Since 1912, we’ve known that presbyopia is age-related. However, recent research shows that presbyopia is also related to a region’s ambient temperature — the higher the ambient temperature, the earlier the onset of presbyopia. For example, the age of onset in India is 37 years vs 46 years in Norway. Also, since life expectancy is lower in developing countries where the ambient temperatures are usually high, fewer persons with presbyopia are found in those general populations. In Haiti, the prevalence rate of presbyopia is 16%, whereas the U.S. prevalence rate is 31%.

Uncorrected presbyopia causes widespread, avoidable vision impairment. So, as life spans increase, uncorrected presbyopia will require us to increase the availability of sustainable, affordable spectacle delivery systems in the developing countries.

In contrast, in the developed world, especially in the United States and Europe, we are rapidly developing new technologies to offer surgical and pharmacologic alternatives to glasses, and possibly to slow down or reverse the progression of presbyopia. The reason: Research is homing in on the reasons why presbyopia occurs.

LOSSES AND INADEQUACIES

An estimated 1.27 billion people worldwide had presbyopia in 2011, half of whom had inadequate or no spectacles. Of this 1.27 billion, more than 400 million could not perform near tasks appropriately. A total of 244 million cases, uncorrected or undercorrected among people younger than 50 years equaled a potential productivity loss of $11 billion (0.016% of global GDP). If we assume productivity among those older than 65 years, the potential productivity loss would be $25 billion or 0.037% of global GDP.¹

At the moment, vision impairment from uncorrected presbyopia predominantly exists in the developed world, where more than 90% of presbyopes reside. With future population growth, mostly in the developing world, the global number of presbyopes is projected to double in the next 30 years, and the proportion of presbyopes in developing world countries will increase as their life expectancy increases.²

ACCOMMODATION AND PRESBYOPIA

The science of understanding accommodation and presbyopia has dramatically advanced in the past decade. I believe we can demonstrate the mechanism of accommodation and presbyopia without having to debate the merits of prior theories. With this understanding, we will succeed in developing better treatments for presbyopia.

Models are of central importance in science — imagine understanding genetics without the double-helix model of DNA. Findings from scientific models are based on cognitive reasoning, an inference method used in expert systems based on a model of the physical world.³ By building a computer-animated model of accommodation and presbyopia that is based on new knowledge of the anatomy of accommodation and by also using 21st century biometry, we can visualize multiple elements moving in synchrony. And, with model-based reasoning, we can advance our understanding of the underlying mechanisms.

Countless pieces to the accommodation puzzle exist, with thousands of scientific studies and theories generated by leading scientists of the 19^th and 20^th centuries. Hermann von Helmholtz’s lenticular theory of accommodation has been largely confirmed, but the role of the extralenticular components in accommodation has not been fully recognized. The movements of the ciliary body have been well documented, and it is currently recognized that the ciliary body is the engine of accommodation. The distribution of forces from ciliary muscle contraction via the zonular elements, on the other hand, has not been well understood. We now know that loss of elasticity in both lenticular and extralenticular structures of accommodation causes presbyopia.^4,5 A team of investigators have used electron microscopy, video ultrasound biomicroscopy (UBM) and endoscopy to define the complex, separate elements of the zonules and to document the interconnected movements of the extralenticular tissues.^6-8 Their monumental work has made it possible to build the computer-animated model and to understand and demonstrate the mechanism of accommodation.

MODEL OF ACCOMMODATION

Based on this new knowledge of zonular architectural anatomy and aided by video UBM imaging of accommodation, I produced my first model of accommodation in collaboration with a computer animator in 2011.⁹ The concept of reciprocal zonular action was developed via model-based reasoning as follows: “During ciliary body contraction, the anterior zonules lose tension while the posterior zonules stretch. During ciliary body relaxation, the posterior zonules lose tension as the lens flattens and is pulled back by the increasing tension of the anterior zonules.”

In 2015, a second version of the model, the Computer-Animated Model of Accommodation and Presbyopia, version 2.0 (CAMA 2.0) incorporated up-to-date knowledge of the anatomy along with the latest biometry.¹⁰ CAMA 2.0 is based on anatomy and biometry in accommodation and disaccommodation. It represents a biometrically accurate model of a 25-year-old eye with 8.0 D of accommodation. This model is not based on theory but on anatomy, biometry, endoscopy and video UBM; the findings are derived from model-based cognitive reasoning.

It is helpful to separate the anatomic elements to better understand how the structures interconnect and function as a unit: six zonular pathways, the anterior vitreous membrane and Weiger’s ligament. Based on structure and function, I have proposed a new classification of the zonular apparatus separating the six zonular pathways into three groups.

The anterior zonules (Figure 1) lose tension due to the anterior and centripetal movement of the ciliary body, allowing the lens to “round up” because of the intrinsic elasticity of the lens and lens capsule. In disaccommodation, the ciliary body’s relaxation and return to its resting position result in tension on the anterior zonules with flattening of the lens and loss of accommodative effect. Thus, the first division of the zonular apparatus is the anterior zonules, and their function is tension and release on the lens capsule. The anterior zonules have a reciprocal function in concert with the posterior zonules, and this is the concept of reciprocal zonular action from the first model.

The second division of the zonular apparatus are the crossing zonules (Figure 2) including the anterior vitreous zonule (shown in yellow) extending from the ciliary valleys to Weiger’s ligament (shown in white), and the PIZ-LE zonules (shown in purple), which extend from the lens equator to the posterior attachment zone. Along with Weiger’s ligament, the crossing zonules cradle, shape and stabilize the lens and vitreous. Weiger’s ligament surrounds the midposterior region of the lens. It is known that the lens equator and anterior capsule move anteriorly during accommodation, while the posterior pole of the lens capsule moves posteriorly. Weiger’s ligament encompasses the null point of the lens where there is no anterior/posterior displacement during the accommodative cycle. This is the ideal location for supporting the lens. Both the cradle-like shape, notable in the model, and the null point location of Weiger’s ligament suggests an important function for a structure that heretofore has received little attention in accommodative science. The anterior vitreous zonule and Weiger’s ligament together form a scaffolding to support the lens and prevent outside forces from displacing the lens. At the same time, the anterior and posterior zonules work reciprocally to keep focused vision. In a similar fashion, the PIZ-LE zonule prevents anterior displacement of the lens by outside forces.

The third functional group of zonules, the posterior zonules (Figure 3), include the intermediate vitreous zonule (red), the posterior vitreous zonule (off-white) and the pars plana zonule (green). The posterior zonules anchor the ciliary body and extend posteriorly at the PIZ to attach to the elastic foundation in Bruch’s membrane. When the ciliary muscle contracts, the posterior zonules, attached to the elastic elements of the choroid, stretch and store energy for disaccommodation. When the ciliary muscle relaxes, the elastic fibers of the choroid pull the posterior zonules and the ciliary body posteriorly. As the ciliary body moves posteriorly, the anterior zonules stretch and flatten the lens. As a group, the posterior zonules, in concert with the anterior zonules, create the reciprocal zonular action that occurs during accommodation and disaccommodation. The posterior zonules transfer tension and release from the ciliary muscle to the elastic foundation in the choroid.

ACCOMMODATIVE MOVEMENTS OF SCLERA, CHOROID, AQUEOUS AND VITREOUS

In 2013, Croft et al. showed the dynamic movement of the choroid and retina, demonstrating that the stretch and movement of the tissue extends at least 4 mm to 7 mm posterior to the ora serrata (Figure 4).⁸ Subfoveal choroidal thinning and axial elongation during accommodation have been confirmed, demonstrating that all elements of the uveal tract from the iris and pupil to the subfoveal choroid are involved in the accommodative process. Croft et al. also showed inward bowing of the sclera at the limbus in the nasal quadrant during accommodation, which indicates traction in the area of the limbus overlying the scleral spur where the ciliary muscle and uveal tract are anchored to the sclera.⁷

By modeling the aqueous and vitreous spaces, we can add to our understanding of the hydrodynamics of accommodation (Figure 5). The vitreous space is passive during accommodation, and internal movements of the vitreous body are related to the surrounding structures of the uveal tract and lens. Instead of vitreous pressure, movements inside the vitreous space are secondary to the elastic stretch in the choroid transmitted to the vitreous.

A model of presbyopia that uses biometric data from Croft et al.⁷ and Richdale et al.¹¹ (Figure 6) compares a 25-year-old normal eye to a 50-year-old presbyopic eye. The amplitude of accommodation modeled in the 25-year-old eye is 8 D vs 1.25 D in the 50-year-old presbyope. The presbyopic eye demonstrates thickening and stiffening of lens and capsule with steepening of the anterior capsule curvature. Also, the lens equator moves forward with age and the insertion of the anterior zonules moves anteriorly on the lens capsule. The presbyopic lens fails to flatten in disaccommodation and, compared to that of the normal 25-year-old, the presbyopic lens is almost frozen in a thicker state. The anterior movement of the ora serrata is markedly reduced in presbyopia, which is related to the loss of elasticity in the ciliary body and choroid. There is age-related posterior restriction of the ciliary muscle, which, along with lenticular sclerosis, is a critical element causing loss of accommodation in presbyopia. The ciliary muscle undergoes degenerative changes but maintains its ability to contract long after the lens stops accommodating. This demonstrates that age-related changes in the lens and in the elastic foundation in the choroid contribute to the restriction of accommodative movement with age.

CONCLUSION

Many of our efforts in treating presbyopia have occurred without a full understanding of the mechanisms of accommodation and presbyopia. Having a better understanding enhances our likelihood of success. OM

REFERENCES

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2. Holden BA, Fricke TR, Ho SM, et al. Global vision impairment due to uncorrected presbyopia. Arch Ophthalmol. 2008;126:1731-1739.
3. Nersessian NJ. Model-based reasoning in conceptual change. In: Magnani L, Nersessian NJ, Thagard P, eds. In Model-Based Reasoning in Scientific Discovery. New York: Kluwer Academic/Plenum Publishers. 1999:5-22.
4. Grossniklaus HE, Nickerson JM, Edelhauser HF, et al. Anatomic alterations in aging and age-related diseases of the eye. Invest Ophthalmol Vis Sci. 2013;54: ORSF23-ORSF 27.
5. Croft MA, Lutjen-Drecoll E, Kaufman PL. Age-related posterior ciliary muscle restriction — A link between trabecular meshwork and optic nerve head pathophysiology. Exp Eye Res. 2017. 158:187-189.
6. Lutjen-Drecoll E, Kaufman PL, Wasielewski R, Ting-Li L, Croft MA. Morphology and accommodative function of the vitreous zonule in human and monkey eyes. Invest Ophthalmol Vis Sci. 2010;51: 1554-1564.
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8. Croft MA, Nork TM, McDonald JP, et al. Accommodative movements of the vitreous membrane, choroid, and sclera in young and presbyopic human and nonhuman primate eyes. Invest Ophthalmol Vis Sci. 2013; 54:5049-5058.
9. Goldberg DB. Computer-animated model of accommodation and theory of reciprocal zonular action. Clin Ophthalmol. 2011;5:1559-1566.
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11. Richdale K, Sinnott LT, Bullimore MA, et al. Quantification of age-related and per-diopter accommodative changes of the lens and ciliary muscle in the emmetropic human eye. Invest Ophthalmol Vis Sci. 2013;54:1095-1105.

About the Author

Daniel B. Goldberg, MD, FACS, is clinical associate professor of Ophthalmology at Drexel College of Medicine, Philadelphia.

Financial disclosure: Dr. Goldberg is a consultant to Ace Vision Group.