ex Vivo Simulated Accommodation

PurposeHuman cortical opacities are most commonly accompanied by changes in lens fiber structure in the equatorial region at the lens nucleus–cortex interface. Cortex and nucleus have different elastic properties, which change with age. We therefore subjected ex vivo lenses to simulated accommodation and studied the internal deformations to better understand the mechanism of cortical cataract formation.MethodsNine human donor lenses (33–88 years old) were tested using a bespoke radial stretching device for anterior eye segments. Seven of the lenses exhibited cortical cataracts. The other two lenses, without cataract, were used as controls. Frontal and cross-sectional images of the lens obtained during stretching facilitated measurements on equatorial lens diameter and central lens thickness in the stretched and unstretched states.ResultsStretching caused the lens equatorial diameter to increase in all cases. Conversely, the lens central thickness showed no systematic variation during stretching. For four of the lenses with cortical cataract, ruptures were observed during stretching at the nucleus–cortex boundary adjacent to the cortical cataracts. Ruptures were not observed in the control lenses or in the three other lenses with cortical cataract.ConclusionsInternal ruptures can occur in aged ex vivo lenses subjected to simulated disaccommodation. These ruptures occur at the nucleus–cortex interface; at this location, a significant stiffness discontinuity is expected to develop with age. It is hypothesized that ruptures occur in in vivo lenses during accommodation—or attempted accommodation.     

Change in shape of the aging human crystalline lens with accommodation

The objective was to measure the change in shape of the aging human crystalline eye lens in vivo during accommodation. Scheimpflug images were made of 65 subjects between 16 and 51 years of age, who were able to accommodate at least 1D. The Scheimpflug images were corrected for distortion due to the geometry of the camera and the refraction of the cornea and anterior lens surface, which is necessary to determine the real shape of the lens. To ensure accurate correction for the refraction of the anterior lens surface, the refractive index of the crystalline lens must be determined. Therefore, axial length was also measured, which made it possible to calculate the equivalent refractive index of the lens and possible changes in this index during accommodation. The results show that during accommodation there is a decrease in both the anterior and the posterior radius of the lens, although the change in mm per diopter of the latter is much smaller. The increase in lens thickness with accommodation is higher than the decrease in the anterior chamber depth, indicating that the posterior lens surface moves backwards with accommodation. During accommodation the anterior lens surface becomes more hyperbolic. Furthermore, an increase in the equivalent refractive index during accommodation was determined.     

The change in shape and internal form of the lens of the eye on accommodation

A slit-image photographic technique is used to measure changes in the lens of the human eye on accommodation. It is found that the surfaces become conoid in the adult eye, which is more marked anteriorly than posteriorly, but in the child's eye the increase in curvature is spherical. The effect of the cornea in distorting the appearance is investigated and discounted. The anterior pole of the lens moves forward and the posterior pole moves back to a lesser extent. The lens centre moves forward. The equator of the lens and of the nucleus are reduced in diameter. The lens cortex is unchanged in thickness and the nucleus is markedly thickened. It is considered to be the nucleus which is active in changing the shape of the lens.     

Modeling internal stress distributions in the human lens: can opponent theories coexist?

The effects of material properties and equatorial stretching forces on the stress distribution and shape profile of human lenses were investigated to see whether support could be found for either or both current theories of accommodation. Finite element analysis was used to create models using shape parameters and material properties from published data. Models were constructed for two lenses of different ages. Material properties were varied to show differences between models with a single elastic modulus and those with different moduli for the cortex and the nucleus. Two levels of stretching forces were applied at the equator. Comparisons between experimental and model profiles were made, and stress distribution patterns were constructed. In all models, stretching produces a flattening in the peripheral curvature of the lens. In the younger lens, model and experimental results show that central curvature at some points is steeper for stretched than for unstretched profiles. In the older lens, gradients are flatter at all central points for stretched model and experimental profiles compared to the unstretched profile. In all models, there is a region of higher stress distribution within the lens that corresponds with the position of an inflection point that appears on the anterior surface and, in the older lens, also on the posterior surface. The results show that equatorial stretching forces can produce shape changes in support of both current theories of accommodation depending on the lens age, shape, and applied force.     

Changes in lens dimensions and refractive index with age and accommodation.

PURPOSE: To measure changes in human eye lens dimensions and refractive index with age and state of accommodation. METHODS: MRI methods were used to measure refractive index maps and lens geometry (diameter and thickness) of an axial slice through the lens in 44 volunteers aged 18 to 59 years, with an accommodation stimulus of 0.17 D (unaccommodated state). In a subpopulation of 26 young volunteers aged 18 to 33 years, lens dimensions were also measured in an accommodated (6.67 D stimulus) state. For a subpopulation of six of the young volunteers (22 to 33 years), refractive index maps were also acquired with an accommodation stimulus of 6.67 D. RESULTS: Unaccommodated lens thickness increased significantly with age (T = 3.31 +/- 0.10 mm + 0.0180 +/- 0.0036 mm x Age; p < 0.0001). Lens diameter (D = 9.33 +/- 0.0033 mm) and central refractive index (nc = 1.4198 +/- 0.0067) showed no significant age dependence. Lens thickness increased (DeltaT = 0.050 +/- 0.024 mm/D) and diameter decreased (DeltaD = -0.067 +/- 0.030 mm/D) on accommodation. A slight decrease in central refractive index with accommodation was not statistically significant. CONCLUSIONS: The results are consistent with the Helmholtz theory of accommodation.     

Age-related changes in refractive index distribution and power of the human lens as measured by magnetic resonance micro-imaging in vitro

We report a new technique for non-invasively mapping the refractive index distribution through the eye lens using magnetic resonance micro-imaging. The technique is applied to map the refractive index distribution throughout the sagittal plane of 18 human eye lenses ranging in age from 14 to 82 years in vitro. The results are compared with standard models for the human eye lens. They confirm that the refractive index distribution, when plotted as a function of normalised lens radius, is a function of lens age and differs both between the equatorial and axial directions and between the anterior and posterior halves of the optical axis. The refractive index of the lens nucleus exhibits a significant reduction with age amounting to 3.4+/-0.6 x 10(-4) years(-1). The contribution of the gradient index (GRIN) to the lens power decreases by 0.286+/-0.067 D/year, accounting almost entirely for the estimated overall change in lens power with age for these lenses, which were probably in their most accommodated state. The results provide experimental verification of hypothesised changes in the GRIN that have previously been invoked as contributing to presbyopia and support the hypothesis that changes in the GRIN are sufficient to offset effects of increasing curvature of human lenses with age in their unaccommodated state.     

Internal deformation of the human crystalline lens during accommodation

Purpose: To describe the internal deformations in the crystalline lens that occur during accommodation. Methods: A computer‐based mechanical model of accommodation was created using the finite element method. The lens geometry of the model was based on in vivo measurements of human lenses in the accommodated state. The mechanical properties of the lens were based on ex vivo measurements of human lenses. To achieve a state of disaccommodation, the lens equator was stretched by 7%. The internal strains and displacements were calculated for a young accommodating lens, a lens of pre‐presbyopic age and a lens of presbyopic age (20, 40 and 60 years old, respectively). Results: The model showed that the radial strain was maximal in the nucleus for the young accommodating lens and minimal in the nucleus for the oldest non‐accommodating lens. In the young lens the deformations occurred throughout the entire lens, whereas in the older non‐accommodating lens the deformations were concentrated in the equatorial region. Conclusions: The model predicted that during accommodation, changes in lens thickness are mainly caused by deformation of the nucleus. In the older, non‐accommodating lens, the deformations occur predominantly in the equatorial region and do not affect the central curvatures of the lens.     

Mathematical models for describing the shape of the in vitro unstretched human crystalline lens

We developed orthogonal least-squares techniques for fitting crystalline lens shapes, and used the bootstrap method to determine uncertainties associated with the estimated vertex radii of curvature and asphericities of five different models. Three existing models were investigated including one that uses two separate conics for the anterior and posterior surfaces, and two whole lens models based on a modulated hyperbolic cosine function and on a generalized conic function. Two new models were proposed including one that uses two interdependent conics and a polynomial based whole lens model. The models were used to describe the in vitro shape for a data set of twenty human lenses with ages 7-82 years. The two-conic-surface model (7 mm zone diameter) and the interdependent surfaces model had significantly lower merit functions than the other three models for the data set, indicating that most likely they can describe human lens shape over a wide age range better than the other models (although with the two-conic-surfaces model being unable to describe the lens equatorial region). Considerable differences were found between some models regarding estimates of radii of curvature and surface asphericities. The hyperbolic cosine model and the new polynomial based whole lens model had the best precision in determining the radii of curvature and surface asphericities across the five considered models. Most models found significant increase in anterior, but not posterior, radius of curvature with age. Most models found a wide scatter of asphericities, but with the asphericities usually being positive and not significantly related to age. As the interdependent surfaces model had lower merit function than three whole lens models, there is further scope to develop an accurate model of the complete shape of human lenses of all ages. The results highlight the continued difficulty in selecting an appropriate model for the crystalline lens shape.     

The biomechanical properties of the crystalline lens capsule in emmetropia and myopia

Morphometric and electronmicroscopic studies of the capsule of a clear lens depending on the degree of myopia and age as compared with the capsule of a clear lens in emmetropia and myopia have shown that with age the anterior capsule of a clear lens becomes thicker, while the posterior capsule becomes thinner and increases in length. This is connected with the weakening of accommodation in the presence of different curvature of the anterior and posterior surfaces of the lens on the background of the lowering of the metabolic level in elderly persons. In myopia, with the development of age changes the thickness of the lens capsule remains almost unchanged. The degree of myopia doesn't influence the thickness and the length of the anterior capsule of the lens, while with the rise of myopia the thickness of the posterior capsules increases. No dystrophic changes in the structure of such a capsule in high myopia were revealed. Hypertrophy of the posterior capsule speaks about the increase of its mechanic strength in a clear lens and is connected with the weakness of accommodation. Such a capsule can serve as a support for IOL implants in patients with myopic refraction.     

Comparisons between pharmacologically and Edinger-Westphal-stimulated accommodation in rhesus monkeys

PURPOSE: Accommodation results in increased lens thickness and lens surface curvatures. Previous studies suggest that lens biometric accommodative changes are different with pharmacological and voluntary accommodation. In this study, refractive and biometric changes during Edinger-Westphal (EW) and pharmacologically stimulated accommodation in rhesus monkeys were compared. METHODS: Accommodation was stimulated by an indwelling permanent electrode in the EW nucleus of the midbrain in one eye each of four rhesus monkeys. Dynamic refractive changes were measured with infrared photorefraction, and lens biometric changes were measured with high-resolution, continuous A-scan ultrasonography for increasing stimulus current amplitudes, including supramaximal current amplitudes. Accommodation was then stimulated pharmacologically and biometry was measured continuously for 30 minutes. RESULTS: During EW-stimulated accommodation, lens surfaces move linearly with refraction, with an increase in lens thickness of 0.06 mm/D, an anterior movement of the anterior lens surface of 0.04 mm/D, and a posterior movement of the posterior lens surface of 0.02 mm/D. Peak velocity of accommodation (diopters per second) and lens thickness (in millimeters per second) increased with supramaximal stimulus currents, but without further increase in amplitude or total lens thickness. After carbachol stimulation, there was initially an anterior movement of the anterior lens surface and a posterior movement of the posterior lens surface; but by 30 minutes, there was an overall anterior shift of the lens. CONCLUSIONS: Ocular biometric changes differ with EW and pharmacological stimulation of accommodation. Pharmacological stimulation results in a greater increase in lens thickness, an overall forward movement of the lens and a greater change in dioptric power.     

Radius of curvature and asphericity of the anterior and posterior surface of human cadaver crystalline lenses

The purpose of this study was to measure the shape of the anterior and posterior surface of human cadaver lenses in situ using a corneal topography system. Measurements were performed on 13 pairs of eyes using the PAR Corneal Topography System (PAR-CTS). The age of the donors ranged from 46 to 93 years, with an average age of 76.4 years. Anterior lens topography was measured after excision of the cornea and iris. Posterior lens topography was measured after sectioning the posterior segment and adherent vitreous. The PAR-CTS files providing raw surface height were exported for analysis. In each surface, 18 meridians separated by 10 degrees were fitted using conic sections to obtain values of the apical radius of curvature (R) and shape factor (p). The average apical radius of curvature and asphericity were R=10.15+/-1.39mm and p=4.27+/-1.39 for the anterior surface and R=-6.25+/-0.79mm and p=-0.64+/-1.85 for the posterior surface. A significant variation of the radius of curvature and shape factor as a function of the meridian angle (lens astigmatism) was found in some lenses. Contrary to previous findings, the anterior lens surface was found to steepen toward the periphery.