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 eye's 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.

Assessment of cataracts from photographs in the Beaver Dam Eye Study.

Presence and severity of age-related cataract was determined in adults 43 to 84 years of age in Beaver Dam, Wisconsin. Duplicate photograph gradings for nuclear sclerosis (n = 1160), cortical opacities (n = 1159), and posterior subcapsular cataract (n = 1137) were performed. There are five levels of nuclear sclerosis. Exact agreement occurred in 64.7% of the cases; agreement within one category in 99.8%. For cortical opacities, graders estimate involved area in nine segments of the lens. When the continuous scale is divided into 12 categories of severity, exact agreement varied between 73.5 and 82.4%; for agreement within one category, rates varied between 84.6 and 89.9%. For posterior subcapsular cataracts, exact agreement for involvement of the central circle occurred in 95.0% and agreement within one category occurred in 97.7%. Intraobserver comparisons disclosed similar concordance. These grading schemes are semiquantitative, reproducible, and can be performed for the large numbers of photographs from population-based studies.

In vivo videography of the rhesus monkey accommodative apparatus. Age-related loss of ciliary muscle response to central stimulation.

Fourteen rhesus monkeys, aged 1 to 24 years, underwent permanent implantation of a bipolar stimulating electrode into the Edinger-Westphal nucleus and complete unilateral or bilateral iridectomy. Slit-lamp Scheimpflug videography of the lens and slit-lamp goniovideography of the lens equator, zonule, and ciliary body allowed direct real-time observation and video recording of the movements of these structures during centrally stimulated accommodation and during disaccommodation. Scalloping of the lens capsule at the zonular insertion sites was clearly visible during disaccommodation and even during accommodation when the zonules were folded. During accommodation, the lens became axially thicker, the ciliary ring narrowed, and, at high levels of accommodation, the zonular fibers slackened and even folded and the lens moved downward. With increasing age and concomitantly decreasing accommodative amplitude, these excursions all diminished, so that in the oldest animals, they were very minimal or absent. Maximum centrally stimulated accommodative amplitude declined with age on a time scale similar to that for cholinomimetic drug-induced accommodation in the rhesus monkey and voluntary accommodation in the human.

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.

Accommodation and presbyopia in the human eye. 1: Evaluation of in vivo measurement techniques.

As part of a cross-sectional study of aging of the human accommodative apparatus, unaccommodated anterior chamber depth, unaccommodated lens thickness, and accommodative amplitude were each determined by two or more independent techniques in 100 normal emmetropic subjects, age 18-70 yr. For anterior chamber depth, the order of accuracy seemed to be: optical pachymetry > slit-lamp Scheimpflug photography > Ascan ultrasonography, although there was good agreement among all three methods. For lens thickness, slitlamp Scheimpflug photography seemed more accurate than A-scan ultrasonography when the generally accepted lenticular sound velocity of 1641 m . s(-1) was used for the ultrasonographic calculation. The agedependent divergence allowed calculation of a putative relationship between lenticular sound velocity and age, indicating that velocity decreased by ~3 m . s(-1) . yr(-1). Accommodative amplitude declined with age, reaching a minimum, by age 50 yr, of 0.5 diopters as measured by coincidence refractometry. This residual 0.5 diopters may represent the inherent focal depth of the eye's optical system, rather than active accommodation. Maximum accommodative amplitude based on the subject's ability to clearly visualize a target through minus lenses was always 1.50 diopters greater than the refractometrically measured maximum, regardless of age. This difference presumably represents increased depth of field provided by pupillary constriction, rather than active accommodation.

Slit-lamp studies of the rhesus monkey eye: III. The zones of discontinuity.

The rhesus monkey lens exhibits two zones of discontinuity, one anteriorly and one posteriorly. They are first discernible by slit-lamp photography as performed in this study at around age 7 years in iridectomized eyes, and become more distinct with increasing age. Their thickness and distance from each other along the polar axis are independent of lens age, but their distance from the lens surface increases with increasing age. Upon accommodation, the distance between the two zones increases while all other distances along the polar axis remain unchanged, indicating that, as in the human, overall alterations in rhesus lenticular shape and thickness with accommodation primarily reflect changes in the shape of the central region. The curvature of each zone becomes sharper in a linear fashion with accommodation, with the slope of the relationship being similar to those for lens surfaces.

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.

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.

Diabetic retinopathy as detected using ophthalmoscopy, a nonmydriatic camera and a standard fundus camera.

The study was performed to evaluate whether the severity of diabetic retinopathy as assessed by three alternative methods was concordant with the severity of retinopathy as determined from 30 degrees stereoscopic photographs. The three methods were direct ophthalmoscopy through an undilated pupil, nonstereoscopic 45 degrees retinal photography through a pharmacologically undilated pupil and nonstereoscopic 45 degrees photography through a dilated pupil. A single 45 degrees photograph centered between the disc and fovea was taken and direct ophthalmoscopy was performed on 99 persons prior to pharmacological dilation of the pupil. After dilation, another 45 degrees photograph was taken of the same field, as well as 30 degrees stereoscopic color photographs of DRS fields 1, 2 and 4 (modified). Corresponding photographic fields were graded by masked, trained graders for the severity of retinopathy and for the presence of specified diabetic lesions using the Modified Airlie House Classification scheme. For three levels of severity of retinopathy (none, nonproliferative or proliferative) exact agreement between direct ophthalmoscopy and grading of retinopathy from stereoscopic photographs taken with the standard 30 degrees camera was 54.3% (n = 94). For four levels of severity of retinopathy (none, microaneurysms only, all other nonproliferative retinopathy and proliferative retinopathy), exact agreement between gradings of retinopathy of the 45 degrees photographs taken through undilated pupils and 30 degrees photographs taken through dilated pupils was 82.5% (n = 63); and for 45 degrees photographs and 30 degrees photographs taken through dilated pupils it was 86.5% (n = 74). These data suggest that 45 degrees nonstereoscopic fundus photographs, when graded according to a standard classification scheme, provide reasonably reliable photographic representation of the severity of retinopathy when broad overall categories are used.

Echothiophate iodide cataracts in monkeys. Occurrence despite loss of accommodation induced by retrodisplacement of ciliary muscle.

Five cynomolgi underwent unilateral 360 degrees ciliary muscle retrodisplacement. Beginning several months later, they received 150 to 210 micrograms of echothiophate iodine topically once daily in both eyes for five months. In all eyes anterior and posterior subcapsular lens opacities developed that were characteristic of those caused by echothiophate. There were no apparent differences in biomicroscopic appearance or time course of the cataracts between eyes with or without retrodisplaced ciliary muscles. Since eyes with retrodisplaced ciliary muscles accommodate only minimally in response to echothiophate, possible mechanical stress on the lens due to sustained, intense accommodation cannot explain echothiophate cataractogenesis.