Article

THE ZOOMING EYE LENS: Effects of Age on Dynamic Range of Focus

DYNAMIC RANGE OF FOCUS (DRoF), or the total range of clear vision in a natural system, is an important biomechanical function of the accommodative apparatus responsible for adjusting the crystalline lens from both far to near (accommodation) and near to far (disaccommodation). DRoF is defined by true accommodation, pseudoaccommodation, and pupillary diaphragmatic changes, which work together biomechanically to selectively focus at various distances upon a neuromuscular stimulus from the brain.1 There is an entire kinematic chain of events that lead to lens shape changes in both directions. The effects of age on the remodeling of microtissue layer interactions and collagenous structures detrimentally impact the eye’s normal biomechanical and physiological functions, which produce the symptoms of presbyopia”.2 Biomechanical dysfunction increases mechanical load, shear stress, and consequential tissue strain, affecting microtissue layer interactions, collagenous structures, and tissue remodeling. These changes ultimately affect extracellular matrix chemical balance and biomechanical efficiency.3 Why is this important? Because accommodation involves more than simply changing the shape of the crystalline lens—it also involves multiple tissue and extralenticular pathways.

The hallmark symptom of presbyopia is the progressive loss of DRoF throughout all distances. Addressing this symptom has been the Holy Grail in the ophthalmic industry since its description by Helmholtz in his Treatise on Physiological Optics. Specifically, Helmholtz described the “organ of vision” and the “sense of sight” holistically, with a complex rendering of the physical characters of the eye as an optical instrument, the physiological processes of the visual system, and the psychological processes of image perception via the optic nerve—declaring the entire process of visual perception “marvellous.”4

Figure 1. Helmholtz in 1867, the year in which the three parts of his Handbuch der physiologischen Optik were published in a single volume. Portrait after an engraving in Koenigsberger (1902). Diagram of the eye after Figure 2 in Helmholtz (11867A). Reprinted from: Wade NJ, The eye of Helmholtz. Published online June 4, 2021.

Throughout most of modern ophthalmology, presbyopia has been described as merely a result of increased stiffness of the crystalline lens, substantially neglecting the extralenticular biomechanical structures contributing to this complex visual skill.5,6 Moreover, the ocular physiological functions of the accommodative apparatus have not been addressed in parallel with the DRoF kinematics. Doing so necessitates an intimate look at the biomechanics of the lens and the ciliary muscle, the major force transducer responsible for changing the dioptric power of the lens and its extralenticular component with consideeration of the roles of the other structures, such as the vitreous and sclera. In addition, these kinematic motions should be further contemplated alongside other elastic structures in the outer and vascular tunics, such as the sclera, the vitreous, and the Bruch’s membrane–choroid complex (BMCC), respectively.6 This approach would provide a deeper appreciation for how the structure and function of the many anatomical elements involved in accommodation impact not only the visual capabilities of the eye but also its overall physiological function.

The normal responses of our connective tissues to the effects of age-related accumulation of advanced glycation end products (AGEs) include increased crosslinking of collagen microfibrils, a greater number of tropocollagen molecules per fibril, and decreased elastin fibers.7-10 These progressive, age-related changes largely explain the stiffening of the sclera as it ages, known as ocular rigidity.11 Despite the known correlation between age-related ocular rigidity and disease in the posterior segment, the link between increased ocular rigidity and biomechanical accommodative dysfunction, yielding the progressive loss of DRoF in presbyopia, has received limited attention in research.12 This may be due to lack of awareness and of the core knowledge about biomechanics and muscle physiology residing largely outside of the anterior segment literature.

A New Model of DRoF

Hipsley introduced a model that, for the first time, describes the loss of DRoF occurring with presbyopia in terms of age-related changes in the eye, which affect its normal biomechanical and therefore its physiological function.13 Such a model offers a greater understanding of normal biomechanical relationships, defining the effects of age on these biomechanics and illuminating the potential ways to restore normal biomechanical function to the aging eye. There are many benefits to a biomechanical, physical, and mathematical approach to the pathogenesis of presbyopia and its related pathophysiological manifestations. Mainly, it may facilitate the development of rejuvenating therapies, which could restore ocular biomechanical efficiency and DRoF.

Understanding DRoF requires in-depth study of the movement of and forces generated by the anatomical components of accommodation in various stages of function. Various studies have illuminated the importance of the capsule, zonules, ciliary muscle fibers, BMCC, hydrodynamics, and even retina for the proper biomechanical function of the accommodative apparatus that is necessary for DRoF.5,14-17 Croft et al provided a comprehensive overview of the extralenticular components of accommodation, while Knaus et al published a thorough finite element model with a focus on the mechanism of action of the ciliary muscles and their corresponding anatomical synergists.16 Goldberg provided the first computer animated model of accommodation, allowing for the first time a visualization of the biomechanical movements of accomodation.18

These studies and others represent great strides toward building a body of knowledge emphasizing a kinematics approach to understanding DRoF, as well as the overall presbyopic dysfunction as it relates to the accommodative biomechanics, hydrodynamics, and biodynamics of the visual organ.19,20 However, none thus far have proposed a combined model to analyze DRoF as it relates to the accommodative biomechanics, hydrodynamics, and biodynamics aspects of the visual organ until now.19,20

A biomechanical and kinematic model could provide a worthy achievement in understanding the movements and forces involved in the production of DRoF of the eye. Youthful DRoF relies on the ability of the accommodative apparatus to alter the shape of the crystalline lens during accommodation and disaccommodation. In its disaccommodated posture, the equatorial lens capsule is under tension from the anterior zonules, which is resisted by the elastic forces of the lens capsule.15,16,21

Anterior and inward movement of the ciliary muscle during contraction releases tension from the anterior zonules, permitting the elastic lens capsule to assume its preferred accommodated posture. Efficient contraction and movement of the ciliary muscle are essential to achieve the DRoF seen in youth.

The ciliary muscle has been shown to generate the same contractile force as we age and to even produce hypertrophy in presbyopia.22 So why is it that we lose accommodative power? Ideally, the contractile forces on the lens must translate sufficient biomechanical energy to achieve DRoF throughout the full range of accommodative motion, but this translation of force is affected by more than just the lenticular zonular apparatus. In alignment with Helmholtz, while the lens plays the central role in accommodation, it does not achieve DRoF independently. The primary biomechanical elements creating and translating the bulk of the resultant accommodative forces include the ciliary muscle, the zonular fibers, the BMCC, the vitreous chamber, and the scleral shell.23-26

Posteriorly, the ciliary muscle contains elastic tendons, which attach to the elastic lamina of BMCC at the ora serrata, through which it behaves as a spring that resists lens movement during accommodation and facilitates returning the ciliary muscle to its resting position upon relaxation.15,21,25-27 In all phases of accommodation, the anterior fibers of the hyaloid membrane of the vitreous chamber impose vitreous pressure on the posterior lens capsule, dynamically loading the eye throughout the DRoF cycle. Additionally, the scleral shell facilitates physiologic movement of the ciliary muscle and BMCC during accommodation and disaccommodation, while maintaining the shape of the globe and resisting intraocular pressure. The biomechanical properties of the sclera, ocular rigidity in particular, have significant implications in DRoF through scleral influence on the performance of the accommodative apparatus.

Figure 2. Dynamic range of focus requires complex biomechanics and visual skills.

Damage to the Eye

As the eye ages, nearly all ocular structures accumulate damage from long-term exposure to oxidative stress and AGEs. These cumulative insults result in an age-associated decline in the biomechanical function of the entire accommodative apparatus, manifesting in the loss of DRoF seen in presbyopia. In the lens, for instance, sustained oxidative stress induces crosslinking of lens crystalline proteins and increased capsular thickness, resulting in significantly increased lens stiffness.26,28 While these changes in the lens certainly result in greater resistance to accommodation, it is important to acknowledge how age-related damage to the other ocular structures involved in accommodation also contributes to diminished DRoF over time.

In response to chronic age-related insults, such as AGEs and oxidative stress, the posterior elastic tendons of the ciliary muscle, as well as the BMCC, show marked increases in collagen composition and crosslinking, with subsequent loss of elasticity.29-33 In the aging sclera, the cross-sectional area of collagen fibrils increases, the density of elastin microfibrils decreases, and there is an accumulation of intermolecular collagen crosslinking.7,8,10,34 The result of these changes is a progressive, age-related increase in biomechanical stiffness and ocular rigidity.

The additive effect of decreased elasticity in the ciliary muscle tendons and BMCC, in addition to the much greater ocular rigidity from scleral collagen crosslinking, is significantly impaired anterior-inward ciliary muscle displacement upon contraction and an incomplete return to baseline upon relaxation. The resultant decrease in dynamic movement of the ciliary muscle compromises the potential accommodative amplitude by limiting the release of equatorial zonular tension on the lens capsule during accommodation, while also impairing disaccommodation. Taken together, the age-related changes in these structures yield diminished DRoF function through significant biomechanical dysfunction of the entire accommodative apparatus.

Conclusion

In conclusion, DRoF is a vital function of the eye, which allows us to navigate the visual world around us. However, there is much more to this function than meets the eye. The pathophysiology producing biomechanical dysfunction in accommodation and disaccommodation also contributes to common disorders, such as glaucoma, macular degeneration, myopia, and all aspects of presbyopia.35 The extensive impact of this progressive, age-related biomechanical dysfunction continues to make the treatment of these conditions elusive.

Although DRoF biomechanics remain largely understudied, stimulating new enthusiasm for ocular biomechanics as a field of interest in the anterior segment may inspire a more deterministic approach in methods to rejuvenate this remarkable function in the aging eye. ■

References

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