Ординатура / Офтальмология / Английские материалы / Hyperopia and Presbyopia_Tsubota, Boxer Wachler, Azar_2003

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apply to the lens equator decreases linearly with age, resulting in a linear decrease in the amplitude of accommodation (i.e., presbyopia).

1. Schachar’s Supporting Data

Schachar first showed experimental support of his theory by progressively stretching the sclerae and ciliary bodies of bovine eyes and then measuring the change in focal length and equatorial diameter of the lens. All eyes showed a decrease in focal length and therefore an increase in the optical power as well as an increase in equatorial diameter (3). Schachar

(4) has also constructed a physical model of the variable-focus lens using a gelatin-filled balloon that can change optical power to 10 D, simulating an aspect of his theory of accommodation. Profile photographs were taken of a gelatin-filled balloon relaxed and stretched at the equator. He was able to prove, both with the photographs and mathematically, that with equatorial stretching, the central anterior lens becomes steeper, the peripheral anterior lens becomes flatter, and there is no change in the posterior radius of curvature. Schachar (5) used a vertical scanning interference microscope to measure the mean radius of curvature of both anterior and posterior surfaces of constant-volume, deformable, waterfilled lenses prior to and during stepwise equatorial stretching. Central steepening and peripheral flattening of the lens was again demonstrated.

In another study, high-frequency, high-resolution anterior segment ultrasound biomicroscopy was used to measure in vivo changes occurring at the lens equator in 12 young human subjects during pharmacologically controlled accommodation (6). The patients ranged in age from 20 to 34 years with a mean age of 26 years and a standard deviation of 5 years. The patients had a correctable visual acuity of 20/20 and accommodative mean amplitude of 9.5 D. One drop of 1% tropicamide was placed in the right eye. The pupil and the near point without correction were measured 25 min later using four-point print. Ultrasound biomicroscopy (UBM) was performed using the Humphrey Instruments biomicroscope to image the lens equator in the unaccommodated state. A video recording was made of the UBM images. Later, one drop of 2% pilocarpine was administered in the right eye, and 1 h later the pupil and the near point without correction were measured. Ultrasound biomicroscopy was then performed, after which a video recording was made of the UBM images. The induced accommodation was the difference between the near point measurements after pilocarpine and tropicamide.

A frame-by-frame comparison was made between the two videos for each patient, using a video mixer and computer subtraction techniques. Over 20,000 images of each of the 12 subjects were compared. Separate and different images of the same patient in the unaccommodated and the accommodated states were superimposed. The cornea and sclera were used as positional references, which provided a reliable method to avoid errors that accompany misalignment and rotation, since the cornea and sclera do not change position during accommodation. In this study it was demonstrated that, during accommodation, the lens equator moves toward the sclera. The mean displacement of the lens equator toward the sclera was 6.8 1 m for each diopter of increase in accommodation (6). This confirmed predictions of previous mathematical and physical models (4,7,8) and was consistent with the increase in the optical power of the bovine lens with equatorially stretching that occurred in Schachar’s previous study (3).

Schachar and his colleagues mathematically modeled the human crystalline lens to approximate both the Schachar and the Helmholtz theories of accommodation (9). They used nonlinear finite-element analysis that included the material properties and proper

boundary conditions approximating the human crystalline lens. They used ANSYS 5.6, a general-purpose, nonlinear, finite-element computer program to perform their analysis. They calculated the amount of force necessary to produce a given amount of equatorial displacement. The thick-lens formula was used to establish the optical power of the crystalline lens. Then the longitudinal spherical aberration of various levels of crystalline lens accommodation was investigated using Zemax EE, an optical computer program.

The results of nonlinear finite-element analysis by Schachar et al. demonstrated that only the tension produced solely by the equatorial zonules was able to produce the known properties of the accommodative process, which include an increase in central optical power, and also accounts for the physiological force limitations of the ciliary muscle. They also demonstrated that the increase in equatorial diameter associated with the tension produced by the equatorial zonules was consistent with the ultrasound biomicroscopy measurements showing that the lens equator moves toward the sclera during pharmacologically controlled accommodation. The analysis demonstrated that when the anterior and posterior zonules or all three sets of zonules totally relax, the central optical power of the crystalline lens would decrease, not increase. These results contradict Helmholtz’s theory of accommodation.

2. Clinical and Experimental Data Supporting Helmholtz’s Theory

Schachar’s hypothesis of accommodation has recently been challenged. Glasser and Campbell (11,12) isolated human lenses from 27 human eyes aged 10 to 87 years. An in vitro scanning laser technique was used to measure the focal length and spherical aberration of the lenses as the lenses were exposed to increasing and decreasing radial stretching forces through the ciliary body–zonular complex. They demonstrated that for the three youngest lenses (11,31, and 39 year old), the focal length did change with stretch. On the other hand, the older lenses, 54 and the 87 years old, demonstrated no change in focal length over the extent of stretch applied. These results contradict Schachar’s hypothesis of accommodation, which maintains that the lens remain malleable even with increasing age. In a different investigation by Glasser and Campbell (12,13), another group of 19 lenses 5 to 96 years of age were studied. In this group, which included older lenses with signs of early cataract, the focal length increased up to approximately age 65, but then their focal length decreased. Both studies demonstrated that over the years when accommodation is gradually lost due to presbyopia, the focal length of the unstretched lenses gradually increased linearly, supporting a lens/capsule compliance and elasticity-based theory of presbyopia.

Glasser and Kaufman (14) studied the accommodative mechanism in six cynomolgus monkeys (10 to 13 year old) and eight rhesus monkeys (6 to 17 years old) with stimulated accommodative amplitudes ranging from 7 and 18 D. The monkeys had complete bilateral iridectomies. Stimulating electrodes surgically implanted in the Edinger-Westphal nucleus were used to induce varying amplitudes of accommodation. Accommodation was also induced and reversed in several other cynomolgus and rhesus monkeys. Carbachol chloride iontophoresis, topical pilocarpine hydrochloride, and systemic pilocarpine hydrochloride were the agents used to stimulate accommodation, and topical and systemic atropine sulfate was used to reverse the accommodation.

Goniovideography of the iridectomized eyes was performed, demonstrating the tips of the ciliary processes, the anterior zonular fibers, and the lens equator. Ultrasound biomicroscopy was also performed using the Humphrey Instruments biomicroscope. Gonioscopy

was imaged and recorded at the slit lamp. Measurements of the movement of the lens equator and ciliary processes were taken from image analysis of the goniovideography sequences. The refractive state of the eye during accommodation was recorded using the Hartinger coincidence refractometer (Jenoptik, Jena, Germany). Refractions at baseline and with accommodation were recorded at each stimulus amplitude. The accommodative amplitude at each stimulus was the difference between the two refractions. The results of these studies of dynamic accommodation showed that the ciliary body and the lens equator moved away from the sclera during both centrally and pharmacologically stimulated accommodation, contrary to Schachar’s theory of accommodation, which states that the lens equator moves toward the ciliary processes.

Schachar has claimed that the experiments by Glasser and Kaufman were flawed (15). He states that because the sutures placed in the cornea as a reference point and the corneal Purkinje images did not subtract out, there was eye movement between the imaging device and the eye. He then states that Glasser and Kaufman did not have any controls to prove that the small amount of eye movement seen in their experiments did not account for the changes in the crystalline lens size. In Glasser and Kaufman’s experiments, when they fixated the lateral rectus to reduce eye movement, the crystalline lens equator moved toward the sclera with anterior and posterior zonular relaxation. The authors state that this movement of the lens was secondary to lateral translation of the crystalline lens, but Schachar has argued that this mechanism is mechanically impossible. He states that with anterior and posterior zonular relaxation, because the crystalline lens is denser than water and vitreous, the crystalline lens equator can only move toward the temporal sclera by an active force generated by the equatorial zonules.

Wilson and Merin (16–18) also demonstrated, using infrared videophotography in a young human subject with ocular albinism, that the lens equator moved away from the sclera and that its diameter decreased during accommodation. However, Schachar (15) has challenged their study. He states that since the measurements were taken only when the circular light was concentric with the pupil and that, in order to keep the light concentric with the pupil, the alignment between the eye and the camera must have changed between the measurements made of the unaccommodated and accommodated states, since the pupil moves nasally during pupillary constriction. He also notes the presence of rotation of the eye relative to the axis of the camera, which is demonstrated by measuring the horizontal diameter of the cornea in the unaccommodated and accommodated states.

Strenk et al. used high-resolution magnetic resonance imaging (MRI) to examine changes in the human ciliary muscle and crystalline lens during minimal and maximal accommodation (18). Magnetic resonance images from 25 subjects, ranging from 22 to 83 years of age, were taken. Measurements of the ciliary muscle ring’s diameter, lens thickness, and equatorial diameter of the lens under minimum and maximal accommodation were obtained from the magnetic resonance images. A nonmagnetic accommodative stimulus device was used to provide a minimal (0.1 D) or a strong (8.0 D) binocular accommodative stimulus during magnetic resonance imaging. They found that ciliary muscle contractile activity remained active in all the subjects and was reduced only slightly with advancing age. They did find a decrease in the diameter of the unaccommodated ciliary muscle ring and retrolenticular space that correlated highly with advancing age. There was an age-related increase in the unaccommodated lens thickness, but the lens thickness under accommodative effort was only modestly age-dependent. Of note, the lens equatorial diameter did not show any significant change with advancing age in either accommodative state. This latter finding appears to directly challenge one of Schachar’s

basic tenets—i.e., that a primary mechanism underlying presbyopia is crowding of the ciliary muscle because of a linear increase in lens diameter with age. [Others (12) have argued that the early studies of the diameter of isolated lenses of enucleated eyes did not reflect the diameter of the unaccommodated lens in the living eye, because the younger lenses rounded up when the zonules were cut.] This stresses the importance of being able to make reliable in vivo measurements using techniques such as MRI.

As to the subject of reliable measurements, Schachar contends that the results of the MRI study by Strenk et al. were caused by artifact (15). He states that an MRI image of their patient’s eye during accommodation showed that the eye was turned nasally and that there was a change in configuration of the orbital bones, demonstrating that the head and the eye moved during accommodation. He further attests that the measurements of the transverse diameter of the globe, the corneal diameter, and the equatorial diameter of the lens all decrease during accommodation, demonstrating that the image plane of the eye in the unaccommodated and accommodated states was not the same.

3. Studies of Scleral Expansion Surgery to Improve Near Vision

Based upon his theory of accommodation and presbyopia, Schachar has developed a number of surgical techniques to expand the sclera, using bands or segments (22), in an effort to increase the effective working distance between the ciliary muscle and the equator of the crystalline lens. Others have attempted to expand the sclera by incisions or laser treatment (15), and these cumulative studies have shown some significant albeit nonuniform improvement in near vision using standard subjective testing.

Whether such surgical methods truly restore accommodation has recently been challenged by Matthews (10), who examined three presbyopic patients shortly after scleral expansion surgery and three young control subjects. The presbyopic patients ranged between 50 and 58 years of age. The control subjects were 22, 27, and 29 years of age. All of the patients were asked to focus on an approaching target while accommodation was monitored with a high-speed infrared optometer. The accommodative targets used were either the Maltese cross or a reduced Snellen chart presented monocularly in a Badal optical system. The target luminance was 100 cd/m. The accommodative stimulus changed in increments of 1 D every 10 s, ranging from 0 to 4 D. The investigator concluded that scleral expansion surgery did not restore accommodation in the presbyopic patients tested with this optometer device, which monitors the central 2.2 mm of the pupil. There was no difference in accommodative responses between the two preoperative presbyopic patients and the three postoperative presbyopic patients tested at each incremental accommodative stimulus level. There was also no accommodative response in either presbyopic group. This is in contrast to the three young control subjects, in whom the accommodative response increased by about 450 A/D values per diopter of accommodative stimulus change.

Schachar’s response to Matthews’ study can be summarized as follows. First, this group of patients was independently examined by Yang and coworkers (20), who documented a significant improvement in near vision without a change in distance refraction, axial length, or corneal power. Matthews’ study with the optometer did not include any near vision measurements using standard testing methods. The patients had an early prototype of the scleral expansion band (rather than segments) not currently in use, and they were all tested in the very early postoperative period, when tear film abnormalities and superficial punctate keratitis were present. In addition, the infrared optometer, which is generally

operated in a darkened room, does not offer the usual accommodative stimulus but relies purely on defocus. The instrument, which requires the subject to use a bite plate for stability and alignment, generally takes practice to obtain reliable data, and it was unclear if this level of training and reproducibility was achieved. Glasser and colleagues (12) have speculated that the possible restoration of near vision via scleral expansion could function via nonaccommodative mechanisms, such as inducing multifocality of the crystalline lens. A number of patients in the phase I clinical trial of scleral expansion in the United States are now undergoing wavefront analysis to provide an objective measurement and assess mechanisms that may underlie improvement in near vision after this procedure.

B. CONCLUSION

There are few subjects in ophthalmology capable of generating as much lively debate as that of accommodation and presbyopia. The processes of accommodation and disaccommodation are complex, to say the least, and involve changes in muscular, lenticular, and extralenticular components. At some time, almost every one of these components has been proposed as a factor in the development of presbyopia.

We have tried in this chapter to present a balanced view of Schachar’s versus Helmholtz’s theory of accommodation, along with experimental evidence and arguments that have been espoused by proponents of both sides. In a number of key respects, the proposed mechanisms are antithetical. The universal nature of presbyopia and the intense interest in its reversal justifies further research in this area to elucidate its pathophysiology.

ACKNOWLEDGMENT

Supported by the Midwest Corneal Research Foundation, Inc.

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