Mary Ann Croft

Accommodation and presbyopia.

Accommodation is a dioptric change in power of the eye that occurs to allow near objects to be focused on the retina. The ability to accommodate is lost with increasing age in humans and monkeys. This phenomenon, called presbyopia, is the most common human ocular affliction, and its pathophysiology remains uncertain. The progressive loss of human accommodative amplitude begins early in life and results in a complete loss of accommodation by age 50 to 55 years. Presbyopia is correctable by various optical means and, although not a blinding condition, its cost in devices, lost productivity, and (more recently), for surgical interventions is considerable. The classic theory of accommodation in humans proposes that the ciliary muscle moves forward and axially in the eye during contraction, releasing tension on the anterior zonular fibers and allowing the lens to become more spherical and thicken axially. During disaccommodation, the ciliary muscle relaxes, allowing the elastic choroid to pull the ciliary muscle posteriorly, increasing the tension on the anterior zonules to flatten the lens. Alteration of every component of the accommodative apparatus has been proposed to explain presbyopia. Rhesus monkeys and humans exhibit a similar accommodative mechanism and lens growth throughout life and develop presbyopia with a similar relative age course. Theories to explain the pathophysiology of presbyopia fall into two main categories, involving dysfunction of either the lens or the ciliary muscle. Another theory is based on a proposed mechanism of accommodation different from that which is classically accepted. We summarize what is known about the anatomy and aging of the accommodative apparatus and how such changes might contribute to the loss of accommodative amplitude.

Accommodation dynamics in aging rhesus monkeys

Accommodation, the mechanism by which the eye focuses on near objects, is lost with increasing age in humans and monkeys. This pathophysiology, called presbyopia, is poorly understood. We studied aging-related changes in the dynamics of accommodation in rhesus monkeys aged 4-24 yr after total iridectomy and midbrain implantation of an electrode to permit visualization and stimulation, respectively, of the eyes accommodative apparatus. Real-time video techniques were used to capture and quantify images of the ciliary body and lens. During accommodation in youth, ciliary body movement was biphasic, lens movement was monophasic, and both slowed as the structures approached their new steady-state positions. Disaccommodation occurred more rapidly for both ciliary body and lens, but with longer latent period, and slowed near the end point. With increasing age, the amplitude of lens and ciliary body movement during accommodation declined, as did their velocities. The latent period of lens and ciliary body movements increased, and ciliary body movement became monophasic. The latent period of lens and ciliary body movement during disaccommodation was not significantly correlated with age, but their velocity declined significantly. The age-dependent decline in amplitude and velocity of ciliary body movements during accommodation suggests that ciliary body dysfunction plays a role in presbyopia. The age changes in lens movement could be a consequence of increasing inelasticity or hardening of the lens, or of age changes in ciliary body motility.

Aging of the human crystalline lens and presbyopia

The primary function of the crystalline lens is to increase the vergence of light that enters the pupil after passing through the cornea. In an emmetropic eye, the refractive power of the lens will increase the vergence of light to focus on the retina. The young human crystalline lens also serves the function of accommodation whereby the optical power of the lens is increased through the action of a ciliary muscle contraction (see the chapter, “Accommodation and Presbyopia”). Preservation of these two important optical functions throughout life would require that the lens optical and physical properties remain constant. In fact, very little, if anything, about the crystalline lens remains unchanged with increasing age. The rapidity and inevitability of the changes in the lens are evident from both presbyopia, which begins early in life and results in a complete loss of accommodation roughly midway through the human life span, and from the high incidence of cataract in the elderly. Both presbyopia and cataract, in all likelihood, represent part of a larger continuum of events that occur with aging of the eye and lens and are not end points in themselves.

Ultrasound biomicroscopy of the aging rhesus monkey ciliary region.

Ultrasound biomicroscopy of the living rhesus monkey ocular ciliary region was undertaken to identify age-dependent changes that might relate to the progression of presbyopia. Monkeys were anesthetized and pharmacologically cyclopleged, the eyelids were held open with a lid speculum, and sutures were placed beneath the medial and lateral rectus muscles. Ultrasound biomicroscopy imaging of the nasal and temporal quadrants of the eye were performed, and the live images were recorded to videotape. Subsequent image analysis was performed to obtain objective morphometric measurements of the ciliary body region. The ciliary body inner radius of curvature, outer radius of curvature, inner arc length, area, thickness, perimeter, zonular fiber length, and circumlental space were measured. Zonular space was calculated. The circumlental space decreased with increasing age in the temporal quadrant. The other morphologic measurements were not significantly correlated with age or body weight. Most morphologic measurements were significantly different comparing temporal vs. nasal quadrants. Bifurcation of the posterior zonular fibers was frequently observed. Although temporal circumlental space was the only measurement found to change with age, ultrasound biomicroscopy of the living rhesus ciliary region did identify distinct nasal vs. temporal asymmetries, which may reflect anatomical requirements for convergence-associated accommodation.

Accommodative Movements of the Vitreous Membrane, Choroid, and Sclera in Young and Presbyopic Human and Nonhuman Primate Eyes

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.

Morphology and accommodative function of the vitreous zonule in human and monkey eyes.

PURPOSE To explore the attachments of the posterior zonule and vitreous in relation to accommodation and presbyopia in monkeys and humans. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Extralenticular and lenticular aspects of accommodation and presbyopia in human versus monkey eyes.

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.

Lens diameter and thickness as a function of age and pharmacologically stimulated accommodation in rhesus monkeys

Uncertainty exists regarding accommodative and age changes in lens diameter and thickness in humans and monkeys. In this study, unaccommodated and accommodated refraction, lens diameter, and lens thickness were measured in rhesus monkeys across a range of ages. Iridectomized eyes were studied in 33 anesthetized monkeys aged 4-23 years. Refraction was measured using a Hartinger coincidence refractometer and lens thickness was measured with A-scan ultrasound. Lens diameters were measured with image analysis from slit-lamp images captured via a video camera while a saline filled, plano perfusion lens was placed on the cornea. Accommodation was pharmacologically stimulated with 2% pilocarpine via the perfusion lens in 21 of the monkeys and lens diameters were measured until a stable minimum was achieved. Refraction and lens thickness were measured again after the eye was accommodated. Unaccommodated lens thickness increased linearly with age by 0.029 mm/year while unaccommodated lens diameter showed no systematic change with age. Accommodative amplitude decreased by 0.462 D/year in response to pilocarpine. The accommodative increase in lens thickness decreased with age by 0.022 mm/year. The accommodative decrease in lens diameter declined linearly with age by 0.021 mm/year. Rhesus monkeys undergo the expected presbyopic changes including increasing lens thickness and a decreasing ability of the lens to undergo changes in thickness and diameter with accommodation, however without an age-related change in unaccommodated lens diameter. As in humans, the age-related decrease in accommodative amplitude in rhesus monkeys cannot be attributed to an age-related increase in lens diameter.

Age-related changes in centripetal ciliary body movement relative to centripetal lens movement in monkeys

The goal was to determine the age-related changes in accommodative movements of the lens and ciliary body in rhesus monkeys. Varying levels of accommodation were stimulated via the Edinger-Westphal (E-W) nucleus in 26 rhesus monkeys, aged 6-27 years, and the refractive changes were measured by coincidence refractometry. Centripetal ciliary process (CP) and lens movements were measured by computerized image analysis of goniovideographic images. Ultrasound biomicroscopy (UBM) at 50 MHz was used to visualize and measure accommodative forward movements of the ciliary body in relation to age, accommodative amplitude, and centripetal CP and lens movements. At approximately 3 diopters of accommodation, the amount of centripetal lens movement required did not significantly change with age (p = 0.10; n = 18 monkeys); however, the amount of centripetal CP movement required significantly increased with age (p = 0.01; n = 18 monkeys), while the amount of forward ciliary body movement significantly decreased with age (p = 0.007; n = 11 monkeys). In the middle-aged animals (12-16.5 years), a greater amount of centripetal CP movement was required to induce a given level of lens movement and thereby a given level of accommodation (p = 0.01), compared to the young animals (6-10 yrs). Collectively, the data suggests that, with age, the accommodative system may be attempting to compensate for the loss of forward ciliary body movement by increasing the amount of centripetal CP movement. This, in turn, would allow enough zonular relaxation to achieve the magnitude of centripetal lens movement necessary for a given amplitude of accommodation.

Surgical intervention and accommodative responses, II: forward ciliary body accommodative movement is facilitated by zonular attachments to the lens capsule.

PURPOSE To determine the role of the lens and the lens capsule in the three-dimensional architecture of the ciliary muscle at rest and during accommodation, in live rhesus monkeys and in histologic sections, by removing the entire lens, or only the lens nucleus and cortex, while leaving the posterior capsule in place. METHODS In 15 rhesus monkey eyes, aged 6 to 27 years, accommodation was induced by central stimulation of the Edinger-Westphal nucleus before and after intra- or extracapsular lens extraction (ICLE, ECLE). Forward ciliary body movement and ciliary body width were measured by ultrasound biomicroscopy (UBM, 50 MHz). The monkeys were then killed, the eyes were examined morphologically in 1-microm sections, and the shape of the ciliary muscle was compared with that obtained from UBM images. RESULTS The shape of the ciliary muscle in eyes undergoing ECLE (n = 5) did not differ from that in control eyes. In contrast, after ICLE (n = 10), accommodative forward ciliary body movement (P < 0.01) and thickness were decreased (P < 0.001), length was increased (P = 0.058), and the inner apex was located more posteriorly than in control eyes (P < 0.005). Histologic and in vivo data were similar and showed that the ciliary muscle maintained its triangular shape only if the lens capsule (with or without the lens substance) was present. CONCLUSIONS The posterior lens capsule and anterior zonular attachments facilitate forward accommodative ciliary body movement. Lens substance extraction procedures that leave the posterior capsule intact, similar to those used clinically, do not affect the capsule/zonular/muscular system movements, an important finding for accommodating intraocular lens development.