A Novel Pharmacological Treatment of Pseudophakic Presbyopia

Almamoun Abdelkader

Almamoun Abdelkader, MD, Department of Ophthalmology, Faculty of medicine, Al-Azhar University, Cairo, Egypt

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Almamoun Abdelkader, MD, Assistant professor of ophthalmology, Faculty of Medicine, Al-Azhar University. Consultant of cornea and refractive surgery, Head of Ophthalmology Department, Saudi German Hospital, Aseer, Kingdom of Saudi Arabia, P.O Box 2553.
Email: mamounkader@gmail.com
Telephone: +(+966) 17 235 5000
Fax: +(+966) 17 2354500

Received: October 6, 2018
Revised: December 10, 2018
Accepted: December 13, 2018
Published online: December 31, 2018


AIM: To evaluate the efficacy of using a parasympathomimetic drops (carbachol) together with an alpha agonist (brimonidine) to create beneficial miosis aiming to ameliorate the effect of presbyopia in pseudophakic subjects.

METHODS: A prospective, double-masked, randomized, placebo-controlled clinical trial. Forty emmetropic and presbyopic pseudophakes between 30 years and 80 years old with an uncorrected distance visual acuity of at least 20/20 in both eyes without additional ocular pathology were eligible for inclusion. Subjects were divided into 2 groups. Treatment group (n = 25 eyes) received single dose of 3% carbachol combined with 0.2% brimonidine eye drops in their non-dominant eyes. Control group (n = 15 eyes) received placebo drops. Initial pupil size and both near and distance visual acuities were measured before treatment and at 1, 2, 4 , and 8 hours after treatment by the same independent examiner at the same room illumination.

RESULTS: Statistically significant improvement in near visual acuity was achieved in all pseudophakic subjects who received carbachol plus brimonidine drops (p < 0.0001). All subjects were satisfied with the drops and none liked the placebo.

CONCLUSIONS: Making the pupil small creates a pinhole camera like effect which safely improves near visual acuity in pseudophakic candidates through increased depth of focus.

Key words: Presbyopia; Pseudophakia; Carbachol; Brimonidine; Depth of focus; Miosis

© 2018 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Abdelkader A. A Novel Pharmacological Treatment of Pseudophakic Presbyopia. International Journal of Ophthalmic Research 2018; 4(2): 291-294 Available from: URL: http://www.ghrnet.org/index.php/ijor/article/view/2442


Near vision can be improved by increasing the depth of focus as well as by increasing the accommodation. Increased depth of focus can come from making the pupil smaller like a smaller aperture in a camera. Corrective lenses and invasive procedures are common traditional ways for correcting presbyopia. Invasive procedures involve different approaches on the cornea (inlays), the crystalline lens and the sclera. There still remains a need for new non-invasive ways of reducing presbyopia for patients that do not like to undergo invasive procedures or use corrective lenses.

Presbyopia symptoms are present in patients after cataract lens extraction. Methods of corrections of pseudophakic presbyopia primarily include: (1) implantation of multifocal and accommodative intraocular lens (IOLs); (2) pseudophakic monovision induced by monofocal IOLs[1] and (3) corneal inlays. The KAMRA (AcuFocus, Irvine, California, USA) corneal inlay creates a pinhole-type effect that increases the depth of focus and improves near visual acuity[2-7]. I attempt here with drops to approach this goal without surgery.

I present here a non-invasive alternative which is a pharmacological treatment to improve near vision in presbyopic pseudophakes by means of ophthalmic drops which contain two drugs: a parasympathomimetic (3% Carbachol) and an alpha agonist agent (0.2% brimonidine) (treatment group). Placebo eye drops were used in some subjects as a control. The aim of this pilot study is to evaluate in a masked fashion the efficacy of using a parasympathomimetic drug together with an alpha agonist to temporarily improve near vision in pseudophakic subjects by increasing the depth of focus.


This study was begun after approval was obtained from The RCRC Independent Review Board, LLC 2111 West Baker Lane, Suite 400 Austin, Texas 78758. Written informed consent was obtained from each participant, and the study followed the tenets of the Declaration of Helsinki. The pharmacological stimulation protocol was developed in accordance with that used previously in the invention of Dr. Herbert Kaufman[8].

Study participants were randomly selected volunteers. Presbyopia was considered present if an uncorrected end-point print size ≥ Jaeger (J) 5 improved by ≥ 1 optotype with the use of a lens ≥ +1.00 D. All pseudophakic subjects were screened to be in good physical and ocular health. Dilated fundus examination was performed for all subjects before they are considered eligible for the study. The examination screened for contraindications to the drops and susceptibility to retinal detachment. Inclusion criteria were as follows: age between 30 and 80 years, emmetropic pseudophakes[cycloplegic spherical equivalent (SE), ± 0.25 D; astigmatism, ≤ 0.25 D], round pupil, good position of the implant and binocular uncorrected distance visual acuity ≥ 20/20. Exclusion criteria included patients with refractive errors higher than 0.25 diopter as well as those with ocular meadia opacities, pupil irregularities, and drugs that would potentially interact with carbachol and brimonidine.


A single dose of 3% carbachol combined with 0.2% brimonidine, or placebo was instilled in a masked fashion in the non-dominant eye of the subjects. Initial pupil size and both near and distance visual acuities were documented before treatment and at 1, 2, 4 , and 8 hours after treatment by the same independent examiner at the same room illumination.. Distance visual acuity was measured using the standard Snellen projector chart at 4 meter. Near visual acuity (NVA) was measured at 40 cm using a hand-held Rosenbaum chart with Jaeger notation, always employing the same luminosity of 160 cd/m2. Pupil size (PS) was measured using Colvard handheld Infrared pupillometer (Oasis Medical, Glendora, CA, USA). Any adverse symptoms and subject satisfaction with near and distance vision were also monitored.

Statistical analysis

Data analysis was carried out with the Mann-Whitney U test, using MedCalc version 16.8 statistical software. P value of less than 0.05 was considered statistically significant. Data were expressed as mean, range, and standard deviation (SD).


Forty emmetropic and presbyopic pseudophakes between 30 years and 80 years old with an uncorrected distance visual acuity of at least 20/20 in both eyes were included in the study. The mean age of the treatment group (n = 25 eyes) was 54.21 ± 14.49 years (range, 30-80 years); 16 males and 9 females. The mean age of the control group (n = 15 eyes) was 54.42 ± 3.1 years (range, 40-75 years); 10 males and 5 females. No statistically significant difference in mean age or sex was found among the 2 groups.

In the treatment group, the mean near visual acuity (NVA) improved significantly from J-7.5 ± 1 before treatment to J- 1.42 ± 0.5 at 1 hour, J- 1.57 ± 0.5 at 2 hours, J- 2.14 ± 0.5 at 4 hours and J- 2.35 ± 0.49 at 8 hours posttreatment (p < 0.0001). The mean pupil size (PS) decreased significantly from 4.1 ± 0.5 mm before treatment to 1.2 ± 0.3 mm at 1 hour, 1.6 ± 0.3 mm at 2 hours, 2 ± 0.2 mm at 4 hours and 2.5 ± 0.4 mm at 8 hours posttreatment (p < 0.0001).

Placebo (control) group

No statistically significant difference in mean (NVA) or mean pupil size was found in this group before treatment and at any time point after treatment. Data are summarized in table 1. Figures 1 and 2 show the mean changes in near visual acuity (Jaeger) and pupil size (mm) respectively over time for treatment and control groups.

Distance visual acuity

The uncorrected distance visual acuity was 20/20 of both eyes in all subjects before treatment and remained at 20/20 at all time periods following treatment.

Groups' satisfaction

Carbachol plus brimonidine group (treatment group)

All subjects who received carbachol plus brimonidine would use this drops if it were available. They showed satisfaction with both near and distance vision. 8 subjects out of 25 (32%) reported that the effect was excellent for the first 8 hours then gradually faded. No subject in the treatment group reported headache, dimness, browache or burning sensation.

Placebo group

All subjects who received placebo reported that the drops did not improve their near vision, so that, they would discontinue using the drops.

Figure 1 Distribution of mean change in near visual acuity (Jaeger) over time for treatment and control groups.

Figure 2 Distribution of mean change in pupil size (mm) over time for treatment and control groups.

Table 1 Mean change in near visual acuity (NVA) (J) and pupil size (PS) (mm) overtime using 3% Carbachol plus 0.2% brimonidine drops vs placebo.
Time (Hrs)  Carb+Brim dropsPlaceboP value
1- hourNVA1.46.5< 0.0001
PS1.23.9< 0.0001
2- hourNVA1.56.8< 0.0001
PS1.63.9< 0.0001
4- hourNVA2.16.8< 0.0001
PS1.93.9< 0.0001
8- hourNVA2.36.8< 0.0001
PS2.54< 0.0001


This pilot study aimed at pharmacologically improving near vision in pseudophakic subjects. Rather than improving presbyopia using corrective lenses; pharmacologic treatment relies on the pinhole effect - increasing depth of focus. The principle is being successfully applied in corneal inlays implanted in the non-dominant eye to enhance near vision through increased depth of focus. Although there are some concerns with centering the implant and Pulfrich effect, it is clear that the principle of a small pupil that follows eye movement can improve near vision and preserve distance vision as well[7,9,10]. I attempted with drops to target this effect without invasive interference.

Significant improvement in near visual acuity was found in all subjects who received 3% Carbachol and brimonidine compared to placebo (p < 0.0001).

The present study used 3% carbachol and an alpha agonist (0.2% brimonidine) to improve vision in pseudophakic presbyopes through increased depth of focus by making the pupil smaller. Both drugs are FDA approved and have been used for years as safe and effective treatment for glaucoma. Brimonidine has been effectively used to decrease pupil dilatation under scotopic conditions, and thereby reduces scotopic symptom after laser refractive surgeries.

In monocular treatment, the vision in the fellow eye with the normal untreated pupil will have some blurry near vision, but distant objects are clear and there is no diminished light perception. When the images are merged, all subjects of treatment group had clear vision at both near and distance without having dimness. Carbachol and brimonidine can be used once daily to achieve an 8-hour effect.


The topical treatment of pseudophakic presbyopia using one drop a day of carbachol combined with brimonidine, offers acceptable reading vision for many pseudophakic candidates. Additional studies are planned in the future to use this topical therapy in presbyopia with different refractive errors.


Herbert E. Kaufman was the primary researcher in the development of the study, contributed to data interpretation and took part in the manuscript preparation.


1. Charman WN. Developments in the correction of presbyopia II: surgical approaches. Ophthalmic Physiol Opt 2014; 34(4): 397-426.[DOI: 10.1111/opo.12129]; [PMID: 24716827]

2. Seyeddain O, Hohensinn M, Riha W, Nix G, Rückl T, Grabner G, Dexl AK. Small-aperture corneal inlay for the correction of presbyopia: 3-year follow-up. J Cataract Refract Surg. 2011; 38(1): 35-45.[DOI: 10.1016/j.jcrs.2011.07.027]; [PMID: 22018596]

3. Seyeddain O, Riha W, Hohensinn M, Nix G, Dexl AK, Grabner G. Refractive surgical correction of presbyopia with the AcuFocus small aperture corneal inlay: two-year follow-up. J Refract Surg. 2010; 26(10): 707-15. [DOI: 10.3928/1081597X-20100408-01]; [PMID: 20438021]

4. Dexl AK, Seyeddain O, Riha W, Hohensinn M, Rückl T, Reischl V, Grabner G. One-year visual outcomes and patient satisfaction after surgical correction of presbyopia with an intracorneal inlay of a new design. J Cataract Refract Surg. 2012; 38(2): 262-9. [DOI: 10.1016/j.jcrs.2011.08.031]; [PMID: 22138501]

5. Tabernero J, Schwarz C, Fernández EJ, Artal P. Binocular visual simulation of a corneal inlay to increase depth of focus. Invest Ophthalmol Vis Sci. 2011; 52(8): 5273-7. [DOI: 10.1167/iovs.10-6436]; [PMID: 21436279]

6. Fernández EJ, Schwarz C, Prieto PM, Manzanera S, Artal P. Impact on stereo-acuity of two presbyopia correction approaches: monovision and small aperture inlay. Biomed Opt Express. 2013; 4(6): 822-30. [DOI: 10.1364/BOE.4.000822]; [PMID: 23761846]; [PMCID: PMC3675862]

7. Naroo SA, Bilkhu PS. Clinical utility of the KAMRA corneal inlay. ClinOphthalmol. 2016; 10: 913-9. [DOI: 10.2147/OPTH.S89132]; [PMID: 27274194 ]; [PMCID: PMC4876093]

8. Kaufman HE. Preparations and methods for ameliorating or reducing presbyopia. US patent number 8455494 B2.

9. Huseynova T, Kanamori T, Waring GO 4th, Tomita M. Small-aperture corneal inlay in presbyopic patients with prior phakic intraocular lens implantation surgery: 3-month results. ClinOphthalmol. 2013; 7: 1683-6.[DOI: 10.2147/OPTH.S50397]; [PMID: 24003304]; [PMCID: PMC3755705]

10. Huseynova T, Kanamori T, Waring GO 4th, Tomita M. Outcomes of small aperture corneal inlay implantation in patients with pseudophakia. J Refract Surg. 2014; 30(2): 110-6.[DOI: 10.3928/1081597X-20140120-06]; [PMID: 24763476]

Peer Reviewer: Muawyah Al Bdour


  • There are currently no refbacks.