Efficacy of "Aquoral Lipo" Artificial Tears in Contact Lens Wearers With Discomfort

There are more than 140 million contact lens wearers in the world. However, contact lens use can cause discomfort symptoms in up to 50% of wearers. And these symptoms can lead to contact lens abandonment in 12-51% of symptomatic wearers.

Contact lens discomfort is defined by the Tear Film \& Ocular Surface Society (TFOS) as a condition characterized by episodic or persistent adverse ocular sensations related to contact lens wear, either with or without visual disturbance, resulting from reduced compatibility between the contact lens and the ocular environment, which can lead to decreased wearing time and discontinuation of contact lens wear.

The most common cause of contact lens discontinuation is discomfort and dryness symptoms. This symptomatology is associated with visual acuity alterations, increased risk of ocular surface desiccation, or decreased contact lens wearing time. But the different signs found in contact lens wearers who present discomfort with contact lenses do not always correlate with the symptoms they report. In addition, different factors negatively impact contact lens discomfort such as low relative humidity environments.

In order to alleviate contact lens discomfort, the first option chosen by professionals is fitting another contact lens with different replacement frequency or material. The second option is recommending the use of lubricants or moisturizers, and the third one is changing the maintenance system.

The use of artificial tears is an effective way to improve contact lens discomfort, mainly by instilling them prior to contact lens insertion, since it provides the moisturizing factor that maintenance solutions lack. In addition, it improves comfort, visual quality, and reduces the production of deposits on the contact lens.

The hypothesis of this clinical trial is that "Aquoral Lipo" artificial tears are more effective than control artificial tears to improve symptomatology in contact lens wearers with discomfort symptoms.

The study will compare the effect of both "Aquoral Lipo" and control artificial tears under controlled normal and adverse environmental conditions.

Justification:

The number of contact lens wearers is increasing every year. It is estimated that there are approximately more than 140 million wearers worldwide. However, around 50% of them suffer from discomfort while wearing their lenses, and 12-51% of them stop wearing contact lenses. The most common experienced symptoms are dry eye, redness, foreign body sensation, poor vision, or sensitivity to light.

Contact lens discomfort is defined by the Tear Film \& Ocular Surface Society (TFOS) as a condition characterized by episodic or persistent adverse ocular sensations related to contact lens wear, either with or without visual disturbance, resulting from reduced compatibility between the contact lens and the ocular environment, which can lead to decreased wearing time and discontinuation of contact lens wear.

Symptoms related to contact lens discomfort can be associated with visual acuity alterations, increased risk of ocular surface desiccation, or decreased contact lens wearing time. But the majority of subjects who develop discomfort with contact lenses do not have associated ocular pathology or damage.

Contact lens discomfort can be caused by factors associated with the contact lens itself, such as material, design, and maintenance systems; and factors associated with the environment surrounding the contact lens, such as those of the wearer or environmental conditions.

In order to alleviate contact lens discomfort, 47% of professionals refit another contact lens of a different material or replacement frequency. 22% of professionals recommend the use of lubricants or moisturizers, and 15% change the maintenance system.

The use of artificial tears improves contact lens discomfort, mainly by instilling them prior to contact lens insertion, since it provides the moisturizing factor that maintenance solutions lack. During contact lens wear, they also improve comfort, visual quality, and reduce the production of contact lens deposits.

Aquoral Lipo is a preservative-free lubricant and antioxidant ophthalmic solution based on sodium salt of cross-linked hyaluronic acid, liposomes, and crocin. It provides good hydration and a long permanence time on the ocular surface.

Hypothesis:

"Aquoral Lipo" artificial tears are more effective than control artificial tears to improve symptomatology in contact lens wearers that suffer from discomfort symptoms.

Objective:

To compare the efficacy of Aquoral Lipo artificial tears with a product with 0.15% hyaluronic acid after 15 days of use in subjects with contact lens discomfort, and exposed to normal and adverse controlled conditions created in a controlled environment chamber.

Study plan:

Participants will perform a total of 5 visits (in 5 days): an inclusion visit (V0), two basal visits (V1 and V3), and two study visits (V2 and V4).

V0: Recruitment visit. Contact lens wearers will be recruited after checking inclusion and exclusion criteria. If eligible, participants will sign the informed consent and will be scheduled for V1 within the next 7 days.

V1: Baseline visit. Participants will come to the visit with a new pair of contact lenses and having worn them for at least 2 hours. Participants will enter the environmental chamber at the Controlled Environment Laboratory (CELab), where they will be exposed for 30 minutes to a normal controlled environment (23 degrees Celsius and 50 percentage relative humidity). Then, tests will be performed, and one of the study products will be dispensed to the subject randomly to be instilled 3-6 times a day until the next visit. Participants will come to the next visit within 15 days.

V2: Study visit (V2 NE - V2 AE). Participants will come to the visit having worn the contact lenses the same number of hours as in V1, and they will be exposed for 30 minutes to a normal controlled environment at CELab (V2 NE). Then, tests will be performed, and they will be exposed for 90 minutes to an adverse controlled environment (23 degrees Celsius and 10 percentage relative humidity) at CELab (V2 AE). Test will be repeated at 30, 60, and 90 minutes of the adverse environmental exposure. Subjects will not use artificial tears until the next visit, within the next 7 days.

V3: Baseline visit. The same procedures as in V1 will be followed, but the other study product will be dispensed to participants to be instilled 3-6 times a day until the next visit, within 15 days.

V4: Study visit (V4 NE - V4 AE). The same procedures as in V2 will be followed.

Clinical evaluation:

* Contact lens discomfort symptoms questionnaires
* Visual Acuity measurement
* Tear film lipid layer thickness measurement (interferometry)
* Blinking measurement
* Evaporimetry
* Non Invasive Break Up Time (NIBUT)
* Anterior pole biomicroscopy
* Tear Break Up Time with fluorescein (TBUT)
* Corneal staining with fluorescein
* Conjunctival staining with lissamine green

Data analysis:

Means and standard deviations will be calculated for the quantitative variables of the study. For ordinal variables, medians and interquartile ranges will be calculated. Qualitative variables will be summarized using percentages together with their confidence intervals.

For primary efficacy endpoint, CLDEQ-8 comparisons between V1 and V2 NE, and V3 and V4 NE will be performed by t-Student test for two paired samples.

The evolution of all variables over time will be analyzed through an ANOVA for repeated measures. Their evolution after the exposure to adverse environments will be analyzed through Student's t-test for paired samples (quantitative variables) and McNemar's test (ordinal variables).

Eligibility Criteria:
Inclusion Criteria:

* Age \> 18 years
* Signature of informed consent form
* Regular hydrophilic contact lens wearers: at least 4 times a week and at least 4 hours a day
* Contact lens discomfort measured as a Contact Lens Dry Eye Questionnaire-8 score higher than 11 points

Exclusion Criteria:

* Known sensitivity or intolerance to some of the products used in the study
* Habitual non-compliance of the contact lens replacement frequency
* Any systemic disease or treatment that alters the eye
* Any ocular surgery, infection, inflammation, or active eye disease, in the last year
* Autoimmune dry eye
* Participation in a clinical trial within 30 days prior to entry into this study
* Pregnancy or breastfeeding