Efficacy and safety of the initial hypotensive treatment with an optimized latanoprost composition

Purpose: a comparative study of the efficacy and safety of Latanoprost-Optic, a new composition of excipients and the original latanoprost, in the initial therapy of primary open-angle glaucoma (POAG)

Material and methods. We performed a prospective, randomized, comparative study of 60 previously untreated patients (71 eyes) with early and advanced POAG stages. During the screening visit, patients were randomly divided into the main (Latanoprost-Optic) and the control (original latanoprost) groups. The target points included intraocular pressure (IOP), visual acuity, MD and PSD perimetry indices, RNFL thickness, MRW, NFL, GCL, IPL, tear film break time, OSDI, and adverse events. The observation period was 12 weeks. IOP was measured 4 and 12 weeks from observation start.

Results. The average decrease in IOP in the study group by the end of the observation was 32% and did not show any statistically significant differences from the original drug at any control point. A positive unreliable dynamic of the values of most functional parameters was noted, which may indicate the presence of an indirect neuroprotective effect. In the study group, there was a positive trend in tear film rupture time and OSDI. According to corneal confocal microscopy, no negative changes in dynamics were noted, in contrast to the control group. Reversible discomfort and mild redness of the bulbar conjunctiva were recorded in both groups. No serious or systemic adverse events were noted.

Conclusion. Latanoprost-Optic has a hypotensive efficacy, comparable to the original latanoprost, and a high favorable safety profile.

1. Neroev V.V., Kiseleva O.A., Bessmertny A.M. The main results of a multicenter study of epidemiological features of primary open-angle glaucoma in the Russian Federation. Russian ophthalmological journal. 2013; 6 (3): 4–7 (In Russ.).

2. Neroev V.V., Mikhailova L.A. Ophthalmic morbidity in Russia. In: Avetisov S.E., Egorov E.A., Moshetova L.K., Takhchidi Kh.P., eds. Ophthalmology. National Guidelines. Moscow: GEOTAR-Media, 2018: 15–9 (In Russ.).

3. Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014; 121 (11): 2081–90. doi: 10.1016/j.ophtha.2014.05.013

4. Tielsch JM, Katz J, Singh K, et al. A population-based evaluation of glaucoma screening: the Baltimore Eye Survey. Am J Epidemiol. 1991; 134 (10): 1102–10. doi: 10.1093/oxfordjournals.aje.a116013

5. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006; 90 (3): 262–7. doi:10.1136/bjo.2005.081224

6. Sotimehin AE, Ramulu PY. Measuring disability in glaucoma. J Glaucoma. 2018; 27 (11): 939–49. doi: 10.1097/IJG.0000000000001068

7. Statistical compilation of the Department for monitoring analysis and strategic development of health care of the Federal State Budgetary Institution “TsNIIOIZ” of the Ministry of Health of Russia “General incidence of the adult population of Russia in 2022” (In Russ.). Available at: https://rosstat.gov.ru/folder/210/document/13218

8. Peters D, Bengtsson B, Heijl A. Factors associated with lifetime risk of openangle glaucoma blindness. Acta Ophthalmol. 2014; 92 (5): 421–5. doi: 10.1111/aos.12203

9. Clinical Gidelines “Primary open angle glaucoma”. 2020 (16.02.2021), Approved by the Ministry of Health of the Russian Federation (In Russ.)]. Available at: http://avo-portal.ru/documents/fkr/Klinicheskie_rekomendacii_POUG_2022.pdf

10. Neroev V.V., Zolotarev A.V., Karlova E.V., et al. Influence of treatment adherence on the progression of primary openangle glaucoma in clinical setting. Vestnik oftalmologii. 2019; 135 (6): 42–51 (In Russ.). doi:10.17116/oftalma201913506142

11. Kim JM, Sung KR, Kim HK, et al. Long-term effectiveness and safety of Tafluprost, Travoprost, and Latanoprost in Korean patients with primary openangle glaucoma or normal-tension glaucoma: A multicenter retrospective cohort study (LOTUS Study). J Clin Med. 2021; 10 (12). doi: 10.3390/jcm10122717

12. Tong J, Huang J, Kalloniatis M, Coroneo M, Zangerl B. Clinical trial: Diurnal IOP fluctuations in glaucoma using Latanoprost and Timolol with self-tonometry. Optom Vis Sci. 2021; 98 (8): 901–13. doi: 10.1097/OPX.0000000000001751

13. Instruction for Xalatan medical using (In Russ.)]. Available at: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=2bd5b77a-6c85-4a1d-bfe1-07b63f1ccab7 (date of the application: 22.08.2023)

14. Instruction for Latanoprost-Optic medical using. Electronic image 1 (In Russ.)]. Available at: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=500d6b96-abe0-48d4-870e-0f81941f4c17 (date of the application: 22.08.2023).

15. Petrov S.Yu., Kalinina O.M., Yakubova L.V., et al. Initial hypotensive therapy of primary glaucoma with the domestic latanoprost generic: efficacy and safety. Russian ophthalmological journal. 2021; 14 (4): 7–14 (In Russ.). https://doi.org/10.21516/2072-0076-2021-14-4-supplement-7-14

16. Domagk G. Eine neue Klasse von Desinfectionsmitteln. Dtsch Med Wochenschr 1935; 61 (21): 829–32. doi: 10.1055/s-0028-1129654

17. De Saint Jean M, Brignole F, Bringuier AF, et al. Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells. Invest Ophthalmol Vis Sci. 1999 Mar; 40 (3): 619–30. PMID: 10067965

18. Kim MS, Choi CY, Kim JM, Chang HR, Woo HY. Microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers. Br J Ophthalmol. 2008; 92 (11): 1518–21. doi:10.1136/bjo.2008.144469

19. Tasli H, Cosar G. Microbial contamination of eye drops. Cent Eur J Public Health. 2001 Aug; 9 (3): 162–4. PMID: 11505742

20. Wilson WS, Duncan AJ, Jay JL. Effect of benzalkonium chloride on the stability of the precorneal tear film in rabbit and man. Br J Ophthalmol. 1975; 59 (11): 667–9. doi:10.1136/bjo.59.11.667

21. Pisella PJ, Fillacier K, Elena PP, Debbasch C., Baudouin C. Comparison of the effects of preserved and unpreserved formulations of timolol on the ocular surface of albino rabbits. Ophthalmic Res. 2000; 32 (1): 3–8. https://doi.org/10.1159/000055579

22. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007; 5 (2): 93–107. doi: 10.1016/s1542-0124(12)70082-4

23. Chung SH, Lee SK, Cristol SM, et al. Impact of short-term exposure of commercial eyedrops preserved with benzalkonium chloride on precorneal mucin. Mol Vis. 2006 Apr 26; 12: 415–21. PMID: 16688112

24. Herreras JM, Pastor JC, Calonge M, Asensio VM. Ocular surface alteration after long-term treatment with an antiglaucomatous drug. Ophthalmology. 1992; 99 (7): 1082–8. doi:10.1016/s0161-6420(92)31847-0

25. Albietz JM, Bruce AS. The conjunctival epithelium in dry eye subtypes: effect of preserved and non-preserved topical treatments. Curr Eye Res. 2001; 22 (1): 8–18. doi: 10.1076/ceyr.22.1.8.6977

26. Baudouin C. [A new approach for better comprehension of diseases of the ocular surface]. J Fr Ophtalmol. 2007; 30 (3): 239–46. doi:10.1016/s0181-5512(07)89584-2

27. Baudouin C, Liang H, Hamard P, et al. The ocular surface of glaucoma patients treated over the long term expresses inflammatory markers related to both T-helper 1 and T-helper 2 pathways. Ophthalmology. 2008; 115 (1): 109–15. doi:10.1016/j.ophtha.2007.01.036

28. Epstein SP, Chen D, Asbell PA. Evaluation of biomarkers of inflammation in response to benzalkonium chloride on corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009; 25 (5): 415–24. doi:10.1089/jop.2008.0140

29. Ichijima H, Petroll WM, Jester JV, Cavanagh HD. Confocal microscopic studies of living rabbit cornea treated with benzalkonium chloride. Cornea. 1992; 11 (3): 221–5.

30. Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther. 2001; 18 (5): 205–15. doi: 10.1007/BF02853166

31. Codling CE, Hann AC, Maillard JY, Russell AD. An investigation into the antimicrobial mechanisms of action of two contact lens biocides using electron microscopy. Cont Lens Anterior Eye. 2005; 28 (4): 163–8. doi:10.1016/j.clae.2005.08.002

32. Rosenthal RA, Henry CL, Stone RP, Schlech BA. Anatomy of a regimen: consideration of multipurpose solutions during non-compliant use. Cont Lens Anterior Eye. 2003; 26 (1): 17–26. doi: 10.1016/S1367-0484(02)00085-1

33. Instruction for Travatan medical using. Electronic image 3 (In Russ.). Available at: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=b578b8c5-c2a9-4dd2-a4c8-692bb102af4b (date of the application: 22.08.2023)

34. Codling CE, Maillard JY, Russell AD. Aspects of the antimicrobial mechanisms of action of a polyquaternium and an amidoamine. J Antimicrob Chemother. 2003; 51 (5): 1153–8. doi: 10.1093/jac/dkg228

35. Siketu D, Nelm DS, inventors. Preserved ophthalmic drug compositions containing polymeric quaternary ammonium compounds. US patent 5603929. 1997 18 Feb.

36. Tripathi BJ, Tripathi RC, Kolli SP. Cytotoxicity of ophthalmic preservatives on human corneal epithelium. Lens Eye Toxic Res. 1992; 9(3–4): 361–75. PMID: 1301792

37. Pham XT, Huff JW. Cytotoxicity evaluation of multipurpose contact lens solutions using an in vitro test battery. CLAO J. 1999 Jan; 25 (1): 28–35. PMID: 10073634

38. Meloni M, Pauly A, Servi BD, Varlet BL, Baudouin C. Occludin gene expression as an early in vitro sign for mild eye irritation assessment. Toxicol in Vitro. 2010; 24 (1): 276–85. doi: 10.1016/j.tiv.2009.08.016

39. Ubels JL, McCartney MD, Lantz WK, et al. Effects of preservative-free artificial tear solutions on corneal epithelial structure and function. Arch Ophthalmol. 1995; 113 (3): 371–8. doi: 10.1001/archopht.1995.01100030127036

40. Brignole-Baudouin F, Riancho L, Liang H, Baudouin C. Comparative in vitro toxicology study of travoprost polyquad-preserved, travoprost BAKpreserved, and latanoprost BAK-preserved ophthalmic solutions on human conjunctival epithelial cells. Curr Eye Res. 2011; 36 (11): 979–88. doi: 10.3109/02713683.2011.578781

41. Instruction for Latanoprost-Optic medical using. Electronic image 4 (In Russ.). Available at: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=500d6b96-abe0-48d4-870e-0f81941f4c17 (date of the application: 22.08.2023)

42. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000; 118 (5): 615–21. doi: 10.1001/archopht.118.5.615

43. Walt J, Rowe M, Stern K. Evaluating the functional impact of dry eye: the Ocular Surface Disease Index. Drug Inf J. 1997; 31 (1436). doi: https://eprovide.mapitrust.org/instruments/ocular-surface-disease-index

44. Majumdar S, Hippalgaonkar K, Repka MA. Effect of chitosan, benzalkonium chloride and ethylenediaminetetraacetic acid on permeation of acyclovir across isolated rabbit cornea. Int J Pharm. 2008; 348 (1–2): 175–8. doi: 10.1016/j.ijpharm.2007.08.017

45. Rathore MS, Majumdar DK. Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin from aqueous drops. AAPS PharmSciTech. 2006; 7 (3): 57. doi: 10.1208/pt070357

46. Yenice I, Mocan MC, Palaska E, et al. Hyaluronic acid coated poly-epsiloncaprolactone nanospheres deliver high concentrations of cyclosporine A into the cornea. Exp Eye Res. 2008; 87 (3): 162–7. doi: 10.1016/j.exer.2008.04.002

47. Ciancaglini M, Carpineto P, Agnifili L, et al. An in vivo confocal microscopy and impression cytology analysis of preserved and unpreserved levobunololinduced conjunctival changes. Eur J Ophthalmol. 2008; 18 (3): 400–7. doi: 10.1177/112067210801800314

48. Frezzotti P, Fogagnolo P, Haka G, et al. In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel formulation therapy for glaucoma. Acta Ophthalmol. 2014; 92 (2): e133–140. doi: 10.1111/aos.12261

49. Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea. 2004; 23 (5): 490–6. doi: 10.1097/01.ico.0000116526.57227.82

50. Martone G, Frezzotti P, Tosi GM, et al. An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol. 2009; 147 (4): 725–35 e721. doi: 10.1016/j.ajo.2008.10.019

51. Avetisov S.E., Egorova G.B. Possibilities of confocal microscopy (preliminary communication). Russian journal of clinical ophthalmology. 2006; 7 (2): 45–9 (In Russ.).

52. Fogagnolo P, Dipinto A, Vanzulli E, et al. A 1-year randomized study of the clinical and confocal effects of tafluprost and latanoprost in newly diagnosed glaucoma patients. Adv Ther. 2015; 32 (4): 356–69. doi: 10.1007/s12325-015-0205-5

53. Bergonzi C, Giani A, Blini M, et al. Evaluation of prostaglandin analogue effects on corneal keratocyte density using scanning laser confocal microscopy. J Glaucoma. 2010; 19 (9): 617–21. doi: 10.1097/IJG.0b013e3181ca7c7a

54. Konstas AG, Quaranta L, Katsanos A, et al. Twenty-four hour efficacy with preservative free tafluprost compared with latanoprost in patients with primary open angle glaucoma or ocular hypertension. Br J Ophthalmol. 2013; 97 (12): 1510–5. doi: 10.1136/bjophthalmol-2012-303026

55. Oliveira-Soto L, Efron N. Morphology of corneal nerves using confocal microscopy. Cornea. 2001; 20 (4): 374–84. doi: 10.1097/00003226-200105000-00008

56. Patel S, McLaren J, Hodge D, Bourne W. Normal human keratocyte density and corneal thickness measurement by using confocal microscopy in vivo. Invest Ophthalmol Vis Sci. 2001; 42 (2): 333–9. https://iovs.arvojournals.org/article.aspx?articleid=2123419