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Open Access 07-12-2023 | Timolol | Original Research Article

Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension

Authors: John P. Berdahl, Steven R. Sarkisian Jr, Robert E. Ang, Long V. Doan, Angela C. Kothe, Dale W. Usner, L. Jay Katz, Tomas Navratil, the Travoprost Intraocular Implant Study Group

Published in: Drugs | Issue 1/2024

Abstract

Purpose

A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication.

Methods

Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1–2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters.

Results

Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months.

Conclusion

The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months.

Trial Registry

ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.

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

Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–13. https://doi.org/10.1001/archopht.120.6.701.CrossRefPubMed

Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):714–20. https://doi.org/10.1001/archopht.120.6.714.CrossRefPubMed

Heijl A, Leske MC, Bengtsson B, et al. Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:1268–79. https://doi.org/10.1001/archopht.120.10.1268.CrossRefPubMed

Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2003;121(1):48–56. https://doi.org/10.1001/archopht.121.1.48.CrossRefPubMed

Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126:498–505. https://doi.org/10.1016/s0002-9394(98)00272-4.CrossRef

Lichter PR, Musch DC, Gillespie BW, et al. CIGTS Study Group. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943–53. https://doi.org/10.1016/s0161-6420(01)00873-9.CrossRefPubMed

Chauhan BC, Mikelberg FS, Balaszi AG, et al. Canadian Glaucoma Study: 2. risk factors for the progression of open-angle glaucoma. Arch Ophthalmol. 2008;126:1030–6. https://doi.org/10.1001/archopht.126.8.1030.CrossRefPubMed

Gedde SJ, Vinod K, Wright MM, et al. Primary open-angle glaucoma preferred practice Pattern^®. Ophthalmology. 2021;128(1):71–150. https://doi.org/10.1016/j.ophtha.2020.10.022.CrossRef

10.

Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;385:1295–304. https://doi.org/10.1016/S0140-6736(14)62111-5.CrossRefPubMed

11.

Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140(4):598–606. https://doi.org/10.1016/j.ajo.2005.04.051.CrossRefPubMed

12.

Newman-Casey PA, Robin AL, Blachley T, et al. The most common barriers to glaucoma medication adherence: a cross-sectional survey. Ophthalmology. 2015;122(7):1308–16. https://doi.org/10.1016/j.ophtha.2015.03.026.CrossRefPubMed

13.

Tsai JC. A comprehensive perspective on patient adherence to topical glaucoma therapy. Ophthalmology. 2009;116:S30–6. https://doi.org/10.1016/j.ophtha.2009.06.024.CrossRefPubMed

14.

Schwartz GF, Quigley HA. Adherence and persistence with glaucoma therapy. Surv Ophthalmol. 2008;53(Suppl 1):S57-68. https://doi.org/10.1016/j.survophthal.2008.08.002.CrossRefPubMed

15.

Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116(2):191–9. https://doi.org/10.1016/j.ophtha.2008.09.004.CrossRefPubMed

16.

Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 2011;86(4):304–14. https://doi.org/10.4065/mcp.2010.0575.CrossRefPubMedPubMedCentral

17.

Kholdebarin R, Campbell RJ, Jin Y-P, et al. Multicenter study of compliance and drop administration in glaucoma. Can J Ophthalmol. 2008;43(4):454–61. https://doi.org/10.1139/i08-076.CrossRefPubMed

18.

Robin AL, Covert D. Does adjunctive glaucoma therapy affect adherence to the initial primary therapy? Ophthalmology. 2005;112:863–8. https://doi.org/10.1016/j.ophtha.2004.12.026.CrossRefPubMed

19.

Siani SD, Schoenfeld P, Kaulback K, et al. Effect of dosing frequency on adherence in chronic diseases. Am J Manag Care. 2009;15(6):e22-33.

20.

Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995;26(3):233–6.PubMed

21.

Stone JL, Robin AL, Novack GD, et al. An objective evaluation of eye-drop instillation in glaucoma patients. Arch Ophthalmol. 2009;127:732–6. https://doi.org/10.1001/archophthalmol.2009.96.CrossRefPubMed

22.

Hennessey AL, Katz J, Covert D, et al. A video study of drop instillation in both glaucoma and retina patients with visual impairment. Am J Ophthalmol. 2011;152(6):982–8. https://doi.org/10.1016/j.ajo.2011.05.015.CrossRef

23.

Grant WM, Burke JF Jr. Why do some people go blind from glaucoma? Ophthalmology. 1982;89(9):991–8. https://doi.org/10.1016/s0161-6420(82)34675-8.CrossRefPubMed

24.

Sleath B, Blalock S, Covert D, et al. The relationship between glaucoma medication adherence, eye drop technique, and visual field defect severity. Ophthalmology. 2011;118:2398–402. https://doi.org/10.1016/j.ophtha.2011.05.013.CrossRefPubMed

25.

Paula JS, Furtado JM, Santos AS, et al. Risk factors for blindness in patients with open-angle glaucoma followed-up for at least 15 years. Arq Bras Oftalmol. 2012;75:243–6. https://doi.org/10.1590/s0004-27492012000400004.CrossRefPubMed

26.

Rossi GC, Pasinetti GM, Scudeller L, et al. Do adherence rates and glaucomatous visual field progression correlate? Eur J Ophthalmol. 2011;21:410–4. https://doi.org/10.5301/EJO.2010.6112.CrossRefPubMed

27.

Skalicky SE, Goldberg I, McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012;153(1):1–9. https://doi.org/10.1016/j.ajo.2011.05.033.CrossRefPubMed

28.

Nordmann JP, Auzanneau N, Ricard S, et al. Vision related quality of life and topical glaucoma treatment side effects. Health Qual Life Outcomes. 2003;1:75. https://doi.org/10.1186/1477-7525-1-75.CrossRefPubMedPubMedCentral

29.

Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5):350–5. https://doi.org/10.1097/IJG.0b013e31815c5f4f.CrossRefPubMed

30.

Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29(6):618–21. https://doi.org/10.1097/ICO.0b013e3181c325b2.CrossRefPubMed

31.

Rossi GCM, Tinelle C, Pasinette GM, et al. Dry eye syndrome related quality of life in glaucoma patients. Eur J Ophthalmol. 2009;19(4):572–9. https://doi.org/10.1177/112067210901900409.CrossRefPubMed

32.

Inoue K. Managing adverse effects of glaucoma medications. Clinical Ophthalmol. 2014;8:903–13. https://doi.org/10.2147/OPTH.S44708.CrossRef

33.

Janz NK, Wren PA, Lichter PR, et al. Quality of life in newly diagnosed glaucoma patients: the Collaborative Initial Glaucoma Treatment Study. Ophthalmology. 2001;108(5):887–97. https://doi.org/10.1016/s0161-6420(00)00624-2. (discussion 898).CrossRefPubMed

34.

Brandt JD, Wittpenn JR, Katz LJ, et al. Conjunctival impression cytology in patients with glaucoma using longterm topical medications. Am J Ophthalmol. 1991;112:297–301. https://doi.org/10.1016/s0002-9394(14)76730-3.CrossRefPubMed

35.

Baudouin C, Labbe A, Liang H, et al. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29:312–34. https://doi.org/10.1016/j.preteyeres.2010.03.001.CrossRefPubMed

36.

Baudouin C, Pisella CJ, Fillacier K, et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology. 1999;106(3):556–63. https://doi.org/10.1016/S0161-6420(99)90116-1.CrossRefPubMed

37.

Johnson DH, Yoshikawa K, Brubaker RF, et al. The effect of long-term medical therapy on the outcome of filtration surgery. Am J Ophthalmol. 1994;117:139–48. https://doi.org/10.1016/s0002-9394(14)73068-5.CrossRefPubMed

38.

Arici MK, Arici DS, Topalkara A, et al. Adverse effects of topical antiglaucoma drugs on the ocular surface. Clin Exp Ophthalmol. 2000;28:113–7. https://doi.org/10.1046/j.1442-9071.2000.00237.x.CrossRefPubMed

39.

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

40.

Broadway DC, Grierson I, O’Brien C, et al. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol. 1994;112:1437–45. https://doi.org/10.1001/archopht.1994.01090230051020.CrossRefPubMed

41.

Broadway DC, Grierson I, O’Brien C, et al. Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery. Arch Ophthalmol. 1994;112:1446–54. https://doi.org/10.1001/archopht.1994.01090230060021.CrossRefPubMed

42.

Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and signs with preserved and preservative-free glaucoma medication. Br J Ophthalmol. 2002;86(4):418–23. https://doi.org/10.1136/bjo.86.4.418.CrossRefPubMedPubMedCentral

43.

Broadway D, Hitchings R, Grierson I. Topical antiglaucomatous therapy: adverse effects on the conjunctiva and implications for filtration surgery. J Glaucoma. 1995;4(2):136.CrossRefPubMed

44.

Cvenkel B, Kolko M. Devices and treatments to address low adherence in glaucoma patients: a narrative review. J Clin Med. 2023;12:151–71. https://doi.org/10.3390/jcm12010151.CrossRef

45.

Gooch N, Molokhia SA, Condie R, et al. Ocular drug delivery for glaucoma management. Pharmaceutics. 2012;4(1):197–211. https://doi.org/10.3390/pharmaceutics4010197.CrossRefPubMedPubMedCentral

46.

Shalaby WS, Shankar V, Razeghinejad R, et al. Current and new pharmacotherapeutic approaches for glaucoma. Expert Opin Pharmacother. 2020;21(16):2027–40. https://doi.org/10.1080/14656566.2020.1795130.CrossRefPubMed

47.

Allergan. DURYSTA^TM (bimatoprost implant), for intracameral administration [Prescribing Information]. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3f59da84-0bcc-4c84-b3e2-e215681ef341. Accessed 29 May 2023.

48.

Craven ER, Walters T, Christie WC, et al. 24-Month phase I/II clinical trial of bimatoprost sustained-release implant (bimatoprost SR) in glaucoma patients. Drugs. 2020;80(2):167–79. https://doi.org/10.1007/s40265-019-01248-0.CrossRefPubMed

49.

Medeiros FA, Walters TR, Kolko M, et al. ARTEMIS 1 Study Group. Phase 3, randomized, 20-month study of bimatoprost implant in open-angle glaucoma and ocular hypertension (ARTEMIS 1). Ophthalmology. 2020;127(12):1627–41. https://doi.org/10.1016/j.ophtha.2020.06.018.CrossRefPubMed

50.

Bacharach J, Tatham A, Ferguson G, et al. ARTEMIS 2 Study Group. Phase 3, randomized, 20-month study of the efficacy and safety of bimatoprost implant in patients with open-angle glaucoma and ocular hypertension (ARTEMIS 2). Drugs. 2021;81(17):2017–33. https://doi.org/10.1007/s40265-021-01624-9.CrossRefPubMedPubMedCentral

51.

Nouri-Mahdavi K, Hoffman D, Coleman AL, et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111:1627–35. https://doi.org/10.1016/j.ophtha.2004.02.017.CrossRefPubMed

52.

Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134–42. https://doi.org/10.1097/00061198-200004000-00002.CrossRefPubMed

53.

Caprioli J, Coleman AL. Intraocular pressure fluctuation a risk factor for visual field progression at low intraocular pressures in the advanced glaucoma intervention study. Ophthalmology. 2008;115:1123–9. https://doi.org/10.1016/j.ophtha.2007.10.031.CrossRefPubMed

54.

Leske MC, Heijl A, Hyman L, et al. Early Manifest Glaucoma Trial Group. Predictors of long-term progression in the Early Manifest Glaucoma Trial. Ophthalmology. 2007;114:1965–72. https://doi.org/10.1016/j.ophtha.2007.03.016.CrossRefPubMed

55.

Sharif NA, Kelly CR, Crider JY. Agonist activity of bimatoprost, travoprost, latanoprost, unoprostone isopropyl ester and other prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor. J Ocul Pharmacol Ther. 2002;18(4):313–24. https://doi.org/10.1089/10807680260218489.CrossRefPubMed

Title: Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension
Authors: John P. Berdahl
Steven R. Sarkisian Jr
Robert E. Ang
Long V. Doan
Angela C. Kothe
Dale W. Usner
L. Jay Katz
Tomas Navratil
the Travoprost Intraocular Implant Study Group
Publication date: 07-12-2023
Publisher: Springer International Publishing
Keywords: Timolol
Glaucoma
Hypertension
Hypertension
Published in: Drugs / Issue 1/2024
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-023-01973-7

2024 ASCO Annual Meeting

Springer Medicine

Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension

Abstract

Purpose

Methods

Results

Conclusion

Trial Registry

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Trial Registry

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