A comparative study of benzalkonium chloride-free latanoprost versus benzalkonium chloride-preserved latanoprost on ocular surface health in patients of primary open angle glaucoma

Hema Chhabra, Anita Gupta, Gursatinder Singh


Background: Prolonged use of anti-glaucoma therapy leads to development of ocular surface disease (OSD). The purpose of this study was to compare the effect of Benzalkonium chloride (BKC)-free latanoprost and Benzalkonium chloride (BKC)-preserved latanoprost on ocular surface health in patients of primary open angle glaucoma (POAG).

Methods: This was a prospective, open-label, randomized, interventional, switch trial. 30 established cases of POAG who were already on BKC-preserved latanoprost for atleast more than three months were enrolled. Their Schirmer test and Tear film break-up time (TBUT) were recorded at the baseline. They were required to answer an ocular surface disease index (OSDI) questionnaire from which an OSDI score was calculated. They were switched to BKC-free latanoprost for another three months. On their follow-up visit at 6 weeks and 12 weeks, Schirmer test and Tear film break up time were performed again and OSDI score was calculated.

Results: Schirmer test increased from 6.73±3.77 mm at baseline to 9.53±3.67 mm at 6 weeks and 11.97±3.53 mm at 12 weeks (p=0.001). Mean TBUT improved significantly from 6.77±3.82 seconds at baseline to 8.63±3.91 seconds at 6 weeks to 10.47±3.76 seconds at 12 weeks (p=0.001). OSDI score decreased from 31.55±23.32 at baseline to 23.42±21.93 at 6 weeks to 15.82±20.10 at 12 weeks (p=0.001).

Conclusions: BKC-free latanoprost led to improvement in tear film status or ocular surface health of glaucoma patients as compared to BKC-preserved latanoprost.


Benzalkonium chloride, Dry eye, Glaucoma, Latanoprost, Ocular surface disease, Preservative free

Full Text:



Causes of blindness and visual impairment: Prevention of Blindness and Visual Impairment: World Health Organization;2002. Available at 6 December 2016.

Lee DA, Higginbotham EJ. Glaucoma and its treatment: A review. Am J Health Syst Pharm. 2005;62(7):691-9.

Guidance for industry – container and closure system integrity testing in lieu of sterility testing as a component of the stability protocol for sterile products. Rockville, MD, USA: Food and Drug Administration. 2008 Feb. Available at Accessed 6 December 2016.

Freeman PD, Kahook MY. Preservatives in Topical Ophthalmic Medications: Historical and Clinical Perspectives. Expert Rev Ophthalmol. 2009;4(1):59-64.

De Saint JM, Debbasch C, Brignole F, Rat P, Warnet JM. Toxicity of preserved and unpreserved antiglaucoma topical drugs in an in vitro model of conjunctival cells. Curr. Eye Res. 2000;20:85-94.

De Saint JM, Brignole F, Bringuier A, Bauchet A, Feldmann G. Effects of BKC on growth and survival of Chang conjunctival cells. Invest Ophthalmol Vis Sci.1999;40:619-30.

Baudouin C, de Lunardo C. Short-term comparative study of topical 2% carteolol with and without benzalkonium chloride in healthy volunteers. Br J. Ophthalmol. 1998;82:39-42.

Sachdeva M, Yadava U, Bamrolia N. Pharmacokinetics of Antiglaucoma Medications. J Current Glaucoma Practice. 2011;5(2):21-6.

Jandrokovic S, Suic SP, Kordic R, Kuzman T, Petricek I. Tear Film Status in Glaucoma Patients. Coll Antropol. 2013;37(1):137-40.

Özcura F, Aydin S, Helvaci MR. Ocular surface disease index for the diagnosis of dry eye syndrome. Ocular Immunol Inflamm. 2007;15(5):389-93.

Kuppens EVMJ, de Jong CA, Stolwijk TR, de Keizer RJW, Best JAV. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol. 1995;79:339-42.

Martone G, Frezzotti P, Tosi GM. 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.

Uusitalo H, Chen E, Pfeiffer N. Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication. Acta Ophthalmol. 2010;88(3):329-36.

Cvenkel B, Stunf S, Kirbis IS, Flezar MS. Symptoms and signs of ocular surface disease related to topical medication in patients with glaucoma. Clin Ophthalmol. 2015;9:625-31.

Katz G, Springs CL, Craven ER, Palmer MM. Ocular surface disease in patients with glaucoma or ocular hypertension treated with either BAK-preserved latanoprost or BAK-free travoprost. Clin Ophthalmol.2010;4:1253-61.

Walimbe T, Chelerkar V, Bhagat P, Joshi A, Raut A. Effect of benzalkonium chloride-free latanoprost ophthalmic solution on ocular surface in patients with glaucoma. Clin Ophthalmol. 2016;10:821-7.

Tomić M, Kaštelan S, Soldo KM, Rabatić JS. How ocular surface disease impacts the glaucoma treatment outcome. Biomed Res Int. 2013;2013:1-7.

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.

Jaenen N, Baudouin C, Poliquen P. Ocular symptoms and signs with preserved and preservative-free glaucoma medications. Eur J Ophthalmol. 2007;17:341-9.

Uusitalo H, Egorov E, Kaarniranta K, Astakhov Y, Ropo A. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta-analysis of two phase IIIb clinical trials. Clin Ophthalmol. 2016;10:445-54.