Presbyopia - Cause and Treatment

Presbyopia, defined as the loss of the ability to see clearly at a normal near working distance while fully corrected for distance vision, affects 100% of the population by the fifth decade of life. Presbyopia is one of the earliest and most predictable signs of middle age. Its etiology remains a source of controversy. ^[1]

Presbyopia does not occur suddenly. It is the consequence of the slow and progressive universal decline in the amplitude of accommodation with age. ^[2] A young eye, while fully corrected for distance vision, can accommodate as much as 15 diopters (D) and see clearly at 6.7 cm (2.6 inches) from the cornea. The young eye has the remarkable ability to focus over a broad range from infinity to 2.6 inches within a second. This process, called accommodation, is due to a change in shape of the lens.

The lens is a transparent biconvex spheroid suspended at its equator by zonulas, which are connected to the ciliary body. The ciliary body contains the ciliary muscle. When this muscle contracts as an autonomic nervous system response, tension on the zonules is altered, resulting in a change in the shape of the lens. There are various theories on how ciliary muscle contraction alters zonular tension to increase the optical power of the lens during accommodation.

The Helmholtz theory of accommodation is based on the concept that the crystalline lens changes in shape with relaxation of zonular fibers. Helmholtz believed that contraction of the ciliary muscle causes relaxation of the zonular fibers, with a subsequent curvature increase of other anterior and posterior lens surfaces. This resulted in an increase in the net power of the lens, causing the change in focus of the eye from far to near. ^[3] Presbyopia, according to Helmholtz, resulted from the decline in elasticity of the lens over decades of time.

There are many other theories of accommodation. These have been met with some skepticism, and the classic Helmholtz model remains the most widely recognized. ^{[4, 5]}

The healthy, young human (< 40 years) or young primate eye can rapidly focus on near and distant objects (ie, it can change focus or accommodate). The mechanism by which the eye can accomplish this amazing task has been speculated on for centuries. Initially, it was suggested that the eye was divinely created; therefore, it did not follow known physical laws of optics.

In 1619, Scheiner, a Jesuit priest, proved that accommodation resulted from a change in the optical power of the eye and that the eye obeyed the laws of optics. ^[6]

Some of the most famous philosophers and scientists were interested in how the eye accommodates. In 1611, Kepler and others thought the crystalline lens moved forward and backward. ^[7] In 1677, Descartes suggested that the shape of the crystalline lens changed. ^[8] In 1742, Lobe postulated that the shape of the cornea changed. ^[9] Sturm and Listing believed that the eye elongated. ^{[10, 11]}

In 1801, Thomas Young, using ingenious experiments, provided evidence that accommodation results from changes in shape of the crystalline lens. He proved that the eye does not elongate during accommodation. He demonstrated that accommodation did not occur in aphakes. He realized that accommodation had to result from a change in position or shape of the crystalline lens. He concluded that accommodation results from a change in shape of the crystalline lens. Since the ciliary body had not yet been discovered, he postulated that the change in shape of the crystalline lens is induced by a muscular mechanism within the crystalline lens. ^[12]

In 1823, Purkinje noted the reflected images of a candle from the anterior and posterior crystalline lens surfaces. ^[13] In 1849, Langenbeck was able to observe in a patient that the Purkinje image from the anterior surface of the crystalline lens became smaller during accommodation by using a candle and a magnifying glass. He correctly concluded that the anterior surface of the crystalline lens becomes more convex during accommodation. ^[14] He proposed that the ciliary muscle, which had been discovered independently by Bruecke and Bowman in 1847, ^{[15, 16]} squeezes the crystalline lens.

In 1851, Cramer followed up on Langenbeck's observation and improved on it by making a device that incorporated a telescope to allow accurate observations of the Purkinje images during accommodation. He observed that the anterior surface of the crystalline lens became more convex, but the posterior surface did not change shape. ^[17]

In 1855, Helmholtz improved on the Cramer device by placing crossed glass plates between the patient's eye and the telescope, so that the Purkinje images were doubled and could be measured more accurately. In addition to observing that the anterior and posterior surfaces of the crystalline lens became more convex, he noted that the lens became thicker during accommodation. He hypothesized that the ciliary muscle relaxes during accommodation allowing the lens to become more spherical under the influence of its own elasticity. According to his hypothesis, the equatorial diameter of the lens should decrease as it becomes more spherical during accommodation. ^[18]

In 1864, Donders studied the change of the amplitude of accommodation with age. He found that the amplitude of accommodation declined in a linear fashion with age. This decline occurs universally and predictably. If patients are corrected properly for distance vision, their age can be determined within 1.5 years by measuring their amplitude of accommodation. Donders also observed that patients become slightly hyperopic when they become presbyopic. ^[2] In 1870, Adamük and Woinow suggested that presbyopia, the loss of accommodation with age, resulted from lens sclerosis (ie, loss of elasticity of the lens with age). ^[19]

In 1904, Tscherning examined the curvature changes of the anterior crystalline lens surface by observing the changes in the Purkinje images when 4 lights are used as objects. He placed the lights so that 2 formed reflected images from the central anterior surface and 2 formed reflected images from the peripheral anterior surface of the crystalline lens. He observed that the central images moved closer together during accommodation, while the peripheral images moved further apart. He concluded that the crystalline lens was becoming more convex centrally but was becoming flatter in the periphery during accommodation. ^[20] This was consistent with Young's observation that the spherical aberration of the eye decreases during accommodation.

The Helmholtz theory did not explain the peripheral surface flattening of the crystalline lens without additional assumptions. For example, the iris constricts during accommodation and it was imputed to produce the peripheral flattening of the crystalline lens. However, von Graefe had demonstrated accommodation in a patient with a total iridectomy. ^[21]

Tscherning further postulated that during accommodation the ciliary muscle exerted tension on the crystalline lens, pressing the crystalline lens against the anterior vitreous. The resistance of the vitreous transmitted sufficient force to effect central bulging of the anterior surface of the crystalline lens. His theory predicts that the central thickness should decrease during accommodation. He did not accept Helmholtz's measurements of increasing crystalline lens thickness with accommodation. Tscherning thought that presbyopia was the result of enlargement of the crystalline lens nucleus. ^[20] All subsequent theories, including those by Gullstrand (1911) and Fincham (1937), used Helmholtz's hypothesis that the zonules are relaxed during accommodation. ^{[22, 23]} Helmholtz's hypothesis and subsequent modifications attribute presbyopia to sclerosis of the crystalline lens stroma or capsule, atrophy of the ciliary muscle, or stiffening of the ciliary muscle attachments.

Because presbyopia is an age-related refractive error and universal, usually starting to cause problems around age 40-45 years, it occurs in all individuals, regardless of any pre-existing refractive error. Nonetheless, symptoms of presbyopia vary depending on the nature of the pre-existing refractive error.

Individuals with myopia who develop presbyopia will notice difficulty reading with their myopic correction and quickly discover that they are able to see better at near by removing their eyeglasses. Individuals with myopia can see at near without their eyeglasses. These myopic patients, in the habit of wearing their eyeglasses all the time, may not have realized before that they were always able to read without eyeglasses and may now believe that their vision is improving. Many persons with myopia may not desire any additional treatment for their presbyopia, being satisfied with simply removing their eyeglasses for close work.

Individuals with hyperopia that has been latent and that has not necessitated eyeglasses in the past will begin experiencing reading difficulties at a somewhat younger age. This results not from a more rapid progression of presbyopia or a younger onset, but rather from the hyperopia changing from latent to manifest. When provided with assistance for near in the form of an optical correction, these patients will also note some additional increase in comfort and clarity of their distance vision.

Individuals with astigmatism, whether hyperopic or myopic, simple or compound, will experience the symptoms of presbyopia at a relatively variable age, depending on the axis and degree of the astigmatism. In general, reading speed and acuity decreases with increasing uncorrected astigmatism, even as low as -0.75 D. In general, the effect is worse in "with-the-rule" astigmatism (the vertical meridian of the cornea is steepest and a minus cylinder is placed in the horizontal axis for correction) than in "against-the-rule" astigmatism (the horizontal meridian of the cornea is steepest and a minus cylinder is placed in the vertical axis for correction). ^[24]

Although it is common for an individual to have a different type or degree of refractive error (myopia, hyperopia, and/or astigmatism) in one eye versus the other, the degree of presbyopia in anatomically normal eyes is usually approximately equal in each eye.

Presbyopia is an ongoing process but is usually asymptomatic until tasks at close distance become more difficult to perform. Presbyopia may develop as early as the teenaged years in individuals with significant uncorrected hyperopia. A myopic person who has habitually removed eyeglasses for near work may not experience symptoms of presbyopia. Most emmetropic individuals first complain of difficulty with near work at age 40-45 years.

Difficulty with near work, the need to move reading material away from the face, and feelings of eye strain (asthenopia) are all symptoms of presbyopia.

When discussing the treatment of presbyopia, it is important to define the word "treatment." To date, no technique effectively decreases or eliminates presbyopia, as defined as the loss of accommodative power of the eye. Numerous optical and surgical methods are available to decrease the symptoms of presbyopia. Optical methods reduce the symptoms when the optical device is in place. Surgical methods, directed either at the cornea or lens, alter the structure of the eyes to reduce presbyopic symptoms. In November 2021, the FDA approved the first topical ophthalmic solution (pilocarpine 1.25% [Vuity]) for presbyopia. 

Eyeglasses

Eyeglasses are the simplest and safest means of correcting presbyopia. Presbyopia initially was treated with near vision optical aids using magnifying lenses, reading eyeglasses, and monocles. Eyeglasses for presbyopia have increased focusing power (more plus power) than the distance correction required. In eyes that have no additional refractive error, a simple plus lens relieves the symptoms of presbyopia. Such a plus lens replaces the decrease in accommodative ability of the eye. The power of such a correction usually ranges between +0.75 and +3 D, depending on the degree of presbyopia. If a visual task requires near vision at a working distance of less than one third of a meter (approximately 13 inches), lenses with powers of greater than +3 D may be used.

Patients wearing single-vision reading eyeglasses continue to have symptoms of presbyopia when they remove their glasses. Visual acuity at distance with such reading eyeglasses is blurry since the point of focus is set for near rather than distance.

Reading eyeglasses can be purchased with a prescription but are also available in various powers without a prescription. Reading eyeglasses available without a prescription have plus powers that are equal in both lenses. Most patients have a small difference in their refractive error between the two eyes, and a written prescription for reading eyeglasses could incorporate that distance.

In patients with underlying myopia with or without astigmatism or hyperopia with or without astigmatism, reading eyeglasses can incorporate the need for ametropic and astigmatic correction. Just as in eyeglasses that correct only the presbyopia, such single-vision eyeglasses are designed for near and cause blurring of distance vision.

Multifocal eyeglasses are those that incorporate differing powers within each lens. They are designed to allow both distance and near vision to be corrected within the same pair of eyeglasses. Multifocal eyeglasses may have two or more distinct powers within the same lens, separated by a distinct border, or may have the powers blended in a linear fashion. Multifocal lenses with distinct borders may be bifocal, incorporating two powers within the same lens, or trifocal, incorporating three powers within the same lens.

Benjamin Franklin was the first person to fuse the distance lens with the near reading lens to give us bifocals. The powers within the same lens differ only in the amount of plus power "added" to the lens in a certain area. If the powers within a lens are blended, the glass is called a progressive multifocal. The degree of plus power added onto the distance correction varies according to the degree of presbyopia and the nature of the tasks to be performed. The working distance of the patient also must be considered when the prescription is written.

Bifocals correct for near and far vision. A line, which may or may not be visible, divides the lens. The bottom of the lens refracts light for close vision. The top portion refracts light to allow the wearer to see distant objects. A wearer of a bifocal who has little accommodation remaining could have difficulty seeing at an intermediate distance.

Trifocals have three lens areas to correct for close-up, mid-range, and far vision.

Progressive lenses, unlike bifocals and trifocals, lack a distinct border at the division between each refractive area. In a progressive lens, the refraction changes gradually in the lens from top to bottom.

Contact lenses

Contact lenses provide optical correction similar to that of eyeglasses. A reading contact lens, just as a reading glass, optically improves the symptoms of presbyopia but blurs distance vision. While reading eyeglass can be removed multiple times in a brief period to allow for clear distance vision, this is difficult to do with a contact lens.

Multifocal contacts lenses have been developed and, in theory, correct the vision at all distances without the need for spectacle glasses. These lenses have several rings or zones set at different powers, providing simultaneous distance and near vision. Patients are often dissatisfied with multifocal contact lenses because of ghosting of images, lack of clarity, and loss of contrast sensitivity.

Monovision

Monovision is defined as a visual situation in which the optical correction allows one eye to see well at distance and the other eye to see well at near. An expected corollary of this is that the near-seeing eye is not seeing well at distance, while the distance-seeing eye is not seeing well at near. Some patients neuro-adapt readily to this situation, while others have difficulty with blurring and ocular discomfort with monovision, even after attempting it for an extended period. ^{[25, 26]} Monovision can be achieved with single-vision eyeglasses, with one lens of the spectacle focused for distance and the other for near. This is rarely used, since patients can more easily adjust to a multifocal spectacle if they are going to wear eyeglasses for optical correction of presbyopia. Monovision optical correction is usually attempted with monofocal contact lenses, which provide a difference in focal points between the two eyes. If the patient has a similar refractive error in each eye, such contact lenses will differ in power.

Studies comparing patient acceptance of multifocal contact lenses and monovision contact lenses have shown mixed preferences, with many patients in both groups discontinuing these lenses within the trial period. ^{[27, 28]}

Monovision contact lenses correct one eye for distance vision and the other for close-up vision. The patient needs to adapt to monovision lenses and train the brain to see this way. In general, the dominant eye is corrected for distance, and the nondominant eye is corrected for near. Monovision as a treatment for presbyopia is generally accepted by less than 30% of the population. The loss of stereopsis and learning to ignore a blurry image from one half of the binocular visual field are problems for most patients. Patients often complain of difficulty with depth perception or clearly visualizing objects that are rapidly moving toward them.

Monovision impairs stereo acuity, and the effect increases as the degree of induced anisometropia increases. ^[29] However, monocular cues to depth perception are still operative and can be powerful. ^[30]

Although it is well established that these passive optical methods of treating presbyopia, such as monovision, bifocal, other multifocal, or progressive addition spectacle lenses or contact lenses, provide functional distance and near vision to presbyopes, they do not restore the active change in power of the eye that occurs during accommodation in the young eye.

Various surgical methods have been used to achieve permanent monovision without the use of eyeglasses or contact lenses. These methods do not restore accommodative power of the eye to its youthful state. A trial of monovision using contact lenses (or one lens for near if the fellow eye is emmetropic) should be tried prior to surgery to ascertain whether the patient can indeed tolerate monovision. ^{[31, 32]}

Traditional Corneal-Based Refractive Surgery for the Achievement of Monovision

This is performed using an excimer laser via hyperopic photorefractive keratectomy (PRK), other surface laser techniques, or LASIK surgery, with the goal of flattening the cornea in the nondominant eye for improved visual acuity at near. Essentially, this achieves permanent monovision. As such, it is generally contraindicated in patients who need good stereopsis to perform their daily activities (eg, airplane pilots or professional drivers). This may be combined with a surgical procedure, if necessary, to place the dominant eye's unaccommodated focus at distance. Myopia was historically corrected using radial keratotomy (RK), and both myopia and hyperopia can currently be addressed using PRK, advanced surface techniques, or LASIK. Associated astigmatism in either eye also can be addressed using the excimer laser.

LASIK and PRK for myopia and hyperopia have shown reasonable safety, efficacy, and predictability profiles in the presbyopic age group. ^{[32, 33]}

Potential complications of all traditional corneal-based refractive surgery include visual distortion, induced corneal ectasia, anisometropia, haze, glare, regression of effect, decrease in uncorrected and/or corrected distance vision, halos around lights at night, and decreased contrast sensitivity. ^{[34, 35]}

Nontraditional Corneal Approaches to Presbyopic Symptoms

Conductive keratoplasty for the achievement of monovision

Conductive keratoplasty (CK) involves the use of radiofrequency or holmium-laser–based energy delivered to the cornea to cause corneal steepening. In patients with emmetropia, CK usually is performed in one eye, providing monovision, with the treated eye becoming myopic from the collagen-shrinking procedure. ^[36] CK rarely is used today, and regression of the effect is common and unpredictable. ^[37]

Laser-induced multifocality of the cornea

Many different approaches have been attempted to alter the corneal shape in order to increase the depth of focus at the corneal level. One of the main limitations of this type of surgery is the lack of strong scientific evidence and the absence of long-term follow-up. Spectacle independence has been variable, and it often is difficult to ascertain whether decrease in spectacle usage is due to the surgery or the monovision often produced when operating on only one eye. ^[38]

PresbyLASIK, first described in 1996 by Ruiz, uses excimer laser technology under a corneal flap to change the corneal surface optics to one of multifocality. Computer algorithms to achieve this include multifocal corneal transition profiles, a peripheral PresbyLASIK profile, and a central-only modelling profile. ^[39] The latter technique has been the most popular, but none of the ablation profiles has achieved much acceptance owing to the significant amount of higher-order aberration induced, especially coma. ^{[40, 41, 42]}

Other attempts to alter corneal shape with excimer laser have included Supracor (Technolas), ^{[43, 44]} PresbyMAX (Schwind), ^{[45, 46]} and Laser Blended Vision ([LBV] by Carl Zeiss Meditec). ^[47] None of these has produced consistently acceptable results.

The advent of the femtosecond laser theoretically has allowed manipulation of the refractive power of the cornea to be manipulated to achieve multifocality without the need for corneal incision to create a corneal flap. In 2007, Ruiz et al in Colombia used femtosecond lasers to treat presbyopia in the Technolas femtosecond laser IntraCor technique. ^[48] Various subsequent studies have shown disappointing results. ^{[49, 50, 51]}

Intracorneal inlays

Corneal inlays are tiny optical devices that are inserted into the corneal stroma to improve reading vision. Some of these devices resemble very small contact lenses. The primary purpose of these devices is to improve near vision and to reduce the need for reading eyeglasses in older adults who have presbyopia.

Corneal inlays are placed within the central stromal layer of the cornea under a microkeratome-created flap or, more commonly today, into a femtosecond laser–created pocket.

Corneal onlays, which are devices placed just beneath the corneal epithelium, have not proven to be successful.

Corneal inlay surgery has been combined with LASIK surgery to correct both presbyopia and myopia, hyperopia, and astigmatism.

Corneal inlay surgery is less invasive than lenticular-based surgical procedures and, because no corneal tissue is removed during inlay surgery, is a better alternative than other corneal procedures among patients with thin corneas.

In 2015, the Kamra corneal inlay (formerly the AcuFocus intracorneal inlay) was the first corneal inlay to gain US FDA approval for use in patients with presbyopia. The Kamra inlay has an opaque outer ring with a small central opening. Correct positioning within the cornea is critical. The inlay is implanted in the nondominant eye, theoretically preserving distance vision in that eye while improving near vision in the eye from the miotic effect of the inlay. The resultant monovision is at near only. ^[52]

Other corneal inlays have been developed with multifocal optics. These include the investigational Flexivue Microlens, a hydrogel inlay with a central zone for distance and a peripheral refractive zone, available in various addition powers. ^[53] The Icolens (Neoptics), an acrylic hydrogel inlay with a similar optic design, ^[54] the Presbia Flexivue Microlens, also in clinical trials, and the Raindrop Near Vision Inlay (ReVision Optics), which received FDA approval in 2016 but is no longer available, all are devices that involve considerable surgical manipulation and have significant adverse effects.

Lenticular  approaches to presbyopic symptoms

Any lens-based surgical attempt to correct presbyopia involves operative removal of the lens and placement of an intraocular lens (IOL) implant. The choice of lenses that may be implanted include traditional monofocal IOLs (with the intent of creating monovision), bifocal and trifocal IOLs, extended-depth-of-focus IOLs, and accommodating IOLs.

Lens-based refractive surgery techniques

Lens extraction with IOL insertion can be used to achieve optical correction of presbyopia. This can be performed in patients with cataract or those without significant lens opacities. The latter procedure is called clear lens extraction (CLE). IOL options include bilateral surgery with intentional pseudophakic monovision, in which the dominant eye is corrected for distant vision and the nondominant eye for near, ^[55] and multifocal and accommodating IOLs. Pseudophakic monovision does not preserve accommodation, so a significant difference in refraction between the two eyes is necessary to obtain both acceptable distance and near visual acuity.

Although multifocal implants are an alternative to monovision, they result in decreased visual quality, noticeable by some, but not all, patients. Multifocal IOLs may cause visual haloes or other dysphotopsias, some to an unacceptable degree. Accommodating IOLs, in theory, would be optimal, but the existing choices currently result in unpredictable patient acceptance. Most patients undergoing cataract surgery undergo implantation of a monofocal IOL or a small amount of monovision, with a small degree of myopia being targeted for the nondominant eye. Spectacles for near vision are required in these patients.

Multifocal intraocular lenses

The implantation of any multifocal lens requires accurate preoperative biometry and lens calculations. Astigmatism control is vital for patient satisfaction, and patients must be carefully selected and their visual expectations realistic. The cost of multifocal lens implantation is significant and requires out-of-pocket payment by the prospective patient, typically further heightening patient expectations regarding the eventual visual results.

All multifocal IOLs possess multiple points of focus, resulting in multiple images at the various focal planes. Suppression of the unwanted image(s) is part of the neuroadaptation that the patient will experience postoperatively. Multifocal IOLs include bifocal and trifocal IOLs, with the former providing two focal planes, usually calculated to provide distance and near correction, and the latter with 3 focal planes, correcting also for intermediate vision. Multifocal IOLs may have apodized or non-apodized optics. Apodized IOLs have a gradual reduction in diffractive step heights from the center to the periphery, while non-apodized diffractive multifocal IOLs use uniform height diffractive steps. Multifocal IOLs may diminish contrast sensitivity, which is a necessary optical result of an IOL with multiple refractive zones. Glare and halo complaints are not unusual. ^[56]

Diffractive IOLs divide the incoming light for both distance and near focal points. Those approved for the correction of presbyopia in patients undergoing cataract surgery include the AcrySof ReSTOR lens (Alcon Laboratories) and the Tecnis lens (Abbott Medical Optics). The ReZoom lens (Abbott Medical Optica) refractive multifocal IOL has zones of different refractive powers to focus incoming light onto differing focal points.

Trifocal IOLs have not been approved by the FDA but are being used in Europe with reportedly good patient satisfaction. ^{[57, 58]} Extended-depth-of-focus IOLs have a unique achromatic design that allows a greater depth of focus than standard monofocal lenses and reduces the incidence of adverse effects often experienced with standard multifocal lenses.

Extended-depth-of-focus intraocular lenses

This is the most recently investigated presbyopia-correction IOL category and is the first that provides an extended range of vision. These lenses use diffractive optics to address chromatic aberration, providing crisp vision and extended depth of focus without the drawbacks of a multifocal system. An example of a lens in this category is the TECNIS Symfony (Abbott Medical Optics). This IOL was approved for use in the United States in 2016 and also has a toric version for the correction of astigmatism. ^{[52, 59]}

Accommodative intraocular lenses

The goal of accommodative IOLs is to correct presbyopia by changing the location of the IOL with attempted accommodation through anterior movement of the lens. The Crystalens (Bausch and Lomb) is a monofocal lens with plate haptics that includes flexible hinges, allowing anteroposterior movement of the optical part of the lens. This lens is FDA-approved, as is the toric version of this lens (Trulign Toric). Clinical trial and postmarketing data have shown that the actual degree of accommodation achieved is 1 D or less. ^{[60, 61]} Positioning of the lens is critical, as is minimizing the risk for posterior capsular opacification, since any fibrosis of the capsule fornices may alter the optics.

Other accommodative lenses currently in clinical trials include the Tetraflex (Lenstec), the NuLens (Visiogen), the Synchrony lens (Visiogen), and the LiquiLens (Vision Solutions).

Scleral implants

Surgical procedures involving anterior scleral modification or intrascleral implants have been investigated for more than 15 years. ^{[62, 63]} Given the many different approaches that have been considered and then discarded, most of these procedures have been abandoned. ^{[64, 65, 66]} The use of an Erbium:Yag laser probe to excise sclera tissue in the four quadrants is in clinical trials (AceVision LaserACE). ^{[67, 68]} The Micro-Insert scleral implant (VisAbility) is also currently in clinical trials. ^{[69, 70]}

Presbyopia is a growing cause of disability because of an aging population. Approximately 100 million emmetropic individuals with presbyopia currently reside in the United States, which is about 50% more than the number of individuals with myopia.

Symptoms of presbyopia can be alleviated with multiple approaches. Treatment needs to be individualized according to each patient's needs and desires, expectations, hobbies, stage of cataract, and other ocular characteristics. Various treatment options may be available, but the patient and ophthalmologist must decide what is best for the patient with the knowledge that each option involves some compromises.

The standard approach to presbyopic complaints for centuries has been the use of spectacles. Production of functional monovision with contact lenses has a long record of safety and frequent success. Surgical options, including corneal, lenticular, and scleral options are relatively new and carry significant risks compared with eyeglasses or contact lenses. Additional devices and technologies are certainly on the horizon. Although these surgical methods can frequently improve uncorrected near visual acuity, much of the claimed success results from functional monovision come at a cost of lost contrast sensitivity, decreased image brightness, and/or reduction in distance vision due to optical aberrations.

The large number of devices currently in clinical trials is a testament to the innovation and skill present within today's medical and scientific communities.

Pilocarpine 1.25% ophthalmic solution (Vuity) gained FDA approval in November 2021 for treatment of presbyopia. One drop is instilled in each eye once daily. May administer 1 additional drop in each eye 3-6 hours after the first dose. Onset of action begins at about 15 minutes and lasts up to 6 hours to improve near and intermediate vision without impacting distance vision. 

Approval was based on the phase 3 GEMINI I and GEMINI II clinical trials (n = 750). Patients aged 40 to 55 years with presbyopia were randomly assigned in a 1:1 ratio to receive either pilocarpine or placebo. Both studies met their primary endpoints with a statistically significant proportion of participants treated with pilocarpine gaining at least 3 lines in mesopic (in low light), high contrast, binocular distance corrected near visual acuity (DCNVA), without losing more than 1 line (5 letters) of Corrected Distance Visual Acuity (CDVA) at Day 30, Hour 3, compared with placebo (p < 0.01). ^{[71, 72]}  

A second lower-strength brand (Qlosi 0.4%) was approved by the FDA in October 2023. Similarly, 1 drop is instilled in eye once daily. The dose may be repeated after 2-3 hours for an effect up to 8 hours. It can be administered on a daily basis, or as needed, up to twice each day. 

Results from the phase 3 NEAR-1 and NEAR-2 clinical trials (n >600) showed statistically significant results of treated patients with a gain of 3 lines or more in distance-corrected near visual acuity, and no loss of 1 line or more in distance visual acuity. ^[73]