Currently, tear supplements are available as solutions, ointments and gels. They can be used as often as necessary to keep the corneal surface and conjunctiva wet. Preferably, the topical application of a well-formulated tear supplement and lubricating agent should provide relief for both aqueous- and mucin-deficient dry eye. Moreover, functions associated with the lipid layer of the precorneal tear film should not be altered by the tear supplement.
There are several objectives that tear supplements aim to fulfil in the treatment of dry eye.
Objectives of tear supplements
Ideally, tear supplements should fulfil the physico-chemical role of a normal tear film. In addition, they should not disturb corneal metabolism nor be toxic to the eye, even with frequent use. It should also have a refractive index similar to that of the cornea to see correctly. This involves consideration of certain characteristics in the formulation if tear supplements are to resemble physiological tears. These include electrolyte concentration, viscosity, mucomimetic properties, pH, osmolarity and the absence of preservatives.
The ideal tear supplement
1 Enhance tear volume
Tear supplements should enhance the tear volume lost in the dry eye condition. As there is a deficit in the aqueous component of the precorneal tear film in KCS, tear supplements need to have a formulation that is closest to that of the physiological aqueous layer (i.e. water + electrolytes). Several electrolytes found in normal tears are known to play an essential role in maintaining the correction function of the cornea: calcium and magnesium are important in cell adhesion, cell junctions and cellular transport, while potassium contributes to the maintenance of corneal thickness. Thus, it is important that the balance of electrolytes in tear supplements resembles that seen in normal tears.
2 Stay longer on the eye
For greatest efficacy, tear supplements should have a long retention time on the ocular surface. Thus, a solution should be used that has a greater viscosity than saline solutions. This has led to the use of viscosity-enhancing agents to increase the residence time of the solution in the conjunctival sac and on the ocular surface. Viscosity-enhancing agents are now considered the main ingredient of tear supplements.
Methyl cellulose was the first viscosity agent to be used, followed by a whole range of substituted cellulose ethers. It was quickly realised that although improved retention time occurred with the lower viscosities, no further increase occurred with increasing viscosity. In fact, high viscosity was associated with discomfort and crusting of the lids.
Unlike normal tears, many of the agents in commercial preparations are Newtonian fluids. However, preparations that contain hyaluronan behave as non-Newtonian fluids (i.e. offer considerable resistance at low speed, but are less viscous at higher speed), with characteristics similar to tear mucous glycoprotein. Such preparations have been found to be effective clinically. Although their relative viscosity is considerably higher than that of normal tears or other tear supplements, the non-Newtonian behaviour and shear-thinning at each blink permits the advantages of high viscosity between blinks (increasing the residence time of the product) and lower viscosity during the blink (allowing the smooth movement of the lids over the ocular surface).
Preparations with a higher viscosity can also increase the thickness of the pre-corneal tear film, an effect that lasts for at least 20 minutes and which is expected to delay the onset of hyperosmolarity.
3 Physico-chemical properties
Tear supplements should also have mucomimetic properties (mimic the functional properties of a normal mucin layer). The formulation should be able to increase the wettability of the hydrophobic corneal surface by aiding in the formation of a hydrophilic layer that can bind to mucin. This will enhance corneal adhesion and increase the stability of the tear film. If possible, tear supplements should also lower the surface tension of the tear film.
Certain polymers have been shown to lower the surface tension of aqueous solutions in a way that mimics the action of natural mucous glycoproteins. Some polymers will also interact favourably with the surface lipid layer in a manner that will encourage stability and spreading of the aqueous film on a non-polar surface. Thus, tear supplements with mucomimetic properties will provide better coating of the ocular surface, maintain a thicker tear film for a longer period and improve surface wetting, all characteristics that are important in the treatment of dry eye.
4 Be well tolerated
Tear supplements should be non-toxic and non-irritating to the eye. The inclusion of preservatives in tear supplements is necessary if they are to be dispensed for prolonged periods from the same bottle. However, even in low concentrations some preservatives can result in irritation and damage to the ocular surface (superficial punctate keratitis), causing stinging, burning and redness of the eyes.
The pH of the tear supplement is also important to tolerability. The normal corneal epithelium can tolerate a wide range of pH. However, solutions instilled into the conjunctival sac with a pH that deviates from the normal tear pH (which can vary between 7.0 and 7.4) are associated with irritation. The usual method of insuring that a solution remains at the approximate pH of the normal tears is the introduction of a buffering system, including phosphates. Most tear supplements have a pH around 7.0.
Natural products are always better tolerated than synthetic products. Moreover, products with an animal origin are not as well accepted by patients and doctors. Therefore, a tear supplement that has a natural, non-animal origin will be more tolerable and acceptable to patients with KCS.
5 Restore tear film osmolarity
Dry eyes are known to be hypertonic (hyperosmolar). Therefore to counteract this, the use of hypotonic tear supplements has been recommended in the treatment of KCS to restore the osmolarity of the tear film to normal.
6 Refractive index
The normal refractive index of the eye (1.3361 to 1.3379) is dependent on a smooth refractive surface. Thus, tear supplements must be transparent and should have a low viscosity during blinking in order to prevent distortion or blurring of vision.
Therefore, the ideal tear supplement should:
- Enhance tear volume in case of aqueous deficiency
- Possess viscoelastic properties
- Possess mucomimetic properties
- Contain essential ions, in the same concentration found in normal tears, to maintain the physiology and integrity of the cornea
- Be neutral or slightly alkaline (pH between 7 and 8)
- Be slightly hypotonic compared to normal tears to counteract the hypertonicity usually found in dry eye
- Be non-toxic, therefore preservative free
- Have a refractive index similar to the cornea
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