PF alternatives exist to avoid potential challenges with preservatives 

Use of Preservatives

Preservatives have been in use since the 1970s when regulatory authorities instituted antimicrobial usage in multi-dose containers to prevent eye infections and sustain drug potency.1 

The table below displays some preservatives in use today, where benzalkonium chloride (BAK) is the most common variety used in 70% of eye drops.2  BAK is a quaternary ammonium surfactant used in concentrations of 0.004% to 0.025% to break down bacterial cell structures and prevent microbial growth.3

PreservativeClassMedication UsedBrand NamePreservative
Benzalkonium Chloride (BAK or BAC)Quaternary AmmoniumLatanoprost
Artificial Tear
Advanced Eye Relief
Polyquaternium-1 (Polyquad or PQ1)DetergentTravoprost
Artificial Tear
Tears Naturale II
Sodium Chlorite (Purite)OxidantBrimonidineAlphagan PN/A

Potential Challenges with Preservatives

The effectiveness to which preservatives like BAK attack microbes and bacteria unfortunately also may present adverse effects to the cornea, conjunctival epithelium, and trabecular meshwork.4  BAK-filled eye drops can be most problematic when used to treat chronic conditions such as glaucoma and dry eye disease, where long-term exposure may lead to deleterious effects.5,6

  • 80% toxicity level increase of cultured cornea and conjunctiva cells after exposure to BAK at 0.025%.4
  • 53% reduction of cultured trabecular meshwork (TM) cells after exposure to BAK 0.020%7, which may cause further TM degeneration and potentially reduce the effectiveness of IOP-lowering glaucoma medications. 8
  • 59% of glaucoma patients treated with BAK-preserved medications report symptoms of OSD (Ocular Surface Disease includes dry eye, lid disease, conjunctivitis, and keratitis). 9
  • 7 out of 10 patients feel significantly reduced OSD symptoms when using glaucoma medications free of BAK preservatives.10

Available Preservative-Free Formulations*

Along with the use of single-dose vials which can be more costly and cumbersome to maintain, ImprimisRx® has several preservative-free ophthalmic formulations* (Simple Drops® and Total Tears®) utilizing our PureFlow® technology.11

Several factors affect tolerance of preservatives, including their concentration, frequency of the use of the medication, duration of treatment, the physiologic state of the cornea, the use of contact lenses, and the number and type of concurrent medications.12 Consult with a medical professional about which preservative-free options from ImprimisRx® may be right for you.

*For professional use only. ImprimisRx® specializes in customizing medications to meet unique patient and practitioner needs. ImprimisRx dispenses only to individually identified patients with valid prescriptions. No compounded medication is reviewed by the FDA for safety or efficacy. ImprimisRx does not compound essential copies of commercially available products. References available upon request.


  1. The United States Pharmacopeia, 24. Revision ; NF 19 : the National Formulary, 19 Ed. Supplement
  2. Rosin LM, Bell NP. Preservative toxicity in glaucoma medication: clinical evaluation of benzalkonium chloride-free 0.5% timolol eye drops. Clin Ophthalmol. 2013;7:2131-2135.
  3. Berdy GJ, Abelson MB, Smith LM, George MA. Preservative-free artificial tear preparations. Assessment of corneal epithelial toxic effects. Arch Ophthalmol. 1992 Apr;110(4):528-32.
  4. Epstein SP, Ahdoot M, Marcus E, Asbell PA. Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009 Apr;25(2):113-9. 
  5. Champeau EJ, Edelhauser HF. Effect of ophthalmic preservatives on the ocular surface: conjunctival and corneal uptake and distribution of benzalkonium chloride and chlorhexidine digluconate. In: Holly F., Lamberts D., MacKeen D., eds. The Preocular Tear Film in Health, Disease, and Contact Lens Wear. Lubbock, TX: Dry Eye Institute, Inc.; 292–302, 1986
  6. Samples JR, Binder PS, Nayak S. The effect of epinephrine and benzalkonium chloride on cultured corneal endothelial and trabecular meshwork cells. Exp Eye Res. 1989 Jul;49(1):1-12.
  7. Ammar DA, Kahook MY. Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells. Mol Vis. 2011;17:1806-13.
  8. Baudouin C, Denoyer A, Desbenoit N, Hamm G, Grise A. In vitro and in vivo experimental studies on trabecular meshwork degeneration induced by benzalkonium chloride (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2012 Dec;110:40-63.
  9. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008 Aug;17(5):350-5.
  10. Batra R, Tailor R, Mohamed S. Ocular surface disease exacerbated glaucoma: optimizing the ocular surface improves intraocular pressure control. J Glaucoma. 2014 Jan;23(1):56-60.
  11. Nemera Novelia Product Performance & Microbiological package. (2017)
  12. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):163-78.