TOPICAL LEVODOPA-CARBIDOPA EYE DROPS FOR MYOPIA CONTROL: A PILOT STUDY IN A RABBIT MODEL OF FORM-DEPRIVATION MYOPIA

Authors

  • CHRISTINA ARITONANG Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya-60132, Indonesia. Department of Ophthalmology, Faculty of Medicine, Universitas Airlangga, Surabaya-60286, Indonesia. Dr. Soetomo General Academic Hospital, Surabaya-60286, Indonesia https://orcid.org/0000-0001-5768-064X
  • IRWANTO IRWANTO Department of Child Health, Faculty of Medicine, Universitas Airlangga, Surabaya-60286, Indonesia. Dr. Soetomo General Academic Hospital, Surabaya-60286, Indonesia https://orcid.org/0000-0002-7573-8793
  • RENI PRASTYANI Department of Ophthalmology, Faculty of Medicine, Universitas Airlangga, Surabaya-60286, Indonesia. Dr. Soetomo General Academic Hospital, Surabaya-60286, Indonesia

DOI:

https://doi.org/10.22159/ijap.2026v18i1.56071

Keywords:

Dopaminergic signaling, Levodopa-carbidopa, Ocular pharmacology, Myopia, Health

Abstract

Objective: Dopaminergic drugs may be repurposed to modulate ocular growth. Our study aims to evaluate the safety, stability, and efficacy of a novel levodopa-carbidopa topical ophthalmic formulation for controlling myopia progression in the form-deprivation myopia (FDM) rabbit model.

Methods: A 4:1 molar ratio of levodopa to carbidopa was formulated into an eye drop with a pH of 5.8 and stored at 4 °C in light-protected glass containers. We used 14 New Zealand white rabbits, which received form-deprivation myopia induction and were divided into two groups: seven into the control group and the other seven into the intervention group, the latter receiving treatment with the prepared levodopa-carbidopa formulation. Ocular safety was assessed using a slit-lamp exam, Schirmer’s test, and behavioral observations. Efficacy was represented by axial length and refraction, with retinal tissues being harvested for ELISA quantification of dopaminergic markers.

Results: Levodopa-carbidopa formulation remained clear and stable with no visual signs of microbial contamination or degradation during the study period. No signs of ocular irritation or systemic toxicity were observed. Schirmer’s test values showed no significant difference pre-and post-treatment, proving the absence of drug-induced ocular irritation (p>0.05). Treatment with levodopa–carbidopa significantly inhibited axial elongation (18.16 mm vs. 23.12 mm, p = 0.013) and reversed myopic refractive error (4.57±1.06 vs. 2.64±1.41, p = 0.013) compared to the control group. Retinal tyrosine hydroxylase (TH) and dopamine receptor D2 (D2R) expression were significantly elevated in the treated group (p = 0.006 and p = 0.036, respectively), supporting enhanced dopaminergic signaling.

Conclusion: Topical levodopa–carbidopa is a stable, well-tolerated formulation that suppresses progression of myopia in a rabbit model. The therapeutic effect is associated with enhanced retinal dopamine activity. These findings further support a pharmacologic strategy for myopia control.

References

1. Morgan IG, French AN, Ashby RS, Guo X, Ding X, He M. The epidemics of myopia: aetiology and prevention. Prog Retin Eye Res. 2018;62:134-49. doi: 10.1016/j.preteyeres.2017.09.004, PMID 28951126.

2. Pan CW, Ramamurthy D, Saw SM. Worldwide prevalence and risk factors for myopia. Ophthalmic Physiol Opt. 2012;32(1):3-16. doi: 10.1111/j.1475-1313.2011.00884.x, PMID 22150586.

3. Feldkaemper M, Schaeffel F. An updated view on the role of dopamine in myopia. Exp Eye Res. 2013 Sep;114:106-19. doi: 10.1016/j.exer.2013.02.007, PMID 23434455.

4. Zhou X, Pardue MT, Iuvone PM, Qu J. Dopamine signaling and myopia development: what are the key challenges. Prog Retin Eye Res. 2017;61:60-71. doi: 10.1016/j.preteyeres.2017.06.003, PMID 28602573.

5. Dong F, Zhi Z, Pan M, Xie R, Qin X, Lu R. Inhibition of experimental myopia by a dopamine agonist: different effectiveness between form deprivation and hyperopic defocus in guinea pigs. Mol Vis. 2011;17:2824-34. PMID 22128230.

6. Chen S, Zhi Z, Ruan Q, Liu Q, Li F, Wan F. Bright light suppresses form-deprivation myopia development with activation of dopamine D1 receptor signaling in the ON pathway in retina. Invest Ophthalmol Vis Sci. 2017;58(4):2306-16. doi: 10.1167/iovs.16-20402, PMID 28431434.

7. Shu Z, Chen K, Wang Q, Wu H, Zhu Y, Tian R. The role of retinal dopamine D1 receptors in ocular growth and myopia development in mice. J Neurosci. 2023;43(48):8231-42. doi: 10.1523/JNEUROSCI.1196-23.2023, PMID 37751999.

8. Thomson K, Karouta C, Morgan I, Kelly T, Ashby R. Effectiveness and safety of topical levodopa in a chick model of myopia. Sci Rep. 2019;9(1):18345. doi: 10.1038/s41598-019-54789-5, PMID 31797988.

9. Thomson K, Morgan I, Kelly T, Karouta C, Ashby R. Coadministration with carbidopa enhances the antimyopic effects of levodopa in chickens. Invest Ophthalmol Vis Sci. 2021;62(4):25. doi: 10.1167/iovs.62.4.25, PMID 33877264.

10. Haddad F, Sawalha M, Khawaja Y, Najjar A, Karaman R. Dopamine and levodopa prodrugs for the treatment of Parkinson’s disease. Molecules. 2017;23(1):40. doi: 10.3390/molecules23010040, PMID 29295587.

11. Kim DH, Hwang JM, Yang HK. Topical dopamine application on form-deprivation myopia in rabbits. Life (Basel). 2025;15(3):461. doi: 10.3390/life15030461, PMID 40141806.

12. Barathi VA, Boopathi VG, Yap EP, Beuerman RW. Two models of experimental myopia in the mouse. Vision Res. 2008;48(7):904-16. doi: 10.1016/j.visres.2008.01.004, PMID 18289630.

13. Schuerer N, Stein E, Inic Kanada A, Pucher M, Hohenadl C, Bintner N. Implications for ophthalmic formulations: ocular buffers show varied cytotoxic impact on human corneal limbal and human conjunctival epithelial cells. Cornea. 2017;36(6):712-8. doi: 10.1097/ICO.0000000000001199, PMID 28399036.

14. Remenar J, Almarsson O, Meehan AJ, Zhong Z. Pharmaceutical compositions and method of using levodopa and carbidopa. US Patent US8815950B2. United States: United States Patent and Trademark Office; 2014.

15. Sanchez Rivera AE, Corona Avendano S, Alarcon Angeles G, Rojas Hernandez A, Ramirez Silva MT, Romero Romo MA. Spectrophotometric study on the stability of dopamine and the determination of its acidity constants. Spectrochim Acta A Mol Biomol Spectrosc. 2003;59(13):3193-203. doi: 10.1016/S1386-1425(03)00138-0, PMID 14583295.

16. Aminoff MJ. Pharmacologic management of Parkinsonism and other movement disorders. In: Vanderah TW, editor. Katzung’s basic and Clinical Pharmacology. 16th ed. McGraw-Hill Medical; 2023.

17. Daubner SC, Le T, Wang S. Tyrosine hydroxylase and regulation of dopamine synthesis. Arch Biochem Biophys. 2011;508(1):1-12. doi: 10.1016/j.abb.2010.12.017, PMID 21176768.

18. Yan T, Xiong W, Huang F, Zheng F, Ying H, Chen JF. Daily injection but not continuous infusion of apomorphine inhibits form deprivation myopia in mice. Invest Ophthalmol Vis Sci. 2015;56(4):2475-85. doi: 10.1167/iovs.13-12361, PMID 25744977.

19. Baumans V. Environmental enrichment for laboratory rodents and rabbits: requirements of rodents rabbits and research. ILAR J. 2005;46(2):162-70. doi: 10.1093/ilar.46.2.162, PMID 15775025.

20. Whittaker AL, Williams DL. Evaluation of lacrimation characteristics in clinically normal New Zealand white rabbits by using the schirmer tear test i. J Am Assoc Lab Anim Sci. 2015;54(6):783-7. PMID 26632789.

21. Sorriento D, Santulli G, Del Giudice C, Anastasio A, Trimarco B, Iaccarino G. Endothelial cells are able to synthesize and release catecholamines both in vitro and in vivo. Hypertension. 2012;60(1):129-36. doi: 10.1161/hypertensionaha.111.189605, PMID 22665130.

22. De Souza GA, Godoy LM, Mann M. Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors. Genome Biol. 2006;7(8):R72. doi: 10.1186/gb-2006-7-8-r72, PMID 16901338.

23. Thomson K, Morgan I, Karouta C, Ashby R. Levodopa inhibits the development of lens-induced myopia in chicks. Sci Rep. 2020;10(1):13242. doi: 10.1038/s41598-020-70271-z, PMID 32764736.

24. Repka MX, Kraker RT, Beck RW, Atkinson CS, Bacal DA, Bremer DL. Pilot study of levodopa dose as treatment for residual amblyopia in children aged 8 y to younger than 18 y. Arch Ophthalmol. 2010;128(9):1215-7. doi: 10.1001/archophthalmol.2010.178, PMID 20837811.

25. Ward AH, Siegwart JT, Frost MR, Norton TT. Intravitreally administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews. Vis Neurosci. 2017;34:E003. doi: 10.1017/S0952523816000195, PMID 28304244.

26. Ashby R, McCarthy CS, Maleszka R, Megaw P, Morgan IG. A muscarinic cholinergic antagonist and a dopamine agonist rapidly increase ZENK mRNA expression in the form-deprived chicken retina. Exp Eye Res. 2007;85(1):15-22. doi: 10.1016/j.exer.2007.02.019, PMID 17498696.

27. Ashby R, Kozulin P, Megaw PL, Morgan IG. Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens. Mol Vis. 2010;16:639-49. PMID 20405027.

28. Zhao C, Cai C, Ding Q, Dai H. Efficacy and safety of atropine to control myopia progression: a systematic review and meta-analysis. BMC Ophthalmol. 2020;20(1):478. doi: 10.1186/s12886-020-01746-w, PMID 33287746.

29. Tinu TS, Thomas L, Kumar BA. Polymers used in ophthalmic in situ gelling system. Int J Pharm Sci Rev Res. 2013;20(1):176-83.

Published

07-01-2026

How to Cite

ARITONANG, C., IRWANTO, I., & PRASTYANI, R. (2026). TOPICAL LEVODOPA-CARBIDOPA EYE DROPS FOR MYOPIA CONTROL: A PILOT STUDY IN A RABBIT MODEL OF FORM-DEPRIVATION MYOPIA. International Journal of Applied Pharmaceutics, 18(1), 325–331. https://doi.org/10.22159/ijap.2026v18i1.56071

Issue

Section

Original Article(s)

Similar Articles

<< < 2 3 4 5 6 > >> 

You may also start an advanced similarity search for this article.