Reproducibility of LipiView Ocular Surface Interferometer (LipiView) for Measuring Tear Lipid Layer Thickness
Condition: Dry Eyes
MeSH terms: Dry Eye Syndromes
Study type: Interventional

Summary: 
      Dry eye clinical research is limited to follow up of disease progression. While a large
      catalogue of tests, such as corneal staining grading, tear break up time (TBUT) and
      Schirmer's test, is available, objective assessments demonstrate poor to moderate
      repeatability. Among these assessments, TBUT has the best repeatability while the Schirmer's
      test shows good repeatability for more severe forms of the disease.1 As such, currently, most
      research outcomes are based on subjective patient complaints rather than objective assessment
      of the condition.

      LipiView Ocular Surface Interferometer (LipiView) is a HSA-approved imaging device that has
      the ability to assess optical interference pattern produced by light reflected off the tear
      film in a safe and non-invasive manner.2 Software analysis of the image then measures the
      tear LLT, which is used to objectively quantify the diagnosis of lipid-deficient dry eye.

      This current study aims to investigative the inter and intra-examiner reproducibility of
      measuring tear lipid layer thickness (LLT) with LipiView, which is used in our current
      clinical setting. LipiView has not been evaluated on its reproducibility of measuring tear
      lipid layer thickness. The study will also assess for correlation between the magnitude of
      tear LLT and the inter and intra-examiner reproducibility of LipiView.

      Once this method is found to be repeatable, this can be used in future clinical settings and
      trials as an additional tool to investigate dry eye treatments.
    

Detailed description: 
      This study will be conducted in compliance with the protocol, SGCP and the applicable
      regulatory requirements.

      Dry eye is a condition that affects 5-35% of the population.11 Common symptoms of this
      condition include eye irritation, heaviness of the eyelids, visual disturbances, tearing and
      light sensitivity.12 This significantly impacts the quality of life and vision of dry eye
      patients. In addition, there is a significant socioeconomic burden. In 2009, 54,051 patients
      sought treatment for dry eye in the Singapore National Eye Centre (SNEC). In total, the costs
      for dry eye medication amounted to $181,354.17.14 Additionally, dry eye affects work
      productivity which further adds on to the socioeconomic burden.15

      Currently, the diagnosis and assessment of dry eye is hindered by tests that have poor
      repeatability, some of which cause discomfort due to their invasiveness. As a result most
      clinical studies involving dry eye treatment rely on symptomatic improvements as a primary
      outcome measure. However, symptomatic improvements are a poor measure in determining
      treatment effectiveness because with disease progression, the eye becomes desensitized from
      nerve damage. Also, it is common for patients to feel a reduction of discomfort of the eye
      before objective improvements can be noted by the clinician. An assessment based on symptoms
      alone is therefore inappropriate.13

      Over the last few years, SNEC/SERI has built up a dedicated team of dry eye researchers for
      trials and evaluation of diagnostic devices. There is an increasing interest internationally,
      especially from industry, to partner us for testing of commercial products.

      The LipiView Ocular Surface Interferometer is a HSA-approved imaging device that allows
      clinicians evaluate the characteristics and thickness of the tear lipid layer thickness (LLT)
      in a safe and non-invasive manner. The device utilizes white light from a LED source that is
      directed at the tear film over the inferior corneal region. Reflected light is captured by a
      high resolution camera and the optical inference pattern is evaluated by software to
      determine the LLT. 2 It also was found to correlate with other dry eye diagnostic tests, such
      as tear film break-up time (TBUT), Schirmer's test and corneal staining 3,4,5,6. LLT is also
      reported to better correlate with symptoms than other objective dry eye tests. 2

      While several studies have investigated and shown the association between dry eye syndrome
      and low LLT 2,7,8,9, it is not known if LipiView would be able to make reproducible
      measurements of LLT for the objective diagnosis of dry eye syndrome.

      Clinical importance Should this modality of imaging be shown to be repeatable, it can be
      incorporated into current protocol/workflow for assessment and monitoring of dry eye and
      treatment progress in our centre, as well as enhancing our capability to perform clinical
      trials and increase our international reputation.

      Study Objectives and Purpose The primary purpose is to evaluate intra-examiner repeatability
      of the LipiView Ocular Surface Interferometer (LipiView) for imaging tear lipid layer
      thickness.

      Study design:

      Prospective study

      Rationale:

      Repeatability is an important issue in the objective assessment of dry eye. There is lack of
      studies that investigate LipiView for assessment of the tear film lipid layer thickness in
      dry eyes. LipiView is potentially useful as a non-invasive procedure for objective
      measurements of dry eyes.

      Methods:

      Participants and target sample size 20 healthy volunteers will be recruited for this study.
      During recruitment, a simple questionnaire is given to confirm for the absence of any dry eye
      symptoms. Each volunteer will also be given a study serial number to ensure anonymity.

      All 20 volunteers will participate in the LipiView repeatability and inter-rater agreement
      study.

      Visit schedules One visit is required for participants.

      Duration of study:

      10 months.

      Procedures:

        1. Assessment of Dry Eye Symptoms Participants will be asked to score and fill up a dry eye
           questionnaire that assesses the symptomatic severity of dry eyes in the participant and
           the extent of its disruption to daily activities. Basic biodata such as age, race,
           gender will also be recorded.

        2. LipiView Ocular Surface Interferometer Tear Lipid Layer Thickness Measurement During the
           measurement of each eye, the participants place their chins on a chin rest and look at a
           single white light source for 30 seconds. During this period, participants are
           encouraged to blink freely at a comfortable rate which the assessor measures the LLT.
           Afterwards, the aforementioned steps will be repeated for the same eye by another
           assessor after a 5 minutes interval. Assessor 1 will perform the measurement at time 0
           min, 10min and 20min while Assessor 2 will perform the measurement at time 5 min, 15
           min, 25min.

           Similar steps would be taken for the other eye. Therefore, 12 measurements would be
           taken altogether per participant. Between measurements, participants are advised not to
           rub or touch their eyes, or instill any eye drops or ointment.

           Assessment of fluorescein tear break up time and corneal staining will be conducted only
           after LipiView LLT measurement.

        3. Fluorescein Dye Tear Break-up Time (TBUT) Fluorescein dye is introduced onto the lower
           eyelid by a wetted fluorescein strip. The tear film will then be observed with blue
           light using a slit lamp to the point where it breaks. The time from the previous blink
           to the breaking of the tear film will be recorded to the nearest second.

        4. Fluorescein Dye Corneal Staining After fluorescein dye is introduced, the cornea will be
           examined for green stains indicating epithelial erosion, a sign of damage due to
           dryness. The number of green stains and their location on the cornea (superior, central,
           inferior, temporal, nasal fields) will be recorded.
    

Intervention name(s): LipiView
Intervention type(s): Device
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: Dry Eyes; LipiView; Lipid thickness