This was a prospective study that enrolled 28 dry eye participants. The key inclusion and exclusion criteria are outlined in Table 1.

The study was conducted at the Centre for Contact Lens Research (CCLR), at the University of Waterloo (UW). The study was conducted in conformance with the ethical principles of the Declaration of Helsinki, the ICH guidelines for Good Clinical Practice, the UW Guidelines for Research with Human Participants. Informed consent was obtained from all participants prior to enrollment in the study. Ethics clearance was obtained through a UW Research Ethics Committee prior to commencement of the study.

All participants were screened at the baseline visit to determine their eligibility. Once eligibility was determined, participants were enrolled and baseline measurements were obtained. Participants were then asked to cease their current dry eye treatment and provided with the TheraTears® Lubricant Eye Drop, TheraTears® SteriLid, and the TheraTears® Nutrition to use, as per label. Details about the study products can be found in Table A.1.

After leaving the CCLR at the baseline visit, participants were asked to start using the products immediately. All participants were contacted at 2 weeks into the study to ensure that adherence to product use was maintained, to monitor adverse events, and to measure symptoms. All participants returned at 1 month and 3 months for follow up measurements.

This study showed that a combination of lubricant eye drops, lid hygiene, and oral omega-3 supplements was effective in improving moderate to severe dry eye.

Because of the study design, it is not possible to determine from the data how much each separate component contributed to the improvement in dry eye. Due to differences in clinical testing and grading scales it is also very difficult to compare results to other published studies. For example, the oral omega-3 supplements used in this study (450mg eicosapentaenoic acid (EPA)/300mg docosahexaenoic acid (DHA)/450mg alpha linolenic acid (ALA), total omega-3 content of 1200mg daily) have been shown to be effective in reducing dry eye symptoms,26,27 however the methods for symptoms assessment or reporting were different from this study. Two previous studies reporting OSDI outcomes using oral omega-3 supplements showed that OSDI scores improved by 11.6 units (participants taking 6000mg flaxseed oil daily),28 and 8.3 units in a separate study (participants taking 360mg EPA, 240 DHA daily).29

The scenario is similar for the lubricant eye drop and the eyelid hygiene product used in this study. This is the first clinical study documenting the effectiveness in relieving symptoms using the TheraTears® lubricant eye drop in conjunction with other dry eye treatments. However, there are no studies with TheraTears® lubricant eye drops as a stand-alone product documenting symptom relief. In other studies that have reported OSDI outcomes with other artificial tears, one had reported a change of approximately 14.0 units with three separate artificial tear drops formulations (used 2–3 times daily) each,30 and another study showed that OSDI improved by approximately 13 units with 4 different formulations (used 3 times daily) each.31 Similarly, the only study that reported an OSDI outcome with an eyelid hygiene product (Blephaclean twice a day) showed an improvement of 10 units.12

If we follow the assumption that artificial tears, eyelid hygiene, and omega-3 supplements provide an improvement to OSDI of 13, 10, and 10 points respectively, then a complete additive effect of combined therapy would yield a theoretical improvement of 33 points to the OSDI. However, the differences between reported therapy ingredients, duration of therapy, dosage, population sampling, and study design make it very difficult to estimate the true potential improvement for OSDI scores and it is unlikely that these benefits are summative in this manner. The total improvement in OSDI score in this study (21.2) suggests that combination therapy is approximately twice as effective as reported single therapies in relieving symptoms. Although we have not examined the effectiveness of the single therapies in this combination, it is unlikely that any single one product here could be responsible for an improvement in OSDI of this magnitude. Therefore, an additive effect from at least two of the therapies is likely the case.

The improvement in eyelid margin scores suggests that the combination therapy had an effect in relieving blepharitis. The decrease in clinical inflammation can likely be attributed to the actions of the oral omega-3 supplements, eyelid hygiene, and even the lubricant eye drops. Oral omega-3 supplements have been studied extensively and have been shown to reduce inflammatory biomarkers in the body.32 The antimicrobial activity of SteriLid against the eyelid bacteria strains have previously been studied in vitro (and compared with povidone iodine).13 A combination of omega-3 supplements and eyelid hygiene together have been previously studied,33 and have shown improvements in tear break up time, MG expression, eyelid margin inflammation, and symptomatic relief. These findings are mirrored very well by our study, as we also found significant improvements in MG function, tear breakup time, eyelid margin inflammation and symptoms.

Despite improvements in MG function, there was no significant change in gland atrophy (meibography) over time. This was an expected finding, as MG atrophy occurs at a very slow rate and may take many years for any change to be detectable. A previous study by Arita et al.25 documenting the prevalence of age-related MG atrophy showed that changes to MG atrophy can take decades to occur. Therefore, any change (if present) could not have been detected within the course of this study. However, it would be helpful to run a prospective longitudinal study spanning several years to see whether or not adding an intervention can impact gland atrophy rates.

This study was not able to detect any changes in corneal and conjunctival staining. The low amounts of corneal and conjunctival staining presenting at baseline could be due to the fact that participants were already on drops when they presented for this study. Any improvement (if present) from the treatment effect would have been very small, and therefore hard to detect. For future reference, it may be a good idea to consider having participants go on a “washout” period prior to beginning a study such as this, to allow them to manifest their full corneal and conjunctival staining at baseline.

Osmolarity also did not change throughout the study period. Osmolarity is considered to be a complex aspect of dry eye disease involving the breakdown of homeostatic mechanisms.34 Similar to some of the other measures, the osmolarity readings may have been impacted by the participants presenting at baseline already on drops. A “washout” period prior to the baseline osmolarity reading would have been expected to provide higher initial readings. The 2007 Dry Eye Workshop defines dry eye as high osmolarity readings for participants with dry eye.1 It would be expected that those participants with high osmolarity readings using the lubricant eye drop in this study containing a hypo-osmolarity component would have decreased osmolarity over time. A previous study showed that higher variability was attributed to blepharitis and Sjögren's syndrome dry eye compared to normals.35 In our study, we had found that the standard deviations in our osmolarity measurements remained similar over time (12.6 at baseline, 11.1 at 1 month, 11.1 at 3 months) even though we observed improvements in many other areas (e.g. OSDI, NIBUT, eyelid margin scores). One possible reason for this is that participants in this sample did not exhibit high osmolarity to begin with, therefore making it appear that undergoing treatment had no effect over time.

A limitation of this study was that since there were no placebo controls, a placebo effect may be present and cannot be ruled out. For future work, implementation of an independent control group would help us better understand the findings in this study.

The combined therapy of TheraTears® Lubricant Eye Drops, TheraTears® SteriLid, and TheraTears® Nutrition improved both symptoms and a variety of signs in participants with moderate to severe dry eye.

This study was funded by Advanced Vision Research Inc.

Members of the Centre for Contact Lens Research (William Ngo, Sruthi Srinivasan, Lyndon Jones) have received funding/honoraria from the following companies over the past 3 years; Advanced Vision Research, Alcon, AlgiPharma, Allergan, Contamac US, CooperVision, Essilor, Johnson & Johnson Vision Care, Ocular Dynamics, OCULUS, TearScience.