Presbyopia, an age-related condition affecting the eye’s ability to focus on near objects, has long posed a challenge for patients and eye care professionals. With the advent of pharmacological solutions, new opportunities have arisen to manage this common issue beyond traditional corrective lenses and surgery. In a recent episode of the Defocus Media podcast, Dr. Darryl Glover and Dr. Jennifer Lyerly explored the potential of a new presbyopia treatment in development, aceclidine, with their guest, Dr. Marc Odrich, a seasoned expert in ophthalmology. The conversation delved into the science behind aceclidine, its advantages over existing treatments like pilocarpine, and its potential to revolutionize presbyopia management.

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Key Topics:The Challenges of Existing Presbyopia TreatmentsAceclidine: A Pupil-Selective ApproachReal-World Applications and Patient OutcomesThe Importance of a Preservative-Free FormulationAceclidine vs. Pilocarpine: A Comparative PerspectiveLooking Ahead: The Future of Presbyopia TreatmentConclusion: Embracing Innovation in Eye Care

The Challenges of Existing Presbyopia Treatments

The discussion began with an acknowledgment of the current landscape of presbyopia treatment. Pilocarpine, the first presbyopia-correcting eyedrop, generated significant excitement upon its release. However, many eye care professionals, including Dr. Lyerly, expressed disappointment with its performance. Pilocarpine works by stimulating the ciliary muscle to induce miosis, creating a small pupil size that enhances depth of focus. While this mechanism can temporarily improve near vision, it often comes at the cost of distance vision, as pilocarpine can induce myopia (nearsightedness).

Dr. Odrich pointed out that this myopic shift, along with the short duration of action of pilocarpine, limited its usefulness for many patients. “Imagine telling a 58-year-old patient that while a drop can improve their near vision, it might worsen their distance vision and require them to get new glasses,” Dr. Odrich explained. “That’s a tough sell, especially when the drop needs to be reapplied every three to four hours.”

These limitations highlighted the need for a better solution—one that could enhance near vision without compromising distance vision or requiring frequent dosing. This need set the stage for the introduction of aceclidine, a novel presbyopia treatment in development by LENZ Therapeutics.

Aceclidine: A Pupil-Selective Approach

Aceclidine represents a significant advancement in the pharmacological treatment of presbyopia, primarily due to its pupil-selective mechanism. Unlike pilocarpine, which affects the ciliary muscle, aceclidine works by selectively constricting the pupil without inducing a myopic shift. This is achieved through what Dr. Odrich described as “pupil-selective, ciliary-sparing” action. By reducing the pupil size to less than two millimeters, aceclidine creates a “pinhole effect” that enhances depth of focus, allowing patients to see clearly at both near and far distances.

One of the key potential advantages of aceclidine is its ability to improve both near and distance vision without the side effects commonly associated with pilocarpine. Dr. Odrich emphasized this point, noting that aceclidine does not significantly affect the ciliary muscle, thereby avoiding the myopia-inducing effects seen with pilocarpine. “We see a minimal impact on the ciliary muscle with aceclidine, which is crucial for maintaining distance vision while improving near vision,” he said.

Real-World Applications and Patient Outcomes

The podcast discussion also touched on the real-world applications of aceclidine, particularly its clinical trial population which included patients who have undergone refractive surgery such as LASIK or PRK. These patients, who may have enjoyed excellent distance vision post-surgery, often find presbyopia to be a frustrating development as they age. Aceclidine has the potential to offer a non-invasive solution that can restore their ability to see clearly at all distances without the need for additional corrective lenses.

Dr. Odrich shared insights from clinical trials involving aceclidine, highlighting its potential to deliver significant improvements in vision for a broad range of patients. In one study, over 70% of participants experienced a three-line gain in near vision three hours after using aceclidine, with minimal impact on distance vision. “It’s remarkable to see how well aceclidine works, especially for older presbyopes who have the most to gain,” Dr. Odrich noted.

These outcomes are particularly encouraging for eye care professionals who seek to offer their patients effective, non-surgical solutions for presbyopia. Dr. Glover and Dr. Lyerly both expressed enthusiasm about the potential of aceclidine to enhance patient care, especially for those who have been disappointed by existing treatments. “We’re at the dawn of a new era in presbyopia management,” Dr. Odrich remarked, reflecting the optimism shared by his colleagues.

The Importance of a Preservative-Free Formulation

Another significant aspect of aceclidine discussed in the podcast is its preservative-free formulation. Preservatives like benzalkonium chloride (BAK) are commonly used in eyedrops to prolong shelf life, but they can cause ocular surface toxicity with long-term use. This is particularly concerning for patients who may use presbyopia drops daily over many years.

LENZ Therapeutics addressed this issue by developing aceclidine without preservatives, given the potential chronic use, if approved. Dr. Lyerly, who regularly treats patients with ocular surface disease, emphasized the importance of this innovation. “A preservative-free formulation is critical for ensuring that patients can use aceclidine long-term without damaging the ocular surface,” she explained. “This is especially important for patients who are already dealing with conditions like dry eye or limbal stem cell deficiency.”

The decision to create a preservative-free drop was a deliberate one, informed by the clinical experience of Dr. Odrich and his colleagues.

"We wanted to ensure that aceclidine could be used safely over many years, so we formulated it without BAK," Dr. Odrich said. "This is a key differentiator that sets aceclidine apart from other treatments."

Aceclidine vs. Pilocarpine: A Comparative Perspective

Throughout the podcast, the hosts and their guest drew comparisons between aceclidine and pilocarpine, highlighting the advantages of the newer treatment. While pilocarpine served as a valuable first step in the development of presbyopia-correcting eyedrops, its limitations have become increasingly apparent. These include its short duration of action, the need for frequent dosing, and the potential for inducing myopia.

In contrast, aceclidine in its clinical trial demonstrated a longer duration of action, with effects lasting up to ten hours after a single dose. This extended duration reduces the need for frequent reapplication, making it more convenient for patients to use throughout the day. Additionally, aceclidine’s minimal impact on the ciliary muscle means that patients did not experience the myopic shift associated with pilocarpine, preserving their distance vision.

Dr. Odrich also pointed out that aceclidine was well-tolerated by patients in the clinical trial, with mild side effects such as temporary dimming of vision due to the small pupil size. However, he noted that these side effects were generally mild and resolved quickly. “Patients reported some mild stinging and dimness, but these effects were transient and did not deter them from using the drop,” he said.

Looking Ahead: The Future of Presbyopia Treatment

As the conversation drew to a close, the hosts and Dr. Odrich looked ahead to the future of presbyopia treatment. With aceclidine expected to enter the market as early as the second half of 2025, pending FDA review and approval, they expressed excitement about the possibilities it holds for improving patient outcomes and expanding the range of options available to eye care professionals.

Dr. Lyerly highlighted the importance of staying informed about new treatments and preparing to integrate them into clinical practice. “As eye care professionals, we need to be ready to offer our patients the best possible solutions,” she said. “Aceclidine represents a significant advancement, and it’s up to us to educate our patients about this exciting new option.”

Dr. Glover echoed this sentiment, emphasizing the need for eye care professionals to be proactive in discussing new treatments with their patients.

Dr. Darryl Glover, Optometrist and Co-Founder of Defocus Media | LENZ Therapeutics Photoshoot

"It’s all about setting our patients up for success," he said. "By staying ahead of the curve and being knowledgeable about the latest advancements, we can ensure that our patients receive the highest standard of care."

Conclusion: Embracing Innovation in Eye Care

The Defocus Media podcast episode featuring Dr. Marc Odrich offered a comprehensive look at aceclidine which is in development for the treatment of presbyopia and its emerging potential for presbyopes. Through an in-depth discussion of its mechanism of action, real-world applications, and advantages over existing treatments, the hosts and their guest highlighted the potential of this new eyedrop to transform presbyopia management.

As the field of eye care continues to evolve, innovations like aceclidine will play a crucial role in shaping the future of patient care. For eye care professionals, staying informed about these developments and being prepared to integrate them into practice is essential for providing the best possible outcomes for patients. With aceclidine on the horizon, the future of presbyopia treatment looks brighter than ever.