The Artful Science of Artificial Tears

Meeting the goals of clinicians and patients.

BY SHACHAR TAUBER, M.D.

Through improved testing and increased awareness, it has become apparent in recent years that dry eye affects the quality of life of millions of people worldwide.¹ Depending on the parameters used and the population studied, estimates of the prevalence of dry eye range from roughly 7.4% to 22.0%.^2,3,4 Research has demonstrated that among these patients, 37% exhibit either signs or symptoms, but not the other.⁵ With this discrepancy, it's important to remember to treat both the clinical signs and subjective symptoms of dry eye, and not to neglect either aspect of the disease.

The modern Hippocratic oath⁶ reminds us that, "there is art to medicine as well as science," and we must seek to recommend well-rounded treatments that improve not only the scientific measurements of dry eye, but also the uncomfortable sensations of our patients.⁶ Matching the correct option for each individual requires one to be well-versed in the mechanisms of dry eye and the unique attributes of the various palliative options, which will be the focus of this feature.

Modern Ocular Drying Mechanisms

Visual tasking has changed drastically over the last few decades. With 82% of Americans working with either a computer or PDA throughout the day, the impact of these changes has become a prominent concern for ocular health.⁷ A national survey of optometrists demonstrated that more than 14% of their patients present with ocular symptoms related to work with a computer or visual display unit.⁷ Ocular surface health relies on its protection afforded by the tear film between blinks. The reduced blink rate seen during this visual tasking can lead to ocular dryness if the tear film disperses between blinks.⁸ Patients can experience symptoms and exhibit signs of dry eye as a result.

Targeting the Clinical Signs

Clinically, several objective components of dry eye — tear film instability, ocular surface exposure and dessication — enter into the equation for treatment. Clinicians employ a battery of clinical tests to evaluate these aspects, most notably tear film break-up time (TFBUT) following fluorescein dye instillation.⁹ If a video imaging system with an on-screen timer is incorporated, TFBUT can be more accurately timed. Using this system of measurement, 5 seconds is usually used as a cutoff — break-up times below this cutoff are considered indicative of dry eye.⁹

Artificial tear products strive to extend the TFBUT by increasing aqueous volume, reducing evaporation, or both. All are generally effective for immediate symptomatic relief. Those that can prolong the improvement in TFBUT, however, will be received more favorably by patients, as this reduces the number of instillations needed throughout the day. A recent study presented at the 2009 ARVO conference found that once-daily use of a hydroxypropyl cellulose insert (Lacrisert, Aton Pharma) during contact lens wear was longer lasting 93% of the time when compared to rewetting solutions.¹⁰ Another study presented at this year's ARVO conference demonstrated the ability of a new artificial tear (Systane Ultra, Alcon) to extend the amount of time a patient maintains his visual acuity (within one line of BCVA) between blinks 90 minutes post-instillation; a finding which may have substantial implications during visual tasking.¹¹ Numerous other studies of duration of effect have been performed or are underway. Prolonged symptomatic improvement has been shown in other agents as well. Another artificial tear (Blink Tears, AMO) demonstrated moisture retention times exceeding 60 minutes via inferometry analysis.¹²

Newer diagnostics looking at other aspects to tear film stability offer further insight into artificial tear evaluation. One diagnostic called the Ocular Protection Index (OPI) relates tear film stability to blink frequency in order to ascertain whether or not the ocular surface is sufficiently protected between blinks. OPI is calculated by dividing TFBUT by the "interblink interval" (IBI) time. Tear substitutes may be assessed for their tendency to improve OPI values to ≥ 1, which indicates that, on average, the epithelium is protected.¹³ OPI values rely on precise measurement of IBI and may not be a practical option for clinicians who lack video recording capabilities at the slit lamp, but the index is being used in research settings.

The first clinical trial to compare artificial tears using OPI demonstrated that the parameter could be used to distinguish artificial tears' efficacy in providing sufficient protection to the ocular surface.¹⁴ The ability to confer extended ocular surface protection suggests to clinicians that an artificial tear is providing the eye with the opportunity to heal itself — much of medicine, after all, consists of helping the body enact its own natural defenses.

Inadequate ocular surface protection as a result of tear film instability is the aspect of dry eye that allows initial or further desiccation of corneal and conjunctival epithelial cells. The primary tests to evaluate the extent of this surface damage involve the instillation of one of two vital dyes — sodium fluorescein for corneal cells, and lissamine green for conjunctival cells. Historically, rose bengal dye was also used to highlight conjunctival dessication, but lissamine green has been found to be equally effective and considerably more tolerable for patients.¹⁵ Reductions in corneal staining are considered more biologically beneficial — after all, the cornea lies directly over the vital apparatus of the visual system and has refractive qualities itself. When an artificial tear can provide extended break-up times and ocular surface protection, this can impact staining favorably.¹⁶

These evaluations can allow clinicians to match an artificial tear's results to the patient's dry eye signs. Since research has demonstrated that 19% of dry eye patients only experience dry eye symptoms and that 63% of patients exhibit a mixture of signs and symptoms,¹⁷ signs cannot be the only determining factor. What they do not provide is a measure of patient satisfaction and quality of life.

Soothing Patients' Symptoms

Ultimately these tests for clinical signs are insufficient on their own — a doctor needs feedback from patients in order to determine what is best helping to improve their quality of life. From a patient's perspective, dry eye manifests in the form of numerous symptoms that range from irritating to borderline debilitating in their severity. These include, but are not limited to, burning, stinging, foreign body sensation, grittiness, general dryness or ocular discomfort, photophobia, photopsia, and blurring of vision. Symptom improvements can be what makes or breaks a treatment for a patient, so it is important not to ignore patient complaints throughout treatment.

Some formulations have the tendency to produce discomfort — often in the form of burning or stinging — upon instillation. It may seem illogical to patients (and justifiably so) that a product they are supposedly using to treat their ocular discomfort is causing them further ocular discomfort when they put it into their eyes. Drop comfort upon instillation is obviously important to artificial tear users, but so is drop clarity. Blurring upon instillation is most frequently a concern with thick petroleum-based ointments and liquid gels. Dry eye ointments may confer favorable overnight results, but are limited to before-bed application due to the visual blurring that follows application.

Asking the Correct Questions

In addition to remaining tolerable during and after instillation and requiring simple and infrequent dosing, a tear substitute should address at least some of the symptoms associated with dry eye in order to win a patient's approval. A clinical trial may assess a tear substitute's ability to improve overall ocular discomfort, or specific types of dryness. For instance, a questionnaire may ask subjects to evaluate the severity of dryness they experience in the morning or the evening—both notoriously bad times of day for dry eye symptoms. More detailed, symptom-by-symptom analyses may also be performed to help best determine which patients a particular formulation would benefit (or to assess a particular patient's reaction to management). Ultimately, the way patients experience symptoms can vary and the best way to determine the tolerability of a tear substitute for a given patient is to have that patient try dosing with it.¹⁸

Certain special circumstances can also influence treatment regimen for patients. Contact lens wearers can benefit from artificial tears that improve comfort by being applied before and after contact lens wear. Patients using Restasis (Allergan) can benefit from an artificial tear that has shown efficacy when used concomitantly with the treatment. It is important to take these circumstances into account when tailoring treatment.

Obviously there must be reflexivity between a patient's goals and a clinician's goals. Meeting a patient's needs and preferences surrounding artificial tear use can certainly take some patience, but through patient education an ophthalmologist can help a patient understand the more technical medical goals of dry eye management as well.

This may entail a brief overview of the nature of dry eye, and can include pointers on the influence blinking has on the tear film and ocular surface protection, especially during visual tasking, or how to estimate tear film break-up at home using a simple test called the symptomatic break-up time (SBUT). This test involves a patient holding their eyes open until the first sensation of ocular awareness and timing this interval. The resulting value has been shown to fall within one second of actual TFBUT for roughly 70% of dry eye patients, and for this reason the test is a good way to get patients actively involved and interested in their dry eye treatment.¹⁹

Patient education can improve patient compliance, which can improve treatment efficacy. For many reasons, then, patient-doctor interaction and artful balancing of treatment goals, can lead to a treatment plan with a proven tear substitute. OM

References

1. Casavant J, Ousler GW, Wilcox Hagberg K, Abelson MB. A correlation between the signs and symptoms of dry eye and the duration of dry eye diagnosis. Invest Ophthalmol Vis Sci. 2005;46:E-abstract 4455.
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13. Ousler GW, Emory TB, Welch D, Abelson MB. Factors that influence the inter-blink interval (IBI) as measured by the ocular protection index (OPI). Poster presented at: The Association of Research in Vision and Ophthalmology (ARVO) annual meeting, 2002.
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15. Ousler GW III, Gomes PJ, Welch D, Abelson MB. Methodologies for the study of ocular surface disease. Ocular Surface. 2005 Jul;3(3):143-154.
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17. Casavant J, Ousler GW, Wilcox Hagberg K, Abelson MB. A correlation between the signs and symptoms of dry eye and the duration of dry eye diagnosis. Invest Ophthalmol Vis Sci. 2005;46:E-abstract 4455.
18. Christensen MT, Cohen S, Rinehart J, Stein JM, et al. Clinical evaluation of an HP-guar gellable lubricant eye drop for the relief of dryness of the eye. Curr Eye Res. 2004 Jan;28(1):55-62.
19. Nally L, Ousler GW, Abelson MB. Ocular discomfort and tear film break-up time in dry eye patients: a correlation. IOVS 2000 41;4:E-abstract 1436.