1. Background 2. Mechanism of Action 3. Indications 4. Clinical Trial Data 5. Safety and Precautions 6. Considerations and Comparisons 7. References
Approximately 1.8 billion individuals around the world are currently affected with by presbyopia, a condition that will eventually affect everyone at some point in their lifetime.5 Presbyopia is the age-related gradual loss of the eye’s ability to accommodate.6 Accommodation is the ability of the lens to modify its curvature to focus on nearby objects.7, 8 Currently, there are multiple modalities available for the treatment of presbyopia including multifocal intraocular lens implants, corneal inlays, as well as monovision in the form of corneal refractive surgery. 9 However, each of these methods involves surgery, and studies have shown that some patients with presbyopia prefer a more non-invasive solution, like topical eye drop therapy.10 Pilocarpine 1.25% ophthalmic solution (Vuity) was developed for presbyopia correction in the form of topical therapy, and represents the first FDA-approved ophthalmic solution specifically for the treatment of presbyopia. Although Vuity is 1.25% pilocarpine, it is transmitted in a proprietary buffer (“pHast”) to increase bioavailability through more rapid equilibration to the ocular surface pH, and to results in a decrease side effect profile.11
Mechanism of Action
Pilocarpine is a muscarinic receptor agonist which binds to muscarinic receptors located on smooth muscle cells.12 It is a direct acting cholinergic agonist that functions by directly binding to muscarinic receptors.13 These smooth muscle cells include the ciliary muscle and the iris sphincter muscle.1,14 Iris sphincter contraction results in pupillary miosis, which increases the depth of field and improves near visual acuity.1,15 Contraction of the ciliary muscle results in decreased zonular tension which causes the lens to thicken and shifts focus to near targets.16 One study found the half-life of Pilocarpine to be about 31.83 minutes in aqueous humor.17
VUITY is currently the only FDA-approved treatment for presbyopia in adults.4 The proprietary buffer allows for increased bioavailability and a diminished side effect profile.18
Dosing, Administration, Preparation and Cost
The recommended dosage for Vuity is one drop in each eye once daily.1 Studies are currently in process to evaluate multiple-doses per day (source). Any contact lens that is being worn should be removed prior to drop administration. A proprietary vehicle with pHast™ technology is used to more effectively deliver the pilocarpine solution by quickly adjusting to the physiologic pH of the tear film. After instillation, the solution begins to have an effect within 15 minutes and provides a sharper near image for 6 to 10 hours.19
Clinical Trial Data
There were two Phase III clinical trials that led to FDA- approval.20GEMINI 1 and GEMINI 2 were two pivotal, randomized, double-masked, phase 3 clinical studies which lasted 30 days each. The purpose of both studies were to evaluate the efficacy and safety of VUITY use to treat presbyopia.4 Throughout the clinical trials, mild side effects, such as headaches and conjunctivitis were noted with Vuity usage.19 Post-market use has also revealed additional potential side effects such as a burning sensation on instillation, dimming of vision and an unanticipated amount of myopic shift. Across GEMINI 1 and GEMINI 2, there were 750 participants diagnosed with presbyopia aged 40 to 55 years old. Participants were randomized across both studies to be given either the placebo or VUITY. Each participant was instructed to use one drop of the VUITY or placebo once daily.4
In the GEMINI 1 study, 8% of patients treated with the placebo drops met the primary goals compared to 31% of patients that were given VUITY. In the GEMINI 2 study, 11% of patients treated with the placebo drops met the primary goals compared with 26% of patients that were given VUITY.21 Additionally, about nine out of ten participants that were given VUITY achieved greater than or equal to 20/40 mesopic, high-contrast binocular distance-corrected near visual acuity (DCNVA).22
Primary and secondary endpoints were met according to the results from phase 3 of the GEMINI 1 study. Compared to the placebo, a greater number of participants that were treated with VUITY gained three or more lines in mesopic, high contrast and binocular distance corrected near visual acuity.23 The improvement in near vision in mesopic conditions was without a loss of distance vision on day 30 at hour three.24 In addition, the improvement in vision was seen in as quickly as 15 minutes and lasted for six hours.
No life threatening or serious adverse events were noticed in any of the participants given VUITY in the trials. Headache and eye redness were the most common adverse events seen and were seen in less than five percent of patients.4
Safety and Precautions
Certain multi–drug interactions and medical conditions must be considered prior to prescribing VUITY. As a precaution, any patients interested in taking VUITY should know there are contraindications with certain medications. For example, if a patient is taking the chemotherapeutic medication Tegafur its metabolism can be decreased when VUITY is administered. 25,26,27 The use of VUITY is also not recommended in patients with iritis. Any patient with other eye diseases besides presbyopia should use extreme caution with VUITY as it can make these conditions worse.27 Vuity should be used with caution at night and when operating heavy machinery as temporary problems may occur with altering focus on near and distant objects.4 Any patient wearing contact lenses should remove them prior to VUITY administration. If a patient is using multiple topical eye medications, they should be administered at least 5 minutes apart from each other.4 Both GEMINI trials found the most common side/adverse effects of VUITY were eye redness and headache. However, these are not the only side effects that can present when using Pilocarpine eye drops. According to trial data, other treatment emergent adverse events that were found included, blurred vision, eye pain, visual impairment, eye irritation as well as increased lacrimation.4,26,28 Other common side effects that are seen with Pilocarpine use include increased sweating, muscle tremors, nausea, vomiting, shortness of breath and watering of the mouth.27
Although retinal detachment has previously been noted as a side effect of pilocarpine solution in myopes, no retinal detachments were noted during the GEMINI 1 and 2 trials. 4
Considerations and Comparisons
There are multiple surgical and non-surgical treatments that can be used to treat presbyopia. The most common and simplest treatment for presbyopia is through the use of trifocal, bifocal, or progressive lenses in the form of spectacle correction (eyeglasses). Multifocal contact lenses also exist for treatment of presbyopia. Multifocal spectacles and contact lenses are split into two sections, which requires the patient to adjust the angle of gaze in order to switch between distance and near vision.9 Some people are intolerant of multifocal spectacles, and significant astigmatism can cause multifocal contact lens intolerance as visual acuity can diminish with toric contact lens rotation.
Surgical treatments for age related presbyopia include corneal inlays which work by aperture optics and through central corneal steeping. Examples of corneal inlays include Kamra, Presbyopia, and Raindrop. Corneal refractive surgery to induce monovision is another surgical option for the treatment of presbyopia. This is where the dominant eye’s refractive error is fully corrected, and the non-dominant eye is set for some level of near vision (usually -0.50 sphere to -1.50 sphere depending on the patient’s age and previous level of monovision tolerance).
Presbyopia can also be surgically corrected through lens or cataract extraction and intraocular lens implantation. This can be done in the form of refractive lens exchange (RLE) or cataract surgery. A wide variety of multifocal, extended depth of focus, and “monofocal plus” IOLs exist to provide varying degrees of near vision after surgery. The IC-8 IOL is pending FDA approval but is available in other parts of the world that utilizes aperture optics for presbyopia correction, similar to the Kamra inlay and Vuity.
Risks associated with any corneal or lens-based surgery range from corneal edema and inflammation, rejection, infection, capsular rupture, retinal detachment, and elevated intraocular pressure. 29
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