Non-surgical presbyopia treatment methods

Corrective eyeglasses are the most commonly used method of presbyopia treatment. One alternative to monofocal near-vision eyeglass lenses are bifocal lenses, comprising two areas with different optical powers, for distance vision (top and central segment) and for near vision (lower segment). The lower segment may be circular or semi-circular, with a clear split line. Progressive lenses use something called a “transition channel”, with a seamless progression of lens power for clear vision at any distance. In some cases, progressive lenses cannot be used or are less comfortable, and so it is really important to talk about each patient’s individual needs when making the choice. Semiprogressive lenses may be a good alternative for those who work a lot at near and intermediate vision distances.

Monovision is a technique for presbyopia correction used in contact lenses, refractive surgery, and cataract surgery. It involves the deliberate creation of anisometropia, or unequal optical power, so that one eye is corrected for distance, and the other — for near vision. The natural configuration, with the dominant eye set for distance vision and the non-dominant eye for near vision, is most commonly used. Alternatively, crossed monovision may be used, with the non-dominant eye corrected for distance and the dominant eye corrected for near vision, but this is much less common. Historically, monovision involved establishing anisometropia of more than 2 diopters (D), but such a large difference was unacceptable to many patients due to problems with differences in the perceived size of images from each eye (aniseikonia) and loss of stereopsis, i.e. depth perception. With mini-monovision, resulting in anisometropia of 1.0–1.5 D, or micro-monovision (anisometropia below 1 D), stereopsis is affected to a much lesser extent. Thus, the methods are well tolerated by the vast majority of patients. Micro-monovision does not allow for dispensing with reading glasses altogether, but limits the need to use them, e.g. just to reading very small print.

With contact lenses , options include monovision and multifocal lenses. Multiple focal points in contact lenses can be achieved by making them segmented or concentric. Segmented contact lenses have a near vision area in the bottom part, similarly to progressive eyeglass lenses. Concentric multifocal contacts can be adjusted for near vision in the central zone and for distance vision in the peripheral zone (N-lens), or for distance vision in the center and for near vision in the periphery (D-lens). Currently, concentric contact lenses with near addition in the center are commercially available. To optimize near vision in patients with presbyopia, various configurations of lenses may be used:
– multifocal lenses on both eyes
– monofocal lens on the dominant eye, monofocal lens for near vision on the non-dominant eye (monovision)
– monofocal lens on the dominant eye, multifocal lens on the non-dominant eye
– any of the above optionally combined with near-vision eyeglasses used for a limited number of activities (e.g. precision work).

Richdale et al. compared quality of vision in patients using contact lenses for presbyopia correction. Their study included 38 patients randomly assigned to one of two groups. Patients in group one received a monofocal lens with distance correction for the dominant eye, and a monofocal lens with near correction (full addition) for the non-dominant eye. In the other group, patients requiring addition up to +1.5 D received a low-add multifocal lens for each eye, and those requiring addition between +1.75 D and +2.25 D received a low-add lens a low-add multifocal lens for the dominant eye and a high-add lens for the non-dominant eye. After one month, patients in group one switched to multifocal lenses and patients in group two switched to monovision with monofocal lenses, following the same protocol. Under high-contrast conditions, patients in both groups retained full distance visual acuity. Under low-contrast conditions, all patients lost less than 1 line of distance visual acuity when using the contact lenses. Under the same conditions, patients with monovision lost 2 symbols, and those with multifocal lenses — 6 symbols for near vision. Stereoacuity was worse by 79 arc seconds in the monovision group. Patients in both groups reported more satisfaction in terms of appearance, but poorer quality of vision and more dysphotopsias in the National Eye Institute Refractive Error Quality of Life (NEI-RQL) survey. 76% patients preferred multifocal lenses, and only 24% preferred monovision. One conclusion of the study was that multifocal lenses offer good visual acuity without a loss of stereoacuity.

Experimental non-surgical methods

Another presbyopia correction method involves the use of lenses with an extended depth of focus (EDOF - Extended Depth of Focus).). This model is often used in premium intraocular lenses (IOLs). In the study by Bakaraju et al., 43 patients with presbyopia used AirOptix Aqua Multifocal (Alcon Laboratories, USA), Acuvue Oasys for Presbyopia (Johnson & Johnson Vision Care, USA), ), and prototype EDOF contact lenses for a week. The researchers assessed distance, intermediate, and near visual acuity under high- and low-contrast conditions. They also used a survey for patients to evaluate quality of vision, dysphotopsias, and satisfaction with vision. Under high-contrast conditions, visual acuity at all evaluated distances was better with EDOF lenses. These lenses also offered better stereopsis. Under low-contrast conditions, contrast sensitivity was lower than in the case of AirOptix Aqua Multifocal lenses AirOptix Aqua Multifocal. In the subjective survey, patients reported better quality of vision with EDOF lenses compared to Acuvue Oasys at each distance evaluated, and compared to AirOptix at near and intermediate distances. Patient satisfaction was significantly higher when using EDOF lenses. Furthermore, laboratory studies demonstrated that image quality with an EDOF lens is less dependent on changes in pupil size, total eye aberration, and lens decentration than in the case of other available multifocal lenses. EDOF contact lenses are not yet commercially available.

An alternative concept of presbyopia correction involves exercising the ciliary muscle to help restore its function. Gualdi et al. investigated ciliary muscle electrostimulation to restore accommodation in patients with presbyopia.6 The study included patients aged 40–51 with emmetropia, requiring an addition between +0.75 and +1.5 Dsph. The intervention group included 27 patients, and the control group — 13. Patients in the intervention group underwent eight-minute sessions of bilateral pulsed electrostimulation with a 26 mA current every 2 weeks. A total of 4 electrostimulation sessions were provided. Uncorrected distance visual acuity did not change in either group. However, after the second session, uncorrected near visual acuity, both monocular and binocular, improved in the intervention group. The number of words read per minute was also higher in the intervention group than in controls. No adverse effects of the treatment were observed. After the study, 18 patients (66.7%) reported being very satisfied with the treatment, and only 1 patient (3.7%) was dissatisfied. Based on these observations, the authors concluded that ciliary muscle electrostimulation is safe and allows for short-term restoration of accommodative ability in patients with presbyopia.

Pharmaceutical treatment of presbyopia

Various combination of pharmaceuticals administered into the conjunctival sac have been described that could improve accommodation and thus allow patients to dispense with reading glasses. This can be achieved by narrowing the pupil, stimulating the ciliary muscle, or increasing lens flexibility.

Pharmaceutical pupil constriction and ciliary muscle stimulation

It is generally known that reducing the diameter of the pupil is one way of increasing the depth of focus in the eye’s optical apparatus. Multiple studies on pharmaceutical presbyopia treatment involved stimulating the parasympathetic system with the use of widely known pharmaceuticals. First attempts to correct presbyopia in this way involved the use of muscarinic receptor agonists, which cause ciliary muscle contraction and relaxation of the ligament system, thus increasing the sphericity of the lens, and a contraction of the pupillary sphincter, leading to depth of focus extension. In 2012, Benozzi et al. presented findings from their 5 years of research. They investigated the impact of 1% pilocarpine and 0.1% diclofenac on accommodation in patients above the age of 40. The study group included 100 patients aged between 45 and 50 years, with no ophthalmic or systemic comorbidities. According to the authors, the combination of a non-steroidal anti-inflammatory drug (NSAID) with the muscarinic receptor agonist reduced the intensity of miosis and ciliary muscle spasm, thus preserving the lens’ ability to change its thickness and position, required for sharp vision at different distances. This allowed for obtaining good near visual acuity without adversely affecting distance vision. In turn, long-term muscarinic receptor stimulation without an NSAID prompts a localized inflammatory reaction in the anterior segment of the uvea, potentially inducing the formation of posterior adhesions, causing a fixed pupil, pigment dispersion, and refractive error change toward myopia. Based on their 5 years of research, the authors suggested that the above-mentioned combination of drugs can be used on an ongoing manner, with a very good impact on accommodation and no significant adverse effects. Throughout the follow-up period, all patients retained unchanged distance visual acuity.

In 2013, Patel et al. presented a paper evaluating the effects of muscarinic receptor agonists combined with an NSAID in a group of 15 patients. They reported pupil size reduction from 4.1 to 2.7 mm, uncorrected distance visual acuity improvement from 0.8 to 1.0, and uncorrected near visual acuity improvement from 0.54 to 0.8. The authors emphasized that the addition of the NSAID prolongs the effects of the primary drug by inhibiting prostaglandin synthesis in the anterior segment of the uvea.

In 2015, a paper on pharmaceutical presbyopia treatment was published by Abdelkader. His study included 48 patients without a concurrent refractive error, aged between 43 and 56 years (30 subjects and 18 controls). The purpose of the study was to evaluate the effectiveness of a muscarinic receptor agonist — 2.25% carbachol — and an α2-adrenergic agonist — 0.2% brimonidine — administered once daily into the conjunctival sac of the non-dominant eye. Parasympathetic receptor stimulation caused a temporary depth of focus increase through pupil constriction and a temporary improvement of near visual acuity both in patients above 40 and in those above 50 years of age. The authors presumed that the addition of an α2 agonist enhanced and prolonged the therapeutic effect of the muscarinic receptor agonist. All treated patients dispensed with reading glasses and declared they would be willing to use the eye drops in the long term if such a treatment became generally available. No patients in the placebo group reported improvement, reduced use of reading glasses, or willingness to continue the treatment. Uncorrected distance visual acuity remained unchanged in both groups throughout the study. Notably, this local treatment with carbachol and brimonidine did not produce any adverse effects.

The purpose of the pilot study by Renna et al., published a year later, was to evaluate the efficacy and safety of eye drops combining multiple pharmaceuticals. The study included 14 patients (28 eyes) and involved administering eye drops containing 0.247% pilocarpine, 0.78% phenylephrine, 0.09% polyethylene glycol, 0.023% nepafenac, 0.034% pheniramine, and 0.003% naphazoline into the conjunctival sacs of both eyes. The authors decided to administer the combination of these ingredients to both eyes so as to retain the natural changes in pupil size and avoid vision deterioration under poor lighting conditions. Pilocarpine is a parasympathomimetic which induces pupil constriction through a contraction of the pupillary sphincter and the longitudinal fibers of the ciliary muscle. Phenylephrine, pheniramine, and napafenac prevent excessive miosis and ciliary muscle over-contraction caused by pilocarpine, whereas naphazoline enhances the relaxing effect of pilocarpine on the pupillary dilator muscle while reducing its side effects and minimizing redness. The authors emphasized the synergistic effect of the ingredients, producing an initial improvement of uncorrected near visual acuity by 2–3 lines, compared to visual acuity before administration of the eye drops. As in the study by Abdelkader, distance visual acuity remained unchanged. Findings from major studies are shown in Table 1. More details are listed in Tables 2 and 3.

 

 

Table 2. Review of studies evaluating the effectiveness of pharmacological agents in the treatment of presbyopia 

Table 3. Clinical trials evaluating various pharmacological compounds in the treatment of presbyopia registered at ClinicalTrials.gov.

 

Pharmaceutical stimulation of lens flexibility

An entirely different approach to pharmaceutical treatment of presbyopia has been presented by Encore Vision, whose phase 1/2 clinical trial included 75 patients aged between 45 and 55 years, randomized to receive either 1.5% lipoic acid choline ester (EV06) (Fig. 1) or placebo twice a day. EV06 is a prodrug which penetrates the cornea of the eye, transforms into lipoic acid and choline, and then enters the crystalline lens, where it transforms into active dihydrolipoic acid and breaks disulfide bonds. This acid, through its action on disulfide bonds, affects lens flexibility, making it softer and naturally more pliable just 8 days after local administration. Lipoic acid choline ester at a 1.5% concentration is expected to reverse the adverse changes in the crystalline lens resulting from natural aging processes and the effects of sunlight. The authors reported that the use of eye drops with this composition may delay or even reverse sclerotic processes responsible for the development of nuclear cataracts and presbyopia. Their results are very promising, showing that as many as 84% of patients gained at least 1 line of near visual acuity, 53% — 2 or more lines, 22% — 3 lines, and 12% — 4 lines after 90 days, compared to their reading-distance visual acuity at the beginning of the trial. Safety assessment for the tested medication did not reveal any significant adverse effects or intolerances resulting in exclusion from the study.

Pharmaceutical methods of presbyopia treatment remain a novel topic in ophthalmology. Few publications and the limited number of patients having undergone such treatments make it difficult to form conclusions on the subject. Published studies show that even single-agent treatment with one of the widely known pharmaceuticals commonly used for other ophthalmic conditions, administered once daily into one eye, may significantly improve near visual acuity even in older patients with advanced presbyopia. Based on an analysis of results from studies presented above, eye drops affecting the physiology and flexibility of the lens seem a more promising option due to their long-term effects and a high safety level. In summary, it seems that the large prevalence of presbyopia should prompt researchers to intensify efforts to find new, effective, non-invasive treatment methods that would significantly improve quality of life in the large population of patients with this condition.

Fig. 1

Literature

  1. Finkelman YM, Ng JQ, Barrett GD. Patient satisfaction and visual function after pseudophakic monovision. J Cataract Refract Surg. 2009;35(6):998-1002.
  2. Zhang F, Sugar A, Arbisser L, Jacobsen G, Artico J. Crossed versus conventional pseudophakic monovision: Patient satisfaction, visual function, and spectacle independence. J Cataract Refract Surg. 2015;41(9):1845-1854.
  3. Richdale K, Mitchell GL, Zadnik K. Comparison of multifocal and monovision soft contact lens corrections in patients with low-astigmatic presbyopia. Optom Vis Sci. 2006;83(5):266-273.
  4. Bakaraju RC, Tilia D, Sha J, et al. Extended depth of focus contact lenses vs. two commercial multifocals: Part 2. Visual performance after 1 week of lens wear. J Optom. 2018;11(1):21-32.
  5. Bakaraju RC, Ehrmann K, Ho A. Extended depth of focus contact lenses vs. two commercial multifocals: Part 1. Optical performance evaluation via computed through-focus retinal image quality metrics. J Optom. 2018;11(1):10-20.
  6. Gualdi L, Gualdi F, Rusciano D, et al. Ciliary Muscle Electrostimulation to Restore Accommodation in Patients With Early Presbyopia: Preliminary Results. J Refract Surg. 2017;33(9):578-583.
  7. Benozzi J, Benozzi G, Orman B. Presbyopia: a new potential pharmacological treatment. Med Hypothesis Discov Innov Ophthalmol. 2012;1(1):3-5.
  8. Schalnus R, Schalnus R. Topical Nonsteroidal Anti-Inflammatory Therapy in Ophthalmology. Ophthalmologica. 2003;217(2):89-98.
  9. Patel S Salamun. Pharmacological correction of presbyopia. In: Poster Presented at the XXXI Congress of the ESCRS, Amsterdam. ; 2013. http://escrs.org/amsterdam2013/programme/posters-details.asp?id=19804.
  10. Abdelkader A. Improved Presbyopic Vision With Miotics. Eye Contact Lens. 2015;41(5):323-327.

Polish “Presbyopia 21” Club section

The Polish “Presbyopia 21” Club was established in April 2016 in Poznań, Poland, by Professor Andrzej Grzybowski. The creation of this first-ever Polish group of experts on presbyopia was motivated by the ophthalmologic community’s virtually unanimous view that access to reliable knowledge on modern presbyopia correction methods was insufficient.

The club brings together Polish and international ophthalmology practitioners and professors interested in modern methods for presbyopia correction.

The Foundation for the Development of Ophthalmology “OPHTHALMOLOGY 21”

Adam Mickiewicz Street 24/3b
60-836 Poznań
Greater Poland Voivodeship
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