The etiology of presbyopia

January 1, 2008

It has been discovered that the equatorial diameter of a lens directly influences accommodation and thus presents a sound target for presbyopia treatment interventions

Understanding the etiology of presbyopia is essential to the discovery of highly effective methods for its treatment and/or prevention.

Presbyopia is clinically manifested when the near point of a patient becomes more remote than their usual near working distance. The near point is converted to amplitude of accommodation (diopters) by the following formula:

Accommodative amplitude (diopters) = 100 cm /near point (cm)

Any proposed mechanism for the etiology of presbyopia must therefore account for the rapid decline in accommodative amplitude that occurs during childhood.

What causes the rapid decline in accommodative amplitude during childhood?

In order to determine what might be responsible for the age-related decline in accommodative amplitude, we need to examine each ocular component in turn.

1. Cornea

The cornea does not change shape during accommodation.

2. Axial length

Careful partial optical coherence tomography measurements demonstrate that axial length changes minimally during accommodation, ~12 μm. This is too small to account for the large changes in accommodative amplitude. Moreover, 90% of the growth of the eyeball is completed by three years of age.

3. Ciliary muscle and zonules

The ciliary muscle and zonules do not undergo rapid changes during childhood.

4. Neurosensory mechanism

There is no evidence for a rapid change in the neurosensory mechanism of accommodation during childhood. To the contrary, in the linear range of accommodative amplitude of patients less than 40 years of age, the peak velocity and time constant of accommodation do not change.

Therefore, we can eliminate a change in the cornea, axial length, zonules, ciliary muscle or alterations in the neurosensory mechanism as possible causes for the rapid decline in accommodative amplitude during childhood. The only possible remaining cause for the rapid decline of accommodative amplitude during childhood is a dramatic change in the geometric or material properties of the lens.

5. Material properties of the lens

a) Hardness and/or stiffness of the lens nucleus
It is generally assumed that a change in stiffness and/or hardness of the nucleus is responsible for presbyopia; however, lens hardness and/or stiffness does not rapidly change during childhood. In fact, careful viscoelastic measurements with a calibrated validated parallel plate rheometer demonstrate that stiffness and/or hardness of fresh human lens nuclei obtained from donors less than 40 years of age does not correlate with age.2 The lack of significant change in lens hardness and/or stiffness during this time period is further supported by the in vivo observations that optical density of the lens does not significantly change until after 40 years of age and yellowing of the lens does not correlate with accommodative amplitude.

b) Stiffness and/or thickness of the lens capsule
The lens capsule thickens and stiffens at a uniform rate during the first three decades of life. The lens capsule does not undergo any dramatic changes during childhood. Moreover, the increase in lens capsule thickness and/or stiffness actually enhances the effectiveness of zonular tension, and therefore cannot account for the rapid decline in accommodative amplitude during childhood.