Ten Facts Every Ophthalmologist Should Know About Lubricating Eye Drops

Dr Sharon DSouza, MS, FCE
Published Online: April 5th, 2022 | Read Time: 12 minutes, 50 seconds


Artificial tear substitutes lubricate and protect the ocular surface and provide relief from ocular dryness, irritation, and burning sensation. They play a major role in providing symptomatic relief and are widely used for all types of dry eye diseases and nonspecific causes of ocular fatigue as well. Choosing the right kind of lubricating drops is of utmost importance. A number of reasons including lifestyle changes, increased computer and digital screen usage, and awareness of dry eye have resulted in an increase in the utilization of these eye drops. It is important to understand a few simple features of these drops to optimize their beneficial effects.[1] Commercially available lubricating eye drops have varying composition, viscosity, duration of action, preservatives, osmolarity, and pH. This article discusses the composition of tear substitutes and the mechanism of action on the ocular surface.

1. Role of lubricating eye drops on the ocular surface

The main purpose of lubricating eye drops is to decrease dryness and related ocular discomfort by various modes of action depending on it’s content-

  • Humectant - promotes hydration
  • Lubricant- decreases friction on the ocular surface
  • Increases tear retention by increasing tear viscosity, increasing the adherence of the tears to the ocular surface, decreasing tear evaporation, and decreasing tear clearance
  • Protect the eye from hyperosmolarity and counters inflammation.

2. Basic constituents of lubricating eye drops:

  • Viscosity agents
  • Additives
  • Electrolytes
  • Preservatives

3. Viscosity agents

Most lubricants contain a demulcent which is a polymer that can protect and lubricate mucous membranes. These can include-

  • Cellulose derivatives like Carboxymethylcellulose (CMC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC) are viscoelastic polysaccharides that have a good retention time by increasing the viscosity of tears.
  • Polyols include Propylene glycol (PG), and polyethylene glycol (PEG)- need to be combined with another agent to increase viscosity and retention on the ocular surface
  • Carbomers (polyacrylic acid) are synthetic polymers that are viscous but may be associated with blurred vision.
  • Polyvinyl alcohols have good water solubility and low viscosity.
  • Polyvinyl pyrrolidone (PVP) forms hydrophilic coatings in the form of adsorbed layers. They have a good wetting ability when co-formulated with polyvinyl alcohols.[2]
  • Sodium Hyaluronate contains a naturally occurring linear biopolymer called hyaluronic acid which has repeating disaccharide units of N-acetyl-D-glucosamine and sodium-D-glucoronate.[3] Hyaluronic acidbinds multiple times its weight in water thereby lowering tear osmolarity. It also stabilizes the tear film by adhering to the ocular surface.


Emollients are usually fat or oil-based and are applied locally to protect or soften tissues. They are available ashighly viscous formulations like ointments or gel-based solutions and can be used for patients with more severe dry eye who are symptomatic. They have higher viscosity and retention time. These medications are therefore generally advised for bedtime application to stabilize, protect and lubricate the ocular surface for longer periods. Lanolin, mineral oil, paraffin, and petrolatum-based ointments are available in addition to HPMC-based preparations.

5. Additive ingredients

  • L-carnitineandErythritolare seen in combination as osmoprotectants which reduce the damage caused by high osmolarity on the ocular surface. They prevent the activation of stress cascade and the release of proinflammatory mediators.
  • Hydroxypropyl Guar (HP Guar)is a bean protein that stabilizes the tear film by increasing viscosity. It mimics the mucin layer strengthening the attachment of the aqueous layer to the glycocalyx-mucin interface on the ocular surface. It is pH sensitive and pH above 7 results in cross-linking and gelling.
  • Sorbitollowers the viscosity of gelling agents such as HP Guar and HPMC which are too viscous to instill directly onto the eye. After instillation, the dissipation of the sorbitol makes the eyedrop more viscid again.
  • Glycerinacts as a demulcent and a humectant thereby promotes hydration of the ocular surface. It also has additional protective effects against high osmolarity and improves epithelial cell growth.
  • Electrolytes are present in natural tears and also in the various lubricating eye drops. The common electrolytes present in the lubricating eye drops are

Sodium- maintains the osmolarity

Potassium – helps in maintaining goblet cell health

Bicarbonate – has a role in preserving corneal epithelium, maintaining mucin gel.

6. Preservatives vs preservative-free

Artificial tears can contain various types of preservatives or be preservative-free.

Preservatives inhibit bacterial growth and help increase the longevity and shelf life of the medication. Preservatives can be oxidizing, detergent-based, or ionic buffered. The commonly used preservatives currently in artificial tear preparations are quaternary ammonium compounds (benzalkonium chloride (BAK), cetrimide, polyquad, alcohols (chlorobutanol), and other compounds (chlorhexidine, sorbic acid, potassium sorbate). Mercurial agent thimerosal is not preferred as it has a high potential to provoke toxic and allergic reactions. There is an additional group of preservatives known as ‘disappearing’ preservatives.

  • Benzalkonium chloride (BAK): It is a commonly used detergent preservative in concentrations varying from 0.015% to 0.05%. It is a quaternary ammonium compound and in high frequency of instillation over longer duration, it may affect the tear film stability and have toxic effects on the ocular surface. [4]
  • Another class of preservatives are called ‘disappearing’ preservatives as form hydrogen peroxide and further breakdown into water and oxygen on exposure to the eye. Purite, Stabilized oxychloro complex (SOC) and sodium perborate are included in this group.[5] [6]
  • Non-preserved preparations are usually packaged in small sized single use vials(unims) to reduce the risk of contamination. Due to the absence of preservative they are less toxic to the ocular surface but also have a risk of microbial contamination and therefore should be discarded within a few hours of use. These preparations are preferred in patients who need frequent dosing specially in cases of severe dry eye.

7. Role of pH and temperature:

pH changes on the ocular surface also influence rheological properties and viscosity of the eye drop.[7] Commercially available eye drops are noted to have a wide range of pH.[8] It is important to keep this in mind when prescribing a combination of medications ascertain molecules are more viscous at acidic or alkaline pH.

Temperature also has an inverse relation to viscosity therefore with the increase in temperature there is a reduction in the viscosity of the lubricating drop.

8. Retention time – ocular surface residence time

Ocular surface residence time or retention time of the eye drop on the ocular surface depends on various factors including the viscosity of the eye drops, pH of the ocular surface and the lubricant, temperature of the ocular surface, tear clearance, tear evaporation rate and patient’s blink rate. [7]

9. Guidelines for usage

  • Low viscosity eye drops can be used in mild dry eye. As the severity of the dry eye increases, tear lubricant with a higher viscosity may be more beneficial.
  • Ointments and gel-based medications are preferred for nighttime application in view of the blurring of vision induced by these.
  • Increasing the frequency of the tear substitutes is required in severe dry eye.
  • Different tear substitutes may work more effectively in different eyes. Drops with varied mechanisms of action and active ingredients may be tried to decide on the best-suited drug.
  • It is important to be aware of the different preservatives used in the substitutes. Preservative-free drops are preferred in those with severe dry eye disease and those on chronic medications that may have surface toxicity like certain antiglaucoma medications
  • Health care professionals have to take into consideration the work profile, activities and the requirement of the patient to decide on the frequency and timing of the medications.

10. Combination therapy

Combination therapy with topical anti-inflammatory molecules like cyclosporine and tacrolimus are required in patients with underlying systemic or autoimmune disorders like Sjogren's syndrome, Graft Versus Host Disease, rheumatoid arthritis resulting in dry eye. The lubricating eye drops alone cannot be a stand-alone treatment in these conditions.


Lubricating eye drops are the first line of treatment for dry eye disease. Combination therapy with additional medications may be required for more severe diseases. It should be kept in mind that no single drug /brand works best for every form of dry eye. Hence the perfect treatment plan should be tailored according to individual patients having a more holistic approach based on their individual ocular features, type of dry eye, tolerability, visual needs, and frequency of use.


  1. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):163–78.
  2. Calonge M. The treatment of dry eye. Surv Ophthalmol. 2001;45:S227–39.
  3. Doughty MJ, Glavin S. Efficacy of different dry eye treatments with artificial tears or ocular lubricants: a systematic review. Ophthalmic Physiol Opt. 2009;29(6):573–83.
  4. De Saint Jean M, Brignole F, Bringuier AF, Bauchet A, Feldmann G, Baudouin C: Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells.Invest Ophthalmol Vis Sci1999, 40(3):619-630.
  5. Walsh K, Jones L. The use of preservatives in dry eye drops.Clin Ophthalmol. 2019;13:1409-1425. Published 2019 Aug 1. doi:10.2147/OPTH.S211611
  6. Shigeyasu C, Hirano S, Akune Y, Mochizuki H, Yamada M. Evaluation of the frequency of ophthalmic solution application: Washout effects of topical saline application on tear components. Curr Eye Res. 2013;38(7):722–8.
  7. Rahman MQ, Chuah KS, Macdonald EC, Trusler JP, Ramaesh K. The effect of pH, dilution, and temperature on the viscosity of ocular lubricants--shift in rheological parameters and potential clinical significance. Eye (Lond). 2012 Dec;26(12):1579-84. doi: 10.1038/eye.2012.211. Epub 2012 Oct 19. PMID: 23079749; PMCID: PMC3522845.
  8. Tong L, Petznick A, Lee S, Tan J. Choice of artificial tear formulation for patients with dry eye: where do we start? Cornea. 2012;31:S32-36.
Dr Sharon DSouza, MS, FCE
Senior consultant, Department of Cornea and Refractive Services, Chief coordinator, Ocular surface Clinic, Narayana Nethralaya Eye Hospital, Bangalore
Dr Sharon DSouza, MS, FCE is a senior consultant in the Department of Cornea and Refractive services at Narayana Nethralaya eye hospital, Bangalore and is the chief coordinator of the the Ocular surface Clinic there.She competed her medicaleducationfrom St Johns medical college hospital in Bangalore and completed her post graduation in Ophthalmology from the same institute . She went on to do her longterm fellowship inCorneaand Refractive surgery from Narayana Nethralaya followed by an observership at Singapore National eye centre (SNEC). She has a numerous national and internationalresearch publications and has also been invited faculty at various conferences. She is currently pursuing her PhD in immune trafficking on the ocular surface from Maastricht University, Netherlands. Her areas of interest include management of ocular surface related conditions including dry eye, Stevens-Johnson syndrome, chemical injuries, keratoconus, lamellar corneal surgeries and refractive surgery. She is actively involved in training postgraduates and fellowship trainees in the clinics and wetlab skill transfer.
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