Jane F. Koretz

Accommodation and presbyopia in the human eye—aging of the anterior segment ☆

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.

A possible structure for α-crystallin

α‐Crystallin, the major protein of the mammalian eye lens, is found in vivo as a multimeric aggregate composed of two closely related subunits whose molar ratio is widely variable from species to species. Attempts to determine the arrangement of the subunits within the aggregate, or even to determine the size of the aggregate and the number of subunits composing it, have not resulted in general agreement. Because of the variability in λ‐crystallin particle size, the apparent dependence of this parameter on certain environmental factors (e.g. temperature), the absence of a specific requirement for either α‐crystallin isoform in aggregation, and the sharp division in the amino acid sequence between a strong hydrophobic region and a sharply hydrophilic one, it is suggested that the α‐crystallin aggregate has the properties of a protein micelle. This hypothesis is consistent with what is known of the α‐crystallin molecule and aggregate, and can be tested experimentally. If this hypothesis is shown to be true, then α‐crystallin will be the first example of a naturally occurring protein micelle.

Analysis of human crystalline lens curvature as a function of accommodative state and age

Slit-lamp photographs from four human subjects, aged 11, 19, 29, and 45 were reanalyzed using computer-based digitization and curve-fitting methods in order to obtain more complete information on internal lens curvature changes during accommodation. All discernible curves (N = 742) could be fit to parabolas with chi 2 less than or equal to 0.001 irrespective of lens age, accommodative state, or curve location within the lens. For each lens, the coefficients of the parabolas, when displayed in graphic form, exhibit a linear relationship between location within the lens and the coefficient of the chi 2 term. The slope of this line remains unchanged over accommodation for a given lens, but is shifted in position. The slope changes as a function of age. The age 45 lens exhibits these characteristics to a limited extent only, the differences possibly related to the development of presbyopia. The further a given curve is located from the lens surface, the smaller the region of its arc that can be considered approximately circular. A roughly hourglass figure is generated by these circular bounds; the waist of the hourglass decreases with increasing accommodation, since changes in radius of curvature with accommodation are more pronounced internally. Calculations of arc lengths as a function of increasing accommodation indicate that these lengths change very little over the entire accommodative range.

The development and maintenance of emmetropia.

The development and maintenance of emmetropia The human eye is programmed to achieve emmetropia in youth and to maintain emmetropia with advancing years. This is despite the changes in all eye dimensions during the period of growth and the continuing growth of the lens throughout life. The process of emmetropisation in the childs eye is indicated by a shift from the Gaussian distribution of refractive errors around a hypermetropic mean value at birth to the non-Gaussian leptokurtosis around an emmetropic mean value in the adult. Emmetropisation is the result of both passive and active processes. The passive process is that of proportional enlargement of the eye in the child. The proportional enlargement of the eye reduces the power of the dioptric system in proportion to the increasing axial length. The power of the cornea is reduced by lengthening of the radius of curvature. The power of the lens is reduced by lengthening radii of curvature and the effectivity of the lens is reduced by deepening of the anterior chamber. Ametropia results when these changes are not proportional. The active mechanism involves the feedback of image focus information from the retina and consequent adjustment of the axial length. Defective image formation interferes with this feedback and ametropia then results. Heredity determines the tendency to certain globe proportions and environment plays a part in influencing the action of active emmetropisation. The maintenance of emmetropia in the adult in spite of continuing lens growth with increasing lens thickness and increasing lens curvature, which is known as the lens paradox, is due to the refractive index changes balancing the effect of the increased curvature. These changes may be due to the differences between nucleus and cortex or to gradient changes within the cortex.

Aging of the human crystalline lens and anterior segment

Changes in the unaccommodated human crystalline lens were characterized as a function of subject age for 100 normal emmetropes over the age range 18-70 yr by Scheimpflug slit-lamp photography. With increasing age, the lens becomes thicker sagittally, but since the distance from the cornea to the posterior lens surface remains unchanged, this indicates that the center of lens mass moves anteriorly and the anterior chamber becomes shallower. Sagittal nuclear thickness is independent of age, but both anterior and posterior cortical thicknesses increase with age, shifting the location of the nucleus and the central sulcus in the anterior direction. The amount of light scattered by the lens at high angles, as represented by normalized and integrated lens densities from the digitized images, increases with increasing age in an exponential fashion. Similar relationships to age are observed for the major anterior zone of discontinuity (maximum density) and the central sulcus (minimum density). The relationships of these results to accommodation and presbyopia are discussed.

Model of the accommodative mechanism in the human eye

The crystalline lens of the age 11 human eye has been modelled mathematically, using simplified assumptions about lens curvature, internal organization and elasticity. From this representation, expressions for description of strain and stress during accommodation have been obtained. Solution of these equations indicates that the lens capsule acts as a force distributor, spreading tension applied by the suspensory apparatus evenly over the surface of the underlying lens material. It also becomes clear that the vitreous body provides an essential support function during the accommodative process. Finally, the relative contribution of lens-associated structures has been determined for five different values of the Poisson ratio. In order for accommodation to occur by relaxation of zonular tension, this value must be greater than 0.38; with an additional constraint of the net axial force equalling zero during a small accommodative change, the Poisson ratio equals 0.46.

Slit-lamp studies of the rhesus monkey eye: H. 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.

Scheimpflug and high-resolution magnetic resonance imaging of the anterior segment: a comparative study.

High-resolution imaging with a camera system built on the Scheimpflug principle has been used to characterize the geometry of the anterior segment of the adult human eye as a function of aging and accommodative state but is critically dependent on algorithms for correction of distortion. High-resolution magnetic resonance imaging (MRI), in contrast, provides lower-resolution information about the adult eye but is undistorted. To test the accuracy of the Scheimpflug correction methods used by Cook and Koretz [J. Opt. Soc. Am. A 15, 1473 (1998)]; [Appl. Opt. 30, 2088 (1991)], data on anterior chamber and segment lengths, as well as lens thickness and anterior and posterior curvatures, were compared with corresponding MRI data for adults aged 18-50 at 0 diopter accommodation. Excellent statistical agreement was found between the MRI and the Scheimpflug data sets with the exception of the posterior lens radius of curvature, which is less well defined than the other measurements in the Scheimpflug images. The considerable agreement between data obtained with MR and Scheimpflug imaging, two different yet complementary in vivo imaging techniques, validates the Scheimpflug correction algorithms of Cook and Koretz and suggests the capability of directly integrating information from both. A third, equivalent, data set obtained with a Scheimpflug-style camera system differs considerably from both Scheimpflug and MRI results in magnitude and age dependence, with negative implications for this alternative method and its correction procedures.

Slit-lamp studies of the rhesus monkey eye. I. Survey of the anterior segment.

Slit-lamp photographic studies of 144 caged rhesus monkeys, aged 2 months to 35 years, show age-related changes in anterior-chamber depth, lens thickness, anterior and posterior curvatures of the lens, and location of the posterior lens surface relative to the anterior corneal surface. For these parameters, as well as for those measured by other techniques, a difference in slope magnitude and (or) slope sign was found between the growth phase which lasts for 5-6 years, and the adult phase (greater than 5-6 years). Age-related changes in the adult rhesus eye are qualitatively similar in almost all aspects to those observed in the human eye, indicating that the rhesus is a good animal model for the study of human loss of accommodative amplitude.

The zones of discontinuity in the human lens: Development and distribution with age

Statistical analysis of Scheimpflug images from the crystalline lenses of 100 emmetropic human subjects ranging in age from 18 to 70 yr confirms that specific zones of discontinuity are a function of lens development and growth. At and beyond the age of 40 yr, as many as four sharply demarcated and complementary zones are seen within the anterior and posterior lens cortex. The locations of the inner edges of the anterior cortical zones of discontinuity were characterized relative to the central sulcus of the lens. Consecutively from the central sulcus, the distances were 1.094, 1.415, 1.695, and 1.994 (+/- 0.11 mm). Since nuclear thickness in the adult lens is age-independent and the rate of cortical growth has been characterized, the location of the inner margins of the zones are indicative of the age at which they originated; these ages were 4 (+/- 1 yr), 9 (+/- 2 yr), 19 (+/- 4yr), and 46 (+/- 10 yr). All of the zones become broader along the outer margin and more dense upon aging, with specific zones appearing to merge in older presbyopic lenses. While lens fetal nuclear transparency decreases with age, it does not feature zones of discontinuity; instead, symmetrically amorphous regions appear centrally in the anterior and posterior nucleus. This demonstration of the onset of specific zones of discontinuity in emmetropic individuals, at defined periods of lens growth that are synchronous the production of successively more complex lens sutures, strongly suggests a causal relationship between lens sutures and the zones of discontinuity.