Presbyopia treatment with 1.25% pilocarpine alters free water distribution in the human lens

Abstract

Purpose : Pilocarpine has been approved as a presbyopia treatment by leveraging its ability to constrict the iris and create a pinhole effect to enhance near vision. Animal studies have revealed pilocarpine alters hydrostatic pressure gradients that determine the distribution of free water in the lens. In young adults, free water distribution in the anterior lens has been shown to increase with accommodation. Here we examined whether the application of 1.25% pilocarpine in presbyopic individuals elicits changes in the lens free water distribution.

Methods : 18 middle-aged adults (aged 50±4 years) were recruited to undergo magnetic resonance imaging (MRI) protocols on a 3T clinical scanner (MAGNETOM Vida Fit; Siemens, Germany) at baseline and 30 minutes after 1 drop of 1.25% pilocarpine. Measurements of lens geometry and MRI T1 relaxation times, which approximate free water concentration, were extracted from MR images using custom-written MATLAB software (The MathWorks, Natick, MA). T1 values along the lens optical axis were fitted to a power function (T1(x) = a+bx^p) to obtain the lens free water distribution. Changes with pilocarpine were tested statistically with two-tailed paired t-tests.

Results : Despite a fixed accommodative demand, application of 1.25% pilocarpine elicited a significant 0.04±0.02 mm (1%) increase in thickness (p=0.017) and 0.81±0.16 mm (8%) steepening in anterior curvature (p<0.001) of the presbyopic lens. In addition, free water became more smoothly distributed across the anterior lens, as indicated by a significant (p=0.005) reduction in the p-coefficient value after pilocarpine (4.32±0.21) compared to baseline (7.78±1.05). However, distribution of free water across the posterior lens after pilocarpine (7.54±0.64) did not differ from baseline (7.73±1.06).

Conclusions : In presbyopic subjects, 1.25% pilocarpine induced not only structural but also physiological lens changes similar to those seen in the young accommodating lens. This suggests that modulation of the lens free water distribution may be an additional mechanism through which pilocarpine improves near-focusing in presbyopic individuals.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Distribution of free water across the presbyopic lens at baseline (filled symbols) and after 1.25% pilocarpine treatment (empty symbols). Free water was more smoothly distributed across the anterior lens (A) after pilocarpine but remained unchanged in the posterior lens (B). Bars represent SD.