Human tears are composed of water, electrolytes, small molecules such as carbohydrates and lipids, and a variety of proteins, several of which have an enzymic function. The principal proteins of tears include lysozyme (an enzyme which attacks bacterial cell walls), lactoferrin (a bacteriostatic protein), secretory IgA antibodies, and lipid binding proteins.
The use of artificial tears has obvious limitations. Artificial tears cannot completely substitute complex composition of natural tears. The integrity of the three-layered lipid, aqueous, and mucin structure, vital to the effective functioning of the tear film is not reproduced.

Artificial tears act by adding volume of the tear film, but they can only do this while they remain in contact with the surface of the eye. A simple saline eyedrop will remain in contact with the eye surface for only a few seconds. Therefore to be effective, a viscosity enhancing component is required in the artificial tear formulation.
Hydrogels are the viscosity enhancing ingredients of artificial tears. Hydrogels make the artificial tears more viscous so they stay on the eye for longer time. The mucous adhesive property of hydrogels also help in prolonging the time tears stay on the eye. Hydrogels are actually polymers that are endowed with the property of swelling up in water and retaining the moisture. The following hydrogels have been used in artificial tears: Hydroxypropyl Methylcellulose (HPMC), Carboxy Methylcellulose (CMC), Polyvinyl Alcohol (PVA), Carbopol, polyvinyl pyrrolidone, polyethylene glycol, dextran, hyaluronic acid, or carbomer 940 (polyacrylic acid).
Artificial tears may also contain glycine, magnesium chloride, and zinc chloride, all of which are found in natural tears. Sodium borate, a mild antiseptic, and other desirable ingredients may also be included.

Preservatives are added to increase the shelf life of artificial tears and to facilitate the use of multi-dose bottles. The more commonly used preservatives are Benzalkonium Chloride (BAC) and Chlorobutanol. Benzalkoniun Chloride (BAC) can increase the eye surface irritation and disease. The newer preservatives such as GenAqua (Sodium Perborate) and Polyquad (Polyquaternium-1) are less damaging to the eye surface than BAC. (Graefes Arch Clin Exp Ophthalmol. 1989;227(2):139-41, Curr Eye Res. 1991 Jul;10(7):645-56).
Patients with severe dry-eye who use artificial tears frequently should avoid tear solutions containing BAC. If preserved solutions are used then GenAua or Polyquad containing tears are better choices. Non-preserved solutions are preferable for treatment of these patients. However, non-preserved tears are more expensive and are dispensed in single use vials. A recent study showed that refrigeration of opened preservative free tears in closed zip-lock plastic bags for 12 hours does not have a significant effect on the solution. Storage of preservative free artificial tears for 12 hours in a refrigerator, therefore seems to be reasonable (Optom Vis Sci 2001;78:37-9).

Despite the addition of hydrogels, artificial tears provide short term relief because of brief retention time on the eye surface. There are currently two strategies available to increase the retention time of artificial tears. The more recent development is the introduction of ingredients that have some bioadhesive properties. Systane uses this strategy. It contains HP-Guar. Once exposed to the eye surface pH (7.5), HP-Guar in Systane forms a 'sof gel' with increased viscosity and bioadhesive properties that promote the retention of its two demulcents (polyethylene glycol 400 & polypropylene glycol). (Curr Eye Res. 2004 Jan;28(1):55-62).
The other strategy to increase the retention time is to make more viscous artificial tears. The viscous tears are not easily drained out of the eye through the lacrimal outflow system and therefore have a longer retention time. Viscous artificial tears may cause unacceptable blurry vision in some individuals. Celluvisc is a 1.0% solution of a high-viscosity Carboxymethyl Cellulose (CMC). Liquigel is also a 1.0% solution of CMC , however it is blended from a 0.35% high-viscosity and a 0.65% medium-viscosity CMC. This results in Liquigel being less viscous than Celluvisc. The viscous Celluvisc results in a moderate amount of blurry vision that gradually subsides. It takes about 24 minutes for the vision (contrast sensitivity function) to return to baseline values after a drop of Celluvisc is instilled in the eye. In contrast, after a drop of Liquigel it takes about 13 minutes to return to baseline contrast values. In patients who find the vision blurring after highly viscous artificial tears like Celluvisc unacceptable, the shorter duration of blurry vision with Liquigel, (approximately half that of Celluvisc), may be more acceptable. Higher viscosity tears can cause eye irritation by the crystallization on lids and lashes.(Optom Vis Sci 2005;82:370-377)

ViscosityRetention time on eye surface

Celluvisc350+ + + + + +
Liquigel70+ + +
Systane10+ + +
Refresh Tears3+

We list below guidelines that may be helpful in treating dry eyes. The guidelines listed below are derived from a review of the published literature.

  ● In dry eyes tear osmolarity increases. The tear hyperomolarity has been shown to cause ocular surface disease. Moderately hypotonic artificial tears has been shown to promote ocular surface disease healing in severe dry eyes. Available hypotonic tears include: Thera Tears, Hypotears and Akwa Tears. (Br J Ophthalmol. 2002 Aug;86(8):879-84, Ophthalmologica. 2001 Mar-Apr;215(2):124-7)
  ● Bicarbonate containing artificial tears have been shown to promote healing in severe dry eyes. Available bicarbonate containing tears include: Bion Tears, Murine Tears. (Arch Ophthalmol. 1995 Mar;113(3):371-8, Cornea. 1993 Mar;12(2):115-20)
  ● Prolonging the contact time of artificial tears on the cornea helps. This can be achieved using a gelling agent such as HP-guar (Systane), or using a viscous eye drop (Celluvisc/Liquigel).(Curr Med Res Opin. 2005 Feb;21(2):255-60, Curr Eye Res. 2004 Jan;28(1):55-62)
  ● Non preserved drops are the best. However if preserved eyedrops are to be used, then newer preservatives like GenAqua (Genteal Tears) are preferable to Benzalkonium chloride (BAC). When eyedrops containing Benzalkonium chloride (BAC) preservative are used frequently, some patients develop a condition called 'medicamentosa'. This condition mimics a severely irritated dry eye. The treatment is to stop the eyedrop and switching to non-preserved eyedrops.
  ● Oil containing eyedrops (Refresh Endura, Soothe) may be added if meibomian gland dysfunction is present. These eyedrops will replenish the lipid layer of the tear film and prevent tear evaporation. Warm compresses over closed eyelids for 5 minutes will also replenish the lipid layer.
  ● In severe dry eyes and unresponsive surface disease patients have significant visual impairment and disability. In such patients the use of autologus serum eye drops has been shown to help. . Natural human tears contain many growth factors, antibodies etc. Since these growth factors are present in serum, using serum eyedrops may provide the surface healing properties of natural tears. The major disadvantage of serum treatment is the requirement for blood donation. The active components of serum are stable for up to 6 months therefore bleeding and serum preparation are required two to three times a year. A standard method to prepare the serum eyedrops has been described. Blood banks may help you in preparing serum eyedrops.(Br J Ophthalmol. 2004 May;88(5):647-52, Graefes Arch Clin Exp Ophthalmol. 2005 Mar 9)

It is apparent that there is no single artificial tear eyedrop that provides all of the surface healing strategies (bicarbonate ions, hypotonicity, viscosity, non-preserved). Therefore perhaps it may be beneficial to use different eyedrops interchangeably or sequentially - i.e. a drop of Systane or Refresh liquigel followed 5 minutes later by a drop of Bion Tears (Murine Tears has the preservative BAC, therefore avoid it) followed 5 minutes later by a drop of Thera Tears or Thera Tears liquid gel (Hypo Tears and Akwa Tears has BAC, therefore avoid them). This cycle may be repeated every 2 to 4 hours. At night use a non-preserved ointment like Refresh PM ointment. Avoid Lacrilube as it has preservative (chlorbutanol).

  ● Avoid the use of redness relieving eyedrops (naphazoline or tetrahydrozoline eyedrops) such as Clear Eyes, Murine Plus and Visine and herbals such as witch hazel. Also avoid using Vaseline in the eye. Avoid aggressive washing of the eye with running water or saline. If there are mucous strands in the tear film, avoid using your fingers or tissue paper to sweep them out towards the nose by directly touching the eye surface. This may lead to "Mucous Fishing Syndrome" - a condition wherein the eye is red, irritated and sore because of constant trauma to the eye surface by patient's finger or tissue paper.

Role of anti-inflammatory therapy in dry eye
Evidence suggests that dry eye may be associated with ocular surface inflammation that may further compromise tear secretion and exacerbate ocular surface disease and irritation symptoms. It is reasonable to consider anti-inflammatory therapy for patients using artificial tears who continue to have clinically detectable ocular surface disease, particularly if inflammatory signs (for example, conjunctival redness) and irritation symptoms are present.
Among the treatment options, topical corticosteroids appear to have the most rapid onset of action. They appear to be most appropriate for short-term pulse therapy (2 to 4 weeks). They can be used concomitantly with Restasis (cyclosporin) eye drops. Restasis may require several weeks to produce a clinical therapeutic effect and up to 6 months for maximum improvement.

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