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Which Drop for Dry Eye?

When it comes to treating dry eye, keep your armamentarium well stocked. No single artificial tear works well for every form of dry eye. Rather, each option has benefits in certain situations.
Srihari Narayanan, O.D., Ph.D.

4/15/2009



Dry eye disease is observed often in our practice as primary eye care providers. In general, dry eye is characterized as a disease that occurs due to increased tear evaporation or decreased tear secretion that resulted in symptoms of ocular irritation.1


The recent International Dry Eye WorkShop (DEWS) defined dry eye disease as follows: Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.2 As outlined in the DEWS definition, dry eye disease not only causes ocular irritation, but also affects the quality of the patients visual acuity and can affect the integrity of the ocular surface.


Estimates of the prevalence of dry eye vary considerably between different populations of the world. In the United States, it is thought that dry eye occurs in 5% to 30% of the population.3 As practitioners, we are well aware that this disease affects women more than men and also increases in incidence in the older population.3


Dry eye disease does cause significant economic burdens on the patient through the costs for obtaining treatment, follow-up visits, additional testing and loss of working hours.4 Furthermore, it has been shown that dry eye disease affects the quality of life of a patient.5


A wide variety of therapeutic options are available for dry eye disease. Various treatment strategies, such as artificial tears or rewetting agents (henceforth called artificial tears), punctal plugs, anti-inflammatory agents (topical steroids or oral fatty acids), moisture goggles, secretogogues, autologous serum, prescription immunomodulatory drugs (topical and oral) as well as surgical options, are available for the treatment of dry eye disease.


Identification of the underlying cause of dry eye aids in successful treatment of this disease. However, its multifactorial nature makes it complicated to identify a single cause in a particular patient.


The diagnostic challenge is further increased for dry eye disease because no single test is available to correctly diagnose its various forms. Current research suggests that inflammation at the ocular surface plays an important role in the pathogenesis of dry eye.6


Among all therapeutic options for dry eye disease, artificial tears are still the mainstay in the initial management of a dry eye patient.7 Ophthalmic physicians usually begin a newly-diagnosed dry eye patient on a regimen of topical artificial tears and then add to or modify the course of treatment from there.


Currently, there are various artificial tears available over-the-counter; one brand (FreshKote, Focus Laboratories) is available by prescription only. Artificial tears are generally designed to lubricate the ocular surface and replace tear volume.


Due to the complex nature of the tear film, it is difficult to design an artificial tear solution that is identical to human tears. However, many artificial tear brands try to improve their quality by altering the composition, viscosity and/or osmolarity of the solution.


This article details some of the commonly available compositions of artificial tears and discusses their potential use in specific causes of dry eye disease. There is no single brand of artificial tears that works well for every form of dry eye. Rather, each option (organized here by formulation composition) has benefits for certain clinical situations.


CMC-Based Artificial Tears

Carboxy methylcellulose (CMC, discussed below) and hydroxypropyl methylcellulose (discussed later) are polysaccharides known as mucilages.8 The methyl and hydroxpropyl cellulose derivatives are widely used in artificial tear formulations. They increase the residence time of tears as well as increase the viscosity of tears.8 Interestingly, the refractive index of 1% methylcellulose is 1.336, which closely matches that of human tears.8


Commonly available CMC artificial tears include the Refresh brand of tears (Allergan) as well as TheraTears (Advanced Vision Research). CMC-based artificial tears may protect the integrity of the ocular surface.9


Refresh is available in both preserved and non-preserved as well as in liquigel formulations. It has been shown that the mid-viscosity (1.0% CMC) Refresh Liquigel promotes significant reduction in the signs and symptoms of dry eye compared to lower viscosity agents.9 So, CMC-based artificial tears may be indicated in patients who demonstrate ocular surface staining with vital dyes.
TheraTears has the added benefit of being a hypotonic solution. Hyperosmolarity is a common feature of most forms of dry eye disease.1 Therefore, the hypotonic TheraTears solution may provide comfort in dry eye patients.

 

HMC-Based Artificial Tears

Several brands of artificial tears, such as Tears Naturale and Bion Tears (Alcon), GenTeal (Novartis) and Visine Tears (Pfizer) are hydroxypropyl methylcellulose (HMC) based. Tears Naturale is available both with and without preservatives. Bion Tears is preservative free and has been suggested for use in patients with severe dry eye.10 GenTeal is available in three different formulations, one each for mild, moderate or severe dry eye.11 Visine Tears is available with or without preservatives. HMC-based artificial tears work on the simple principle of lubricating the ocular surface in order to promote the integrity of the surface.10

 

HP Guar-Based Artificial Tears

Systane (Alcon) is formulated with hydroxypropyl guar (HP guar). The HP guar in this artificial tear brand is gel-forming and offers a unique mechanism to approach the problem. These properties of HP guar improve recovery of the ocular surface due to possible increased retention time of the artificial tear drop.12


Also, the increased retention time may be responsible for the increase in tear film break-up times observed with HP guar-based artificial tears compared to CMC-based tears.13
Tear evaporation may be reduced by the use of HP guar containing artificial tears.14 So, HP guar-based artificial tears may be helpful in patients with conditions causing evaporative dry eye (e.g., meibomian gland disease) as well as patients demonstrating ocular surface staining.

 

SH-Based Artificial Tears

Blink Tears and Blink Contacts (Abbott Medical Optics) and AQuify comfort drops (CIBA Vision) are brands that include sodium hyaluronate (SH) as an inactive ingredient. Blink Tears and AQuify comfort drops have been advertised for use in contact lens wearers. Blink Tears has a unique OcuPure preservative that dissipates upon exposure to light. Therefore, Blink Tears become preservative free upon instillation in the eye. AQuify comfort drops are blink-activated.15 Sodium hyaluronate in the AQuify comfort drops aids in a gradual release of water molecules, which increases the duration of wettability as well as relieves lens-related dryness.15


Recent studies have shown that SH eye drops are useful in improving subjective symptoms (as well as the ocular health) of dry eye patients, treating lipid tear-deficient patients and managing Sjgrens syndrome patients.16-20
Sodium hyaluronate also seems to have protective effects on the corneal epithelium.21

Based on the above evidence, it appears that SH-based artificial tears may be useful in a wide variety of patients with dry eye. Interestingly, Blink Tears may also provide relief to dry eye patients post-LASIK surgery or post-cataract surgery.22 So, this formulation appears to provide a wide range of beneficial effects for dry eye patients.

 

PVA-Based Artificial Tears

Polyvinyl alcohol (PVA) based artificial tears, such as Murine Tears (Murine Eye Care), Tears Again (Cynacon/Ocusoft) and HypoTears (Novartis), also work on the principle of lubricating the ocular surface. Tears Again is available in the eyedrop as well as the gel formulation.


HypoTears, as the name suggests, is a hypotonic solution. It is available with or without preservatives. So, HypoTears has the added advantage of addressing hyperosmolarity issues observed in dry eye patients (similar to TheraTears, which is CMC based).


One recent article concluded that Murine Tears provided the drop volume closest to the volume of the natural tear fluid and was also the least expensive per year of treatment compared to artificial tears from seven other manufacturers.23

 

Oil-Based Tears

Refresh Endura (Allergan) and Soothe XP Emollient eye drops (Bausch & Lomb) are the two brands that use oils in their composition. Refresh Endura is a preservative-free castor oil-based formulation. Castor oil aids in the reformation of the lipid layer of the tear film and prevents evaporation of the existing tear film.24,25


Castor oil-based eye drops also improve tear stability and aid in the treatment of meibomian gland disease.26 So, it is evident that the use of castor oil-based artificial tears is indicated in evaporative dry eyes. Unfortunately, the production of Refresh Endura was discontinued as of December 2008.


Soothe XP Emollient eye drops, on the other hand, are mineral oil-based. This brand of artificial tears has been shown to increase the thickness of the lipid layer of the tear film.27 So, Soothe XP eye drops can also be considered for use in evaporative dry eye patients who have a poor quality of the lipid layer.27

 

Rx Tears

FreshKote eyedrops (Focus Laboratories) are the only brand of artificial tears that require a prescription. The main ingredients of FreshKote include PVA as well as polyvinyl pyrrollidone. FreshKote also includes the companys proprietary Amisol Clear which is intended to stabilize the lipid layer of the tear film and prevent evaporation of the tear fluid. Because the manufacturer of FreshKote describes Amisol Clear as a phospholipid, FreshKote functions somewhat akin to the oil-based tears. Additionally, these eyedrops are designed to achieve better wetting by aiding the combination of all three layers of the tear film. FreshKote has a high oncotic pressure, which helps in increasing ocular surface integrity.28 And, FreshKote can be used daily on an as needed frequency.28

 

No single artificial tear solution will work for all dry eye patients. Each patients symptoms, complaints and diagnosis will play a role in your selection of the best dry eyedrop for his or her needs.


The different components of artificial tears offer distinct advantages, and it is your responsibility to choose the best formulation for your patients dry eye therapy.


Dr. Narayanan is an Assistant Professor at the Pennsylvania College of Optometry at Salus University, Elkins Park, Pa.

 

1. Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J 1995;21(4):221-32.

2. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5(2):75-92.

3. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5(2):93-107.

4. Reddy P, Grad O, Rajagopalan K. The economic burden of dry eye: a conceptual framework and preliminary assessment. Cornea 2004;23(8):751-61.

5. Mertzanis P, Abetz L, Rajagopalan K, et al. The relative burden of dry eye in patients" lives: comparisons to a U.S. normative sample. Invest Ophthalmol Vis Sci 2005;46(1):46-50.

6. McCabe E, Narayanan S. Advancements in anti-inflammatory therapy for dry eye syndrome. Optometry 2009; in press.

7. Perry HD, Donnenfeld ED. Medications for dry eye syndrome: a drug-therapy review. Manag Care 2003;12(12 Suppl):26-32.

8. Murube J, Paterson A, Murube E. Classification of artificial tears. I: Composition and properties. Adv Exp Med Biol 1998;438:693-704.

9. Simmons PA, Vehige JG. Clinical performance of a mid-viscosity artificial tear for dry eye treatment. Cornea 2007;26(3):294-302.

10. Alcon. Tears Naturale. Available at: www.tearsnaturale.com/tears-naturale-bion-tears.asp (Accessed January 2009).

11. Novartis-Opthalmics. GenTeal. Available at: www.us.novartisophthalmics.com/info/products/genteal.jsp (Accessed January 2009).

12. Gifford P, Evans BJ, Morris J. A clinical evaluation of Systane. Cont Lens Anterior Eye 2006;29(1):31-40.

13. Ousler GW, Michaelson C, Christensen MT. An evaluation of tear film breakup time extension and ocular protection index scores among three marketed lubricant eye drops. Cornea 2007;26(8):949-52.

14. Uchiyama E, Di Pascuale MA, Butovich IA, et al. Impact on ocular surface evaporation of an artificial tear solution containing hydroxypropyl guar. Eye Contact Lens 2008;34(6):331-4.

15. CIBA Vision. AQuify. Available at: www.

aquify.com/html/drops.html (Accessed January 2009).

16. Brignole F, Pisella PJ, Dupas B, et al. Efficacy and safety of 0.18% sodium hyaluronate in patients with moderate dry eye syndrome and superficial keratitis. Graefes Arch Clin Exp Ophthalmol 2005;243(6):531-8.

17. Johnson ME, Murphy PJ, Boulton M. Carbomer and sodium hyaluronate eyedrops for moderate dry eye treatment. Optom Vis Sci 2008;85(8):750-7.

18. McDonald CC, Kaye SB, Figueiredo FC, et al. A randomised, crossover, multicentre study to compare the performance of 0.1% (w/v) sodium hyaluronate with 1.4% (w/v) polyvinyl alcohol in the alleviation of symptoms associated with dry eye syndrome. Eye 2002;16(5):601-7.

19. Prabhasawat P, Tesavibul NKasetsuwan N. Performance profile of sodium hyaluronate in patients with lipid tear deficiency: randomised, double-blind, controlled, exploratory study. Br J Ophthalmol 2007;91(1):47-50.

20. Aragona P, Di Stefano G, Ferreri F, et al. Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjogren"s syndrome patients. Br J Ophthalmol 2002;86(8):879-84.

21. Choy EP, Cho P, Benzie IF, et al. Investigation of corneal effect of different types of artificial tears in a simulated dry eye condition using a novel porcine dry eye model (pDEM). Cornea 2006;25(10):1200-4.

22. Donnenfeld ED, Holland EJ, McDonald MB, et al. New artificial tear developments. Rev Ophthalmol 2009 Jan;16(1 Suppl):8-15.

23. Enzenauer RW, Kao A, Williams T, et al. Relative costs of various preserved artificial tear solutions for the treatment of dry eye conditions. Eye Contact Lens 2003;29(4):238-40.

24. DiPascuale MA, Goto E, Tseng SC. Sequential changes of lipid tear film after the instillation of a single drop of a new emulsion eye drop in dry eye patients. Ophthalmology 2004;111(4):783-91.

25. Khanal S, Tomlinson A, Pearce EI, et al. Effect of an oil-in-water emulsion on the tear physiology of patients with mild to moderate dry eye. Cornea 2007;26(2):175-81.

26. Goto E, Shimazaki J, Monden Y, et al. Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction. Ophthalmology 2002;109(11):2030-5.

27. Korb DR, Scaffidi RC, Greiner JV, et al. The effect of two novel lubricant eye drops on tear film lipid layer thickness in subjects with dry eye symptoms. Optom Vis Sci 2005 July;82(7):594-601.

28. Focus Laboratories. FreshKote. Available at: www.freshkote.com/about_freshkote.asp (Accessed January 2009).

Vol. No: 146:04Issue: 4/15/2009



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