Tear Osmolarity Changes in Habitual Contact Lens Wearers
Condition: Tear Film Hyperosmolarity
Study type: Interventional

Summary: 
      Tear osmolarity refers to the amount of osmotically active particles in tears and has been
      reported as one of the best diagnostic test for dry eye disease. Our research focused on
      following changes in tear osmolarity and ocular symptoms in the time-course of one year after
      refitting habitual contact lens wearers or fitting novices with modern daily disposable soft
      contact lenses. Fifty-six contact lens wearers aged (mean ± standards deviation) 26 ± 4 y/o
      were refitted with Silicone-Hydrogel (Delefilcon A) or Hydrogel (Omafilcon A) lenses.

      Study included seven visits: baseline measurement before the study, two visits for contact
      lens fit and control and follow-up measurements after three, six, and 12 months of contact
      lens wear followed by measurements on bare eye according to the baseline scheme (post-study
      visit).

      An impedance-based osmometer was used to collect samples from the lower tear meniscus. A
      standard Ocular Surface Disease Index (OSDI) questionnaire was used to monitor
      subject-reported ocular symptoms. Statistically significant differences were noted in tear
      osmolarity in the time course of the study for both eyes.

      An improvement in tear osmolarity was most prevalent among subjects with high initial tear
      osmolarity. Low osmolarity levels were maintained after the study.

      The findings of this prospective study will reveal that habitual contact lens wearers or
      novices may benefit from refitting with modern daily disposable soft contact lenses.
    

Detailed description: 
      Tear osmolarity refers to the amount of osmotically active particles in tears and is defined
      as the number of osmoles per litre of solution. It is mostly determined by the electrolytes
      of the aqueous component of tears and less significantly by proteins and sugars. It has been
      described as a single clinical measure that gives insight into the balance between tear
      production, evaporation, drainage and absorption of tears. Studies support the use of tear
      osmolarity as the best single diagnostic test for dry eye disease (DED) and the objective
      numerical measure for diagnosing, grading severity, and managing DED. Clinical application
      was facilitated after introducing a chip-based osmometer (TearLab® Osmolarity System, TearLab
      Corp, San Diego, California, USA)7, which allows collection of a relatively small sample of
      50 nL from the inferior tear meniscus and automatic determination of tear osmolarity, based
      on the sample's conductivity.

      The osmolarity of 308 mOsm/L is considered to be the most sensitive threshold to distinguish
      normal from mild/moderate forms of DED and 315 mOsm/L the most specific cut off. Also the
      inter-eye difference in osmolarity increases with DED severity and beyond the threshold of 8
      mOsm/L it is considered an indication of the loss of tear film homeostasis. In normal
      subjects this variation between eyes is around 6.9 ± 5.9 mOsm/L. Tear film with a contact
      lens undergoes biophysical and biochemical changes, which have the potential to influence
      tear function and impact comfort and contact lens tolerance. Many factors have been
      associated with lowering of comfort and changes in tear dynamics during lens wear, however
      the literature is divided over whether or not contact lens wear increases, or has no effect
      on tear osmolarity.

      The differences in reported values are likely a function of the wearer's ability to maintain
      tear film homeostasis, overcoming the drying effect of contact lenses.

      Tear osmolarity was reported as the least variable of all the common signs across a
      clinically relevant timeframe, and was the only sign to reduce its variation upon application
      of effective therapy.

      Tear hyperosmolarity is a clinical starting point in the pathogenesis of DED, responsible for
      ocular surface damage, both directly and by initiating a chain of inflammatory responses
      leading to ocular surface damage. Contact lens wear increases the risk of developing DED from
      between 2.01 and 2.96 times. Wearers are much more likely to report discomfort, mostly
      described as dryness and end of day dryness, than non-wearers and this factor remains the
      single largest cause of contact lens wear discontinuation. However, a multifactorial nature
      of DED, disguised as a lack of association between clinical signs and reported symptoms,
      leads to underlying cause of contact lens discomfort and remains poorly understood. Contact
      lens related DED may be explained by increased tear film thinning times resulting in
      increased tear film osmolality or by the loss of corneal sensation particularly associated
      with long-standing wear of hard and extended-wear contact lenses. Lowered corneal sensitivity
      leads to decreased tear secretion in response to reflex stimuli presumably causing an
      increase in tear osmolarity. Tear hyperosmolarity has been reported in daily and extended
      wear of both soft and hard contact lens wearers, especially in symptomatic subjects.
      Extended-wear soft contact lenses can decrease corneal sensitivity more than daily-wear soft
      contact lenses. A significant increase in tear osmolarity could not be confirmed in subjects
      wearing daily disposable soft contact lenses.

      Few studies have been conveyed to investigate the longitudinal effects of soft contact lens
      wear on ocular physiology. These studies generally focused on different lens designs and
      oxygen permeability and their impact on the ocular surface morphology, tear stability or
      ocular surface sensory function.

      Changes in ocular physiology during contact lens wear are evident, however the effect of
      modern daily disposable contact lens on tear film osmolarity still remains unknown. In the
      last decade significant advancements have been made in both contact lens technology and DED
      diagnosis. Therefore, further evaluation of the influence of modern contact lenses on ocular
      physiology is necessary.

      The hypothesis of this research is that the wear of modern daily disposable soft contact
      lenses maintains tear film osmolarity in compliant habitual contact lens wearers or novices.
      Hence, the objective was to investigate the potential changes in tear osmolarity experienced
      during the wear of such lenses across a period of 12 months.

      The study adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained
      from each participant after the nature and possible consequences of the study were explained.
      The study recruited 60 healthy young novices or habitual contact lens wearers (41 F and 19
      M), aged (mean ± standard deviation) 26 ± 4 y/o, ranging from 20 to 37 y/o. Habitual contact
      lens users were advised to cease wearing their lenses and instilling ophthalmic solutions at
      least three days prior to commencing the study.

      This was to ensure subjects previously wearing different types of contact lenses achieved a
      more consistent baseline (bare eye) result. Subjects were also requested to present an
      up-to-date optical prescription. Exclusion criteria were signs and symptoms of severe eye
      dryness, inflammation or substantial tear flow impairment and any systemic disorders known to
      compromise the ocular surface or tear film quality. Additionally, subjects were excluded if
      demonstrated at least two out of the following signs of DED: OSDI higher than 23,
      conjunctival staining higher or equal to 2 or/and corneal staining higher or equal to 2
      present (Efron grading scale) and fluorescein tear film break-up time of less than 7 seconds.
      The refractive error was limited to ±5.00 spherical and ±0.75 cylindrical diopters, as the
      spherical equivalent of the correction was provided

      The study protocol consisted of a qualifying visit (Baseline), contact lens fitting visit
      (following day - Day 2 visit), a control visit at 2 weeks and follow-up visits at 3 months, 6
      months and 12 months post-refitting, followed by the visit for the post-study assessment
      after three days (post-study visit). Laboratory temperature (°C) and humidity (%Rh) were
      monitored with the thermo-hygrometry device (C3121, Comet, Czech Republic). Subjects could
      have an environmental adjusting period if they arrived at the laboratory directly from the
      outdoors. At each of the visits (except Day 2) OSDI questionnaire was filled-in by the
      participants to assess ocular symptoms during the last week preceding each visit and to
      distinguish symptomatic subjects.

      Subjects with OSDI ≥ 13 were reported as symptomatic, as this is the reported threshold
      between healthy and mild/moderate DED subjects. The questionnaire was adapted to the
      subjects' native language. During the Baseline visit, together with OSDI, the review of
      medical history was performed including general and ocular health, refractive correction
      type, modality and refractive power, visual acuity (distance and near), the date of last eye
      examination and last medical examination, history of previous contact lens wear, family
      ocular history, allergies, medication, occupation, driving, visual display unit use, smoking
      and hobbies. This was followed by tear osmolarity measurements with TearLab Osmolarity System
      (TearLab Corp. San Diego, CA. Measurements performed at Baseline were used for qualifying
      subjects to the study and formed the baseline database for comparative analyses with the
      measurements performed at follow-up visits. Measurements at Baseline and post-study visit
      were performed at the same time of the day.

      At Day 2 (the following day) subjects were fitted with Silicone-Hydrogel (Si-Hy, Delefilcon
      A) or Hydrogel (Hy, Omafilcon A) daily disposable soft contact lenses.

      Newly-fitted lens was chosen based on contact lens fit, reported subjective comfort after 4
      hours of wear and pre-lens tear film surface quality. Contact lens fit assessment included
      contact lens centration, corneal coverage, horizontal lag, blink movement, push-up test and
      the binocular corrected visual acuity rating for distance and near vision.

      A supply of contact lenses was provided for each subject, with the instruction to wear the
      lenses for any five days per week, minimum eight hours and up to 12 hours per day. The same
      wearing schedule was followed for the whole duration of the study.

      All subjects were fully instructed on insertion, safe removal and lens care together with the
      given written instructions. The purpose of the 2-week control visit was to ensure good
      contact lens performance, comfort and fit and to qualify subjects for 12 months of contact
      lens wear. At three-, six- and 12-month visits subjects were advised to wear their contact
      lenses at least five hours prior to attending. The protocol for these follow-up visits
      included OSDI questionnaire filled in during an environmental adjusting break, osmolarity
      measurements on bare eye and ocular anterior surface check-up with the slit-lamp
      biomicroscope to assess ocular surface health.

      Tear osmolarity was measured for both eyes of each subject from the inferior lateral tear
      meniscus. Electronic check cards calibration of the instrument was performed daily according
      to the manufacturer's instruction. The calibration using a control solution was performed
      every time a new box of test cards was opened.

      The device was powered for the whole duration of the study where diagnostic pens were kept
      fully charged. The device and the test cards were stored in the laboratory in which the
      measurements were conducted. The same diagnostic pen was used for all measurements, starting
      the assessment, every time, with the right eye. Samples were collected by the same
      experienced researcher from the eye without contact lens, 10 minutes after subject taking the
      lenses off. Subjects were asked to sit with their chin tilted slightly upward and eyes
      directed toward the ceiling. The tip of the pen was positioned just above the lower eyelid
      and gently applied to the thin line of tears on the lower eyelid margin. Care was taken not
      to induce reflex lacrimation. After successful collection, the values were recorded. At least
      two measurements for each eye were performed. If the results were not consistent (differed
      more than 10 mOsm/L), the third measurements was conducted. The tear film osmolarity was
      measured at the Baseline, three-month, six-month, 12-months and the post-study visits.
    

Intervention name(s): Daily-disposable soft contact lens
Intervention type(s): Other
Intervention description(s): Subjects were refitted with Silicone-Hydrogel (Delefilcon A) or Hydrogel (Omafilcon A) daily-disposable soft contact lenses based on their fit, reported comfort and tear film surface quality.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Other
Keywords: Tear film; Tear osmolarity; Contact lenses