Ocular surface toxicity from glaucoma topical medications and associated preservatives such as benzalkonium chloride (BAK)

References

• Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262–267.
   PubMed Web of Science ®Google Scholar
• Varma R, Lee PP, Goldberg I, et al. An assessment of the health and economic burdens of glaucoma. Am J Ophthalmol. 2011 Oct;152(4):515–522.
   PubMed Web of Science ®Google Scholar
• 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 Jun;120(6):701-13;discussion 829-30.
   Google Scholar
• Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001 Nov;108(11):1943–1953.
   PubMed Web of Science ®Google Scholar
• Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative normal-tension glaucoma study group. Am J Ophthalmol. 1998 Oct;126(4):487–497.
   PubMed Web of Science ®Google Scholar
• Organization WH. Priority eye diseases: glaucoma [ cited 2016]. Available from: http://www.who.int/blindness/causes/priority/en/index6.html.
   Google Scholar
• Rafuse PE, Buys YM, Damji KF, et al. Canadian ophthalmological society evidence-based clinical practice guidelines for the management of glaucoma in the adult eye. Can J Ophthalmol. 2009;44(Suppl 1):S7–93.
   Google Scholar
• Prum BE Jr, Rosenberg LF, Gedde SJ, et al. Primary open-angle glaucoma preferred practice pattern((R)) guidelines. Ophthalmology. 2016 Jan;123(1):p41–p111.
   PubMed Web of Science ®Google Scholar
• Anwar Z, Wellik SR, Galor A. Glaucoma therapy and ocular surface disease: current literature and recommendations. Curr Opin Ophthalmol. 2013 Mar;24(2):136–143.
   PubMed Web of Science ®Google Scholar
• The Tear Film & Ocular Surface Society. 2007 report of the international dry eye workshop (DEWS). Ocul Surf. 2007;5(2):127.
   Google Scholar
• Rossi GC, Pasinetti GM, Scudeller L, et al. Risk factors to develop ocular surface disease in treated glaucoma or ocular hypertension patients. Eur J Ophthalmol. 2013 May–Jun;23(3):296–302.
   PubMed Web of Science ®Google Scholar
• Baudouin C, Renard JP, Nordmann JP, et al. Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. Eur J Ophthalmol. 2013;23(1):47–54.
   Web of Science ®Google Scholar
• Baudouin C, Labbé A, Liang H, et al. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010 Jul;29(4):312–334.
   PubMed Web of Science ®Google Scholar
• Nakagawa S, Usui T, Yokoo S, et al. Toxicity evaluation of antiglaucoma drugs using stratified human cultivated corneal epithelial sheets. Investig Opthalmol Vis Sci. 2012 Aug;53(9):5154–5160.
   PubMed Web of Science ®Google Scholar
• Ayaki M, Iwasawa A, Niwano Y. Comparative study of in vitro ocular surface cytotoxicity of a fixed combination of 0.5% timolol/1% dorzolamide eyedrop and its components with 0.005% benzalkonium chloride. Biocontrol Sci. 2012;17(3):115–120.
   PubMed Web of Science ®Google Scholar
• Baudouin C. Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma. Acta Ophthalmol. 2008 Nov;86(7):716–726.
   PubMed Web of Science ®Google Scholar
• Boimer C, Birt CM. Preservative exposure and surgical outcomes in glaucoma patients: the PESO study. J Glaucoma. 2013 Dec;22(9):730–735.
   PubMed Web of Science ®Google Scholar
• Baudouin C. Mechanisms of failure in glaucoma filtering surgery: a consequence of antiglaucomatous drugs? Int J Clin Pharmacol Res. 1996;16(1):29–41.
   PubMedGoogle Scholar
• Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008 Aug;17(5):350–355.
   PubMed Web of Science ®Google Scholar
• Charnock C. Are multidose over-the-counter artificial tears adequately preserved? Cornea. 2006 May;25(4):432–437.
   PubMed Web of Science ®Google Scholar
• Kim MS, Choi CY, Kim JM, et al. Microbial contamination of multiply used preservative-free artificial tears packed in reclosable containers. Br J Ophthalmol. 2008 Nov;92(11):1518–1521.
   PubMed Web of Science ®Google Scholar
• Freeman PD, Kahook MY. Preservatives in topical ophthalmic medications: historical and clinical perspectives. Expert Rev Ophthalmol. 2009;4(1):5.
   Google Scholar
• Paimela T, Ryhänen T, Kauppinen A, et al. The preservative polyquaternium-1 increases cytoxicity and NF-kappaB linked inflammation in human corneal epithelial cells. Mol Vis. 2012;18:1189–1196.
   PubMed Web of Science ®Google Scholar
• López Bernal D, Ubels JL. Quantitative evaluation of the corneal epithelial barrier: effect of artificial tears and preservatives. Curr Eye Res. 1991 Jul;10(7):645–656.
   PubMed Web of Science ®Google Scholar
• Kaur IP, Lal S, Rana C, et al. Ocular preservatives: associated risks and newer options. Cutan Ocul Toxicol. 2009;28(3):93–103.
   PubMed Web of Science ®Google Scholar
• Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma. 2002 Apr;11(2):119–126.
   PubMed Web of Science ®Google Scholar
• Liang H, Pauly A, Riancho L, et al. Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system. Br J Ophthalmol. 2011 Jun;95(6):869–875.
   PubMed Web of Science ®Google Scholar
• Ye J, Wu H, Zhang H, et al. Role of benzalkonium chloride in DNA strand breaks in human corneal epithelial cells. Graefe’s Arch Clin Exp Ophthalmol. 2011 Nov;249(11):1681–1687.
   PubMed Web of Science ®Google Scholar
• Chung S-H, Lee SK, Cristol SM, et al. Impact of short-term exposure of commercial eyedrops preserved with benzalkonium chloride on precorneal mucin. Mol Vis. 2006;12:415–421.
   PubMed Web of Science ®Google Scholar
• Tripathi BJ, Tripathi RC. Cytotoxic effects of benzalkonium chloride and chlorobutanol on human corneal epithelial cells in vitro. Lens Eye Toxic Res. 1989;6(3):395–403.
   PubMedGoogle Scholar
• Debbasch C, Brignole F, Pisella PJ, et al. Quaternary ammoniums and other preservatives’ contribution in oxidative stress and apoptosis on Chang conjunctival cells. Invest Ophthalmol Vis Sci. 2001 Mar;42(3):642–652.
   PubMed Web of Science ®Google Scholar
• Debbasch C, Pisella PJ, De Saint Jean M, et al. Mitochondrial activity and glutathione injury in apoptosis induced by unpreserved and preserved beta-blockers on Chang conjunctival cells. Invest Ophthalmol Vis Sci. 2001 Oct;42(11):2525–2533.
   PubMed Web of Science ®Google Scholar
• Ayaki M, Yaguchi S, Iwasawa A, et al. Cytotoxicity of ophthalmic solutions with and without preservatives to human corneal endothelial cells, epithelial cells and conjunctival epithelial cells. Clin Experiment Ophthalmol. 2008 Aug;36(6):553–559.
   PubMed Web of Science ®Google Scholar
• Ammar DA, Kahook MY. Effects of glaucoma medications and preservatives on cultured human trabecular meshwork and non-pigmented ciliary epithelial cell lines. Br J Ophthalmol. 2011 Oct;95(10):1466–1469.
   PubMed Web of Science ®Google Scholar
• Chen W, Hu J, Zhang Z, et al. Localization and expression of zonula occludins-1 in the rabbit corneal epithelium following exposure to benzalkonium chloride. PLoS One. 2012;7(7):e40893.
   Google Scholar
• Baudouin C, Riancho L, Warnet J-M, et al. In vitro studies of antiglaucomatous prostaglandin analogues: travoprost with and without benzalkonium chloride and preserved latanoprost. Investig Opthalmol Vis Sci. 2007 Sep;48(9):4123–4128.
   PubMed Web of Science ®Google Scholar
• Chen W, Li Z, Hu J, et al. Corneal alternations induced by topical application of benzalkonium chloride in rabbit. PLoS One. 2011;6(10):e26103.
   PubMed Web of Science ®Google Scholar
• Chen W, Zhang Z, Hu J, et al. Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride. Cornea. 2013 Dec;32(12):1599–1606.
   PubMed Web of Science ®Google Scholar
• Sarkar J, Chaudhary S, Namavari A, et al. Corneal neurotoxicity due to topical benzalkonium chloride. Investig Opthalmol Vis Sci. 2012 Apr;53(4):1792–1802.
   PubMed Web of Science ®Google Scholar
• Ichijima H, Petroll WM, Jester JV, et al. Confocal microscopic studies of living rabbit cornea treated with benzalkonium chloride. Cornea. 1992 May;11(3):221–225.
   PubMed Web of Science ®Google Scholar
• Kusano M, Uematsu M, Kumagami T, et al. Evaluation of acute corneal barrier change induced by topically applied preservatives using corneal transepithelial electric resistance in vivo. Cornea. 2010 Jan;29(1):80–85.
   PubMed Web of Science ®Google Scholar
• Noecker R, Miller KV. Benzalkonium chloride in glaucoma medications. Ocul Surf. 2011 Jul;9(3):159–162.
   PubMed Web of Science ®Google Scholar
• Chen W, Dong N, Huang C, et al. Corneal alterations induced by topical application of commercial latanoprost, travoprost and bimatoprost in rabbit. PLoS One. 2014;9(3):e89205.
   Google Scholar
• Barabino S, Antonelli S, Cimbolini N, et al. The effect of preservatives and antiglaucoma treatments on the ocular surface of mice with dry eye. Investig Opthalmol Vis Sci. 2014 Oct;55(10):6499–6504.
   PubMed Web of Science ®Google Scholar
• Brignole-Baudouin F, Desbenoit N, Hamm G, et al. A new safety concern for glaucoma treatment demonstrated by mass spectrometry imaging of benzalkonium chloride distribution in the eye, an experimental study in rabbits. PLoS One. 2012;7(11):e50180.
   PubMed Web of Science ®Google Scholar
• Desbenoit N, Schmitz-Afonso I, Baudouin C, et al. Localisation and quantification of benzalkonium chloride in eye tissue by TOF-SIMS imaging and liquid chromatography mass spectrometry. Anal Bioanal Chem. 2013 May;405(12):4039–4049.
   PubMed Web of Science ®Google Scholar
• Acheampong AA, Small D, Baumgarten V, et al. Formulation effects on ocular absorption of brimonidine in rabbit eyes. J Ocul Pharmacol Ther. 2002 Aug;18(4):325–337.
   PubMed Web of Science ®Google Scholar
• Baratz KH, Nau CB, Winter EJ, et al. Effects of glaucoma medications on corneal endothelium, keratocytes, and subbasal nerves among participants in the ocular hypertension treatment study. Cornea. 2006 Oct;25(9):1046–1052.
   PubMed Web of Science ®Google Scholar
• 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 Apr;147(4):725–735.e1.
   PubMed Web of Science ®Google Scholar
• 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 Mar;92(2):e133–e140.
   Google Scholar
• Friedlaender MH, Breshears D, Amoozgar B, et al. The dilution of benzalkonium chloride (BAK) in the tear film. Adv Ther. 2006 Nov–Dec;23(6):835–841.
   PubMed Web of Science ®Google Scholar
• Tressler CS, Beatty R, Lemp MA. Preservative use in topical glaucoma medications. Ocul Surf. 2011 Jul;9(3):140–158.
   PubMed Web of Science ®Google Scholar
• Skalicky SE, Goldberg I, McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012 Jan;153(1):1–9.e2.
   PubMed Web of Science ®Google Scholar
• Jaenen N, Baudouin C, Pouliquen P, et al. Ocular symptoms and signs with preserved and preservative-free glaucoma medications. Eur J Ophthalmol. 2007 May–Jun;17(3):341–349.
   PubMed Web of Science ®Google Scholar
• Goldberg I, Graham SL, Crowston JG, et al. Clinical audit examining the impact of benzalkonium chloride-free anti-glaucoma medications on patients with symptoms of ocular surface disease. Clin Experiment Ophthalmol. 2015 Apr;43(3):214–220.
   PubMed Web of Science ®Google Scholar
• Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular symptoms and signs with preserved and preservative-free glaucoma medication. Br J Ophthalmol. 2002 Apr;86(4):418–423.
   PubMed Web of Science ®Google Scholar
• Herreras JM, Pastor JC, Calonge M, et al. Ocular surface alteration after long-term treatment with an antiglaucomatous drug. Ophthalmology. 1992 Jul;99(7):1082–1088.
   PubMed Web of Science ®Google Scholar
• Ishibashi T, Yokoi N, Kinoshita S. Comparison of the short-term effects on the human corneal surface of topical timolol maleate with and without benzalkonium chloride. J Glaucoma. 2003 Dec;12(6):486–490.
   PubMed Web of Science ®Google Scholar
• Shedden A, Adamsons IA, Getson AJ, et al. Comparison of the efficacy and tolerability of preservative-free and preservative-containing formulations of the dorzolamide/timolol fixed combination (COSOPT) in patients with elevated intraocular pressure in a randomized clinical trial. Graefe’s Arch Clin Exp Ophthalmol. 2010 Dec;248(12):1757–1764.
   PubMed Web of Science ®Google Scholar
• Katz G, Springs CL, Craven ER, et al. Ocular surface disease in patients with glaucoma or ocular hypertension treated with either BAK-preserved latanoprost or BAK-free travoprost. Clin Ophthalmol. 2010;4:1253–1261.
   PubMedGoogle Scholar
• Aydin Kurna S, Acikgoz S, Altun A, et al. The effects of topical antiglaucoma drugs as monotherapy on the ocular surface: a prospective study. J Ophthalmol. 2014;2014:1–8.
   Web of Science ®Google Scholar
• Kanamoto T, Kiuchi Y, Tanito M, et al. Comparison of the toxicity profile of benzalkonium chloride-preserved tafluprost and SofZia-preserved travoprost applied to the ocular surface. J Ocul Pharmacol Ther. 2015 Apr;31(3):156–164.
   PubMed Web of Science ®Google Scholar
• Trocme S, Hwang L-J, Bean GW, et al. The role of benzalkonium chloride in the occurrence of punctate keratitis: a meta-analysis of randomized, controlled clinical trials. Ann Pharmacother. 2010 Dec;44(12):1914–1921.
   PubMed Web of Science ®Google Scholar
• Eagle RC. Conjunctiva. In: Eagle RC, editor. Eye pathology an atlas and text. 2nd ed. Philadelphia (PA): Wolters Kluwer Health/Lippincott Williams & Wilkins; 2010. p. 53.
   Google Scholar
• Sehu KaW WR. Conjunctiva. In: Sehu KaW WR, ed. Ophthalmic pathology: an illustrated guide for clinicians. Malden (MA): Blackwell Publishing Ltd.; 2005.
   Google Scholar
• Ahmed I, Patton TF. Importance of the noncorneal absorption route in topical ophthalmic drug delivery. Invest Ophthalmol Vis Sci. 1985 Apr;26(4):584–587.
   PubMed Web of Science ®Google Scholar
• A vG. Therapeutische miscellen. I. Aqua chlori. Arch Fur Ophthalmol. 1864;10(2):191–233.
   Google Scholar
• Wilson FM. Adverse external ocular effects of topical ophthalmic medications. Surv Ophthalmol. 1979 Sep–Oct;24(2):57–88.
   PubMed Web of Science ®Google Scholar
• Albietz JM, Bruce AS. The conjunctival epithelium in dry eye subtypes: effect of preserved and non-preserved topical treatments. Curr Eye Res. 2001 Jan;22(1):8–18.
   PubMed Web of Science ®Google Scholar
• Broadway D, Grierson I, Hitchings R. Adverse effects of topical antiglaucomatous medications on the conjunctiva. Br J Ophthalmol. 1993 Sep;77(9):590–596.
   PubMed Web of Science ®Google Scholar
• Williams DE, Nguyen KD, Shapourifar-Tehrani S, et al. Effects of timolol, betaxolol, and levobunolol on human tenon’s fibroblasts in tissue culture. Invest Ophthalmol Vis Sci. 1992 Jun;33(7):2233–2241.
   PubMed Web of Science ®Google Scholar
• Sherwood MB, Grierson I, Millar L, et al. Long-term morphologic effects of antiglaucoma drugs on the conjunctiva and Tenon’s capsule in glaucomatous patients. Ophthalmology. 1989 Mar;96(3):327–335.
   PubMed Web of Science ®Google Scholar
• Broadway DC, Grierson I, O’Brien C, et al. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol. 1994 Nov;112(11):1437–1445.
   PubMedGoogle Scholar
• Nuzzi R, Vercelli A, Finazzo C, et al. Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study. Graefe’s Arch Clin Exp Ophthalmol. 1995 Mar;233(3):154–162.
   PubMed Web of Science ®Google Scholar
• Baudouin C, Pisella PJ, Fillacier K, et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology. 1999 Mar;106(3):556–563.
   PubMed Web of Science ®Google Scholar
• Huang C, Wang H, Pan J, et al. Benzalkonium chloride induces subconjunctival fibrosis through the COX-2-modulated activation of a TGF-beta1/Smad3 signaling pathway. Invest Ophthalmol Vis Sci. 2014 Dec;55(12):8111–8122.
   PubMed Web of Science ®Google Scholar
• De Saint Jean M, Debbasch C, Brignole F, et al. Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells. Curr Eye Res. 2000 Feb;20(2):85–94.
   PubMed Web of Science ®Google Scholar
• Pisella PJ, Debbasch C, Hamard P, et al. Conjunctival proinflammatory and proapoptotic effects of latanoprost and preserved and unpreserved timolol: an ex vivo and in vitro study. Invest Ophthalmol Vis Sci. 2004 May;45(5):1360–1368.
   PubMed Web of Science ®Google Scholar
• Labbé A, Gabison E, Brignole-Baudouin F, et al. Increased extracellular matrix metalloproteinase inducer (EMMPRIN) expression in the conjunctival epithelium exposed to antiglaucoma treatments. Curr Eye Res. 2015 Jan;40(1):40–47.
   PubMed Web of Science ®Google Scholar
• Epstein SP, Ahdoot M, Marcus E, et al. Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009 Apr;25(2):113–119.
   PubMed Web of Science ®Google Scholar
• Longstaff S, Wormald RP, Mazover A, et al. Glaucoma triple procedures: efficacy of intraocular pressure control and visual outcome. Ophthalmic Surg. 1990 Nov;21(11):786–793.
   PubMedGoogle Scholar
• Lavin MJ, Wormald RP, Migdal CS, et al. The influence of prior therapy on the success of trabeculectomy. Arch Ophthalmol. 1990 Nov;108(11):1543–1548.
   PubMedGoogle Scholar
• Broadway DC, Grierson I, O’Brien C, et al. Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery. Arch Ophthalmol. 1994 Nov;112(11):1446–1454.
   PubMedGoogle Scholar
• Aptel F, Cucherat M, Denis P. Efficacy and tolerability of prostaglandin analogs: a meta-analysis of randomized controlled clinical trials. J Glaucoma. 2008 Dec;17(8):667–673.
   PubMed Web of Science ®Google Scholar
• Aptel F, Cucherat M, Denis P. Efficacy and tolerability of prostaglandin-timolol fixed combinations: a meta-analysis of randomized clinical trials. Eur J Ophthalmol. 2012 Jan–Feb;22(1):5–18.
   PubMed Web of Science ®Google Scholar
• Ayaki M, Iwasawa A, Inoue Y. Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells. Clin Ophthalmol. 2010;4:1217–1222.
   PubMedGoogle Scholar
• Brasnu E, Brignole-Baudouin F, Riancho L, et al. In vitro effects of preservative-free tafluprost and preserved latanoprost, travoprost, and bimatoprost in a conjunctival epithelial cell line. Curr Eye Res. 2008 Apr;33(4):303–312.
   PubMed Web of Science ®Google Scholar
• Pauly A, Roubeix C, Liang H, et al. In vitro and in vivo comparative toxicological study of a new preservative-free latanoprost formulation. Investig Opthalmol Vis Sci. 2012 Dec;53(13):8172–8180.
   PubMed Web of Science ®Google Scholar
• Smedowski A, Paterno JJ, Toropainen E, et al. Excipients of preservative-free latanoprost induced inflammatory response and cytotoxicity in immortalized human HCE-2 corneal epithelial cells. J Biochem Pharmacol Res. 2014 Dec 1;2(4):175–184.
   PubMedGoogle Scholar
• Viswanathan D, Goldberg I, Graham SL. Longitudinal effect of topical antiglaucoma medications on central corneal thickness. Clin Experiment Ophthalmol. 2013 May–Jun;41(4):348–354.
   PubMed Web of Science ®Google Scholar
• Guenoun J-M, Baudouin C, Rat P, et al. In vitro comparison of cytoprotective and antioxidative effects of latanoprost, travoprost, and bimatoprost on conjunctiva-derived epithelial cells. Investig Opthalmol Vis Sci. 2005 Dec;46(12):4594–4599.
   PubMed Web of Science ®Google Scholar
• Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol. 2000 Sep;118(9):1264–1268.
   PubMed Web of Science ®Google Scholar
• Abegão Pinto L, Vandewalle E, Gerlier L, et al. Improvement in glaucoma patient quality of life by therapy switch to preservative-free timolol/dorzolamide fixed combination. Ophthalmologica. 2014;231(3):166–171.
   PubMed Web of Science ®Google Scholar
• Iester M, Telani S, Frezzotti P, et al. Ocular surface changes in glaucomatous patients treated with and without preservatives beta-blockers. J Ocul Pharmacol Ther. 2014 Aug;30(6):476–481.
   PubMed Web of Science ®Google Scholar
• Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419–1431.
   PubMed Web of Science ®Google Scholar
• Lowder C, Belfort R Jr., Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011 May;129(5):545–553.
   PubMed Web of Science ®Google Scholar
• Phase 2b study evaluating safety and efficacy of OTX-TP compared to timolol drops in the treatment of subjects with open angle glaucoma or ocular hypertension; 2016 [cited 2016 Mar 9]. Available from: https://clinicaltrials.gov/ct2/show/NCT02312544?term=Sustained+Release+Travoprost&rank=1.
   Google Scholar
• Brandt JD, DuBiner HB, Benza R, et al. Reduction in IOP from a sustained-release bimatoprost ocular insert: mid-term results of an open-label extension study (OLE study). American Glaucoma Society Annual meeting; 2016 Mar 3–6; FL, USA.
   Google Scholar
• Franca JR, Foureaux G, Fuscaldi LL, et al. Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. PLoS One. 2014;9(4):e95461.
   PubMed Web of Science ®Google Scholar
• Allergan. Safety and efficacy of bimatoprost sustained-release (SR) in patients with open-angle glaucoma or ocular hypertension. ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [2016]; 2016 [cited 2016 May-23]. Available from: https://clinicaltrials.gov/ct2/show/NCT02250651.
   Google Scholar
• Lee SSAA, Almazan AS, Li H, et al. Additive ocular hypotensive effects of bimatoprost sustained-release intracameral implant on potent topical therapy in monkeys. Invest Ophthalmol Vis Sci. 2016 (Abstract 3006):215.
   Google Scholar
• Seal JPS, Perera S, Coote M, et al. Intracameral administration of a sustained release Bimatoprost implant efficiently delivers bimatoprost to target tissue reducing risk of topical prostaglandin analog-associated adverse events. Invest Ophthalmol Vis Sci. 2016; ARVO annual meeting (Abstract 3012):216.
   Google Scholar
• Williams DF, Phase A. 2 study evaluating safety and efficacy of the latanoprost punctal plug delivery system (L-PPDS) in subjects with ocular hypertension (OH) or open-angle glaucoma (OAG). Invest Ophthalmol Vis Sci. 2012;53(14):5095.
   PubMed Web of Science ®Google Scholar
• Hsu K-H, Carbia BE, Plummer C, et al. Dual drug delivery from vitamin E loaded contact lenses for glaucoma therapy. Eur J Pharmaceut Biopharmaceut. 2015;94:312–321.
   PubMed Web of Science ®Google Scholar
• Voss K, Falke K, Bernsdorf A, et al. Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment. J Control Release. 2015 Sep 28;214:1–11.
   PubMed Web of Science ®Google Scholar
• Wong TT, Novack GD, Natarajan JV, et al. Nanomedicine for glaucoma: sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops. Drug Deliv Transl Res. 2014 Aug;4(4):303–309.
   PubMed Web of Science ®Google Scholar
• Fakhraie G, Lopes JF, Spaeth GL, et al. Effects of postoperative cyclosporine ophthalmic emulsion 0.05% (Restasis) following glaucoma surgery. Clin Experiment Ophthalmol. 2009 Dec;37(9):842–848.
   PubMed Web of Science ®Google Scholar