Optically, it is the lens shape change by which the refractive power of the eye is increased and accommodation occurs, and, ultimately, the lens is the prime component/indicator for the loss of accommodation with age in human and monkey eyes. The vast majority of statistical analyses, from various studies, have reported that age also has been one of the main factors predicting accommodative amplitude.19,38–40,60
Some have postulated that this is because it is the single best biomarker, taking into account all aging changes that occur in the eye. However, in our study, stepwise regression analysis showed, for the first time to our knowledge, that accommodative lens thickening and the resting ciliary muscle apex thickness explained accommodative amplitude slightly better than age alone (as explained in the Results) in the 12 human eyes. It is striking that in this model, age was not necessary, that is, age did not explain accommodative amplitude over and above what accommodative lens thickening and age-related resting muscle apex thickening could do. This demonstrates an associative relationship suggesting that an extralenticular component, that is, age-related changes in the muscle, in addition to age-related changes in the lens, may have a role in the pathophysiology of presbyopia.
We chose subjects that were within 2 D of emmetropia and that had pharmacologically-induced maximum accommodative amplitudes ranging from 0 to 15 D, the full range of accommodative amplitude. Further, in all subjects, the images of the sagittal cross-sections of the ciliary muscle were collected systematically, aligned with a known landmark (the vitreous zonule, which lies in the sagittal plane of the eye); and the eyes were imaged at a known level of maximum accommodative amplitude. These techniques substantially reduced variability, and allowed the study of the full range of accommodative amplitude and its decline with age. This comprehensive approach may explain why our study found that the accommodative muscle movement was reduced with age, while other studies did not.61
Brown in 19738
reported the phenomenon referred to as the “lens paradox”17,18
in the human eye: the lens becomes thicker and more sharply curved with age (appearing to be in an “accommodated state”) and yet the ability of the eye to accommodate is lost almost completely. Although the absolute numbers collected by Brown and Koretz are in dispute (due to the distortion of the posterior lens surface), the overall findings are not.20,21
Our data, collected using UBM, also showed that the lens thickens with increasing age in the resting eye and that this is related inversely to accommodative ability, as reported previously.10,20,21
These particular associations are not new, but they do demonstrate that these are normal human subjects and they add additional validity to our measurement techniques as reported previously.7,31,43,44
By direct imaging of the lens equator, we actually measured the accommodative lens equator movements, rather than inferring them from forward translation of the lens mass. As stated previously in the Introduction, the lens shape, while biconvex, is not equiconvex; its anterior surface is flatter than its posterior surface.3,9
Therefore, the forward translation of the lens equator may not necessarily be the same numerically as the forward translation of the lens mass. Accommodative forward movement of the lens equator in our study averaged 0.48 mm in the four young subject eyes accommodating an average of 12.1 D. This is somewhat greater than what Coleman3
reported for accommodative forward movement of the lens center of mass, which ranged from 0.03 to 0.21 mm in human subjects (ages 22–29 years) during voluntary accommodation to a visual stimulus of 6 D. Using Scheimpflug imaging, Brown estimated that, based on extrapolation in one 30-year-old subject eye that accommodated 10 D, the lens equator moved forward by 0.26 mm, but he did not directly image the lens equator,8
and did not correct for distortion of the posterior lens surface.20,21
The differences in forward translation of the lens mass measured by others, versus the forward movement of the lens equator measured in this study, could be due to the amplitude of accommodation induced, or it may be that forward lens equator movement may not be the same as forward translation of the lens mass, because of how the lens is reshaped (i.e., capsular forces, lens geometry, internal lens cells).62–64
According to Duane's curve, the middle age group (27–31 years old; accommodating an average of 8.5 D) was mid-presbyopic (Supplementary Fig. S4
) even if not yet symptomatic, and the results from this group might have differed more from the young age group (accommodating an average of 12.1 D) if younger subjects had been available (i.e., <18 years). Nonetheless, there were significant differences between these two age groups in regard to accommodative forward movement of the insertion zone and resting A/P position of the lens equator.
Our current study showed for the first time to our knowledge, in the rhesus monkey eye and in the human eye, that the young lens equator moves forward during accommodation and that, with age in the resting human eye, the lens equator tends to be in a more anterior (accommodated) position. This may add another aspect to the lens paradox. With respect to the forward movement of the lens mass, it is interesting to note that some carnivores (e.g., raccoons, dogs, and cats) accommodate essentially solely through anterior movement of the lens.65
In the resting human eyes, the CLS declined with age, as we found in the monkey eye.48
Since others have reported that there is no change in lens equatorial diameter with age,52,66
the age-related decline in CLS that we report is likely due to the age-related increase in ciliary muscle apex thickness and corresponds with the age-related decline in the ciliary ring diameter reported by others.52
The decline with age of the distance between the lens equator and the scleral spur that we found suggests that the sclera and muscle apex, as a whole, are closer to the lens equator, possibly due to a change in scleral contour (“bowing inward”) reported in our companion study36
and/or to other age-related changes in the geometry of the eye. The CLS that we measured likely encompassed Hannover's canal,67,68
which lies between the anterior and posterior tines of the anterior zonula. The loss in CLS in the aging eye may limit the space available for Hanover's canal,67,69
and/or affect the physiologic processes that putatively occur there, and it has been speculated that this may lead to cataracts.67,68
However, we are reluctant to speculate further as we did not measure or visualize Hannover's canal (see our companion paper36
). These observations may warrant further investigation, but are beyond the scope of this report.
The accommodative narrowing of the CLS was greater in the oldest eyes because the centripetal lens equator movement was nearly abolished, while some centripetal muscle movement, although reduced, still was present. Thus, the greater the narrowing of the CLS, the lower the accommodative amplitude.
The geometric theory of accommodation and presbyopia posits that the increasing lens thickness with age pulls the ciliary muscle via zonular tension into a more anterior and inward position.70
Our human data show a correlation of borderline significance between lens thickness and muscle apex thickness (with one outlier excluded), but since our findings are equivocal, more subjects are needed to make a definitive conclusion.
These results are in line with the Helmholtz theory of accommodation and Rohen's theory of the role of the zonula in accommodation, with the exception that our data demonstrated that the region of the ora serrata does move forward during accommodation, as theorized by Coleman. However, none of these theories included, nor could they address, the role of the new structures that have been discovered31,36
using different tissue preparation techniques and more current technology. Nonetheless, these earlier pioneers made some amazingly accurate predictions of the accommodative mechanism that still are being discussed in the literature today.
In our study, we demonstrated that the vitreous zonule and its posterior insertion zone have a role in accommodation and presbyopia in the human eye. During accommodation, the lens equator moves forward and inward, and this movement is reduced with age, possibly due to the age-related loss in accommodative forward movement of the vitreous zonule posterior insertion zone, previously demonstrated in the monkey eye31
and now in the human eye. This loss in the insertion zone's forward movement may not only dampen forward muscle movement, but also may dampen lens movements, given its direct attachment to the posterior lens equator (see our companion paper36
) and to the tensile fibers that spread to the walls in the valleys between the ciliary processes. Likewise, this reduced movement of the insertion zone during accommodation could inhibit forward movement of the muscle apex, and cause a posterior “drag” on the ability of the lens equator to move forward and of the lens to thicken.
We have imaged and characterized the vitreous zonule, but further study of the vitreous is needed; other reports in the literature indicate the existence of a network of fibers contained within the vitreous.33,69,71
The study of all these would require specific contrast agents to enhance their visualization, well beyond the scope of this report. We were able to discover one such agent to visualize the anterior hyaloid membrane and those results are reported in the companion article.36
The data in suggested that the forward movement of the vitreous zonule/ciliary muscle has more effect on lens equator forward movement and lens thickening than on centripetal movement of the lens equator during accommodation—perhaps due to the direction of the muscle/vitreous zonule movement and muscle/vitreous zonule/lens architecture. The muscle/vitreous zonule accommodative forward movement is in an A/P direction, as is the accommodative forward lens equator movement, and of course the lens thickens in the A/P direction during accommodation. The data in also suggested that the centripetal movement of the muscle (as measured by apex thickening) releasing tension on the anterior zonule has more to do with centripetal rather than forward movement of the lens equator, again perhaps due to the direction of the muscle/zonule movement and muscle/anterior zonule/lens architecture. These findings supported observations discussed by Helmholtz (p. 405) regarding zonular attachments to the anterior and posterior lens surfaces.1
UBM (see ) in the human eye confirms previous UBM findings42
and earlier histologic findings that forward ciliary body movement diminishes significantly with age, but is never lost completely, even in the oldest eyes.55
It is not surprising to find additional similarities between the accommodative apparatus of the monkey eye and human eye. The muscle moves forward and inward in both species, and the lens thickens and becomes more sharply curved during accommodation. The accommodative amplitude in the monkey eye is higher than in the human eye, and our data showed that this likely is due to greater accommodative lens thickening and muscle apex thickening in the monkey eye versus the human eye. In the monkey, the eyes are placed closer together than in the human, and during accommodative convergence there is a need for higher accommodative amplitudes in the monkey. It is unknown why there was a difference in age-related accommodative amplitude decline between monkeys and humans regarding middle-aged versus older age groups (Supplementary Table S1
). It may relate to the thickness of the vitreous zonule posterior insertion zone, which is far thicker in human eyes than in monkey eyes.31
This may dampen accommodative amplitude differently between these two age groups in the humans. These differences merit further study, but are beyond the scope of this report.