Tackling Ocular Menopause: Presbyopia Management Strategies

Presbyopia is the normal, irreversible, progressive loss of accommodation, which causes inability to focus clearly at near and intermediate objects, starting at the age of 40 years.^{1, 2} It is similar to ocular menopause, occurring universally, announcing middle age due to loss of elasticity (sclerosis) in the lens stroma, capsule and/or ciliary muscles/ attachments attributed by Helmholtz hypothesis and further research.

The most common causes are loss of accommodative ability of the natural crystalline lens, but other mechanisms, like changes in the lens’ curvature from continuous growth and loss of power of the ciliary muscles, have also been postulated as contributing to its pathogenesis.^3,4 Age is the most common cause, but risk factors include diabetes, poor nutrition, gender, certain medications, and trauma.⁵

People performing too much close-up work tend to notice symptoms earlier than others of a similar age group.⁶ The onset may be earlier in women and in individuals living closer to the equator due to premature degradation of the crystalline lens by ultraviolet radiation exposure.₆ Despite its ubiquity, the exact mechanism of presbyopia is unknown.

PREVALENCE

In 2015, it was estimated that 1.8 million people globally had presbyopia and the prevalence is expected to peak at approximately 2.1 billion in 2030.⁷ Studies have revealed that presbyopia is hugely under-corrected in many countries, with reading glasses available to only 6–45% of patients living in developing countries due to lack of diagnosis and funds.³ The burden of uncorrected presbyopia is significant, accounting for near vision impairment in approximately 826 million people globally and a AU$25 billion loss in productivity among individuals younger than 65 years.⁸ Hence, presbyopia should be considered an important medical and social need and treated with the best possible, user-friendly treatments, rather than be considered a lifestyle issue.

At the clinical level, presbyopia is a frustrating and difficult issue, which can negatively impact patients’ quality of life along with the limitations of currently available methods of correction.

Progressive and bifocal glasses are associated with peripheral blur, a constricted visual field, and impaired depth of perception, which can increase the risk of falls in elderly patients.⁹ Contact lenses are associated with dry eye symptoms, risk of corneal infections, and reduced manual dexterity with age.

Other means to correct presbyopia include changing the optics of the cornea by laser and/or surgical means to exchange the natural lens with currently available intraocular lenses (IOLs) including monovision, extended range of vision lenses (EROV)/extended depth of focus (EDOF) and multifocal lenses. While most people are satisfied, some report photic symptoms based on the option used, such as loss of depth, loss of contrast, glare and halos, and the need for glasses for fine work and/or in dim light.

Non-invasive therapies with newer mechanisms of action are currently being investigated, including miotic agents and UNR844, a lipoic acid choline ester.¹⁰

THEORIES BEHIND PRESBYOPIA

Accommodation is a mechanism by which the eye varies its refractive power to focus on objects at different distances, to provide a clear and sharp image focussed on the retina.⁶ Thomas Young is widely credited  with confirming that the loss of natural elasticity of the crystalline lens is the prime reason for loss of accommodation.¹¹

Helmhotz later described the role of ciliary muscle contraction and relaxation of the zonules in changing the lenticular curvature and refractive power.¹² Glasser and Kaufman then verified that the movement of accommodative structures was most consistent with the theory of Helmholtz.¹³ More recently, Goldberg has visually described the inter-relationship of the zonular apparatus’ components in a computer animated model.¹⁴

PRESENTATION

Symptoms of presbyopia include the gradual onset of blurred near vision, the tendency to move objects further away to be able to focus, eyestrain, squinting, headaches, and the need for increased light. Diplopia can also occur as a result of increasing exophoria and decreased vergence amplitude.

TREATMENT OPTIONS

Optical 

Glasses are the most accessible means of correcting presbyopia, whether they are over the counter glasses or prescription glasses. However, no currently available glasses can fully restore the dynamic range of accommodation.¹⁵ The options range from single vison, bifocals, and trifocals to progressive addition glasses. Compared to single vision glasses, variable lens glasses are generally more expensive and have restricted optical zones, impacting subjective visual experiences while driving and performing work place tasks.^16,17 While a popular and the least invasive means of correcting presbyopia, multifocal glasses may require a learning period with head and body movements to try to focus on objects at different distances. Bifocal and trifocal glasses may contribute to image jumps and distortions. People complain of forgetting to carry glasses, along with cosmetic issues and/ or issues with certain hobbies like sports.

Contact Lenses 

Similarly, multifocal contact lenses may result in visually problematic superimposition of images in low contrast_.18 Multiple viewing zones can reduce image quality and may cause glare, halos, and reduced night-time vision, along with the risk of corneal infections and the hassle of wearing and removing them on a regular basis.¹⁹ 

Contact lens selection and a comprehensive pre-fitting trial are important due to patients relying on lens centration, pupil size, ocular optics, and neural adaptation.²⁰ However, the market share for multifocal contact lenses has grown recently, due to technological advances in lens designs, materials, and manufacturing methods.

Females are more likely to wear contact lenses than males due to cosmetic reasons.

Monovision 

Monovision involves correcting one eye for optimal distance viewing and the other eye for near viewing (Figure 2). It is not suitable for everyone so trialling before prescribing is crucial.²¹ Success with monovision is dependent on suppression of interocular blur. Incomplete suppression may be a safety concern, as it increases the risk of falls.²² Most patients can tolerate anisometropia of up to 1.5D without losing binocular summation.²³ It can be done either by contact lenses or corneal/ lens-based methods, with the trade-off being a reduction in stereopsis and contrast sensitivity.^24,25 It also negatively affects quality of vision at all ranges and depth of perception.²⁶ It is not deemed to be a suitable option for patients in whom binocular vision and depth perception are critical to their career and lifestyle. Epidemiological studies have shown an association between decreased monocular visual acuity and stereoacuity, and an increased risk of falls and hip fractures, especially in the elderly.²⁷

Corneal Options 

Excimer Laser Vision Correction 

Figure 3. (A) PresbyMAX and (B) Presbyond treatments.

Monovision or multifocal laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) can be used to remove and reshape corneal tissue to reduce the need for near vision glasses in presbyopes. Monovision, in which the dominant eye is corrected for distance and the non-dominant eye is usually corrected for near, often results in reduced binocular visual acuity and stereopsis, as noted previously.²⁸ Studies have reported success rates of 80–98% with monovision, using corneal laser vision correction, with good satisfaction.²⁵ Success depends upon ability to suppress interocular blur with anisometropia.

“Non-invasive therapies with newer mechanisms of action are currently being investigated, including miotic agents and UNR844, a lipoic acid choline ester”

Multifocal corneal ablation, known as presbyLASIK, aims to correct vision by changing the refractive power of the cornea. This is acheived by either ablating the peripheral cornea to increase depth of focus (peripheral presbyLASIK) or by creating a bifocal cornea (central presbyLASIK).²⁹

In peripheral presbyLASIK, the peripheral cornea is ablated to create negative spherical asphericity, thereby the central cornea is used for distance vision and the mid-peripheral cornea for near vision (Nidel Advanced Vision Excimer Laser; NIDEK, Gamagori, Japan). In central presbyopic LVC, the central cornea is ablated for near vision and the peripheral for distance vision (Supracor, Technolas Perfect Vision GmbH, Munchen, Germany).

Although results are good, some people find it difficult to tolerate the compromise and minor loss of distance visual acuity.³⁰

Presbyond laser blended vision (Carl Zeiss Meditec, Jena, Germany) is an optimised laser treatment with improved monovision, where the wavefront optimised ablation profile is used to create a continuous refractive power gradient for the whole optical zone of the cornea. Studies have shown good results.³¹

More recently, Schwind eye-tech solutions (Kleinostheim, Germany) introduced PresbyMax software, which uses a biaspherical corneal modulation technique and creates a central hyper-positive area for near vision, leaving the pericentral cornea for far vision. Uthoff et al.³² have reported good visual outcomes after a six-month follow-up period. The PresbyMax suite offers various treatment modes (i.e. monocular, micro-monovision, and hybrid), which vary in the degree of depth of field induced in each eye, helping the surgeon tailor the treatment for each patient’s specific lifestyle requirements.³³

Corneal Inlays 

Corneal inlays consist of a minimally invasive surgical implantation of an inlay into the cornea of one eye, with the advantages being it is reversible and repeatable.¹ With all inlay designs, centration is critical for proper performance. There are three types of corneal inlays; corneal reshaping inlays (Raindrop), refractive inlays, and small aperture inlays (Kamra). The Raindrop Near Vision Inlay was recalled by the FDA in 2018 due to an increased risk of corneal haze seen in patients.³⁴ Kamra (Acufocus, Inc.), an FDA-approved small aperture inlay, has more data supporting its efficacy and safety than any other inlay. Unlike monovision, it does not compromise distance vision, but it can restrict light entering the eye, which may reduce night time vision and contrast. Regression is the most commonly noticed disadvantage with corneal inlays. Most patients feel the need to use glasses again.³⁵ Other reported complications include hyperopic shift, haloes, decrease in photopic and mesopic contrast sensitivity (CS), corneal thinning and melting, and reduced simulated retinal blur in the implanted eye.³⁶

Conductive Keratoplasty 

Conductive keratoplasty uses the application of low frequency radio waves to shrink collagen fibrils within the midperipheral cornea, hence inducing net steepening of the central cornea. Eight to 32 treatment spots are placed with a fine tip inserted in the mid peripheral cornea in up to three rings to create central steepening. Due to high rates of regression, it is not a popular technique at present.³⁷

Lenticular Options 

The increased use of digital devices and increased work/life expectancy of patients has led to increased interest in permanent resolution of presbyopia by various lenticular approaches. Advanced lens designs, along with improved technology and surgical techniques over the past decades, have led to its increased popularity and success.

Refractive lens exchange (RLE), in which the natural lens is replaced with an IOL, can reduce the need for reading glasses by using monovision, EROV, EDOF, multifocal diffractive, or accommodative IOL implants.

Current multifocal IOLs (Figure 4) provide good visual outcomes, with trifocal IOLs providing better near vision in comparison to EDOF IOLs, while providing similar intermediate and distance visual outcomes.³⁸

Diffractive multifocal IOLs are based on the principle of diffraction, whereby light slows down and changes direction when it encounters an obstacle. These IOLs have microscopic steps causing obstacles to light, hence creating distance and near focal points (Figure 5). The amount of light is directly related to the step height as a proportion of wavelength. Most studies report good and stable distance and near vision, leading to low spectacle need and reasonable patient satisfaction.^39,40 These IOLs provide the greatest degree of independence from eyeglasses but they have a lower contrast sensitivity and a higher rate of photic phenomenon, such as glare and halo.

EROV and EDOF-like IOLs can be positioned in between monofocal and multifocal IOLs and work on the principle of providing extended range of vision and/ or depth of focus to help with intermediate vision, with no or minimal compromise in distance visual acuity and low to negligible dysphotopsias specific to the design of EDOF IOLs. This elongated focus is meant to eliminate the overlapping of near and far images caused by traditional multifocal IOLs, hence eliminating the halo effect. There are different optical principles used to create these lenses. Currently available technologies include small aperture, diffractive and non-diffractive.

Small aperture design IOLs include IC-8 (Acufocus, Inc), which blocks unfocussed peripheral light rays via its 3.23mm wide opaque mask while allowing central and paracentral rays through its 1.36mm central aperture.

Patients with unusually large pupils, or in scotopic conditions, might experience increased visual disturbances (halo effect) or a drop in defocus range due to the small diameter of the optic.⁴¹

Recent innovations have given range to enhanced monofocal IOLs, such as the Rayner RayOne EMV IOL. Compared to standard monofocal IOLs, the RayOne EMV IOL provides similar defocus tolerance and improved vision in the intermediate range, although with a higher risk of halos.⁴²

Diffractive optics include the Tecnis Symphony IOL, which is pupil dependent; higher order aberrations (HOA) increase with increasing pupil size and, due to its diffractive design, patients experience glare and halos. It is intended to extend the range of vision by correction of chromatic aberration.

Non-diffractive optics include spherical aberration or refractive segments to increase the depth of focus. The optics of Mini Well IOL (Sifi Meditech Srl), consists of a central zone, with positive spherical aberration, a middle zone of negative spherical aberration, and an outer monofocal zone.⁴³ The other non-diffractive wavefront shaping IOL, Vivity lens (Alcon Laboratories, Inc., Fort Worth, TX, USA), has a unique, central optical part, which allows patients to see well from near to distance. It is based on the non-diffractive X-wave technology, which modifies the wavefront and creates one elongated focus without splitting the light. This helps to avoid dysphotopsia and does not affect contrast sensitivity. It has 1.5D of defocus and negative asphericity (-0.2 microns) of the anterior surface, providing superior intermediate and near vision, and reduced spectacle wear in comparison to a monofocal IOL.

All traditional multifocal IOLs (MIOLS) are based on the concept of rotational symmetry. However, MIOLs with rotational asymmetry were recently introduced (Lentis MPlus LS-312; Oculentis GmbH, Berlin, Germany).

Rotationally asymmetrical MIOLs consist of a single piece, aspherical surface that is independent of pupil size.⁴⁴ Results indicate good distance, intermediate and near visual acuity with no loss of contrast sensitivity.

Accommodating IOLs respond to ciliary body contraction, thus inducing accommodation, although current designs cause some inevitable side effects. New generation accommodating IOLs are under current investigation. A light adjustable lens is another recent development, which allows postoperative titrations in IOL power after the eye has settled, thereby facilitating customisation and optimisation of the lens to get the desired prescription.

Lens filling techniques have been under investigation for years, with no published reports to date. The concept uses replacement of the rigid lens with a soft gel, which would allow the shape to be modified for accommodation. The Medennium SmartLens IOL (Medennium, Irvine, California, USA), is a smart hydrophobic acrylic material with unique thermodynamic properties. When implanted into the capsular bag, the body’s temperature causes the material to transform into a gel-like polymer that takes the shape of the natural lens.

POST-KERATOREFRACTIVE PRESBYOPIA

Previous corneal refractive surgery is not an absolute contraindication for presbyopia correcting IOLs, but it does pose several challenges that require additional evaluation and patient counselling.

The IOL power calculation and preoperative corneal assessment is a must to check for any pre-existing corneal aberrations and/ or dry eyes, which may produce unwanted light scatter and dysphotopsias. Routine intraocular examination is also essential.

Larger pupils and irregular pupils are prone to higher order abberations. De Vries et al.⁴⁵ found larger pupils of 5.18mm at low mesopic conditions had more dissatisfaction with their overall results. A larger angle kappa >0.4mm (i.e. the angle between visual axis and pupil centre) and angle alpha >0.5 mm (i.e. the angle between visual axis and limbal centre) may increase the risk of a decentred MIOL, resulting in poorer outcomes with halos and glare.

Corneal refractive surgery alters natural corneal aberration and, generally speaking, aspheric IOL implants with negative spherical aberration are better suited for virgin or post-myopic surgery corneas. Conversely, spherical IOL implants with positive spherical aberration are better for hyper prolate and post-hyperopic surgery corneas.^46,47 In our case series, we found coma of more than +-0.20microns caused reduced contrast sensitivity following cataract surgery in patients with prior radial keratotomy.⁴⁸

Presbyopia correcting IOLs with nondiffractive optics, or postoperatively modifiable IOL technology (when available), may be used in motivated patients undergoing lenticular surgery with proper preoperative counselling.

LENS SOFTENING

There have been some pharmaceutical attempts to selectively act on the less elastic presbyopic crystalline lens and soften it, however, this is currently not a viable alternative. The femtosecond laser has been successfully trialled, in human cadaver and animal lenses,^49,50 to restore flexibility by making precise incision patterns without opening the lens capsule and without producing cataract. However, to the knowledge of the author, no human data has yet been reported.

PHARMACOLOGICAL TREATMENTS

Pharmacological treatments are a new alternative that expand the diversity of current treatment approaches for managing presbyopia. Currently, there are three different strategies. The first one aims to produce miosis and increase depth of focus through pinhole effect. The second aims to restore lens elasticity and finally, the third is based on restoring accommodation.

Traditionally, no medical treatment was available, but recently, the United States Food and Drug Administration approved pilocarpine 1.25% for topical instillation to treat presbyopia. Studies found that subjects report improvement of up to three lines in near and intermediate vision in low light conditions without a loss of >1 line in distance visual acuity. The effect starts within 15 minutes of instillation and lasts for six hours. Mild headaches, blurred vision, eye pain, and eye redness have been reported.⁵¹ A recent non-randomised eight-year retrospective study found that pilocarpine/ diclofenac eye drops were an efficient treatment for emmetropic or presbyopic individuals, providing spectacle independence for near visual tasks.⁵² The rationale is to increase depth of field by parasympathetic-mediated miosis and ciliary muscle stimulation. The other pharmacologic option includes softening the lens to temporarily ameliorate the symptoms of presbyopia.⁵³ A combination of carbachol and brimonidine has been shown to provide a longer-lasting effect to correct presbyopia than pilocarpine.⁵⁴

Other drugs are under investigation to help treat the underlying causes of presbyopia, including age-related lens stiffness and associated increases in lens disulfide content.¹⁰ Such an approach does seem to be a promising alternative to presbyopia correcting lenses and laser and/or other surgical approaches. If successful, this would mark a huge milestone in the management of presbyopia. However, none of these are sufficiently developed to become routine interventions.

EXPERIMENTAL TECHNIQUES

Other experimental techniques include anterior sclerotomy, in which radial incisions are made around the anterior sclera; and segmental scleral expanders, in which physical implants are inserted to expand the sclera.⁵⁵

Scleral approaches are based on Schachar’s theory of accommodation and attempt to preserve or restore the accommodative ability of the eye by expanding the equatorial scleral diameter overlying the ciliary body and restoring zonular tension. Despite controversial theoretical justification of these techniques, there has been increasing interest in these interventions.

CONCLUSION

Presbyopia is a common, inevitable condition with increasing prevalence in a globally growing population with expanding life expectancy. There have been significant developments in treatment modalities for presbyopia over  the past few years, achieving relatively good outcomes. Each one has its own advantages and disadvantages, and some compromise must be made. There is no one size fits all treatment available.

The emergence of new technologies and options will make it easier to quantify accommodation more precisely, and therefore help in choosing the ideal strategy for each patient according to his or her needs. Uncorrected presbyopia can significantly affect patients’ daily activities, productivity and quality of life. A unique and ideal solution, or a treatment that restores true dynamic accommodation or behaves in a similar way to the natural lens, is now becoming a necessity rather than a lifestyle ‘nice to have’.

“The increased use of digital devices and increased work/life expectancy of patients has led to increased interest in permanent resolution of presbyopia by various lenticular approaches”

 

Associate Professor Smita Agarwal MBBS MS(Ophth.) Grad Dip in Refractive Surgery (USyd) FRANZCO is a senior comprehensive ophthalmologist based on the South Coast of New South Wales. She is also a Clinical Associate Professor at the Graduate School of Medicine, University of Wollongong and a Senior Lecturer at the University of Sydney. Assoc Prof Agarwal specialises in cataract and refractive surgery and has special interest in corneal cross-linking for progressive keratoconus, glaucoma and age-related macular degeneration. Over the years, she has published several research papers in peer-reviewed journals locally and overseas. She has been an invited speaker at prestigious ophthalmology meetings and seminars nationally and internationally.

 

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