A new look at an old problem: 3D modeling of accommodation reveals how age-related biomechanical changes contribute to dysfunction in presbyopia.

Presbyopia is an age-related ocular disorder where accommodative ability declines so that an individual's focusing range is insufficient to provide visual clarity for near and distance vision tasks without corrective measures. With age, the eye exhibits changes in biomechanical properties of many components involved in accommodation, including the lens, sclera, and ciliary muscle. Changes occur at different rates, affecting accommodative biomechanics differently, but individual contributions to presbyopia are unknown. We used a finite element model (FEM) of the accommodative mechanism to simulate age-related changes in lens stiffness, scleral stiffness, and ciliary contraction to predict differences in accommodative function. The FEM predicts how ciliary muscle action leads to lens displacement by initializing a tensioned unaccommodated lens (Phase 0) then simulating ciliary muscle contraction in accommodation (Phase 1). Model inputs were calibrated to replicate experimentally measured lens and ciliary muscle in 30-year-old eyes. Predictions of accommodative lens deformation were verified with additional imaging studies. Model variations were created with altered lens component stiffnesses, scleral stiffness, or ciliary muscle section activations, representing fifteen-year incremental age-related changes. Model variations predict significant changes in accommodative function with age-related biomechanical property changes. Lens changes only significantly altered lens thickening with advanced age (46% decrease at 75 years old) while sclera changes produced progressive dysfunction with increasing age (23%, 36%, 49% decrease at 45, 60, and 75 years old). Ciliary muscle changes effected lens position modulation. Model predictions identified potential mechanisms of presbyopia that likely work in combination to reduce accommodative function and could indicate effectiveness of treatment strategies and their dependency on patient age or relative ocular mechanical properties.

Improvement in Accommodation and Dynamic Range of Focus After Laser Scleral Microporation: A Potential Treatment for Presbyopia.

Purpose: To examine the ocular changes in accommodation, wavefront aberrations, and dynamic range of focus (DROF) after laser scleral microporation (LSM) for treating presbyopia. Methods: Four presbyopic aged cynomolgus macaques (>13 years; n = 8 eyes) were included. All eyes received LSM with erbium: yttrium-aluminum-garnet laser. Spherical equivalent, true accommodation, pseudo-accommodation, wavefront aberrations, and extended range of focus (EROF), or collectively known as DROF, were evaluated using a ray tracing aberrometer. True accommodation referred to the difference in spherical equivalent between distance and near vision, whereas EROF (sum of true and pseudo-accommodation) was determined by measuring the difference in diopters (D) between near and distance through-focus curves, at 50% threshold of the visual Strehl ratio of optical transfer function. Results: From before to seven months after surgery, there was a significant increase in true accommodation from 0.6 ± 1.0 D before surgery to 5.9 ± 2.8 D at seven months after surgery (P < 0.001). EROF increased significantly from 3.4 ± 1.0 D before surgery to 11.1 ± 4.6 D at seven months after surgery (P < 0.001). Ocular aberrations did not vary significantly between preoperative and various postoperative timepoints in either disaccommodated or accommodated states (P > 0.05). No adverse event such as scleral perforation or hypotony was noted. Conclusions: This non-human primate study demonstrated that LSM serves as a novel therapy for improving accommodation and DROF function biomechanically, with a positive response observed throughout the seven-month postoperative period. Translational Relevance: This proof-of-concept study highlights the potential of LSM as a novel treatment for vision recovery in presbyopic eyes.

The action of ciliary muscle contraction on accommodation of the lens explored with a 3D model.

The eye's accommodative mechanism changes optical power for near vision. In accommodation, ciliary muscle excursion relieves lens tension, allowing it to return to its more convex shape. Lens deformation alters its refractive properties, but the mechanics of ciliary muscle actions are difficult to intuit due to the complex architecture of the tissues involved. The muscle itself comprises three sections of dissimilarly oriented cells. These cells contract, transmitting forces through the zonule fibers and extralenticular structures. This study aims to create a finite element model (FEM) to predict how the action of the ciliary muscle sections leads to lens displacement. The FEM incorporates initialization of the disaccommodated lens state and ciliary muscle contraction, with three muscle sections capable of independent activation, to drive accommodative movement. Model inputs were calibrated to replicate experimentally measured disaccommodated lens and accommodated ciliary muscle shape changes. Additional imaging studies were used to validate model predictions of accommodative lens deformation. Models were analyzed to quantify mechanical actions of ciliary muscle sections in lens deformation and position modulation. Analyses revealed that ciliary muscle sections act synergistically: the circular section contributes most to increasing lens thickness, while longitudinal and radial sections can oppose this action. Conversely, longitudinal and radial sections act to translate the lens anteriorly with opposition from the circular section. This FEM demonstrates the complex interplay of the three sections of ciliary muscle in deforming and translating the lens during accommodation, providing a useful framework for future investigations of accommodative dysfunction that occurs with age in presbyopia.

Tissue Responses and Wound Healing following Laser Scleral Microporation for Presbyopia Therapy.

Purpose: To investigate the postoperative inflammatory and wound-healing responses after laser scleral microporation for presbyopia. Methods: Thirty porcine eyes were used for the optimization of laser intensities first. Six monkeys (12 eyes) received scleral microporation with an erbium yttrium aluminum garnet (Er:YAG) laser, and half of the eyes received concurrent subconjunctival collagen gel to modulate wound-healing response. The intraocular pressure (IOP) and the laser ablation depth were evaluated. The animals were euthanized at 1, 6, and 9 months postoperatively. The limbal areas and scleras were harvested for histologic analysis and immunofluorescence of markers for inflammation (CD11b and CD45), wound healing (CD90, tenascin-C, fibronectin, and HSP47), wound contraction (α-smooth muscle actin [α-SMA]), vascular response (CD31), nerve injury (GAP43), and limbal stem cells (P63 and telomerase). Results: In the nonhuman primate study, there was a significant reduction in IOP after the procedure. Overall, the ablation depth was 76.6% to 81.2% at 1 month and slightly decreased to 71.5% to 72.7% at 9 months. Coagulative necrosis around the micropores, as well as expression of CD11b, CD45, tenascin, fibronectin, HSP47, and GAP43, was distinct at 1 month but subsided with time. Collagen gel treatment significantly suppressed the upregulation of CD11b, CD45, fibronectin, and tenascin-C. The expression of CD90, α-SMA, and CD31 was minimal in all eyes. Conclusions: The study demonstrated the course of inflammatory and wound-healing responses following laser scleral microporation. The tissue responses were small and self-limited, resolved with time, and were suppressed by concurrent collagen treatment. It provides a useful understanding of this new procedure. Translational Relevance: The results would be helpful in the laser parameter modification to improve the long-term treatment stability.

Long-term visual outcomes of laser anterior ciliary excision.

PURPOSE: To determine the long-term visual outcomes of six eyes of 3 patients up to 13 years following the Laser Anterior Ciliary Excision (LaserACE) procedure. METHODS: Three male patients of ages 59, 59, and 60 presented for evaluation at Storm Eye Institute, Medical University of South Carolina at 8, 10, and 13 years after the LaserACE procedure for presbyopia, respectively. All 3 patients had a history of laser vision correction (LVC) prior to LaserACE treatment. Visual performance was evaluated using ray-tracing aberrometry, specifically higher-order aberrations, visual Strehl of the optical transfer function (VSOTF), depth of focus (DoF), and effective range of focus (EROF). VSOTF was computed as a function of defocus using a through-focus curve. Subjective DoF was overlaid on the VSOTF through-focus curve to establish the best image quality metric threshold value for correlation between subjective and objective DoF. EROF was determined by measuring the difference in diopters between the near and distance DoF curves, at 50% of VSOTF. RESULTS: Distance-corrected visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity for all patients remained at 20/20 or better up to 13 years postoperatively. EROF averaged 1.56 ±â€¯0.36 (D) for all eyes. CONCLUSIONS AND IMPORTANCE: LaserACE provided improvement in near vision functionality in these LVC patients with long-term stability. The LaserACE procedure is not on the visual axis, therefore these patients could still receive correction to their hyperopic regression.

Scleral surgery for the treatment of presbyopia: where are we today?

Presbyopia corrections traditionally have been approached with attempts to exchange power, either at the cornea or the lens planes, inducing multifocality, or altering asphericity to impact the optical system. Treatments that affect the visual axis, such as spectacle and contact lens correction, refractive surgeries, corneal onlays and inlays, and intraocular lenses are typically unable to restore true accommodation to the presbyopic eye. Their aim is instead to enhance 'pseudoaccommodation' by facilitating an extended depth-of-focus for which vision is sufficient. There is a true lack of technology that approaches presbyopia from a treatment based or therapy based solution, rather than a 'vision correction' solution that compromises other components of the optical system. Scleral surgical procedures seek to restore true accommodation combined with pseudoaccommodation and have several advantages over other more invasive options to treat presbyopia. While the theoretical justification of scleral surgical procedures remains controversial, there has nevertheless been increasing interest and evidence to support scleral surgical and therapeutic approaches to treat presbyopia. Enormous progress in scleral surgery techniques and understanding of the mechanisms of action have been achieved since the 1970s, and this remains an active area of research. In this article, we discuss the historic scleral surgical procedures, the two scleral procedures currently available, as well as an outlook of the future for the scleral surgical space for treating presbyopia.

Visual outcomes 24 months after LaserACE.

BACKGROUND: To evaluate the effects on near and intermediate visual performance after bilateral Laser Anterior Ciliary Excision (LaserACE) procedure. METHODS: LaserACE surgery was performed using the VisioLite 2.94 µm erbium: yttrium-aluminum-garnet (Er:YAG) ophthalmic laser system in 4 oblique quadrants on the sclera over the ciliary muscle in 3 critical zones of physiological importance (over the ciliary muscles and posterior zonules) with the aim to improve natural dynamic accommodative forces. LaserACE was performed on 26 patients (52 eyes). Outcomes were analyzed using visual acuity testing, Randot stereopsis, and the CatQuest 9SF patient survey. RESULTS: Binocular uncorrected near visual acuity (UNVA) improved from +0.20 ± 0.16 logMAR preoperatively, to +0.12 ± 0.14 logMAR at 24 months postoperatively (p = 0.0014). There was no statistically significant loss in distance corrected near visual acuity (DCNVA). Binocular DCNVA improved from +0.21 ± 0.17 logMAR preoperatively, to +0.11 ± 0.12 logMAR at 24 months postoperatively (p = 0.00026). Stereoacuity improved from 74.8 ± 30.3 s of arc preoperatively, to 58.8 ± 22.9 s of arc at 24 months postoperatively (p = 0.012). There were no complications such as persistent hypotony, cystoid macular edema, or loss of best-corrected visual acuity (BCVA). Patients surveyed indicated reduced difficulty in areas of near vision, and were overall satisfied with the procedure. CONCLUSIONS: Preliminary results of the LaserACE procedure show promising results for restoring visual performance for near and intermediate visual tasks without compromising distance vision and without touching the visual axis. The visual function and visual acuity improvements had clinical significance. Patient satisfaction was high postoperatively and sustained over 24 months. TRIAL REGISTRATION: NCT01491360 (https://clinicaltrials.gov/ct2/show/NCT01491360). Registered 22 November 2011.