5,557

Influence of Different Concentrations of Carbachol Drops on the Outcome of Presbyopia Treatment – A Randomized Study

Almamoun Abdelkader1, MD

1 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, 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.
Email: mamounkader@gmail.com
Telephone: +(966) 557797107
Telephone: +(966) 17 2354500

Received: May 12, 2019
Revised: July 10, 2019
Accepted: July 14, 2019
Published online: September 18, 2019

ABSTRACT

AIM: To evaluate and compare in a masked fashion the influence of using two different concentrations of carbachol drops on the outcome of presbyopia treatment.

Methods: A prospective, double-masked, randomized study. 57 emmetropic and presbyopic subjects aged between 44 and 60 years 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. Group 1 (n = 32 eyes) received single dose of 2.25% carbachol plus 0.2% brimonidine eye drops. Group 2 (n=25) received single dose of 3% carbachol plus 0.2% brimonidine eye drops. The subjects’ pupil size and both near and distance visual acuities were evaluated before and after treatment at 1, 2, 4, 8 and 12 hr, by a masked examiner at the same room illumination.

Results: Statistically significant improvement in mean near visual acuity (NVA) was achieved in all subjects who received both concentrations of carbachol plus brimonidine drops (p < 0.0001). Significant and sustained improvement in mean NVA was reported in higher concentrations of carbachol drops than in lower concentrations (p < 0.0001). No serious adverse ocular effects were observed in any of the subjects of both groups.

Conclusion: Based on the data, higher concentration of carbachol was found to be safe and provided greater efficacy in improving near visual acuity than lower concentration with prolonged duration of action.

Key words: Presbyopia, Carbachol; Brimonidine; Depth of focus

© 2019 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Abdelkader A. Influence of Different Concentrations of Carbachol Drops on the Outcome of Presbyopia Treatment - A Randomized Study. International Journal of Ophthalmic Research 2019; 5(1): 317-320 Available from: URL: http://www.ghrnet.org/index.php/ijor/article/view/2584

BACKGROUND

Presbyopia refers to age-related visual disorder that results in a progressive impairment of near-focusing ability. This process usually becomes perceptible in emmetropic populations above 40 years old[1]. Presbyopia is manifested as blurry vision and fatigue when targeting near objects[2,3]. The treatment of presbyopia has been the focus of several studies over recent years due to the desire for spectacle independence. The decline in amplitude of accommodation has been attributed to increased lens nucleus hardness and inelasticity of lens capsule. Moreover, the function of the ciliary muscle is often reduced[4,5]. Many lens and nonlens-based approaches have been investigated to treat presbyopia and improve near visual acuity. Near visual acuity can be improved by increasing the depth of focus as well as accommodation. Increased depth of focus can be created from making the pupil smaller. Wearing corrective lenses including pinhole spectacles was a traditional way to improve near vision in presbyopes through increased depth of focus. The KAMRA (AcuFocus, Irvine, California, USA) corneal inlay is designed to create a pinhole-type effect that increases the depth of focus and improves near visual acuity in presbyopes without a detrimental change in distance vision[6-11]. I attempted to use drops to approach this effect but in a noninvasive way. Carbachol stimulates the muscarinic and nicotinic receptors on the iris sphincter muscle and creates optically beneficial miosis to pharmacologically enhance near vision in presbyopics through increased depth of focus. Brimonidine reduces activity of the dilator muscle and thereby producing a more miotic pupil. In this study, I used two different concentrations of carbachol to evaluate and compare in a masked fashion the influence of each concentration on the outcome of presbyopia treatment.

METHODS

Each participant gave written informed consent and the study followed the tenets of the Declaration of Helsinki. Participants were randomly selected volunteers. Presbyopia was considered present if an uncorrected endpoint print size ≥ Jaeger (J) 5 improved by ≥1 optotype with the use of a lens ≥ +1.00 D. Inclusion criteria were as follows: age between 44 and 60 years, emmetropia [cycloplegic spherical equivalent (SE), ± 0.25 D; astigmatism, ≤ 0.25 D] and binocular uncorrected distance visual acuity ≥ 20/20. Exclusion criteria included patients with myopia, hyperopia and astigmatism higher than 0.25 D as well as those with corneal, lens and vitreous opacities, pupil irregularities, anisocoria, amblyopia, chronic general pathologies and medications that would interact unfavorably with carbachol and brimonidine. Group 1 and 2 received a single dose of 2.25% and 3 % carbachol, respectively combined with 0.2% brimonidine in their non-dominant eyes. Initial pupil size and both near and distance visual acuities were documented before treatment and at 1, 2, 4, 8 and 12 hour after treatment by the same independent examiner in the same room with the same instruments. Distance visual acuity was measured using the standard Snellen projector chart at 4 m. Near visual acuity (NVA) was assessed 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

Statistical analysis was performed using the Student’s t test and a p value of less than 0.05 was considered statistically significant. Data were expressed as mean ± standard deviation (SD). Calculations were performed using the Statistical Package for the Social Sciences (SPSS) version 18.0 system for personal computers (SPSS Inc., Chicago, IL).

RESULTS

57 emmetropic and presbyopic subjects aged between 44 and 60 years with an uncorrected distance visual acuity of at least 20/20 in both eyes without additional ocular pathology were eligible for inclusion. The mean age of group1 (2.25% carbachol) was 51.1 ± 4.5 years (range, 44-55 years); 18 men and 14 women. The mean age of group 2 (3% carbachol) was 52.8 ± 3.9 years (range, 47-60 years); 14 men and 11 women. No statistically significant difference in mean age or sex was found among the two groups. In group1, the mean near visual acuity (NVA) improved significantly from J 7.37 ± 1.6 before treatment to J 2.96 ± 0.8 at 1 h, J 3.34 ± 1.1 at 2 h, J 3.93 ± 0.98 at 4 h, and J 4.98 ± 0.85 at 8 h post-treatment (p < 0.0001). At 12 h post-treatment, mean NVA was 6.75 ± 1.58 J (p = 0.11). The mean pupil size (PS) decreased significantly from 4.74 ± 0.47 mm before treatment to 2.68 ± 0.41 mm at 1 h, 3 ± 0.37 mm at 2 h, 3.35 ± 0.4 mm at 4 h and 3.58 ± 0.43 mm at 8 h post-treatment (p < 0.0001). At 12 h post-treatment, mean pupil size was 4.51 ± 69 mm (p = 0.12).

In group2, the mean near visual acuity (NVA) improved significantly from J 7.72 ± 1.48 before treatment to J 1.36 ± 0.56 at 1 h, J 1.4 ± 0.57 at 2 h, J 1.8 ± 0.58 at 4 h, J 2.32 ± 0.47 at 8 h and 2.64 ± 0.7 at 12 h post-treatment (p < 0.0001). The mean pupil size (PS) decreased significantly from 4.55 ± 0.55 mm before treatment to 1.2 ± 0.25 mm at 1 h, 1.34 ± 0.31 mm at 2 h, 1.64 ± 0.3 mm at 4 h, 2 ± 0.28 mm at 8 h and 2.27 ± 0.34 mm at 12 h post-treatment (p < 0.0001). In group2 when 3% carbachol was instilled, the improvement in near visual acuity was statistically significant up to 12 h post-treatment whereas in group1, the improvement in near visual acuity was only significant up to 8 h post-treatment. Significant improvement in mean NVA was reported in 3% carbachol and brimonidine drops than 2.25% concentration (p < 0.0001).

Data are summarized in Table 1. Figures 1 and 2 show the mean change in near visual acuity (Jaeger) and pupil size (mm) over time for both groups.

Burning sensation, browache, dimness or any other serious adverse ocular effects were not observed in any of the patients of both groups. Systemic side effects such as bradychardia, bronchospasm, and digestive problems were not found.

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 periods after treatment.

Table 1 Mean change in near visual acuity (NVA) (Jaeger) and pupil size (PS) (mm) over time for group 1 receiving 2.25% carbachol plus brimonidine versus group 2 receiving 3% carbachol plus brimonidine.
TimeGroup 1 (2.25% Carbachol plus Brimonidine)Group 2 (3% Carbachol plus Brimonidine)P-alue
Pre-treatmentNVA7.377.720.4
PS4.744.550.1
1- hNVA2.961.36P < 0.0001
PS2.681.2P < 0.0001
2- hNVA3.341.4P < 0.0001
PS31.34P < 0.0001
4 -hNVA3.931.8P < 0.0001
PS3.351.64P < 0.0001
8- hNVA4.682.32P < 0.0001
PS3.582.04P < 0.0001
12-hNVA6.752.64P < 0.0001
PS4.512.27P < 0.0001

Figure 1 Distribution of mean change in near visual acuity (Jaeger) over time for group 1 receiving 2.25% carbachol plus brimonidine versus group 2 receiving 3% carbachol plus brimonidine.

Figure 2 Distribution of mean change in pupil size (mm) over time for group 1 receiving 2.25% carbachol plus brimonidine versus group 2 receiving 3% carbachol plus brimonidine.

DISCUSSION

Several studies have been conducted to determine how much each factor involved in the accommodative process contributes to it[12-16]. The few topical treatments for presbyopia currently under study claim to work on different aspects of the accommodative process: they involve monovision parasympathetic-mediated miosis and ciliary muscle stimulation or lens softening in order to restore its shape-changing ability[17-19]. This study aimed at investigating the optimal dose of carbachol to effectively improve near vision in presbyopic subjects for a prolonged duration of time. The principle of pinhole effect is being successfully applied in corneal inlays implanted in the non-dominant eye to improve near vision. Although there are some problems with centering the implant, and some surgical complications, it is clear that the principle of a small pupil that moves with the eye can give a good near vision and preserve distance acuity as well. Operating only on the nondominant eye seems to avoid problems of dimness that are seen when the pupils in both eyes are made small. Patients do not experience dimness of vision as the other untreated eye fills in brightness. I attempted with drops to approach this effect without surgical interference. Statistically significant improvement in mean near visual acuity (NVA) and mean pupil size (PS) was achieved in all subjects who received both concentrations of carbachol plus brimonidine drops (p < 0.0001). Significant improvement in mean NVA and PS up to 12 hours posttreatment was reported in all subjects received 3% carbachol drops (p < 0.0001). No serious adverse ocular effects were observed in higher concentrations of carbachol. Further studies with larger cohorts of patients and longer follow up period are necessary to confirm our outcomes.

In conclusion, based on the data, higher concentration of carbachol was found to be safe and provided greater efficacy in improving near visual acuity than lower concentration with prolonged duration of action.

Authors’ contributions

AA collected the clinical data, conducted the statistical analyses and interpretation of the data, prepared the manuscript and conceived the study design. The author read and approved the final manuscript.

REFERENCES

1. Lu Q, Congdon N, He X, Murthy GVS, Yang A, He W. Quality of life and near vision impairment due to functional presbyopia among rural Chinese adults. Invest Ophthalmol Vis Sci. 2011; 52(7): 4118-23. [PMID: 21508106]; [DOI: 10.1167/iovs.10-6353]

2. Alió JL, Plaza-Puche AB, Piñero DP, Amparo F, Jiménez R, Rodríguez-Prats JL, Javaloy J, Pongo V. Optical analysis, reading performance, and quality-of-life evaluation after implantation of a diffractive multifocal intraocular lens. J Cataract Refract Surg. 2011; 37(1): 27-37. [PMID: 21183097]; [DOI: 10.1016/j.jcrs.2010.07.035]

3. Labiris G, Ntonti P, Patsiamanidi M, Sideroudi H, Georgantzoglou K, Kozobolis VP. Evaluation of activities of daily living following pseudophakic presbyopic correction. Eye Vis (Lond) 2017; 4: 2. [PMID: 28116335]; [DOI: 10.1186/s40662-016-0067-1]

4. Schachar RA. The mechanism of accommodation and presbyopia. Int Ophthalmol Clin. 2006; 46(3): 39-61. [PMID: 16929224]

5. Charman WN. The eye in focus: accommodation and presbyopia. Clin Exp Optom. 2008; 91(3): 207-25. [PMID: 18336584]; [DOI: 10.1111/j.1444-0938.2008.00256.x]

6. 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. [PMID: 22018596]; [DOI: 10.1016/j.jcrs.2011.07.027]

7. 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. [PMID: 20438021]; [DOI: 10.3928/1081597X-20100408-01]

8. 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. [PMID: 22138501]; [DOI: 10.1016/j.jcrs.2011.08.031]

9. 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. [PMID: 21436279]; [DOI: 10.1167/iovs.10-6436]

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

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

12. Benozzi G, Leiro J, Facal S, Perez C, Benozzi J, Orman B. Developmental changes in accommodation evidenced by an ultrabiomicroscopy procedure in patients of Different Ages. Med Hypothesis Discov Innov Ophthalmol. 2013; 2(1): 8-13. [PMID: 24600634]; [PMCID: PMC3939763]

13. Hickenbotham A, Tiruveedhula P, Roorda A. Comparison of spherical aberration and small-pupil profiles in improving depth of focus for presbyopic corrections. J Cataract Refract Surg. 2012; 38(12): 2071-9. [PMID: 23031641]; [DOI: 10.1016/j.jcrs.2012.07.028]

14. Van De Sompel D, Kunkel GJ, Hersh PS, Smits AJ. Model of accommodation: contributions of lens geometry and mechanical properties to the development of presbyopia. J Cataract Refract Surg. 2010; 36(11): 1960-71. [PMID: 21029906]; [DOI: 10.1016/j.jcrs.2010.09.001]

15. Richdale K, Sinnott LT, Bullimore MA, Wassenaar PA, Schmalbrock P, Kao CY, Patz S, Mutti DO, Glasser A, Zadnik K. Quantification of age-related and per diopter accommodative changes of the lens and ciliary muscle in the emmetropic human eye. Investig Ophthalmol Vis Sci. 2013; 54(2): 1095-105. [PMID: 23287789 ]; [DOI: 10.1167/iovs.12-10619]

16. Schwarz C, Manzanera S, Prieto PM, Fernández EJ, Artal P. Comparison of binocular through-focus visual acuity with monovision and a small aperture inlay. Biomed Opt Express. 2014; 5: 3355-66. [PMID: 25360355]; [DOI: 10.1364/BOE.5.003355]

17. Abdelkader A. Improved presbyopic vision with miotics. Eye Contact Lens Sci Clin Pract. 2015; 41(5): 323-7. [PMID: 25806674]; [DOI: 10.1097/ICL.0000000000000137]

18. Glasser A. Accommodation: mechanism and measurement. Ophthalmol Clin N Am. 2006; 19(1): 1-12. [PMID: 16500524]; [DOI: 10.1016/j.ohc.2005.09.004]

19. Benozzi J, Benozzi G, Orman B. Presbyopia: a new potential pharmacological treatment. Med Hypothesis Discov Innov Ophthalmol. 2012; 1(1): 3-5. [PMID: 24600609]; [PMCID: PMC3939740]

Refbacks

  • There are currently no refbacks.