Evaluation of Dry Eye by Tear Film Imager in a Low Humidity Environmental Exposure Chamber (TFI-LH16)
Condition: Dry Eye
MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca
Study type: Observational

Summary: 
      The study consists of 3 study visits to the clinic over at least 9 days. Visit 1 - the
      medical screening visit: subjects will undergo informed consent and will be tested for signs
      and symptoms of Dry Eye Syndrome (DES) including measurements by the TFI.

      Upon conclusion of the screening for DES, the subjects will be divided to the different
      categories: NDE, LDDE and ADDE. For ADDE and LDDE subjects the eye fitting the worst DES
      inclusion criteria will be designated as the study eye. For the NDE subjects the best eye
      will be designated as the study eye.

      During Visit 2 and 3, the TFI measurement and other clinical study endpoint procedures will
      be only conducted on the study eye. The safety endpoint procedures will still be conducted on
      both eyes individually throughout the study. Subjects will be queried for adverse events
      (AEs) at all visits.

      Visit 2 - after two days washout period subject will return for the LH-EEC test. Signs and
      symptoms of dry eye will be recorded before entering the LH-EEC, during the 120 min stay in
      the LH-EEC and at the conclusion of the day.

      Visit 3 - after 7 days washout period subject will return for the last test. The third day
      procedure is identical to the second day, with the addition of: following LH-EEC exit,
      subjects will have a health check and study check out procedures conducted.

      Statistical Analysis:

      Data will be summarized with respect to baseline characteristics, efficacy variables and
      safety variables. Summary statistics will include the number of observations (N), mean,
      standard deviation (SD), median, minimum and maximum values for continuous variables and
      frequencies and percentages for categorical variables.

      Missing values will not be replaced or imputed, i.e., no interpolation or extrapolation will
      be applied to missing values.

      Safety data will be listed and summarized by group (NDE, ADDE, and LDDE).
    

Detailed description: 
      This study consists of 3 study visits to the clinic (a medical screening visit, and 2 LH-EEC
      visits) over at least 9 days. Subjects need to refrain from putting on any makeup near their
      eyes on the morning of each visit.

      At the medical screening visit (Visit 1), subjects will undergo informed consent, fill out
      the Ocular Surface Disease Index (OSDI) questionnaire, and provide
      medical/surgical/ocular/medication histories and demographics. A urine pregnancy test will be
      performed on women of childbearing potential (WOCBP). Prior to any baseline symptom or sign
      collection, subjects will be acclimatized to the clinic environment for at least 30 min.
      Baseline subject rating of ocular symptoms (dryness, burning/stinging, tearing,
      grittiness/sandiness, intermittent blurring, soreness/discomfort, sensitivity to light
      [photophobia]) in both eyes together will be recorded using the electronic Patient Data
      Acquisition Tablet (ePDAT™) on a 0-4 scale with 0.5 increments. To meet eligibility criteria,
      subjects will participate in the following ophthalmic examinations (in the order specified):
      distance visual acuity (VA), slit lamp examination (SLE), undilated fundus examination,
      non-contact tonometry (NCT) followed by at least a 30 min wait, baseline TFI ocular surface
      imaging assessment (duplicate measurements at least 30 min apart in both eyes), Tear Break Up
      Time (TBUT), corneal fluorescein staining (CFS), conjunctival lissamine green staining
      (CLGS), Schirmer's Test without anesthetic, and Meibomian Gland Dysfunction (MGD)testing.
      Upon conclusion of the screening for DES, the eye fitting the worst DES inclusion criteria
      will be designated as the study eye. For the NDE subjects, the best eye will be designated as
      the study eye. During Visit 2 and 3, the TFI measurement and other clinical study endpoint
      procedures (i.e. TBUT, CFS, CLGS, Schirmer's Test) will be only conducted on the study eye,
      however the safety endpoint procedures (i.e. VA, SLE, undilated fundus exam NCT) will still
      be conducted on both eyes individually throughout the study. Subjects will be queried for
      adverse events (AEs) at all visits. The clinic environment will be monitored for relative
      humidity (%RH) and temperature (ºC) at each visit.

      After at least a 2 day washout period, subjects will return to the clinic for Visit 2.

      Prior to any baseline symptom or sign collection, subjects will be acclimatized to the clinic
      environment for at least 30 min. Subjects will be queried for changes in health and
      medication use since the last visit. Baseline subject rating of the 7 subjective ocular
      symptoms will be recorded using the ePDAT™. Baseline ophthalmic evaluations will be conducted
      (in the order specified) including VA, SLE followed by at least a 30 min wait, TFI assessment
      (single measurement only), TBUT, CFS, CLGS and Schirmer's Test without anesthetic. Following
      the Schirmer's Test, subjects will wait at least 60 min in the clinic and during this time,
      baseline blink rate (blink/min, in triplicate) will be measured. Subjects will then have a
      second TFI measurement and then enter the LH-EEC. Subject symptom scoring and staff assessed
      blink rate will be assessed on both eyes together throughout the study.

      Subjects will enter the LH-EEC (<15% relative humidity (RH), temperature 22±5ºC, and 5±3ft/s
      directed air flow velocity) and remain for approximately 120 min. During this time subjects
      are asked to visually task on a digital screen to ensure the ocular surface is exposed to the
      airflow and humidity levels in the room. Environmental conditions in the LH-EEC, including
      relative humidity (%RH) and temperature (ºC), will be monitored. Subject-assessed symptoms
      will be assessed at 15, 30, 60, 90, and 120 min (+5 min), while in the LH-EEC. Blink rate and
      TFI tear film imaging assessment (single measurement on the study eye only) will be assessed
      by qualified staff at 35, 65, 95 min (+15 min), and prior to LH-EEC exit. After all other
      procedures and prior to exiting the chamber, VA, TBUT, CFS, CLGS, and Schirmer's Test without
      topical anesthetic, will be performed. After LH-EEC exit, a health check will be conducted.

      After at least a 7 day washout period, subjects will return to the clinic on Visit 3 for
      their second LH-EEC visit. Subjects will be queried for changes in health and medication use
      since the last visit. Subjects will once again enter the LH-EEC (<15% relative humidity [RH],
      temperature 22±5ºC, and 5±3ft/s directed air flow velocity) for approximately 120 min. All
      procedures prior to LH-EEC entry, during LH-EEC exposure and prior to LH-EEC exit will be
      repeated as in Visit 2.

      Following LH-EEC exit, subjects will have a health check and study check out procedures
      conducted including: VA, SLE, undilated fundus exam, and NCT.

      Analysis Sets:

      The Safety set will consist of all subjects who were enrolled in the study. The Modified
      Intent-to-Treat population (MITT) set will consist of all subjects who were enrolled in the
      study and who entered the LH-EEC and provided at least one post-baseline measurement. The
      Per-Protocol population (PP) set will consist of all subjects from MITT population who
      complete Visit 3 and do not have any protocol violations that may substantially affect the
      results.

      Statistical Analysis:

      Data will be summarized with respect to baseline characteristics, efficacy variables and
      safety variables. Summary statistics will include the number of observations (N), mean,
      standard deviation (SD), median, minimum and maximum values for continuous variables and
      frequencies and percentages for categorical variables. Missing values will not be replaced or
      imputed, i.e., no interpolation or extrapolation will be applied to missing values.

      Safety data will be listed and summarized by group (NDE, ADDE, and LDDE). Any deviation(s)
      from the planned statistical analysis will be described and fully justified in the
      Statistical Analysis Plan (SAP) and/or the final clinical study report (CSR) as appropriate.

      Demographic and Baseline Characteristics:

      Demographic and baseline characteristics of subjects who participated in this study will be
      summarized by study group (NDE, ADDE, and LDDE) and overall using descriptive statistics.
      Distributions of these baseline parameters among study groups will be compared descriptively
      only. No statistical inference will be performed.

      Safety Analysis:

      Safety will be evaluated via the following parameters: AEs, SLE, VA, NCT, Fundus examination
      AEs will be summarized for severity and causality. AEs will be summarized by body system and
      preferred term within each study group (NDE/ADDE/LDDE). Each AE will be counted only once for
      a given subject. If the same AE occurred in a subject on multiple occasions, the highest
      severity and maximum causality relationship will be assumed. Serious AEs (SAEs), if any, will
      be summarized by body system, preferred term and study group. All AEs will be listed, along
      with SAEs and AEs leading to discontinuation. NCT assessment will be performed at Screening
      (Visit 1) and at end of study (Visit 3), to measure the Intra-Ocular Pressure (IOP). The
      collected data (average of 3 readings for each eye) will be listed by study group, subject
      and visit. Summary statistics of the average of 3 readings for each eye will be tabulated for
      Study eye, Right and Left eye. Study eye will be defined in the SAP. VA assessment will be
      performed at each visit. Data will be listed by ADDE/ LDDE/NDE group, subject and visit.

      Statistical Study Termination:

      If the device related SAE rate exceeds 20% in any specific group (ADDE/LDDE/NDE) the study of
      this group will be halted and a report will immediately be sent to the Sponsor. The
      Investigator and the Sponsor will analyze this report and offer a protocol update to the
      Institutional Review Board (IRB) to rectify the problem. If the IRB approves the updated
      protocol, the study will continue based on the updated protocol. If the IRB will not accept
      the updated protocol the specific group study will be terminated.

      Analysis of the Endpoints:

      The analyses of the clinical endpoints will be carried out using both the MITT and PP
      populations. All summary tables will be provided by study group (NDE, ADDE, and LDDE) and
      overall. The repeatability of the TFI will be evaluated from summary of TFI assessments
      between Visit 2 and Visit 3. The sensitivity of the imager to detect changes in ocular
      surface integrity will be evaluated from the summary of baseline to post baseline assessment
      scores by time points and visit. The correlation between the clinical measurements of DE and
      the corresponding TFI measurement of interest will evaluate the association between the two
      assessments. Descriptive statistics of all observed assessment scores at each time point and
      the change at each post LH-EEC time point from pre LH-EEC baseline score will be summarized.
      Individual data listings of all observed values will be presented by study group, visit and
      time points.
    

Intervention name(s): Tear Film Imager; Low Humidity Environmental Exposure Chamber (LH-EEC)
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): Ocular surface imaging assessment by the Tear Film Imager (TFI); Subjects will enter the LH-EEC (<15% relative humidity (RH), temperature 22±5ºC, and 5±3ft/s directed air flow velocity) and remain for approximately 120 min.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Healthy male and female volunteers, aged 18 years or older, either without or with DES
        (aqueous and lipid deficient).
      
Keywords: Tear Film; Hyperspectral imaging; Low Humidity Environmental Exposure Chamber