Background:

Preserved prostaglandin analogs (PGAs) have been linked to ocular surface disease (OSD). While the benefits of preservative-low (PL) or -free (PF) Tafluprost (Santen Inc., Japan) were reported in real-world studies in Western countries, this is the first study in Asia to assess the effectiveness and safety of switching from preserved PGA to PL or PF-Tafluprost.

Methods:

We conducted a meta-analysis on studies that included adults (> 18 years of age) with a Corneal Fluorescein Staining Score (CFS) > 1. These individuals had switched to PL or PF-tafluprost after using a preserved PGA therapy for at least 3 months for glaucoma and were identified from Santen’s tafluprost study database. A total of six studies from South Korea, Philippines, Malaysia, Singapore, Thailand, Taiwan were pooled for analysis.

Results: 

An intraocular pressure (IOP) reduction of 5.9% (0.91 mmHg) was seen in 265 patients. However, this result was not statistically significant (95% CI: − 3.64, 1.81; Figure 1). Among 132 patients, a 47.9% reduction in the CFS (95% CI: − 3.65, − 1.91) was seen. Tear film break-up (n=183) significantly increased by 1.06 seconds (95% CI: 0.65, 1.47). In 88 patients, the bulbar conjunctiva score decreased by − 0.46 (95% CI: − 0.81, − 0.10) and palpebral conjunctiva score decreased by − 0.42 (95% CI: − 0.67– 0.17). One or more new adverse reactions were reported in 3% of the individuals after switching.

Conclusion: 

Tafluprost IOP reduction is comparable to other PGAs, with significant improvements in the ocular surface and minimal adverse reactions which were already previously reported.

1. Chan, E. W., Li, X., Tham, Y. C., Liao, J., Lamoureux, E., Khor, C. C., ... & Cheng, C. Y. (2016). Glaucoma in Asia: Regional prevalence variations and future projections. British Journal of Ophthalmology, 100(1), 78–85. https://doi.org/10.1136/bjophthalmol-2014-306102
2. European Glaucoma Society. (2017). Terminology and guidelines for glaucoma 4th edition - Chapter 3: Treatment principles and options supported by the EGS foundation: Part 1: Foreword; introduction; glossary; chapter 3 treatment principles and options. British Journal of Ophthalmology, 101(6), 130–195. https://doi.org/10.1136/bjophthalmol-2016-EGSguideline.003
3. Harasymowycz, P., Birt, C., Gooi, P., Heckler, L., Hutnik, C., Jin, Y. P., ... & Schlenker, M. B. (2016). Medical management of glaucoma in the 21st century from a Canadian perspective. Journal of Ophthalmology, 2016, Article 6509809. https://doi.org/10.1155/2016/6509809
4. Realini, T. (2011). A history of glaucoma pharmacology. Optometry and Vision Science, 88(1), 36–38. https://doi.org/10.1097/OPX.0b013e3182058ead
5. Baudouin, C., Renard, J. P., Nordmann, J. P., Denis, P., Jean-Louis, A., Lachkar, Y., ... & Labbé, A. (2012). Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. European Journal of Ophthalmology, 22(6), 886–891. https://doi.org/10.5301/ejo.5000181
6. Jaenen, N., Baudouin, C., Pouliquen, P., Manni, G., Figueiredo, A., & Zeyen, T. (2007). Ocular symptoms and signs with preserved and preservative-free glaucoma medications. European Journal of Ophthalmology, 17(3), 341–349. https://doi.org/10.1177/112067210701700311
7. Liu, Y., & Mao, W. (2013). Tafluprost once daily for treatment of elevated intraocular pressure in patients with open-angle glaucoma. Clinical Ophthalmology, 7, 7–14. https://doi.org/10.2147/OPTH.S30951
8. Swymer, C., & Neville, M. W. (2012). Tafluprost: The first preservative-free prostaglandin to treat open-angle glaucoma and ocular hypertension. Annals of Pharmacotherapy, 46(11), 1506–1510. https://doi.org/10.1345/aph.1R229
9. Lanzl, I., Hamacher, T., Rosbach, K., Müller, M., Goldmann, S., Shady, R., & Ropo, A. (2013). Preservative-free tafluprost in the treatment of naive patients with glaucoma and ocular hypertension. Clinical Ophthalmology, 7, 901–910. https://doi.org/10.2147/OPTH.S41640
10. Ansari, E., Pavicic-Astalos, J., Ayan, F., Gunduz, A., & Noone, S. (2021). Treatment of open-angle glaucoma and ocular hypertension with preservative-free tafluprost/timolol fixed-dose combination therapy: UK and Ireland results from the VISIONARY Study. Advances in Therapy, 38(6), 2990–3002. https://doi.org/10.1007/s12325-021-01725-7
11. Ranno, S., Sacchi, M., Brancato, C., Gilardi, D., Lembo, A., & Nucci, P. (2012). A prospective study evaluating IOP changes after switching from a therapy with prostaglandin eye drops containing preservatives to nonpreserved tafluprost in glaucoma patients. The Scientific World Journal, 2012, Article 804730. https://doi.org/10.1100/2012/804730
12. Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., ... & Moher, D. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372, Article n71. https://doi.org/10.1136/bmj.n71
13. Tumbocon, J. A., & Macasaet, A. M. (2019). Efficacy and safety of tafluprost 0.0015% - Retrospective analysis of real-world data from the Philippines. Clinical Ophthalmology, 13, 1627–1634. https://doi.org/10.2147/OPTH.S209942
14. Wong, T. T., Aung, T., & Ho, C. L. (2018). Ocular surface status in glaucoma and ocular hypertension patients with existing corneal disorders switched from latanoprost 0.005% to tafluprost 0.0015%: Comparison of two prostaglandin analogues with different concentrations of benzalkonium chloride. Clinical & Experimental Ophthalmology, 46(9), 1028–1034. https://doi.org/10.1111/ceo.13329
15. Ruangvaravate, N., Choojun, K., Srikulsasitorn, B., Chokboonpiem, J., Asanatong, D., & Trakanwitthayarak, S. (2020). Ocular surface changes after switching from other prostaglandins to tafluprost and preservative-free tafluprost in glaucoma patients. Clinical Ophthalmology, 14, 3109–3119. https://doi.org/10.2147/OPTH.S264984
16. Lim, H. H., & Sangapillai, T. (2021). Ocular surface conditions in Asian glaucoma patients with existing corneal disorders switching from preserved prostaglandin analogue monotherapy to preservative-free tafluprost. Malaysian Journal of Ophthalmology, 3(3), 109–122. https://doi.org/10.35119/myjo.v3i3.185
17. Park, S. W., Lee, J., & Kook, M. S. (2022). Efficacy, safety and patient-reported outcomes with preservative-free (PF) tafluprost or PF-dorzolamide/timolol compared with preserved latanoprost: A prospective multicenter study in Korean glaucoma patients with ocular surface disease. Pharmaceuticals, 15(2), Article 201. https://doi.org/10.3390/ph15020201
18. Yen, Y. C. (2021, April 10–11). Prospective, single center switching study of 0.0015% tafluprost ophthalmic solution in primary open-angle glaucoma and ocular hypertension patients with corneal disorders (Switching from 0.005% latanoprost ophthalmic solution) [Poster presentation]. 2021 Mid-Year Scientific Meeting of the Ophthalmological Society of Taiwan (POA-184), Kaohsiung, Taiwan.
19. Takamura, E., Uchio, E., Ebihara, N., Fukushima, A., Ohno, S., Okamoto, S., ... & Japanese Society of Allergology. (2011). Japanese guideline for allergic conjunctival diseases. Allergology International, 60(2), 191–203. https://doi.org/10.2332/allergolint.11-RAI-0335
20. Ma, L. L., Wang, Y. Y., Yang, Z. H., Huang, D., Weng, H., & Zeng, X. T. (2020). Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: What are they and which is better? Military Medical Research, 7(1), Article 7. https://doi.org/10.1186/s40779-020-00238-8
21. Schünemann, H., Brożek, J., Guyatt, G., & Oxman, A. (2013). GRADE handbook for grading quality of evidence and strength of recommendations. The GRADE Working Group. http://gdt.guidelinedevelopment.org/app/handbook/handbook.html
22. GRADEpro GDT. (2020). GRADEpro guideline development tool. McMaster University; Evidence Prime, Inc. https://gradepro.org
23. Hamacher, T., Airaksinen, J., Saarela, V., Liinamaa, M. J., Richter, U., & Ropo, A. (2008). Efficacy and safety levels of preserved and preservative-free tafluprost are equivalent in patients with glaucoma or ocular hypertension: Results from a pharmacodynamics analysis. Acta Ophthalmologica, 86(Suppl 242), 14–19. https://doi.org/10.1111/j.1755-3768.2008.01381.x
24. Kuwayama, Y., Hashimoto, M., Kakegawa, R., Nomura, A., & Shimada, F. (2017). Prospective observational post-marketing study of tafluprost for glaucoma and ocular hypertension: Effectiveness and treatment persistence. Advances in Therapy, 34(6), 1411–1425. https://doi.org/10.1007/s12325-017-0549-0
25. Erb, C., Lanzl, I., Seidova, S. F., & Kimmich, F. (2011). Preservative-free tafluprost 0.0015% in the treatment of patients with glaucoma and ocular hypertension. Advances in Therapy, 28(7), 575–585. https://doi.org/10.1007/s12325-011-0038-9
26. Hommer, A., Schmidl, D., Kromus, M., Celik, M., Werkmeister, R. M., Kallab, M., ... & Garhöfer, G. (2018). Effect of changing from preserved prostaglandins to preservative-free tafluprost in patients with glaucoma on tear film thickness. European Journal of Ophthalmology, 28(4), 385–392. https://doi.org/10.1177/1120672117753703
27. Uusitalo, H., Chen, E., Pfeiffer, N., Brignole-Baudouin, F., Kaercher, T., Rossi, G. C., ... & Ropo, A. (2010). Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication. Acta Ophthalmologica, 88(3), 329–336. https://doi.org/10.1111/j.1755-3768.2010.01907.x
28. Wilensky, J., Fiscella, R. G., Carlson, A. M., Morris, L. S., & Walt, J. (2006). Measurement of persistence and adherence to regimens of IOP-lowering glaucoma medications using pharmacy claims data. American Journal of Ophthalmology, 141(1 Suppl), S28–S33. https://doi.org/10.1016/j.ajo.2005.09.011
29. Feldman, R. M. (2003). Conjunctival hyperemia and the use of topical prostaglandins in glaucoma and ocular hypertension. Journal of Ocular Pharmacology and Therapeutics, 19(1), 23–35. https://doi.org/10.1089/108076803762718088