The substance of this document was presented at the American
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Presbyopia is
characterized as a progressive age related loss of accommodative amplitude
(Figure 1). The progression of presbyopia begins early in life and culminates
in a complete loss of accommodation by about 50 years of age. Presbyopia is the
most prevalent of all ocular afflictions since it eventually affects 100% of
the population. Presbyopia generally results in a need for a near spectacle
correction or near addition lenses such as bifocal reading glasses in order to
see clearly at a comfortable reading distance.
The Mechanism of Accommodation
Classical studies (Helmholtz, 1909) show that accommodation occurs when the
ciliary muscle contracts to release the resting zonular tension on the
equatorial edge of the lens (Fig. 2). The young lens becomes more spherical
with increased surface curvatures through the inherent elasticity of the lens
substance and capsule. When accommodation ceases, the elastic choroid and
posterior zonular fibers return the ciliary muscle to the unaccommodated state.
The reconfiguration of the ciliary muscle increases the tension on the zonular
fibers at the equatorial edge of the lens. This pulls the edges of the lens
towards the sclera to flatten and unaccommodate the lens.
We (Glasser & Kaufman, unpublished observations) have confirmed the classical description of the mechanism of accommodation using gonioscopy (Figure 3) to image the ciliary processes in iridectomized eyes and an ultrasound biomicroscope (UBM) (Figure 4) to image the ciliary muscle during accommodation. Accommodation is induced by central stimulation (Crawford, et al., 1989). Both imaging techniques show that the ciliary muscle moves anteriorally and axially away from the sclera and that the equatorial edge of the lens moves away from the sclera during accommodation. From UBM imaging the posterior zonular fibers must be stretched during accommodation and their orientation changed by the forward and axial movement of the apex of the ciliary muscle.
Figure 3: (at right)
Image of an eye (OS) in the relaxed (upper half) and accommodated (lower half)
states as seen through a Swan-Jacob gonioscopy lens (Gl). The eye is totally
iridectomized so that the lens (Le), ciliary processes (Cp) and zonular fibers
(Zf) can be seen in the anterior chamber. A 9-0 nylon suture (Su) in the
temporal limbal margin of the cornea is used as a reference point to identify
eye movements. The accommodative changes observed are of a magnitude much
larger than can be explained by ocular movements. The lower half shows the eye
accommodated to about 11 D after central stimulation. Here
is an animation of this eye accommodating as seen using gonioscopy.
Figure 4: (below) UBM images of the posterior zonular fibers (pzf), the
ciliary muscle (cm) and the equatorial edge of the lens (le) of a young eye
(the iris has been surgically removed). (A) Image of the temporal ciliary
region in the relaxed, unaccommodated state. (B) When accommodated, the ciliary
muscle moves forward and axially, stretching the posterior zonular fibers,
relaxing the anterior zonular fibers and moving the equatorial edge of the lens
away from the sclera. (C) The absolute difference between images (A) and (B)
shows movements of the posterior zonular fibers, the ciliary muscle and the
equatorial edge of the lens. While the sclera of the eye is stable, the
equatorial edge of the lens moves away from the sclera. Here
is an animation of this eye accommodating as seen using the UBM.
Measurement of Refractive State and Accommodative Amplitude
Numerous objective and subjective techniques exist for determining the focus of the eye and accommodative amplitude. Subjective techniques typically have the subject report when printed text is in best focus while moving the page towards or away from the eyes (called a "push up" technique). While this is a simple method to employ, it is inaccurate, subject to error and, particularly in older subject with small pupil diameters, overestimates accommodation due to depth of focus of the eye. This is evident in figure 1 where roughly 1 D of accommodation remains even in the oldest subjects. This is almost certainly a depth of focus effect rather than active accommodation.
Objective measurement of the refractive state of the eye is also relatively simple, yet considerably more accurate than subjective methods. Retinoscopy with trial lenses is perhaps the most common approach. Various other instruments such as the Hartinger coincidence refractometer, autorefractors, and infrared optometers exist which facilitate measurement of the refraction of the eye with relative ease, accuracy and without much expertise required. When measuring refractive state or accommodative amplitude the subjective approach should be avoided.
Theories of Presbyopia
The two general and predominant theories of presbyopia consider either hardening or "sclerosis" of the lens substance or a loss of ciliary muscle function. Besides these two, many other theories or contributing factors have been implicated.
Lenticular theories of presbyopia are broadly based in age changes in one or more aspects of the lens. These include the lens substance, the lens capsule and the zonular fibers. These theories stem not only from changes in the elasticity of the tissues, but also from continued growth, changes in thickness and curvature of the lens with age.
a) Lenticular Sclerosis: The belief that the elasticity of the lens capsule molds the lens substance into the accommodated form when zonular tension is released leads to the theory that presbyopia is due to a hardening of the lens substance. In the older eye, when zonular tension is released the lens capsule is unable to exert sufficient force on the hardened lens substance to cause the lens to become accommodated (Fincham, 1937). More recent experimental evidence for this explanation for presbyopia comes from work by Fisher (1971, 1973) who showed that either spinning or mechanical stretching of older human lenses failed to alter the lens shape. Glasser and Campbell (1997) have further demonstrated an age-dependent decline in the ability of the human lens to undergo accommodative optical changes with mechanical stretching. Physical measurements of lens hardness also show a considerable increase with age (Pau & Krantz, 1991).
b) Changes in Capsular Elasticity: Since the capsule is thought to mold the lens substance to accommodate the lens, changes in capsular elasticity have also been implicated in presbyopia. Experiments have demonstrated that the capsule gets thicker with age up to about 60 years (Fisher, 1969) or 75 years (Krag, et al., 1997) and thereafter thins again, and that the capsule becomes less elastic (Fisher, 1969) or less extensible and more brittle with age (Krag, et al., 1997).
c) Geometric Theory of Presbyopia: Evidence shows that the anterior zonular attachment on to the equatorial edge of the lens shifts forward with increasing age (Farnesworth & Shyne, 1979). This has led to the introduction of a geometric theory of presbyopia (Koretz & Handleman, 1986; Koretz & Handleman, 1988; Pierscionek & Weale, 1995). This theory states that because of the increasing lens thickness and the anterior zonular shift with age, there is a decrease in the zonular insertion angle onto the anterior edge of the lens with age. This change in zonular insertion angle with age is said to reduce the ability of the zonular fibers to release the resting tension on the lens during accommodation and thus fail to allow the lens to become accommodated. No experimental support exists for this theory and evidence shows that older human lenses can not undergo any optical changes when the zonular tension is either increased or completely relaxed through mechanical means (Glasser & Campbell, 1997).
d) The 'Disaccommodation' Theory of Presbyopia: The continued growth of the lens through out life and the speculated changes in zonular insertion angle with age have led to the belief that presbyopia may be due to an inability of the zonular fibers in the older eye to hold the lens in the relatively flattened unaccommodated state. The older lens is then said to be in an accommodated state and compensatory age changes in the refractive index of the lens are invoked to explain why the eye does not become myopically focused (Bito and Miranda, 1989). This theory is also without experimental support and the fact that neither relaxing nor increasing zonular tension can cause any optical change in older human lenses disproves it (Glasser & Campbell, 1997).
d) Schachar's Theory of Presbyopia: This theory is rooted in the belief that the accommodative mechanism differs fundamentally from that described by Helmholtz (1909). A contraction of the ciliary muscle, rather than releasing equatorial zonular tension, is thought to actually increase it (Schachar et al., 1995). This is thought to increase the lens diameter during accommodation (Schachar, et al., 1996). Presbyopia is believed to occur because the continued growth of the lens and gradual slackening the zonular tension would prevent the ciliary muscle from increasing equatorial zonular tension during accommodation. A surgically implanted "scleral expansion ring" is suggested to increase the limbal diameter in the presbyopic eye, take up the slack in the zonular fibers and allow the ciliary muscle to again increase the equatorial zonular tension during accommodation (Schachar, 1992). Schachar's theory contradicts countless studies of accommodation since Helmholtz (1909) supporting the classical description of the mechanism of accommodation. From our own observations, shown in figures 3 and 4, the equatorial edge of the lens does not move towards the sclera during accommodation as suggested by Schachar (1996) but moves away from the sclera to decrease the lens diameter just as predicted by Helmholtz. Further, mechanical stretching and relaxation experiments show that stretching young human lenses increases the focal length (flattens the lens into an unaccommodated form) and relaxing zonular tension decreases the focal length (allowing the lens to become accommodated) by amounts exactly matching the age dependent accommodative amplitude (Glasser & Campbell, 1997). Further, even substantial stretching or relaxation of the zonular tension of older presbyopic lenses causes no change in the lens focal length (Glasser & Campbell, 1997). While further experiments to completely remove all confounding ocular micromovements is required, Schachar's mechanism must at present be considered unlikely.
Extralenticular Theories of Presbyopia consider age changes in the accommodative apparatus outside of the lens. The changes include anatomical, morphological and physiological changes in the ciliary muscle, connective tissue and the choroid.
a) Structural neuromuscular changes in the ciliary muscle: Ciliary muscle cells show increasing signs of lysosomes and fingerprints and some nerve endings and nerve terminals within the ciliary muscle show an increased number of myelin figures, all signs suggestive of age related degenerative changes. Degeneration of muscle cells and myelinated nerve fibers can be identified in the ciliary muscle of elderly eyes. Although these changes show concurrent structural and functional deterioration of the accommodative apparatus that parallel the progressive decline in accommodative amplitude (Lütjen-Drecoll, Tamm & Kaufman, 1988a), they are subtle and are insufficient to explain presbyopia since the excised ciliary muscle shows no age dependent loss of contractility (Poyer, Kaufman & Flügel, 1993).
b) Decreased compliance of the posterior insertion of the ciliary muscle: The ciliary muscle of older eyes fails to undergo the same configurational response to pilocarpine stimulation as the ciliary muscle of young eyes as assessed histologically (Lütjen-Drecoll, Tamm & Kaufman, 1988b). The loss of configurational response is not due to a loss of ciliary muscle muscarinic binding sites (True-Gabelt, Kaufman & Polansky, 1990) or due to a loss of ciliary muscle contractile response to muscarinic agonists with age (Poyer, Kaufman & Flügel, 1993), but is due to a decreased compliance of the elastic tendons which form the posterior attachment of the ciliary muscle (Tamm, Croft, Jungkunz, L(tjen-Drecoll, & Kaufman, 1992). These elastic tendons are thicker and have increased amounts of microfibrils and collagen fibrils in aged eyes, thus explaining the decreased compliance or loss of elasticity of this tissue with age (Tamm, Lütjen-Drecoll, Jungkunz, & Rohen, 1991)
c) Configurational changes in the human ciliary muscle: Histological study of the human ciliary muscle has identified several aspects that change with age. The total area of the ciliary muscle decreases, the length of the ciliary muscle decreases almost by half between the ages 30 and 85, the areas of the longitudinal and reticular portions of the ciliary muscle decrease and the area of the circular portion increases, there is an increase in connective tissue in the longitudinal portion of the ciliary muscle, and the distance of the inner apex of the ciliary muscle to the scleral spur decreases (Tamm, Tamm, & Rohen, 1992). This study suggests that the ciliary muscle of the older human eye looks like the accommodated ciliary muscle of the young eye (Tamm, Tamm, & Rohen, 1992).
Multifactorial Theories of Presbyopia
Given the preponderance of evidence for multiple age related changes in the
accommodative apparatus, it is likely that the ultimate end point of presbyopia
is a culmination of many factors together resulting in a loss of accommodative
amplitude. Few studies have addressed the possibility of a truly multifactorial
basis for presbyopia (
Reshaping the Future
Future attempts to reverse presbyopia or prevent its development should carefully consider the relevant experimental evidence. Just as it would be unnecessary to attempt to reintroduce the full 10 D of accommodation to the elderly eye, it would also be futile to implant accommodating intraocular lenses into presbyopic eyes if the ciliary muscle is completely incapable of performing its function. Pharmacological intervention aimed at reversing or preventing age changes in lens or ciliary muscle should also be considered.
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