Prospective, Randomized, Masked, Controlled Trial To Evaluate The Safety And Effectiveness Of The TearCare® System In The Treatment Of The Signs And Symptoms Of Dry Eye Disease (SAHARA)
Phase: NA
Conditions: Dry Eye, Meibomian Gland Dysfunction
Sponsor: Sight Sciences, Inc.

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Agreement of Principal Investigator 
I, 
agree to conduct this trial in accordance 
with this clinical protocol and any amendments. 
Signature 
Date 
Center Name 
City, State, Country 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. It must be held 
confidential and maintained in a secure location. 
Do not copy or distribute without written permission. 
PROSPECTIVE, RANDOMIZED, MASKED, CONTROLLED TRIAL TO EVALUATE THE 
SAFETY AND EFFECTIVENESS OF THE TEARCARE® SYSTEM IN THE TREATMENT 
OF THE SIGNS AND SYMPTOMS OF DRY EYE DISEASE (SAHARA) 
PROTOCOL ID #: 
07093  
CURRENT VERSION: 
H 
REVISION DATE: 
August 26, 2022 
SPONSOR: 
Sight Sciences, Inc. 
4040 Campbell Avenue, Suite 100 
Menlo Park, CA 94025 
877-266-1144
CONFIDENTIAL 
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Revision History 
 
 
Revision 
Date Issued 
ECO 
A 
10-09-2020 
3308 
B 
12-07-2020 
3363 
C 
03-02-2021 
3440 
D 
04-23-2021 
3519 
E 
05-11-2021 
3548 
F 
03-31-2022 
4103 
G 
06-21-2022 
4285 
H 
08-26-2022 
4452 
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TABLE OF CONTENTS 
1 
PROTOCOL SYNOPSIS ........................................................................................................................... 6 
2 
STUDY OBJECTIVE .............................................................................................................................. 10 
3 
BACKGROUND AND JUSTIFICATION FOR THE STUDY .......................................................................... 10 
4. 
DESCRIPTION OF DEVICE .................................................................................................................... 15 
4.1. 
DEVICE DESCRIPTION .................................................................................................................................................................. 15 
4.2. 
DEVICE RECALL ............................................................................................................................................................................ 18 
4.3. 
DEVICE MODIFICATION ............................................................................................................................................................... 18 
4.4. 
INSTRUCTIONS FOR USE ............................................................................................................................................................. 19 
4.5. 
TRAINING .................................................................................................................................................................................... 19 
5. 
PRIOR INVESTIGATIONS ..................................................................................................................... 19 
5.1. 
PRECLINICAL TESTING ................................................................................................................................................................. 19 
5.2. 
PREVIOUS CLINICAL EXPERIENCE ................................................................................................................................................ 20 
5.2.1. CLINICAL STUDY OF THE PROTOTYPE TEARCARE SYSTEM (2013) ......................................................................................... 20 
5.2.2. CLINICAL STUDY OF THE TEARCARE SYSTEM (2017) ............................................................................................................ 21 
5.2.3. CLINICAL STUDY OF THE TEARCARE SYSTEM-CHEETAH (2018) ............................................................................................ 22 
5.2.4. CLINICAL STUDY OF THE TEARCARE SYSTEM-OLYMPIA (2019) ............................................................................................. 23 
6 
STUDY ENDPOINTS............................................................................................................................. 27 
6.1 
EFFECTIVENESS ENDPOINTS ........................................................................................................................................................ 27 
6.2 
SAFETY ENDPOINTS ..................................................................................................................................................................... 28 
7 
STUDY DESIGN ................................................................................................................................... 28 
7.1 
STUDY DEVICE AND CONTROL GROUP ........................................................................................................................................ 28 
7.2 
STUDY CENTERS .......................................................................................................................................................................... 28 
8 
STUDY SELECTION CRITERIA ............................................................................................................... 29 
8.1 
INCLUSION CRITERIA ................................................................................................................................................................... 29 
8.2 
EXCLUSION CRITERIA ................................................................................................................................................................... 29 
9 
STUDY PROCEDURES .......................................................................................................................... 32 
9.1 
TABLE 3: TEARCARE STUDY VISIT SCHEDULE .............................................................................................................................. 32 
9.2 
TABLE 4: RESTASIS STUDY VISIT SCHEDULE ................................................................................................................................ 33 
9.3 
NUMBER OF SUBJECTS, DURATION OF FOLLOW-UP AND STUDY DURATION............................................................................... 34 
9.4 
MATERIAL AND EQUIPMENT ....................................................................................................................................................... 34 
9.5 
INFORMED CONSENT AND POINT OF ENROLLMENT ................................................................................................................... 35 
9.6 
BASELINE AND STUDY GROUP VISIT(S) ........................................................................................................................................ 35 
9.6.1 
SCHEDULING THE BASELINE AND DAY 0 VISIT(S) .................................................................................................................. 35 
9.6.2 
BASELINE EXAMS, TESTS AND QUESTIONNAIRES ................................................................................................................. 35 
9.6.3 
RANDOMIZATION ................................................................................................................................................................ 36 
9.6.4 
PROCEDURE FOR TEARCARE (STUDY DEVICE GROUP) ......................................................................................................... 37 
9.6.5 
RESTASIS DISTRIBUTION (CONTROL GROUP) ....................................................................................................................... 38 
9.6.6 
FOLLOW-UP INSTRUCTIONS FOR SUBJECTS ......................................................................................................................... 39 
9.7 
FOLLOW-UP VISITS ...................................................................................................................................................................... 40 
9.8 
PHOTOGRAPHY DURING EXAMS AND TEARCARE PROCEDURE................................................................................................... 41 
9.9 
MASKED ASSESSOR ..................................................................................................................................................................... 41 
9.10 
MANAGEMENT OF DRY EYE SYMPTOMS DURING FOLLOW-UP .................................................................................................. 41 
9.11 
WITHDRAWAL AND DISCONTINUATION ..................................................................................................................................... 42 
9.12 
SUBJECTS LOST TO FOLLOW-UP .................................................................................................................................................. 42 
10 
ADVERSE EVENTS (AES) ...................................................................................................................... 42 
10.1 
DEFINITIONS OF AE, SAE, SADE, USADE ....................................................................................................................................... 43 
10.2 
LIST OF ANTICIPATED POTENTIAL OCULAR ADVERSE EVENTS ..................................................................................................... 43 
10.3 
REPORTING ADVERSE EVENTS AND UNANTICIPATED ADVERSE DEVICE EFFECTS ........................................................................ 44 
11 
RISK-BENEFIT ANALYSIS ..................................................................................................................... 45 
11.1 
ANTICIPATED CLINICAL BENEFITS ................................................................................................................................................ 45 
11.2 
ANTICIPATED ADVERSE DEVICE EFFECTS ..................................................................................................................................... 45 
11.3 
RISKS ASSOCIATED WITH PARTICIPATION IN THE CLINICAL INVESTIGATION ............................................................................... 45 
11.4 
POSSIBLE INTERACTIONS WITH CONCOMITANT MEDICAL TREATMENTS ................................................................................... 45 
11.5 
STEPS THAT WILL BE TAKEN TO CONTROL OR MITIGATE THE RISKS ........................................................................................... 45 
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12 
STATISTICAL CONSIDERATIONS .......................................................................................................... 46 
12.1 
EVALUABILITY ............................................................................................................................................................................. 46 
12.2 
ANALYSIS POPULATIONS ............................................................................................................................................................. 46 
12.3 
SUBJECT ACCOUNTABILITY .......................................................................................................................................................... 47 
12.4 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................................................................................................... 47 
12.5 
EFFECTIVENESS ENDPOINTS AND ANALYSIS METHODS .............................................................................................................. 47 
12.6 
SAFETY ENDPOINTS AND ANALYSIS ............................................................................................................................................ 50 
12.7 
SAMPLE SIZE CALCULATION ........................................................................................................................................................ 51 
12.8 
DEVIATION FROM THE STATISTICAL PLAN .................................................................................................................................. 51 
13 
MONITORING PROCEDURES .............................................................................................................. 51 
14 
DATA AND QUALITY MANAGEMENT .................................................................................................. 53 
14.1 
DATABASE MANAGEMENT .......................................................................................................................................................... 53 
14.2 
SUBJECT IDENTIFICATION............................................................................................................................................................ 53 
14.3 
SUBJECT ACCOUNTABILITY .......................................................................................................................................................... 53 
14.4 
CONFIDENTIALITY ....................................................................................................................................................................... 54 
14.5 
SOURCE DATA AND CASE REPORT FORMS .................................................................................................................................. 54 
14.6 
RETENTION PERIOD..................................................................................................................................................................... 54 
15 
PROTOCOL MODIFICATIONS AND DEVIATIONS .................................................................................. 55 
16 
DEVICE FAILURES AND MALFUNCTIONS ............................................................................................. 55 
17 
ETHICAL CONSIDERATIONS ................................................................................................................ 55 
17.1 
DECLARATION OF HELSINKI ......................................................................................................................................................... 55 
17.4 
PUBLIC LISTING OF STUDY ........................................................................................................................................................... 56 
18 
STUDY ADMINISTRATION ................................................................................................................... 56 
18.1 
DEVICE AND DRUG ACCOUNTABILITY ......................................................................................................................................... 56 
18.2 
EARLY TERMINATION OR SUSPENSION OF AN INVESTIGATION .................................................................................................. 57 
18.3 
INVESTIGATOR RESPONSIBILITIES ............................................................................................................................................... 57 
18.4 
INVESTIGATOR AGREEMENT ....................................................................................................................................................... 59 
19 
PUBLICATION POLICY ......................................................................................................................... 59 
20 
BIBLIOGRAPHY ................................................................................................................................... 61 
21 
APPENDIX A – METHODS FOR EXAMS, TESTS AND QUESTIONNAIRES ................................................ 64 
21.1 
MEDICATIONS ............................................................................................................................................................................. 64 
21.2 
MANIFEST REFRACTION AND VISUAL ACUITY ............................................................................................................................. 64 
21.3 
SLIT LAMP EXAM ......................................................................................................................................................................... 66 
21.4 
TEAR BREAKUP TIME (TBUT) ....................................................................................................................................................... 66 
21.5 
CORNEAL STAINING .................................................................................................................................................................... 67 
21.6 
CONJUNCTIVAL STAINING ........................................................................................................................................................... 68 
21.7 
SCHIRMER TEST ........................................................................................................................................................................... 69 
21.8 
MEIBOMIAN GLAND SECRETION SCORING ................................................................................................................................. 70 
21.9 
INTRAOCULAR PRESSURE ............................................................................................................................................................ 71 
21.10 BLINK RATE ................................................................................................................................................................................. 71 
21.11 QUESTIONNAIRES ....................................................................................................................................................................... 72 
22 
APPENDIX B – STATISTICAL ANALYSIS PLAN ........................................................................................ 74 
22.1 
ANALYSIS POPULATIONS ............................................................................................................................................................. 74 
22.2 
STATISTICAL HYPOTHESES ........................................................................................................................................................... 74 
22.3 
MULTIPLICITY CONSIDERATIONS ................................................................................................................................................. 76 
22.4 
SAMPLE SIZE CALCULATIONS ...................................................................................................................................................... 76 
22.5 
STATISTICAL ANALYSIS ................................................................................................................................................................ 77 
22.6 
SAFETY ANALYSIS ........................................................................................................................................................................ 79 
23 
APPENDIX D - DECLARATION OF HELSINKI .......................................................................................... 80 
 
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1 PROTOCOL SYNOPSIS 
 
Protocol Title 
Prospective, Randomized, Masked, Controlled Trial to Evaluate 
the Safety and Effectiveness of the TearCare® System in the 
Treatment of the Signs and Symptoms of Dry Eye Disease 
(SAHARA) 
Protocol ID Number 
07093 
Study Device 
TearCare® System 
Control Group 
Restasis® (0.05% Cyclosporine ophthalmic emulsion) 
Primary Objective 
To demonstrate the safety and effectiveness of TearCare® 
procedures compared to Restasis® to treat the signs and 
symptoms of dry eye disease in adult patients. 
Study Design 
Prospective, randomized, masked, multi-center, superiority, non- 
significant risk study. 
Primary Effectiveness 
Endpoint 
Mean Change from baseline in: 
o Tear Break-Up Time (TBUT) 
o Ocular Surface Disease Index (OSDI) score 
Superiority will be assessed at 6 month 
Secondary Effectiveness 
Endpoints 
Mean Change from baseline in: 
o Total Meibomian Gland Secretion Score 
o Corneal staining scores 
o Conjunctival staining scores 
o Number of Meibomian Glands Yielding any liquid 
o Number of Meibomian Glands Yielding clear liquid 
o Symptom Assessment in Dry Eye (SANDE) scores 
o Eye Dryness Score 
o Schirmer score 
o Ocular protection index (OPI): Interblink interval (IBI)/TBUT 
Primary Safety Endpoint 
o Procedure (TearCare)/Treatment (Restasis)-related adverse 
events 
Secondary Safety Endpoints 
o Change in best corrected visual acuity (ETDRS) 
o Change in intraocular pressure (IOP) 
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Inclusion Criteria 
1. At least 22 years of age 
2. Reports dry eye symptoms within the past 3 to 6 months 
3. Reports having to use artificial tears or lubricants regularly 
over the past month to relieve dry eye symptoms. 
4. Schirmer tear test (with anesthesia) ≥5 to ≤15 mm in 5 
minutes 
5. OSDI Score of 23-79 
6. TBUT of ≥1 to ≤7 seconds in both eyes 
7. Meibomian gland obstruction in both eyes based on a total 
Meibomian Gland Secretion Score ≤12 in each eye. 
8. At least 15 glands in each lower eyelid should be expressible, 
with a sterile cotton swab, at the slit lamp. 
9. Best corrected visual acuity of 20/100 or better in both eyes. 
10. Willing and able to comply with the study procedures and 
follow-up 
11. Willing and able to provide informed consent 
12. English-speaking 
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Exclusion Criteria 
1. Use of any of the following medications: 
a) Cyclosporine (Restasis, Cequa etc.) or Xiidra and serum tears 
within 60 days  prior to baseline; 
b) Antihistamines (oral or topical) within 7 days prior to 
baseline. 
c) Systemic medication(s) that is known to cause ocular dryness (e.g., 
diuretics, anti- hypertensives, anti-depressants, antihistamines, 
hormone therapy) and whose dose of this medication(s) has not 
been stable within 30 days prior to baseline. There must be no 
anticipated adjustments to the dose of these medications for the 
duration of the trial. 
d) Accutane (at any time); 
e) Oral tetracyclines or azithromycin within 30 days prior to 
baseline; or 
f) Topical ophthalmic antibiotics, anti-glaucoma medications, 
steroids, non-steroidal anti-inflammatory medications within  30 
days prior to baseline. 
2. Any of the following dry eye treatments: 
a) Office-based dry eye treatment (e.g. IPL, TearCare, thermal 
pulsation [LipiFlow], iLux etc.) within 12 months prior to baseline 
either as part of routine care or clinical investigation; 
b) Planned or recent surgical procedures to the eye or eyelid (90 
days prior to baseline) 
c) Meibomian gland expression within 6 months prior to 
baseline; 
d) Blephex or debridement within 3 months prior to baseline is an 
exclusion; 
e) Punctal occlusion or punctal plugs. Investigators can choose to 
remove the punctal plugs 15 days prior to baseline; 
f) Use of tear neurostimulators (i.e., True Tear, iTear100, Tyrvaya) 
within 2 weeks of the baseline visit. (Subjects must refrain from 
using tear neurostimulators for the duration of the study.); or 
g) Any history of meibomian gland probing 
3. History of eyelid, conjunctiva, or corneal surgery (including refractive 
surgery) within the past year prior to baseline. In addition, subjects 
with  any history of the following are excluded: chalazion surgery, 
surgery on the tarsal conjunctiva, radial keratotomy (RK), complicated 
blepharoplasty, lid reconstruction, or significant complications post-
refractive surgery. 
4. Contact lens use within 2 weeks of the baseline visit. 
5. Active hordeolum, stye, or chalazion at the time of the baseline visit. 
6. History of Herpes Simplex or Herpes Zoster of the eye or eyelid. 
7. Any active, clinically significant ocular or peri-ocular infection,  
inflammation, or irritation.  
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8. Recurrent clinically significant eye inflammation, other than dry eye, 
within 3 months prior to baseline. 
9. Clinically significant anterior blepharitis. In addition, collarettes or flakes 
of more than one quarter of the eyelid are excluded. 
10. Clinically significant eyelid abnormalities in either eye (e.g. 
entropion/ectropion, blepharospasm, aponeurotic ptosis, 
lagophthalmos, distichiasis, trichiasis). 
11. Clinically significant dermatologic or cutaneous disease of the  
eyelid or periocular area. 
12. In the clinical judgement of the investigator, meibomian glands have 
significant capping, atrophy, or are unable to be expressed, digitally or 
with a sterile cotton swab. 
13. Clinically significant ocular surface abnormalities that may affect tear 
film distribution or treatment (e.g., pterygium, anterior membrane 
dystrophy, Salzmann’s nodules, etc.) 
14. Corneal surface abnormalities such as corneal epithelial defects 
(other than punctate staining), ulcers, corneal epithelial dystrophies, 
keratoconus, and ectatic disease of the cornea 
15. Any active, clinically significant allergic, vernal, or giant papillary 
conjunctivitis. 
16. Ocular trauma within 3 months prior to baseline. 
17. Known history of diminished or abnormal facial, periocular, ocular or 
corneal sensation 
18. Systemic diseases resulting in dry eye (e.g. autoimmune diseases such 
as Sjogren’s syndrome, rheumatoid arthritis, lupus, Graves’ disease, 
sarcoidosis, etc.) 
19. Subject is currently using Retin A /Retin A derivatives. 
20. Subject has permanent eyeliner/lid tattoos, eyelash extensions or 
wears false eyelashes. 
21. Subject is currently using Latisse, Lash Boost or any other type of 
eyelash growth serum. 
22. Allergies to silicone tissue adhesives, acrylates and/or copper. 
23. Subject has a pacemaker or implantable cardiac defibrillators (ICD). 
24. Participation in another ophthalmic clinical trial 30 days prior to 
baseline. Subject must also be willing to refrain from another  
ophthalmic study for the duration of the study. 
25. Co-existing condition, either ocular or non-ocular that, in the 
judgement of the investigator could affect the safety or effectiveness 
of treatment or the compliance of the subject to the protocol. For 
example, subjects who are pregnant or nursing or have active, wet 
macular degeneration are excluded. 
 
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Number of Subjects 
Enrolled 
Approximately 412 enrolled 
Randomization 
1:1 
Number of Centers 
Up to 25 
Study Duration for Each 
Subject 
Up to 24 months 
Total Study Duration 
Approximately 40 to 50 months 
Schedule of Visits 
TearCare group (Study Device): 
Baseline, Procedure Day 0, Day 1, Week 1, Month 1, Month 3, Month 
5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 
TearCare procedure will be given within 7 days of Baseline and at 5 
Months. Beginning at 9 Months, subjects will receive an additional 
TearCare procedure when TBUT drops lower than Baseline or within 2 
seconds of baseline AND if OSDI worsens by at least 15 points 
compared to the previous visit*. 
(*Based on the recommended cutoffs for OSDI Total score, the severity of the 
subject’s dry eye symptoms is categorized as; Normal – 0-1, Mild – 13-22, Moderate 
– 23-32, Severe – 33 or higher) 
 
Restasis group (Control): 
Baseline, Restasis Day 0, Day 1, Week 1, Month 1, Month 3, Month 6 
Subjects will be required to self-administer 1 drop twice a day from 
baseline through the Month 6 visit. At Month 6, subjects from the 
Restasis group will be crossed over to the TearCare group and will 
receive one (1) TearCare procedure and will be followed as below: 
Day 1, Week 1, Month 1, Month 9, Month 12 
 
2 STUDY OBJECTIVE 
The objective of this study is to evaluate the safety and effectiveness of TearCare® 
procedures when compared Restasis® to treat the signs and symptoms of dry eye disease 
in adult patients. 
 
3 BACKGROUND AND JUSTIFICATION FOR THE STUDY 
 
Dry Eye Disease (DED) is a chronic eye condition that can cause an array of symptoms in 
patients, ranging from periodic ocular discomfort to severe corneal inflammation, 
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scarring, and vision loss.1,2 Approximately 1/3 of patients visiting their eye doctor 
suffer from dry eye. The prevalence of dry eye disease increases with age, especially in 
postmenopausal women. It is estimated that dry eye disease affects more than 7 
million Americans older 40 years of age1, and approximately 1 million to 4 million 
Americans between 65 to 84 years of age.3 
 
Each year in the U.S., billions of dollars are spent on topical lubricants, medications, tear 
duct occlusions, and other treatments to control the chronic condition of dry eye 
disease. Yu et al reported that the average annual cost of managing a patient with dry 
eye was $783 (range $757 – 809) from the payers’ perspective.4 When adjusted to the 
prevalence of DED nationwide, the overall burden of DED on the US healthcare system 
was estimated to be $3.84 billion. Moreover, there is a great cost to society in terms of 
decreased productivity due to the symptoms of dry eye. Yu, et al estimated the societal 
cost to be $11,302 per patient and $55.4 billion to the US society overall.4 Essentially, 
not only do dry eye patients directly suffer, but there is also a burden to healthcare, 
employers, and society. 
 
Historically, dry eye disease has been categorized into one of two forms, aqueous tear 
deficiency and evaporative tear deficiency. The current understanding is that 
evaporative dry eye is more common than aqueous deficient dry eye.5 However, 
because the symptoms of aqueous-deficient dry eye are difficult to differentiate from 
those of evaporative dry eye, it is often impossible to truly separate patients into 
distinct groups.6 In fact, AAO guidelines state that these conditions coexist in the 
majority of the patients with the disease.7 
 
In terms of the mechanism of action for dry eye disease, the International Dry Eye 
Workshop (DEWS)1 explained that tear hyperosmolarity and the symptoms of dry eye 
result from water evaporation caused by low aqueous tear flow and/or excessive 
evaporation. This reduced, concentrated tear volume, in turn results in further 
inflammation and tear film instability creating a vicious cycle. The DEWS report 
 
1 The definition and classification of dry eye disease: report of the Definition and Classification 
Subcommittee of the International Dry Eye Work Shop. Ocul Surf. 2007;5:75–92. 
2 Lemp MA, Crews LA, et al. Distribution of Aqueous-Deficient and Evaporative Dry Eye in a Clinic-Based 
Patient Cohort: A Retrospective Study. Cornea. 2012: 31: 472-478. 
3 Fiscella RG. Understanding dry eye disease: a managed care perspective. Am J Manag Care 2011; 17 
Suppl 16:S432-9. 
4 Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision 
tree analysis. Cornea 2011;30(4):379-87. 
5 Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tusbota K, 
Stapleton F. TFOS DEWS II Definition and Classification Report. The Ocular Surface 2017;15:276-283. 
6 Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: 
report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest 
Ophthal-mol Vis Sci 2011;52:2050-64 
7 American Academy of Ophthalmology’s Dry Eye Syndrome Preferred Practice Pattern 2013. 
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concluded the following: “Since both aqueous tear deficiency and increased 
evaporative tear loss occur in most cases of dry eye disease and are linked by common 
pathogenetic mechanisms, expert clinicians are increasingly basing treatment decisions 
on an assessment of severity rather than discrete deficiencies.”8 
 
Normal tears coat the ocular surface and perform many functions, including lubrication 
of the ocular surface, protection from infection, nourishing the ocular surface cells, and 
providing an optically clear surface to properly refract light. Tears consist of three layers: 
 
1. An underlying mucin layer which acts as a wetting agent to spread tears 
uniformly on the ocular surface to prevent beading or irregularity. 
2. An aqueous layer to maintain an optically clear medium and to keep the ocular 
surface moist and healthy; and 
3. A superficial lipid layer to retard evaporation of the aqueous layer. 
When any of these layers is disturbed, tears may lose their protective and optical 
properties leading to a constellation of symptoms, a cascade of inflammatory processes, 
and the vicious cycle of dry eye. 
 
With the most recent etiologies of dry eye disease in mind, multiple standard-of-care, 
therapeutic approaches are employed: 
 
1. Supplementation of the tear film with artificial tears to address evaporation and 
maintain tear volume 
2. Use of warm compress and lid massage to improve lipid production and flow on 
the tear film 
3. Use of immunosuppressives (cyclosporine, corticosteroids, lifitegrast) to reduce 
inflammation 
4. Placement of punctal plugs to address evaporation and maintain tear volume 
 
Recently, a great deal of evidence suggests that obstruction of the meibomian glands, 
which are the glands on the eyelid that produce the lipid layer of tears, is strongly 
associated with dry eye disease.9,10,11,12 The DEWS II report states that meibomian 
gland disease is considered the leading cause of dry eye in clinic and population based 
 
8 Lemp M, Foulks, G. The Definition & Classification of Dry Eye Disease: Guidelines from the 2007 
International Dry Eye Workshop. April 2008. 
http://www.tearfilm.org/pdfs/OM%20-%20Definition%20&%20Classification.pdf 
9 Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and 
gland location. Cornea. 2008;27: 1142–1147. 
10 Korb DR, Henriquez AS. Meibomian gland dysfunction and contact lens intolerance. J Am Optom Assoc. 
1980;51:243–251. 
11 Blackie CA, Korb DR, Knop E, et al. Nonobvious obstructive meibomian gland dysfunction. Cornea. 
2010;29:1333–1345. 
12 Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland 
dysfunction. Cornea. 2010;29: 1145–1152. 
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studies.13 As these glands become either inflamed or obstructed, their ability to supply 
the essential lipids to the ocular surface is diminished. This, in turn, leads to rapid 
evaporation of tears and thus to the signs and symptoms of dry eye disease.14 When 
this occurs, it can result in ocular discomfort and, in many cases, ocular surface 
disorders that can affect vision. 
 
Current treatment for MGD includes lid hygiene, oral tetracycline, doxycycline or 
minocycline, topical erythromycin or bacitracin ointments, homogenized castor oil eye 
drops, topical corticosteroids and use of warm compresses and lid massage are 
recommended for the treatment of dry eye by the AOA, AAO, and the International 
Workshop on Meibomian Gland Dysfunction.15,16,17 It has been shown that warm 
compress therapy can lead to improved lipid production and flow on to the tear 
film.18,19, 
This improved lipid delivery is associated not only with an improvement in the profile 
of the tear film but also an improvement in patient symptoms.21,22,23 
 
While warm compress and lid massage can be an effective treatment for dry eye 
disease, it has several shortcomings, including the fact that the warm compress may not 
be sufficiently warm or it may cool too quickly. In addition, use of warm compresses on 
a daily basis is time-consuming and labor-intensive which leads to poor patient 
 
 
 
 
 
 
 
13 Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tusbota K, 
Stapleton F. TFOS DEWS II Definition and Classification Report. The Ocular Surface 2017;15:276-283. 
14 Bron AJ, Tiffany JM. The contribution of meibomian disease to dry eye. Ocul Surf. 2004;2:149–165. 
15 American Academy of Ophthalmology’s Dry Eye Syndrome Preferred Practice Pattern 2013. 
16 American Optometric Association’s Clinical Practice Guidelines for Ocular Surface Disorders, updated 
2010. 
17 Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: 
report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest 
Ophthal-mol Vis Sci 2011;52:2050-64 
18 Goto E, Monden Y, Takano Y, et al. Treatment of non-inflamed obstructive meibomian gland 
dysfunction by an infrared warm compression device. Br J Ophthalmol. 2002;86:1403–1407. 
19 Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: 
executive summary. Invest Ophthalmol Vis Sci. 2011;52:1922–1929. 
20 Lemp MA. Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. CLAO J. 
1995;21:221–232. 
21 Korb DR, Blackie CA. Restoration of meibomian gland functionality with novel thermodynamic 
treatment device–a case report. Cornea. 2010;29:930–933. 
22 Friedland BR, Fleming CP, Blackie CA, et al. A novel thermodynamic treatment for meibomian gland 
dysfunction. Curr Eye Res. 2011;36: 79–87. 
23 Olson MC, Korb DR, Greiner JV. Increase in tear film lipid layer thickness following treatment with warm 
compresses in patients with meibomian gland dysfunction. Eye Contact Lens. 2003;29:96–99. 
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compliance. As a result, various alternative approaches to heating the eyelids have 
been proposed. 24,25,26,27,28 
 
Cyclosporine 0.05% (Restasis®) is a highly specific immunomodulator that primarily 
affects T-lymphocytes, and it does not inhibit the phagocytic system as much as 
corticosteroids. To date, topical cyclosporine has been clinically shown to increase 
production of a patient’s own natural tears in chronic dry eye, MGD, ocular rosacea, and 
contact lens intolerance. 29,30 In the treatment of MGD, after three months post- 
treatment, multiple objective clinical findings were reduced. Lid margin vascular 
injection and tarsal telangiectasis improved, the mean fluorescein staining score was 
decreased, and the tear break-up time was improved after cyclosporine use for 3 
months.31 It is believed that the cyclosporine ameliorates MGD by addressing underlying 
pathophysiology. The abnormal meibum has a melting point above the ocular surface 
temperature that solidifies and obstructs the ducts, leading to further inflammation and 
perpetuating the vicious cycle. As topical cyclosporine is a highly specific 
immunomodulator that affects primarily T-lymphocytes, it may decrease the 
inflammation of the meibomian glands and reduce their plugging and dysfunction. 
 
In this study, the safety and effectiveness of the TearCare System in patients with dry 
eye disease will be evaluated. The objective is to evaluate whether the TearCare System 
is safe and effective in relieving the signs and symptoms of dry eye disease and if it is 
superior to Cyclosporine 0.05% (Restasis®). 
 
 
 
 
 
 
24 Lemp MA, Bardfield L, Blackie CA, et al. Evaluation of a novel method of treatment of dry eye. Invest 
Ophthalmol Vis Sci. 2008; 127/A154. 
25 Majmudar PA. LipiFlow Study Group. A novel thermal pulsation treatment for obstructive meibomian 
gland dysfunction: applying heat to the inner eyelid surfaces. Invest Ophthalmol Vis Sci. 2010; 
6281/D909. 
26 Mori A, Oguchi Y, Goto E, et al. Efficacy and safety of infrared warming of the eyelids. Cornea. 
1999;18:188–193. 
27 Matsumoto Y, Dogru M, Goto E, et al. Efficacy of a new warm moist air device on tear functions of 
patients with simple meibomian gland dysfunction. Cornea. 2006;25:644–650. 
28 Lane SS, DuBiner H, Epstein RJ, et al; A New System, the LipiFlow, for the Treatment of Meibomian 
Gland Dysfunction. Cornea. 2012: 31 : 396-404. 
29 Perry HD, Doshi-Carnevale S, Donnenfeld ED, Kornstein HS. Topical cyclosporine A 0.5% as a possible 
new treatment for superior limbic keratoconjunctivitis. Ophthalmology. 2003;110(8):1578-1581. 
doi:10.1016/S0161-6420(03)00538-4 
30 Stonecipher K, Perry HD, Gross RH, Kerney DL. The impact of topical cyclosporine A emulsion 0.05% on 
the outcomes of patients with keratoconjunctivitis sicca. Curr Med Res Opin. 2005;21(7):1057-1063. 
doi:10.1185/030079905X50615 
31 Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al., Efficacy of commercially available topical 
cyclosporine A 0.05% in the treatment of meibomian gland dysfunction. Cornea (2006);25:pp. 171–175. 
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4. DESCRIPTION OF DEVICE 
 
4.1. DEVICE DESCRIPTION 
The Sight Sciences’ TearCare System being studied in this study is comprised of the 
following components: 
• SmartLidTM devices 
• SmartHubTM Kit, including SmartHub, SmartHub Nest, and Charging Adapter 
• Clearance Assistant PlusTM devices with debridement edge 
The SmartLid devices are custom designed to conform to the tarsal plate of each 
respective eyelid allowing subjects to blink normally throughout the procedure and 
naturally express melted meibum with every blink. Immediately following the thermal 
procedure, the physician uses the Clearance Assistant device to further express the 
meibomian glands manually to maximize the evacuation of melted meibum. The 
Clearance Assistant also provides a tool for debridement to thoroughly remove any 
blockages at the meibomian gland orifices to facilitate and enhance natural and manual 
meibum evacuation. 
The SmartLid Devices, shown below in Figure 1, are single-use, flexible, sensor- 
controlled devices that adhere to each of the 4 eyelids. They contain flexible circuits, 
sensors and a microprocessor which provide accurate and precise thermal energy to the 
eyelids to melt oil in the meibomian glands. Medical grade adhesive on the skin-facing 
surface of the SmartLid devices allow them to be affixed to the external surface of the 
eyelids during the procedure and easily removed at the end of the procedure. The 
flexibility of the SmartLid devices permit them to remain attached to the eyelids 
throughout the procedure while subject blinks normally. 
The SmartLid devices are connected to the SmartHub via a cable. The SmartHub, shown 
below in Figure 2, delivers electrical energy to the SmartLids, and this energy is 
subsequently converted into thermal energy. Embedded software and a closed loop 
sensor system ensures that the temperature delivered at the eyelids is maintained 
within a precise range. A control button on the center of the SmartHub is used to turn 
the system on and off and to initiate or discontinue the TearCare session. Two buttons, 
“+” and “-“, on the left side of the face of the SmartHub allow the user to adjust the 
temperature to a level that is comfortable for the patient. The current warmth setting is 
indicated by the warmth level indicators between the two adjustment buttons. The 
SmartHub also has a display on the right side of its face that indicates how much time is 
left in the session. The SmartHub is battery operated, with a built-in battery, and is 
recharged by placing it on the charging nest. 
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The Clearance Assistant Plus device (shown in Figure 3 below) is single-use, sterile 
device that is designed to facilitate debriding the eyelid margin. It also allows for manual 
expression of the meibomian glands after the application of heat by the TearCare 
SmartLid devices. 
 
Figure 1: SmartLid Devices applied to the Eyelids 
 
 
 
Figure 2:  TearCare SmartHub 
 
 
 
 
 
  
 
 
No
. 
Function 
1 
Power button  
2 
Warmth setting increase 
button 
3 
Warmth setting indicator 
#4 (of 5) 
4 
Active therapy indicator  
5 
Warmth setting decrease 
button 
6a 
SmartLid Port - left 
6b 
SmartLid Port - right 
7 
Charging Port 
8a 
SmartLid error indicator - 
left 
8b 
SmartLid error indicator - 
right 
9 
Remaining Procedures 
(battery indicator) 
10 
Timer complete indicator 
11 
Timer indicators  
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Figure 3: Clearance Assistant Plus Device 
 
 
In this study, the investigator will use the Clearance Assistant device to debride all four 
eyelid margins by sweeping (very gently scraping) the debridement edge across the lid 
margin and line of Marx’s back and forth going over meibomian gland orifices. Then the 
flexible SmartLid device will be applied to the external surface of the upper and lower 
eyelids of the subject (Figure 1). The SmartLids will then be connected to the TearCare 
SmartHub. When the SmartHub is turned on the investigator will initiate the procedure 
and the TearCare System will begin delivering heat to the eyelids. The system should 
automatically and gradually increase the temperature over 2-3 minutes until it reaches 
the maximum set point temperature of 45°C. A complete TearCare procedure under 
this study is anticipated to last 15 minutes. 
The SmartHub has 5 temperature set points (ranging from 41 to 45°C), which are 
intended to allow the investigator to manually adjust the temperature up or down to a 
level that is comfortable for the subject. The set points can be adjusted at any time 
during the procedure. Subjects are able to blink naturally during the session. 
The temperature range for the TearCare System used in this study was selected based 
on research that has shown that meibum will melt at temperatures between 32 to 45°C, 
but obstructed glands may require higher temperatures, around 45°C, to effectively 
melt meibomian obstructions.32,33,34 The maximum temperature and 15 minute 
procedure duration for this study were also chosen because they are below the time- 
temperature threshold at which heat contacting the skin will first show signs of 
 
 
 
 
 
 
 
 
32 Bron AJ, Tiffany JM. The contribution of meibomian disease to dry eye. Ocul Surf. 2004;2:149-165. 
33 Bron AJ, Tiffany JM, Gouveia SM, Yokoi N, Voon LW. Functional aspects of the tear film lipid layer. Exp 
Eye Res 2004;78:347–60. 
34 Jones et al. TFOS DEWS II Management and Therapy Report. The Ocular Surface 2017;15:575-628. 
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cutaneous damage and edema and are within the safety limits specified for medical  
electrical equipment.35,36,37 
Immediately following the TearCare procedure, the investigator will use the Clearance 
Assistant device to manually express the meibomian glands in all four eyelids under 
direct visualization. 
 
4.2. DEVICE RECALL 
In March 2022, Sight Sciences, Inc issued a voluntary recall of the SmartHubs. This recall 
was initiated in response to recent feedback received from the FDA wherein they 
believed the SmartHub devices did not appropriately fall within a 510(k)-exemption due 
to technological variances. The information received from the FDA indicated that the 
SmartHub was incorrectly categorized and consequently outside the 510(k)-exemption 
due to its technological differences from other devices within that product code.   
 
There was no elevated safety concern. As a result, all clinical sites and the IRB were 
notified of the recall and return material authorizations (RMAs) were issued. Sight 
Sciences decided to replace all existing SmartLids and SmartHubs with a newer version 
of SmartLids and SmartHubs which resulted from the insignificant modifications to the 
current study devices as described below in section 4.3.  
 
4.3. DEVICE MODIFICATION 
• The SmartLid device was modified to include pre-curved lids with removeable 
liners on the adhesive elements (temple pad and lids). The pre-curved lids 
conform to the shape of the eyelids with less manipulation by the clinician, 
potentially eliminating the manual bending step.   
• Artwork changes were made to the SmartHub membrane switch to improve 
visualization of the current functions such as (1) Clearly identifiable power button, 
(2) Left/right SmartLid port use indicators, (3) timer indications (0, 3, 15 minutes), 
and (4) remaining battery/procedure counter. All user interactions remain the 
same. No changes were made to the thermal functionality and intended use of 
the system.    
• The intended use for the new 510(k)-cleared TearCare system was updated to the 
following: “The TearCare® System is intended for the application of localized heat 
therapy in adult patients with evaporative dry eye disease due to meibomian 
gland dysfunction (MGD), when used in conjunction with manual expression of 
the meibomian glands”. Additionally, during the 510(k) review, the TearCare 
system software was updated by modifying the temperature regulation 
algorithm.  This algorithm receives feedback regarding the temperatures being 
sensed at the thermistors in the SmartLids and runs continuously in the 
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background during each therapy session. The TearCare system therapeutic 
temperature settings and timing have not changed.    
 
4.4. INSTRUCTIONS FOR USE 
Instructions for Use for the TearCare System and Clearance Assistant device for this 
study will be provided to each  investigator. 
 
4.5. TRAINING 
Prior to the start of the study, investigators and study staff will be trained on the proper 
use of the TearCare System, as needed. Investigators will also be trained in the method 
of lid debridement and manual expression described in this protocol. All study staff will 
receive training on the protocol and execution of the study according to applicable 
regulations and Good Clinical Practices. 
 
5. PRIOR INVESTIGATIONS 
 
5.1. PRECLINICAL TESTING 
The following testing and analyses were performed: 
 
Thermal Requirements: Bench testing was performed to demonstrate that the 
TearCare System meets the operational temperature requirements (range 41- 
45°C). Clinical validation testing was also performed to measure the 
temperature at the inner and outer surfaces of the eyelid during operation of the 
System and at the surface of the cornea immediately following the procedure. 
The testing confirmed that the system meets temperature-related performance 
and safety specifications. No adverse events were observed. 
Software Functionality: Testing was performed to demonstrate that the 
software in the TearCare SmartHub and SmartLid Devices meet all software 
design requirements. 
 
 
35 Moritz AR, Henriques FC. Studies of thermal injury: the relative importance of time and surface 
temperature in the causation of cutaneous burns. Am J Pathol 1947;23:695–720. 
36 Despa F, Orgill DP, Neuwalder J, Lee RC. The relative thermal stability of tissue macromolecules and 
cellular structure in burn injury. Burns 2005;31:568–77. 
37 Medical electrical equipment Part 1: General requirements for basic safety and essential performance 
(IEC 60601-1). 
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Electrical Safety: Testing was performed to demonstrate that the System meets 
the electrical safety requirements specified in IEC 60601-1. 
Electromagnetic Compatibility: Testing was performed to demonstrate that the 
System meets the electromagnetic requirements specified in IEC 60601-1-2. 
Biocompatibility: All patient-contacting materials were reviewed to confirm that 
that they are biocompatible for short-term (<24 hours), skin contact. 
Mechanical Strength: Testing was performed to demonstrate that the system 
meets mechanical strength requirements. 
Shipping, Storage, and Shelf-Life Testing: Testing was performed to demonstrate 
that the TearCare System continues to meet its performance specifications after 
being exposed to environmental and shipping conditions specified in ASTM 
D4169. In addition, accelerated aging testing was performed to demonstrate the 
SmartLid devices have a minimum shelf life of 6 months. 
 
5.2. PREVIOUS CLINICAL EXPERIENCE 
 
5.2.1. CLINICAL STUDY OF THE PROTOTYPE TEARCARE SYSTEM (2013) 
The TearCare System has been evaluated in four studies. The first study was conducted in 
2013 as an Investigator-sponsored study with a prototype version of the TearCare System. 
The second study was initiated in 2017 with a commercial version of the TearCare System 
(Sight Sciences protocol #05429). The third study was conducted in 2018 wherein subjects 
received a single TearCare® treatment. The fourth and most recent study was initiated in 
2019 to study the safety and effectiveness of a single treatment with the TearCare® System 
compared to a single treatment with LipiFlow® (Johnson & Johnson). All four studies are 
summarized below. 
A prototype version of the TearCare System was tested in a single center, 
prospective, randomized study. The study enrolled 18 subjects who were randomized 
to two treatment arms: (a) Prototype TearCare System, or (b) warm compress 
treatment. 
Subjects randomized to the TearCare arm (n=10 subjects) received one, 10-minute 
session with the prototype device followed by manual expression of the meibomian 
glands. Subjects randomized to the warm compress arm (n=8 subjects) received 
standard warm compress therapy (Fire & Ice Mask, Rhein Medical, Inc.) for 5 minutes 
per day for 2 weeks. Subjects were followed for 4 weeks, with follow-up visits at 1 day, 
2 weeks, and 4 weeks. 
 
No adverse events were reported in this study. Table 1 presents the effectiveness 
outcomes from this study. 
 
Results from this study informed the decision to continue development on the 
TearCare System. 
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                             Table 1: Prototype TearCare System - Study Results (2013) 
 
TearCare 
(n=10 subjects, 20 eyes) 
Warm Compress control 
(n=8 subjects, 16 eyes) 
Baseline 
4 weeks 
Change BL 
to 4 wks. – 
p value 
Baseline 
4 weeks 
Change BL 
to 4 wks. – 
p value 
Tear Break-up Time (sec) – Mean (SD) 
4.6 (0.8) 
16.8 (3.1) 
<0.0001 
4.1 (1.1) 
4.6 (1.8) 
0.27 
Dry Eye Symptom Questionnaires 
Total OSDI Score (0 to 100) 
37.0 (17.5) 
19.6 (9.9) 
0.01 
27.8 (23.3) 
34.3 (22.6) 
0.21 
Total SPEED Score (0 to 28) 
13.8 (2.7) 
7.4 (4.0) 
0.001 
13.6 (6.0) 
10.1 (6.7) 
0.19 
Meibomian Gland Assessment 
Total Meibomian Gland Score (0 to 45) 
13.4 (7.4) 
43.2 (1.4) 
<0.0001 
7.6 (4.5) 
15.4 (7.7) 
0.03 
# Glands Secreting Any Liquid (0 to 15) 
3.6 (3.6) 
14.9 (0.3) 
<0.0001 
1.1 (1.1) 
4.4 (3.8) 
0.04 
# Glands Yield Clear Liquid (0 to 15) 
0.3 (0.7) 
12.9 (1.8) 
<0.0001 
0 (0) 
1.25 (1.8) 
0.08 
 
 
5.2.2. CLINICAL STUDY OF THE TEARCARE SYSTEM (2017) 
A single center pilot study was initiated to collect additional clinical data. The results 
from this study were published in Clinical Ophthalmology.38 
 
Objectives 
The objective of this study was to evaluate the clinical utility, safety, and effectiveness 
of the TearCare™ System compared to standardized warm compress therapy for the 
treatment of signs and symptoms of dry eye disease. 
 
Subjects 
Twenty-four (24) subjects with symptoms of dry eye in the past 3 months were enrolled. 
The average age was 67.6 ± 13.5 years (range 29.7 – 89.8 years). All subjects were 
female, white and not Hispanic or Latino. All subjects had a SPEED score ≥6 at the 
Baseline visit. All subjects had a Tear Break-up Time (TBUT) of <10 seconds in at least 
one eye at baseline and 72% (17/24) had a Schirmer 1 score (non-anesthetized) of ≤10 
mm in at least one eye at the Baseline visit. 
 
Methods 
This was a prospective, single-center, randomized, parallel-group, clinical trial. Subjects 
with DED were randomized to either a single TearCare treatment conducted at the clinic 
or 4 weeks of daily warm compress therapy. The TearCare procedure consisted of 12 
minutes of thermal eyelid treatment immediately followed by manual expression of the 
meibomian glands. Warm compress therapy consisted of once daily application of the 
compresses to the eyelids for 5 minutes. Subjects were followed to 6 months post- 
treatment. The primary effectiveness endpoint was defined as change from baseline to 
 
 
 
38 Badawi D. A novel system, TearCare®, for the treatment of the signs and symptoms of dry eye disease. 
Clinical Ophthalmology 2018;12: 683-694. 
 
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4 weeks for Tear Break-up Time (TBUT). Secondary effectiveness endpoints included 
meibomian gland assessment, corneal and conjunctival staining scores, and assessment 
of dry eye symptoms using validated questionnaires. Safety was evaluated by collecting 
device-related adverse events, intraocular pressure, and best spectacle-corrected 
Snellen Visual acuity. 
 
Results 
Twenty-four subjects were enrolled and completed 6 months follow-up. Data are 
summarized in Table 2 below. 
 
No adverse events were reported in either group. 
 
                                         Table 2: TearCare System – Pilot Study Results (2017) 
 
TearCare 
(n=24 eyes, 12 subjects) 
Warm Compress control 
(n=24 eyes, 12 subjects) 
Baseline 
4 weeks 
6 months 
Baseline 
4 weeks 
6 months 
Tear Break-up Time (sec) – Mean (SD) 
3.1 (0.8) 
14.8 (2.6) 
7.9 (1.5) 
3.3 (1.0) 
3.1 (0.8) 
3.0 (1.0) 
Dry Eye Symptom Questionnaires 
Total OSDI Score (0 to 100) 
41.0 (18.4) 
15.7 (12.2) 
30.3 (15.1) 
33.0 (19.9) 
24.6 (15.2) 
30.3 (15.1) 
Total SPEED Score (0 to 28) 
15.7 (5.2) 
7.8 (3.5) 
8.2 (6.0) 
14.4 (3.8) 
12.6 (3.3) 
12.2 (4.0) 
Total SANDE Score 
64.9 (25.9) 
40.2 (18.8) 
45.9 (30.5) 
55.9 (31.5) 
57.5 (25.7) 
62.1 (21.8) 
Meibomian Gland Assessment 
Total Meibomian Gland Score (0 to 45) 
6.3 (3.6) 
41.0 (2.1) 
31.5 (5.5) 
9.0 (4.3) 
8.2 (4.0) 
9.4 (3.5) 
# Glands Secreting Any Liquid (0 to 15) 
0.8 (0.9) 
14.6 (0.8) 
11.5 (2.4) 
1.3 (1.7) 
1.3 (1.6) 
1.7 (1.5) 
# Glands Yield Clear Liquid (0 to 15) 
0.0 (0.0) 
11.4 (1.6) 
5.4 (3.0) 
0.3 (0.7) 
0.0 (0.0) 
0.1 (0.4) 
Corneal Staining Score (0 to 15) 
3.5 (1.8) 
0.2 (0.4) 
3.2 (2.6) 
3.4 (2.9) 
3.2 (2.6) 
3.2 (2.8) 
Conjunctival Staining Score (0 to 15) 
3.7 (2.5) 
0.1 (0.3) 
0.3 (0.7) 
3.0 (3.4) 
4.1 (3.5) 
3.2 (3.1) 
 
5.2.3. CLINICAL STUDY OF THE TEARCARE SYSTEM-CHEETAH (2018) 
The CHEETAH study was a multicenter, prospective, exploratory, interventional trial, 
involving 58 eyes (29 subjects) that received a single TearCare® treatment and were 
assessed at baseline, post-procedure one week and one month. The primary success 
endpoint was assessed as the mean change from baseline in TBUT, Ocular Surface 
Disease Index (OSDI), total Meibomian Gland Secretion Score (MGSS) and 
corneal/conjunctival staining. Adverse events and changes in visual acuity were 
measured to assess safety. 
 
The baseline TBUT of 3.7±1.1 seconds was improved by 2.6±1.6 (70%) seconds at one 
week and by 3.1±2.2 (84%) seconds at one month. Mean baseline OSDI of 54.9±20.2 
improved by 17.9±20.9 at one week and 25.8±24.3 at one month. The baseline MGSS of 
5.6±4.0 improved by 9.3±4.0 at one week and 8.8±5.8 at one month. Corneal and 
conjunctival staining improved by 1.4±2.8 and 1.2±2.9 from a mean baseline of 4.8±2.5 
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and 5.9±3.2, respectively. No device-related adverse events or significant changes in 
visual acuity were observed. Results are shown in Figure 4 below: 
 
Figure 4: MGSS, TBUT, OSDI and Corneal-Conjunctival Staining by Visit 
 
 
5.2.4. CLINICAL STUDY OF THE TEARCARE SYSTEM-OLYMPIA (2019) 
The OLYMPIA study was a prospective, masked, multi-center RCT conducted at ten U.S. 
sites designed to study the safety and effectiveness of a single treatment with the 
TearCare® System in treating the signs and symptoms of DED associated with MGD in 
comparison with a single treatment with LipiFlow® (Johnson & Johnson). 
Subjects with signs and symptoms of DED and MGD (N=136) were randomized 1:1 to a 
single treatment of either TearCare® or LipiFlow®. Key inclusion criteria were regular use 
of lubricating drops, Ocular Surface Disease Index (OSDI score between 23 to 79 
(moderate to severe), Meibomian gland secretion score (MGSS ≤ 12, TBUT of ≤ 7 
seconds, and at least 15 expressible glands in each lower eyelid. TBUT and MGSS were 
measured as primary endpoints. Secondary endpoints included Corneal conjunctival 
staining, number of meibomian glands yielding clear and any liquid recorded. To reduce 
potential bias in subjective endpoint assessments, the clinician performing the 
treatments did not perform the endpoint assessments and the clinician performing the 
endpoint assessment was blinded to which treatment the patient had received. 
Symptoms were recorded in the form of OSDI, Symptom Assessment in Dry Eye (SANDE) 
and Eye Dryness Severity (EDS) questionnaires. Non-inferiority of TearCare® compared 
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to LipiFlow® in improving TBUT and MGSS was evaluated at one month. Any adverse 
events, either patient reported, or observed by the investigators, were recorded for 
safety. 
 
Both groups demonstrated improvements in mean TBUT and MGSS, 3.0 ± 4.4 and 11.2 ± 
11.1 in the TearCare® group and 2.6 ± 3.3 and 11.09 ± 10.4 in the LipiFlow® group. In the 
TearCare® group, mean corneal and conjunctival staining were reduced respectively by 
0.3 ± 1.2 and 0.7 ± 2.2; the mean number of expressible glands and glands expressing 
clear liquid increased respectively by 4.3 ± 3.6 and 1.8 ± 3.7 (Figure 5). The TearCare® 
group showed an improvement in mean SANDE, EDS and OSDI scores respectively by 
38.2 ± 31.0, 35.4 ± 34.1 and 27.9 ± 20.6 (Figure 6). 
 
Device related ocular adverse events were reported in two subjects (loss of visual 
acuity) for the TearCare® group and three subjects (loss of visual acuity, corneal 
abrasion and foreign body sensation) for the LipiFlow® group. 
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Figure 5: TBUT, MGSS, Corneal and Conjunctival staining per follow up time point. Blue legends, line and bars 
represent TearCare group and red legends, line and bars represent LipiFlow group. 
 
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Figure 6: SANDE, EDS and OSDI scores per follow up time point Blue legends, line and bars represent TearCare 
group and red legends, line and bars represent LipiFlow group. 
 
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6 STUDY ENDPOINTS 
 
6.1 EFFECTIVENESS ENDPOINTS 
This study will collect data to assess the impact of each treatment on the signs and 
symptoms of dry eye disease. Tear Break-Up Time which measure the treatment effect 
on the sign of dry eye disease is the primary endpoint. The secondary endpoints have 
been chosen to collect additional data regarding changes in the signs and symptoms of 
dry eye disease in study subjects. 
 
For each outcome measure, results from the TearCare group will be compared with 
results from the Restasis group. Study success will be assessed at 6 months for 
superiority of the TearCare system in treating dry eye disease compared with Restasis as 
measured by Tear Break-Up Time. 
 
• 
Primary effectiveness endpoints 
• Mean Change from baseline in Tear Break-Up Time (TBUT) 
• Mean Change from baseline in OSDI score39 
 
• 
Secondary effectiveness endpoints 
• 
Mean Change in the total Meibomian Gland Secretion Score40 
• 
Mean Change from baseline in corneal staining scores 
• 
Mean Change from baseline in conjunctival staining scores 
• 
Mean Change from baseline in the number of meibomian glands yielding clear liquid 
secretions 
• 
Mean Change from baseline in the number of meibomian glands secreting any liquid 
(clear or cloudy) 
• Mean Change from baseline in SANDE scores 41,42 
• 
Eye Dryness Score 
• 
Ocular protection index (OPI): Interblink interval (IBI)/TBUT Schirmer score 
• 
Use of dry eye lubricants 
 
 
39 Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular 
Surface Disease Index. Arch Ophthalmol 2000;118: 615-621. 
40 Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. Classification and grading of lid changes. 
Eye 1991;5: 395–411. 
41 Schaumberg DA, Gulati A, Mathers WD, Clinch T, Lemp MA, Nelson JD, Foulks GN, Dana R. 
Development and Validation of a Short Global Dry Eye Symptom Index. Ocular Surface. 2007;5(1):50- 
57. 
42 Amparo F, Schaumberg DA, Dana R. Comparison of Two Questionnaires for Dry Eye Symptom 
Assessment: The Ocular Surface Disease Index and the Symptom Assessment iN Dry Eye. 
Ophthalmology. 2015;122(7):1498-1503. 
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6.2 SAFETY ENDPOINTS 
 
• 
Primary Safety Endpoint 
• 
Procedure (TearCare)/Treatment (Restasis)-related adverse events (all adverse events will be 
recorded) 
 
• 
Secondary Safety Endpoints 
• 
Change in best corrected visual acuity (ETDRS) 
• 
Change in intraocular pressure (IOP) 
 
7 STUDY DESIGN 
 
This is a prospective, randomized, masked, multi-center, superiority, non-significant risk 
study. To reduce potential bias in the study, study staff performing the endpoint 
assessments will be masked as to the subject’s treatment allocation. Subjects cannot be 
masked as it will be obvious to them which treatment they are receiving. 
 
7.1 STUDY DEVICE AND CONTROL GROUP 
In this study, TearCare procedures using the TearCare System (study device) will be 
compared with Restasis (control group). 
 
TearCare procedures in this study will include an in-office eyelid debridement, 15-
minute bilateral thermal session with the TearCare System, immediately followed by 
manual expression of the meibomian glands using the Clearance Assistant Plus device. 
Subjects randomized to TearCare will receive one in-office TearCare procedure within 7 
days of the Baseline visit and at 5 Months. Beginning at 9 Months, subjects will receive 
an additional TearCare procedure when TBUT drops lower than Baseline or within 2 
seconds of baseline AND if OSDI worsens by at least 15 points compared to the previous 
visit. 
 
Subjects randomized to Restasis group will be required to self-administer 1 drop twice a 
day from baseline through the Month 6 visit. At Month 6, subjects will be crossed over 
to the TearCare group and will receive one (1) TearCare procedure. 
 
7.2 STUDY CENTERS 
This study will be conducted at up to 25 centers in the United States. No center will 
have more than 20% of the target enrolled and treated (i.e., 70 subjects per site) 
without prior approval from the sponsor. 
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8 STUDY SELECTION CRITERIA 
 
8.1 INCLUSION CRITERIA 
For inclusion in this study, subjects must meet all of the following criteria: 
 
1. At least 22 years of age 
2. Reports dry eye symptoms within the past 3 to 6 months 
3. Reports having to use artificial tears or lubricants regularly over the past month 
to relieve dry eye symptoms. 
4. Schirmer tear test (with anesthesia) ≥5 to ≤15 mm in 5 minutes 
5. OSDI Score of 23-79 
6. TBUT of ≥1 to ≤7 seconds in both eyes 
7. Meibomian gland obstruction in both eyes based on a total Meibomian Gland 
Secretion Score ≤12 in each eye. 
8. At least 15 glands in each lower eyelid should be expressible, with a sterile 
cotton swab, at the slit lamp. 
9. Best corrected visual acuity of 20/100 or better in both eyes. 
10. Willing and able to comply with the study procedures and follow-up 
11. Willing and able to provide informed consent 
12. English-speaking 
 
8.2 EXCLUSION CRITERIA 
A subject who meets any of the criteria listed below (in either eye) will be excluded from 
the study: 
 
1. Use of any of the following medications: 
a) Cyclosporine (Restasis, Cequa etc.) or Xiidra and serum tears within 
60 days prior to baseline; 
b) Antihistamines (oral or topical) within 7 days prior to baseline; 
c) Systemic medication(s) that is known to cause ocular dryness (e.g. 
diuretics, anti-hypertensives, anti-depressants, antihistamines, hormone 
therapy) and whose dose of this medication(s) has not been stable 
within 30 days prior to baseline. There must be no anticipated 
adjustments to the dose of these medications for the duration of the 
trial; 
d) Accutane (at any time); 
e) Oral tetracyclines or azithromycin within 30 days prior to baseline; or 
f) Topical ophthalmic antibiotics, anti-glaucoma medications, steroids, non- 
steroidal anti-inflammatory medications within 30 days prior to baseline. 
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2. Any of the following dry eye treatments: 
a) Office-based dry eye treatment (e.g. IPL, TearCare, thermal 
pulsation [LipiFlow], iLux etc.) within 12 months prior to 
baseline either as part of routine care or clinical 
investigation; 
b) Planned or recent surgical procedures to the eye or eyelid (90 days prior to 
baseline)  
c) Meibomian gland expression within 6 months prior to baseline; 
d) Blephex or debridement within 3 months prior to 
baseline is an exclusion; 
e) Punctal occlusion or punctal plug Punctal occlusion or 
punctal plugs. Investigators can choose to remove the 
punctal plugs 15 days prior to  baseline; 
f) Use of tear neurostimulators (i.e., True Tear, iTear100, 
Tyrvaya) within 2 weeks of the baseline visit. (Subjects must 
refrain from using tear neurostimulators for the duration of 
the study.); or 
g) Any history of meibomian gland probing 
3. History of eyelid, conjunctiva, or corneal surgery (including refractive 
surgery) within the past year prior to baseline. In addition, subjects 
with any history of the following are excluded: chalazion surgery, 
surgery on the tarsal conjunctiva, radial keratotomy (RK), 
complicated blepharoplasty, lid reconstruction, or significant 
complications post-refractive surgery. 
4. Contact lens use within 2 weeks of the baseline visit. 
5. Active hordeolum, stye, or chalazion at the time of the baseline visit. 
6. History of Herpes Simplex or Herpes Zoster of the eye or eyelid. 
7. Any active, clinically significant ocular or peri-ocular infection, inflammation, or 
irritation 
8. Recurrent clinically significant eye inflammation, other than dry 
eye, within 3 months prior to baseline 
9. Clinically significant anterior blepharitis. In addition, collarettes or 
flakes of more than one quarter of the eyelid are excluded. 
10. Clinically significant eyelid abnormalities in either eye (e.g. 
entropion/ectropion, blepharospasm, aponeurotic ptosis, 
lagophthalmos, distichiasis, trichiasis). 
11. Clinically significant dermatologic or cutaneous disease of 
the eyelid or periocular area. 
12. In the clinical judgement of the investigator, meibomian glands have 
significant capping, atrophy, or are unable to be expressed, digitally 
or with a sterile cotton swab. 
13. Clinically significant ocular surface abnormalities that may 
affect tear film distribution or treatment (e.g. pterygium, 
anterior membrane dystrophy, Salzmann’s nodules, etc.) 
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14. Corneal surface abnormalities such as corneal epithelial defects 
(other than punctate staining), ulcers, corneal epithelial 
dystrophies, keratoconus, and ectatic disease of the cornea 
15. Any active, clinically significant allergic, vernal, or giant papillary conjunctivitis. 
16. Ocular trauma within 3 months prior to baseline. 
17. Known history of diminished or abnormal facial, periocular, 
ocular, or corneal sensation 
18. Systemic diseases resulting in dry eye (e.g., autoimmune diseases such as 
Sjogren’s syndrome, rheumatoid arthritis, lupus, Graves’ disease, 
sarcoidosis, etc.) 
19. Subject is currently using Retin A/Retin A derivatives. 
20. Subject has permanent eyeliner/lid tattoos, eyelash extensions or 
wears false eyelashes. 
21. Subject is currently using Latisse, Lash Boost or any other type of eyelash growth 
serum. 
22. Allergies to silicone tissue adhesives, acrylates and/or coppers. 
23. Subject has a pacemaker or implantable cardiac defibrillators 
(ICD). Participation in another ophthalmic clinical trial 30 days 
prior to baseline. Subject must also be willing to refrain from 
another ophthalmic study for the  duration of the study. 
24. Co-existing condition, either ocular or non-ocular that, in the 
judgement of the investigator could affect the safety or 
effectiveness of treatment or the compliance of the subject to the 
protocol. For example, subjects who are pregnant or nursing or 
have active, wet macular degeneration are excluded. 
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9 STUDY PROCEDURES 
9.1 TABLE 3: TEARCARE STUDY VISIT SCHEDULE 
 
Visit 
Baseline 
Day 0 b 
Day 1 
Wk 1 
1 M 
3 M 
5 M 
6 M 
9 M 
12 M 
15 M 
18 M 
24M 
Window days 
-7 to 0 
0 
1 
5-9 
 
21-35 
 
70-100 
 
120-155 
 
170-210 
 
250-300 
 
330-390 
 
420-480 
 
510-570 
 
691-780 
Informed Consent 
X a 
Demographics, Ocular & 
Medical History 
X 
Medication use 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Questionnaires (OSDI, 
SANDE, Eye Dryness Score) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BCVA d 
X 
X e 
X e 
X 
X 
X 
X 
X 
X 
X 
X 
Blink rate 
X 
X 
X 
X 
X 
Slit Lamp Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
TBUT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Corneal Staining 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Conjunctival Staining 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Schirmer Test 
X 
X 
X 
X 
X 
X 
MGSS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IOP f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subject Eligibility 
X 
Randomization 
X 
TearCare Procedure 
X 
X 
AE Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Eye Lubricant/Drop Log 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a    Subjects may sign the informed consent up to 60 days in advance of the baseline visit. 
b   TearCare procedure must be performed within 7 calendar days of the Baseline visit. If scheduling permits, it may be performed on the same day as the Baseline visit following 
Randomization. Beginning at 9 Months, subjects will receive an additional TearCare procedure when TBUT drops lower than Baseline or within 2 seconds of baseline AND if OSDI 
worsens by at least 15 points compared to the previous visit. 
d   BCVA should be collected after manifest refraction using ETDRS visual acuity chart 
e    On Day 1 and Week 1, Best Corrected Spectacle Visual Acuity (BCSVA using ETDRS) is measured without manifest refraction (MR). If the VA has worsened by ≥10 letters (per 
ETDRS) from baseline, then MR should be performed, the ETDRS measurement should be repeated, and the VA post-MR should be recorded. 
f     IOP measured via applanation tonometry should be measured at baseline using standard of practice at each site with the same method to be used for all consecutive visits in the 
study. 
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9.2 
TABLE 4: RESTASIS STUDY VISIT SCHEDULE 
 
Restasis 
1 drop of Restasis ophthalmic emulsion should be instilled in both eyes, approximately 12 hours apart from each other. 
Example: 1st drop should be instilled between 7 to 8 AM and 2nd drop between 7 to 8 PM. In contact lens wearers, drops 
should be administered at least 15 minutes after contact lens removal. 
Restasis CROSSOVER to TearCare 
Visit 
Baseline 
Day 0 
Day 1 
Wk 1 
1 M 
3 M 
6 M/TearCare 
Post Procedure 
9 M 
12 M 
Window days 
-7 to 0 
0 
1 
5-9 
 
21-35 
 
70-90 
 
150-180 
 
Day 1 
Wk 1 
1 M 
220-280 
 
320-390 
 
1 
5-9 
21-35 
Informed Consent a 
X 
Demographics, Ocular & Medical Hx 
X 
Medication use 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Questionnaires (OSDI, SANDE, Eye 
Dryness Score) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BCVA b 
X 
X c 
X c 
X 
X 
X 
X c 
X c 
X 
X 
X 
Blink rate 
X 
X 
X 
X 
X 
Slit Lamp Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
TBUT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Corneal Staining 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Conjunctival Staining 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Schirmer Test 
X 
X 
X 
X 
X 
X 
X 
MGSS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IOP d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subject Eligibility 
X 
Randomization 
X 
Restasis (1gtt BID) 
X 
X 
X 
X 
X 
AE Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Crossover and TearCare Procedure 
X 
Treatment preference questionnaire 
X 
Eye Lubricant/Drop Log 
X 
X 
X 
X 
X 
X 
a    Subjects may sign the informed consent up to 60 days in advance of the baseline visit. 
b   Restasis must be dispensed within 7 calendar days of the Baseline visit. If scheduling permits, it may be dispensed on the same day as the Baseline visit following Randomization. 
c    BCVA should be collected after manifest refraction using ETDRS visual acuity chart 
d     On Day 1 and Week 1, Best Corrected Spectacle Visual Acuity (BCSVA using ETDRS) is measured without manifest refraction (MR). If the VA has worsened by ≥10 letters (per ETDRS) 
from baseline, then MR should be performed, the ETDRS measurement should be repeated, and the VA post-MR should be recorded. 
e    IOP measured via applanation tonometry should be measured at baseline using standard of practice at each site with the same method to be used for all consecutive visits in the 
study. 
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9.3 NUMBER OF SUBJECTS, DURATION OF FOLLOW-UP AND STUDY 
DURATION 
A sample size of 200 subjects is estimated to provide sufficient power (90%) for this 
study. Nonetheless, given the 24 months follow up period, and in an attempt to collect 
additional data regarding changes in the signs and symptoms of dry eye disease, a total of 
up to 350 subjects will be enrolled and randomized in the study. Assuming a 15% screen 
failure rate, approximately 412 subjects will be enrolled to obtain up to 175  randomized 
subjects in each study group. All subjects will be followed for up to 24 months. 
 
It is anticipated that enrollment in the study will take 16-26 months. Including the 24 
months follow-up period, the study is expected to last 40-50 months. 
 
9.4 MATERIAL AND EQUIPMENT 
A listing of general equipment and materials required at the investigational site for the 
study is provided below. 
 
a. TearCare SmartHub Kit (includes a SmartHub, charging nest and charging 
adapter) 
b. TearCare SmartLid Devices and Clearance Assistant Plus Devices 
c. TearCare wipes 
d. Restasis (Cyclosporine 0.05%) Ophthalmic Emulsion 
e. ETDRS Visual Acuity System 
f. Slit lamp 
g. Wratten filter (yellow) (for corneal staining) 
h. Goldmann Tonometer or other applanation tonometer 
i. Meibomian Gland Evaluator (TearScience, Inc.) 
j. Fluorescein sodium strips (for TBUT and corneal staining) 
k. Lissamine green strips (for conjunctival staining) 
l. Filter strips (for the Schirmer test) 
m. Preservative-free sterile saline 
n. Proparacaine 0.5% or tetracaine 0.5% ophthalmic drops 
o. Akten® (lidocaine hydrochloride ophthalmic gel) 3.5% or equivalent 
p. Stopwatch 
q. Ruler 
r. Sterile scissors 
s. Thermometer 
t. Webcam and/or laptop 
 
 
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9.5 INFORMED CONSENT AND POINT OF ENROLLMENT 
The IRB-approved informed consent will be presented and explained to each 
prospective subject by the investigator or a trained clinical professional. Once the 
subject has had ample time to read the consent form, has been informed of all aspects 
of the study, and has had an opportunity to ask questions, the subject will be given a 
choice to voluntarily confirm his or her participation in the study as documented by 
completion of the Informed Consent. After signing the Informed Consent and the HIPAA 
(Health Insurance Portability and Accountability Act) authorization, the subject can then 
proceed with the baseline visit. The baseline visit should be performed within 60 days 
of the subject signing the informed consent. The subject has the right to withdraw from 
the study at any time without consequences, as indicated in the Informed Consent 
Document. 
 
The subject’s signed and dated informed consent must be obtained before conducting 
any procedure specifically for the study. Subjects are enrolled upon signing the ICD 
even if they subsequently fail to meet the eligibility criteria. 
 
The principal investigator(s) must retain the original, signed written Informed Consent 
Document. A copy of the written Informed Consent Document must be given to the 
subject. 
 
9.6 BASELINE AND STUDY GROUP VISIT(S) 
 
9.6.1 SCHEDULING THE BASELINE AND DAY 0 VISIT(S) 
To facilitate scheduling, the Baseline and Day 0 Visits may be performed on the same 
day or on two separate days and following randomization. If these visits are performed  
over two days, Day 0 must be within 7 calendar days of the Baseline Visit. 
 
Refer to Table 3 for which tests and exams are to be performed at each visit for both 
groups. Endpoint assessments performed during the Baseline visit must be performed  
by a Masked Assessor (See Section 9.9). 
 
Since dry eye drops and lubricants can affect the endpoint assessments, instruct 
subjects not to use any of these products within 2 hours of the Baseline visit. 
 
9.6.2 BASELINE EXAMS, TESTS AND QUESTIONNAIRES 
After the subject has signed the informed consent form and agreed to participate in the 
study, the exams, tests, and questionnaires listed in the Baseline column of Table 3 
should be performed. Refer to Appendix A for instructions for performing the exams 
and administering the questionnaires. 
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At this visit, subjects should undergo the following tests and exams, performed in the 
order indicated below, to screen them for the study qualification and to record baseline 
data. Items with an asterisk (*) must be performed by a Masked Assessor (Refer to 
Section 9.9 for more information on the Masked Assessor). 
 
1. Questionnaires: OSDI, SANDE and Eye Dryness VAS 
2. Demographics, medical and ocular history 
3. Medication use: ocular and systemic 
4. Manifest refraction and ETDRS Best-corrected visual acuity* 
5. Blink Rate* 
6. Slit Lamp Exam* 
7. Tear Breakup Time* 
8. Corneal Staining* 
9. Conjunctival Staining* 
10. Schirmer Test* 
11. Meibomian Gland Secretion Scoring* 
12. Intraocular pressure* 
13. Adverse Event Assessment 
 
If, at any point during the visit the subjects fails to meet a subject selection criterion, 
then the visit can be terminated. Subjects who fail to meet all the selection criteria will 
be considered a screen failure and will be withdrawn from the study. 
 
Subjects who fail screening may be re-screened for the study after 30 days. If they are 
re-enrolled, they should be assigned a new subject ID. 
 
NOTE: Questionnaires and exam data collected on subjects prior to enrollment as part 
of the routine clinical practice may be used to pre-screen for the study. However, once 
the subject signs the consent form and is enrolled in the study, these questionnaires and 
exams must be repeated following the protocol procedures. 
 
After all required measurements have been obtained and it has been confirmed that the 
subject meets all the Subject Selection Criteria, then the subject will be Randomized. 
 
9.6.3 RANDOMIZATION 
Subjects will be randomized to either the TearCare (i.e., “device group”) or Restasis 
(i.e., “control group”). Randomization will be performed using a 1:1 ratio and will be 
stratified by site. Computer-generated randomization will be administered through the  
electronic data capture (EDC) system. 
 
Following randomization, the subject should undergo the applicable procedures 
described in the sections below. 
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9.6.4 PROCEDURE FOR TEARCARE (STUDY DEVICE GROUP) 
Subjects randomized to the study device group (TearCare) will undergo the following 
procedure bilaterally. Refer to the TearCare Instructions for Use for detailed 
instructions for operating the TearCare System. 
 
1. Obtain a new set of SmartLid devices and a TearCare SmartHub with enough 
battery left for at least one procedure. 
2. Position the subject at the slit lamp to perform debridement of the eyelid margin 
followed by expression of the meibomian glands such that expression takes 
place within 3 minutes of completion of the thermal portion of the procedure. 
3. Apply 1 drop of proparacaine or tetracaine into each eye. 
4. Visualize the lid margin and line of Marx’s (LOM) and debride eyelid margins by 
sweeping (very gently scraping) the debridement edge across the LOM back and 
forth going over meibomian gland orifices. Start nasally and work laterally 
multiple times using gentle pressure until the eyelid margins appear free of 
debris, keratin, and gland capping. Often the gland orifices become visible at this 
point. 
5. Wipe the subject’s eyelids and temple with the TearCare wipes to remove any 
make-up, oil, dirt, or lotion. Allow the skin to dry or pat dry with a tissue. Use 
care not to allow any of the wipe to get into the eye. 
a. Caution: Eyelid cleansing may lead to skin irritation, which would put a 
patient at increased risk for thermal injury. If the patient is observed to 
have skin irritation, or if the patient complains of skin irritation after 
eyelid cleaning, do not proceed with the TearCare treatment. 
6. Remove the liner from the upper SmartLid to reveal adhesive. Continue to 
prebend the SmartLid, if needed. Peel from temporal tab towards nasal and 
discard the liner. (For each eye) 
7. Place a pair of SmartLid devices on the subject’s eyelids and affix the temple 
housing to the subject’s temple. Use the clip to secure the cables behind the 
subject’s head. 
8. Connect the SmartLid devices to the SmartHub. 
9. Inform the subject that the SmartLid devices will heat up very quickly once the 
TearCare procedure is started. 
10. Start TearCare procedure. Subjects should be encouraged keep their eyes open 
and blink naturally during the TearCare procedure. 
11. If the subject indicates the temperature is too hot, decrease the temperature set 
point to a setting that is comfortable for the subject. 
12. Following the thermal portion of the TearCare procedure, remove the SmartLid 
devices from the subject, position the subject at the slit lamp biomicroscope, 
repeat debridement if deemed necessary and using the Clearance Assistant Plus 
Device, express the meibomian glands in all 4 eyelids using the following 
technique: 
a. Think of each eyelid as having 3 zones: nasal, central & temporal. 
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b. For each zone, start at the fornix and work your way up to the margin. 
c. Position the forceps horizontal, parallel to the margin. 
d. Apply moderate continuous pressure and adjust based on the gland 
output. 
e. Perform a second pass on the same eyelid to further express the glands. 
f. After treating the lower and upper eyelids, repeat expression on all 4 lids 
to ensure complete expression. Additional passes of expression may be 
performed to ensure complete expression. 
g. Should the subject experience discomfort, it is reasonable to apply 
additional topical anesthetic (i.e., proparacaine or tetracaine). 
Alternatively, Akten® (lidocaine hydrochloride ophthalmic gel) 3.5% or 
equivalent may be applied into the lower eyelid fornices. 
h. The goal is to express each zone until the meibum coming out is clear. 
Typically, complete expression takes approximately 5 minutes/eye. 
 
9.6.5 RESTASIS DISTRIBUTION (CONTROL GROUP) 
Subjects randomized to the control group (Restasis) will be provided with Restasis® 
(Cyclosporine 0.05% ophthalmic emulsion) for use in both eyes. Subjects should be 
instructed to follow steps below while administering Restasis: 
 
Preparing the bottle for first-time use: 
a. Pull off shipping cover by pulling straight up. Remove the pull tab on the olive 
green colored protective cap by pulling the end of the pull tab away from the 
bottle then winding it counterclockwise. 
b. Remove the olive green colored protective cap by pulling it straight up. Keep the 
colored protective cap. Prime the bottle for first time use by squeezing 2 drops 
onto a tissue. Do not let the bottle tip touch the tissue. 
c. After use, recap the bottle with the olive green colored protective cap by 
pushing straight down onto the bottle. 
d. Turn the bottle upside down a few times before putting drops in eyes to make 
sure the medicine is mixed well. 
e. Instill one drop in both eyes approximately 12 hours apart from each other. The 
first drop should be instilled between 7 to 8 AM and second drop between 7 to 8 
PM. 
f. Do not discontinue use of medication unless instructed by the site staff. 
 
The site staff should give intermittent calls to the subjects to check if they have enough 
supply of the drops that last until their next visit. Please instruct subjects to inform the 
site staff before they run out of the medication. Each subject will receive the first bottle 
on Day 0 (treatment day). All additional bottles of Restasis will be provided at the 
protocol defined follow-up visits (Week 1, Month 1, and Month 3). To avoid shortage of 
medication, please try to bring the subject in at the early part of the visit window. If this 
requires scheduling an additional visit in between the protocol defined visits, it will be 
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considered an unscheduled visit. 
The subjects should be instructed to: 
a. Store Restasis® between 15-25 °C (59-77 °F) 
b. For contact lens wearers, drops should be instilled at least 15 minutes after the 
removal of the contact lenses. 
c. Restasis® can be used with lubricant eye drops, but you should wait at least 15 
minutes between using each product. The lubricant eye drops/rescue drops 
used should be recorded on the Eye Lubricant/Drop log. Sites should make sure 
to review the log at each visit as described in Section 9.6.6. 
 
9.6.6 FOLLOW-UP INSTRUCTIONS FOR SUBJECTS 
Review the following instructions with subjects at the completion of the visit. 
During study follow-up: 
1. Dry Eye Lubricants/Tear Drops: Subjects should make every effort to refrain 
from using any dry eye drops or lubricants. If they require “rescue therapy” to 
relieve their symptoms, they should use the same type of tear drops or 
lubricants they were using prior to the study. 
2. Dry Eye Lubricant/Tear Drop Log: Provide subjects with the Lubricant/Drop log 
and instruct them to record any use of drops or lubricants during the follow-up 
period. 
3. Other Dry Eye Medications: Subjects should not use any other medications for dry 
eye disease (e.g., Doxycycline, Xiidra, etc.). 
4. Other Treatments for Dry Eyes: Subject should not have any other treatments for 
dry eyes. For example, they should not use warm compresses or perform lid 
massage/scrub. They should not use the True Tear device or have any other in- 
office dry eye treatments. If the investigator feels the need for an alternative 
procedural intervention, administration of these treatments will result in the 
subject being excluded from the “Per Protocol” analysis from the time of initiation 
of these treatments forward. 
5. Other Ocular Procedures: Subjects should be recommended not to opt for an 
elective ocular procedure such as cataract surgery, refractive surgery etc. unless 
medically warranted during the study duration. In case such a surgery/procedure 
is needed, the subjects should be exited from the study prior to the procedure 
unless the procedure is performed to treat an adverse event.   
6. Antihistamines: Subjects should be advised not to use any antihistamines during 
the study duration. In case antihistamines are needed during the study duration, 
topical antihistamines should be tried prior to using oral antihistamines. In case 
oral or systemic antihistamines are required, subjects should be instructed to 
discontinue use of antihistamines at least 7 days prior to scheduled study visits. 
Subjects who are on preexisting stable dose of antihistamines prior to baseline 
should be instructed to discontinue use of antihistamines at least 7 days prior to 
scheduled study visits.  
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7. Use of Contact lens: Subjects should be advised not to use contact lenses at least 
72 hours prior to the scheduled study visits. 
     
9.7 FOLLOW-UP VISITS 
Prior to the Visit: Reminder Call 
 
A few days before the follow-up visit, it is recommended that the coordinator contact 
the subject to remind them not to use dry eye drops or lubricants on the day of the 
follow-up visit since these products can affect the endpoint assessments. For the 
subjects assigned to Restasis group, subjects can use Restasis on day of follow up visits. 
Since Restasis drops can affect the endpoint assessments, instruct subjects not to use 
Restasis within 2 hours of the study visit. 
 
At the Beginning of the Follow-up Visit: Maintaining Masking of Study Personnel 
 
Endpoint assessments performed during the Follow-up visit must be performed by the 
Masked Assessor (See Section 9.9). 
 
At the beginning of the follow-up visit, the coordinator should remind the subject to not 
reveal their randomization group to the study personnel who will be performing the 
follow-up exams. 
 
Order of Procedures During the Follow-Up Visit 
 
Follow-up procedures will be performed per the Study Schedule provided in Table 3 and 
Table 4 (pages 32, 33) and the methods included in Appendix A. Since certain 
tests/exams can impact the ability to perform other tests/exams, the following tests and 
exams should be performed in this order: 
 
1. Questionnaires 
2. Manifest refraction, if required per this protocol, and ETDRS Best-corrected 
visual acuity 
3. Blink Rate 
4. Slit Lamp Exam 
5. Tear Breakup Time 
6. Corneal staining 
7. Conjunctival staining 
8. Schirmer Test 
9. Meibomian Gland Secretion Scoring 
10. IOP 
11. Assessment of adverse events 
The following activities can be performed in any order: 
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• Medication Use 
• Collection of Eye Lubricant/Drop Log (for all visits starting at 1 month) 
 
9.8 PHOTOGRAPHY DURING EXAMS AND TEARCARE PROCEDURE 
Photographs or videos will be made during the baseline or follow-up exams or during 
the TearCare procedure. These images may be used for educational or training 
purposes. Subject consent must be obtained prior to taking any photographs or videos. 
Subjects do not have to agree to consent to being filmed in order to participate in the 
study. 
 
9.9 MASKED ASSESSOR 
To reduce potential bias in the study, study staff performing endpoint assessments will 
be masked as to the subject’s study group. In addition, to ensure consistency in 
performing the endpoint assessments the study staff member who performs the 
baseline assessments should also perform the follow-up assessments. An alternate 
Masked Assessor may be appointed to handle scheduling conflicts, but every effort 
should be made to have the same person performing all endpoint assessments 
throughout the study. Masked Assessors may not perform the randomization, the 
TearCare group procedure, or the distribution of Restasis medication to subjects 
randomized to the Restasis group. 
 
The following assessments must be performed by a Masked Assessor: 
 
• Manifest refraction and ETDRS Best-corrected visual acuity 
• Blink Rate 
• Slit Lamp Exam 
• Tear Breakup Time 
• Corneal Staining 
• Conjunctival Staining 
• Schirmer Test 
• Meibomian Gland Secretion Scoring 
• Intraocular pressure 
 
9.10 MANAGEMENT OF DRY EYE SYMPTOMS DURING FOLLOW-UP 
During follow-up, subjects should refrain from using any non-study dry eye treatments, 
including drops, lubricants etc. If they require “rescue therapy” to relieve their 
symptoms, they should use the same type of tear drops or lubricants they were using 
prior to the study. They should document use of tear drops or lubricants on the Eye 
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Lubricant/Tear Drop Log. 
Subjects should not use other medications for dry eye disease (e.g., Doxycycline, Xiidra, 
etc.) during the study. Use of these drugs will result in the subject being excluded from 
the “Per Protocol” analysis from the time of initiation of these drugs forward. 
 
Subject should not be treated with other in office or at home dry eye treatments (e.g., 
IPL, TrueTear, iLux, punctal plugs, warm compresses, lid scrubs etc.) during the course of 
the study. Administration of these treatments will result in the subject being excluded 
from the “Per Protocol” analysis from the time of initiation of these treatments forward. 
 
9.11 WITHDRAWAL AND DISCONTINUATION 
All subjects have the right to withdraw at any point during the study without prejudice. 
The investigator can discontinue any subject at any time if continued participation in the 
study would result in harm to the subject. All efforts should be made by the investigator 
to retain the subject in the study. If a subject withdraws prematurely from the study, a 
genuine effort must be made to determine the reason(s) the subject discontinued the 
study. The reason must be recorded in the subject’s file and on the Study Exit Form. 
 
If a subject withdraws from the study post-randomization but prior to receiving the 
TearCare Procedure or Restasis®, then that subject may be replaced in the study by a 
newly enrolled subject. 
 
9.12 SUBJECTS LOST TO FOLLOW-UP 
Subjects who do not show up for a follow-up must be contacted to attempt to have 
them come for the follow-up. For those subjects who cannot be reached, at least 3 
phone call attempts should be made and documented. If a subject misses two 
consecutive follow-up visits without any contact with the study staff, the subject will be 
considered lost-to-follow-up unless there is further communication by the subject. 
 
10 
ADVERSE EVENTS (AES) 
 
Adverse Events are defined below. Adverse events that occur in the eye during the trial, 
whether considered to be device related or not, must be documented in the subject’s 
records. Non-ocular adverse events do not need to be recorded as adverse events 
unless they meet the definition of serious adverse event or are believed to be related to 
the study device or a study procedure. Date of the event, its severity, treatment (if any), 
and the assessed relationship of the event to the study device will be recorded on the 
Adverse Event Form. Conditions which exist at the time the subject is enrolled will be 
considered pre-existing conditions and do not need to be recorded as adverse events 
unless they increase in severity during the study. 
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10.1 DEFINITIONS OF AE, SAE, SADE, USADE 
 
Adverse Event 
Any untoward medical occurrence in a subject who has been 
treated with the device that does not necessarily have causal 
relationship with the treatment. 
Adverse Device 
Effect 
Any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease that is possibly related 
to the study device. 
Serious Adverse 
Event (SAE) 
Any untoward medical occurrence that: 
• Results in death 
• Is life-threatening 
• Requires in-patient hospitalization or prolongs existing 
hospitalization 
• Necessitates medical or surgical intervention to preclude 
permanent impairment of a body function or permanent 
damage to a body structure 
• Sight threatening 
Unanticipated 
Adverse Device 
Effect 
Any serious adverse effect on health or safety, any life- 
threatening problem or death caused by, or associated with a 
device if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the 
clinical investigational plan; or any other serious problem 
associated with a device that relates to the rights, safety, or 
welfare of subjects (21 CFR 812.3(s)). Any sight-threatening 
event, whether listed in the protocol or not, is considered to be 
reportable as a UADE 
 
10.2 LIST OF ANTICIPATED POTENTIAL OCULAR ADVERSE EVENTS 
Anticipated potential adverse events include those that might reasonably be expected 
to occur in this study because they are associated with dry eye disease, the risk analysis 
for TearCare System or study testing methods. Please refer to Restasis label for 
potential AEs related to Restasis use. 
• 
Eyelid/eye pain requiring discontinuation of the study procedure 
• 
Eyelid/eye pain requiring treatment ≥1 day after the study procedure 
• 
Eyelid irritation, or inflammation 
• 
Discomfort or pain of eyelids or orbit 
• 
Ocular symptoms (such as burning, redness, tearing, visual disturbance, redness) 
• 
Burn, erythema, or swelling of the eyelids 
• 
Thermal injury to the eye, including conjunctiva, cornea or lens 
• 
Allergic or inflammatory reaction to medical adhesive on the SmartLid device 
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• 
Physical pressure-induced injury to the eyelid 
• 
Corneal deformation 
• 
Foreign body sensation 
• 
Formation of a chalazion or stye 
• 
Infection of the eyelid or ocular surface 
• 
Ocular surface irritation or inflammation (e.g., Conjunctival injection, conjunctival or 
corneal abrasion, chemosis) 
• 
Allergic or inflammatory reaction to the SmartLid 
• 
Worsening of dry eye symptoms 
• 
Loss in BCVA (ETDRS) of ≥10 letters 
 
10.3 REPORTING ADVERSE EVENTS AND UNANTICIPATED ADVERSE DEVICE 
EFFECTS 
Identification, collection, and reporting of adverse event information is the responsibility 
of the principal investigator or designated investigator. The investigator records the 
date of the event, its severity, treatment (if any) and the assessed relationship of the 
event to the study device on the Adverse Event Case Report Form (AE CRF). 
 
Any ocular-related serious adverse event (SAE) should be reported to the study sponsor 
within one working day of learning of the event. Non-ocular-related SAEs should be 
reported to the study sponsor within two working days of learning of the event. Record 
all applicable information in the source document, enter into the EDC system and email 
the AE CRF to TCsafety@sightsciences.com. 
 
Any unanticipated adverse device effects (UADE) must be reported to the following 
two entities: 
 
1. The study sponsor – Within one working day of the investigator first learning of 
the event, record all applicable information in the source document, enter into 
the EDC system and e-mail the AE CRF to TCsafety@sightsciences.com; and 
2. The reviewing IRB – As soon as possible, but no later than 10 working days after 
the investigator first learns of the event, report per the IRB’s instructions. 
 
The sponsor will conduct an evaluation of unanticipated adverse device effects. If the 
sponsor determines that an unanticipated adverse device effect presents an 
unreasonable risk to subjects, parts of the investigation presenting risks will be 
terminated. Termination will occur no later than 5 working days after the sponsor 
makes such a determination and no later than 15 working days after the sponsor first 
received notice of the effect. 
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11 RISK-BENEFIT ANALYSIS 
 
11.1 ANTICIPATED CLINICAL BENEFITS 
The TearCare® procedure will be performed with the aim of reducing the signs and 
symptoms of dry eye. 
 
11.2 ANTICIPATED ADVERSE DEVICE EFFECTS 
Anticipated adverse effects associated with the TearCare System have been described 
above in Section 10.2. 
 
11.3 RISKS ASSOCIATED WITH PARTICIPATION IN THE CLINICAL  
INVESTIGATION 
All anticipated study risks are listed in Section 10.2. 
 
11.4 POSSIBLE INTERACTIONS WITH CONCOMITANT MEDICAL TREATMENTS 
It is anticipated that there will be no interactions with concomitant medical treatments. 
 
11.5 STEPS THAT WILL BE TAKEN TO CONTROL OR MITIGATE THE RISKS 
The major risks to the subjects and the steps taken to control or mitigate them are 
described below: 
 
1. Overheating of the eyelids: All TearCare procedures will be done in the 
investigator’s office under direct supervision of the investigator. During TearCare 
procedures in this study heat will be applied to the eyelids at a temperature 
ranging from 41-45°C. This temperature range was selected based on 
research.43,44,45,46 The investigator can adjust the temperature up or down to a 
level that is comfortable for the subject, and may also shut off the System at any 
time if it is too uncomfortable or painful. In addition, the TearCare System is 
designed to monitor and regulate the temperature at the tissue-contacting 
 
43 Lane SS, DuBiner H, Epstein RJ, et al. A New System, the LipiFlow, for the Treatment of Meibomian 
Gland Dysfunction. Cornea. 2012: 31 : 396-404 
44 Blackie CA, Solomon JD, Greiner JV, Holmes M, Korb DR. Inner Eyelid Surface Temperature as a 
Function of Warm Compress Methodology. Optom Vis Sci 2008;85:675-683. 
45 Moritz AR, Henriques FC. Studies of thermal injury: the relative importance of time and surface 
temperature in the causation of cutaneous burns. Am J Pathol 1947;23:695–720. 
46 Medical electrical equipment Part 1: General requirements for basic safety and essential performance 
(IEC 60601-1). 
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surface of the SmartLid devices and not to exceed the maximum allowable 
temperature. 
 
2. Corneal abrasion: If the SmartLid devices are not positioned properly or come 
loose during the procedure, there is the potential for a corneal abrasion. To 
mitigate this, the investigator will apply the strips to the subject and will monitor 
their position during the procedure to ensure they remain in place and secure. 
 
In addition, there is the possibility of corneal abrasion or abrasion of the eyelid 
surface during expression of the meibomian glands. To reduce the chance of 
abrasion, the forceps have been designed with smooth surfaces (i.e., no rough 
edges) and investigators will be trained on how to perform expression according 
to this protocol. 
 
In addition to the above, the following mitigation steps have also been taken to reduce 
the risks in this study: 
 
• The device has been tested to demonstrate that it meets performance and 
safety specifications, as described in Section 5.1. 
• Instructions for Use on how to use TearCare in this study will be provided to each 
investigator. 
• Investigators will be trained in how to correctly apply and remove the SmartLid 
devices and operate the TearCare System. 
• Investigators will be trained in how to perform lid debridement and meibomian 
gland expression using the TearCare Clearance Assistant as described in this 
protocol. 
• The study staff will be trained to perform procedures required in this protocol. 
 
12 STATISTICAL CONSIDERATIONS 
 
12.1 EVALUABILITY 
All subjects on whom the TearCare or Restasis is attempted will be considered evaluable 
for the safety analysis. All eyes that have at least one follow-up visit and have no major 
protocol deviations will be evaluable for the per protocol analysis. 
 
12.2 ANALYSIS POPULATIONS 
• Intent-to-Treat Population - The intent-to-treat (ITT) population includes all 
randomized subjects. The primary and secondary efficacy analyses will be 
performed on the ITT population. Subjects will be analyzed as randomized. 
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• Per Protocol Population – The per protocol (PP) population includes all subjects 
who have at least one follow-up visit and have no major protocol deviations, 
including specifically no use of dry-eye medications (Doxycycline, Xiidra). 
Subjects will be analyzed as treated. 
• Safety Population – The safety population will include all subjects on whom the 
TearCare or Restasis is attempted. The safety population will be analyzed for all 
safety assessments. Subjects will be analyzed as treated. 
 
12.3 SUBJECT ACCOUNTABILITY 
A complete accounting of subjects by visit will be provided, including reasons for 
dropout, if known. 
 
12.4 DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
Demographic variables gender, race, ethnicity, and age will be summarized for all 
enrolled subjects, along with medical history. Descriptive statistical summaries of pre- 
treatment parameters (min, max, median, mean, standard deviation) will also be 
provided for each group. This includes baseline measurements for each of the study 
endpoints: TBUT, Total Meibomian Gland Secretion Score, Number of Meibomian glands 
with any/clear liquid, Corneal Staining, Conjunctival Staining, Blink Rate, Schirmer Score, 
OSDI Score, SANDE Score, and Eye Dryness Score. 
 
12.5 EFFECTIVENESS ENDPOINTS AND ANALYSIS METHODS 
All primary and secondary endpoints will be evaluated at 6 months. Outcomes 
measured on a per-eye basis will be analyzed using data from both eyes, with linear 
mixed effect models to account for within-person correlation (correlation between right 
and left eyes) as described in Appendix B. 
 
    DESCRIPTIVE ANALYSES 
 
The quantitative variables will be summarized using number of subjects (n), mean, 
median, standard deviation, minimum and maximum. The qualitative variables will be 
summarized using counts and percentages. 
Summaries of all endpoints will be presented by treatment group and visit. Summaries 
will also be provided for demographics, baseline medical history, concurrent therapies, 
and subject disposition. 
 
    PRIMARY EFFECTIVENESS ENDPOINTS 
 
The primary effectiveness endpoints are: 
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• the change from baseline in Tear Break-Up Time (TBUT) at 6 months 
• the change from baseline in total OSDI at 6 months 
The primary endpoint of the change from baseline in Tear Break-Up Time (TBUT) at 6 
months will be analyzed using linear mixed effects (LME) models adjusting for baseline 
and site, and with a random subject effect. These will allow for the proper 
incorporation of within-person correlation into the statistical models and will also allow 
for adjustment for baseline measurements. 
 
Details of the LME models are provided in the Statistical Analysis Plan (SAP) provided in 
Appendix B. Hypotheses regarding the primary and secondary effectiveness outcomes 
are described below. 
 
The primary endpoint of the change from baseline in total OSDI at 6 months will be 
analyzed using ANCOVA models adjusting for baseline and site. 
 
    PRIMARY EFFECTIVENESS HYPOTHESES 
 
The primary study hypotheses regard the superiority of the TearCare treatment as 
compared to Restasis, for Tear Break-Up Time (TBUT) and total OSDI. The primary 
endpoints will be tested for TearCare in a hierarchical fixed sequence. The statistical 
hypotheses are stated in terms of one-sided hypotheses, although statistical testing will 
be two-sided. 
 
To demonstrate superiority of the TearCare treatment to the Restasis control for TBUT 
we will test the following hypotheses: 
 
H01: There is no difference between TearCare and Restasis in the mean change from 
baseline in TBUT at 6 Months. 
 
H11: The mean change from baseline in TBUT at 6 Months is greater with TearCare than 
with Restasis. 
 
If H01 is rejected, then the study will be considered a success and we will test the 
following hypotheses to further evaluate superiority of the TearCare treatment to the 
Restasis control for total OSDI: 
 
H02: There is no difference between TearCare and Restasis in the mean change from 
baseline in total OSDI at 6 Months. 
 
H12: The mean change from baseline in total OSDI at 6 Months is less with TearCare than 
with Restasis. 
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    POOLABILITY 
 
Using a linear mixed effects modeling approach described in Appendix B, poolability of 
the effectiveness outcomes will be evaluated across centers by testing a Treatment-by- 
Center interaction (TxC). If the TxC interaction is significant at α=0.15, a Center effect 
will be included in the final model and results will be reported separately by Center. For 
this analysis, Centers with less than 5 enrolled subjects will be combined into a single, 
virtual center. 
 
    MISSING DATA 
 
No missing data imputation will be carried out beyond what is built-in to the mixed-
effects modeling approach to be used in the primary effectiveness analysis. 
No secondary effectiveness endpoints or safety endpoints will be imputed. 
 
    SECONDARY EFFECTIVENESS ENDPOINTS 
 
The secondary effectiveness endpoints include change from baseline at 6 Months for 
the following outcomes: 
 
1. Meibomian Gland Secretion Score 
2. Symptom Assessment iN Dry Eye (SANDE) scores 
3. Eye Dryness Score 
4. Number of Meibomian Glands Yielding any liquid 
5. Number of Meibomian Glands Yielding clear liquid 
6. Corneal staining scores 
7. Conjunctival staining scores 
8. Schirmer Score 
9. Ocular protection index (OPI): Interblink interval (IBI)/TBUT 
 
All testing of the secondary endpoints will be done using a two-sided alpha of 0.05. We 
will test the secondary endpoints in the order listed, stopping at the point where a test 
fails to reject. This sequential procedure controls the family-wise Type I error rate for 
the secondary endpoints. 
 
The secondary endpoints can be divided into two groups, those which are measured on 
a per-eye basis (Corneal Staining, Conjunctival Staining, Meibomian gland scores, 
Number of Meibomian Glands Yielding any liquid, Number of Meibomian Glands 
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Yielding clear liquid, OPI, Schirmer Score) and those measured on a per-subject basis 
(OSDI Score, SANDE Scores, Eye Dryness Score). 
 
Endpoints assessed at the eye level will be analyzed with linear mixed effects models 
adjusting for baseline and site, and with a random subject effect. Two-sample t-tests 
and Wilcoxon rank sum tests will be conducted on the average of the two eyes as 
supportive analyses. Endpoints assessed at the subject level will be analyzed using 
ANCOVA models adjusting for baseline and site, with two-sample t-tests and Wilcoxon 
rank sum tests as supportive analyses. No imputation will be performed for secondary 
efficacy variables. 
All secondary effectiveness variables collected will be summarized descriptively (n, 
mean, standard deviation, median, min and max) by treatment group and visit. 
 
    ADDITIONAL EXPLORATORY ANALYSES 
 
The use of dry eye lubricants will be summarized by study group. 
 
12.6 SAFETY ENDPOINTS AND ANALYSIS 
 
    DESCRIPTIVE ANALYSES 
 
All adverse events, changes in IOP, and changes in BCVA (EDTRS) will be tabulated by 
visit and study group. 
 
    PRIMARY SAFETY ENDPOINT 
 
The primary safety endpoint is the incidence of procedure (TearCare)/treatment 
(Restasis)-related adverse events. 
 
    SECONDARY SAFETY ENDPOINTS 
 
The secondary safety endpoints include: 
• Change in best corrected visual acuity (ETDRS) 
• Change in intraocular pressure (IOP) 
 
These endpoints will be summarized by treatment group and visit. 
 
    SAFETY ANALYSIS 
 
All adverse events will be reported by study group and AE category. Any serious adverse 
events will be completely described in the study report. The primary safety endpoint 
will be summarized for each study group. 
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We will compute the incidence of ocular events in two ways: first as a simple 
proportion, counting the number of subjects with any event (that is, counting the first 
event per person in either eye), then as an incidence rate, counting all events including 
repeated events per subject. 
 
12.7 SAMPLE SIZE CALCULATION 
A sample size of 200 subjects is estimated to provide sufficient power (90%) for this 
study. Nonetheless, given the 24 months follow up period and in an attempt to collect 
additional data regarding changes in the signs and symptoms of dry eye disease, up to 
300 subjects, approximately 150 in the TearCare group and 150 in the Restasis group, 
will be enrolled and randomized in the study. This will provide more than 90% power to 
meet the TBUT effectiveness endpoint and sufficient precision around the adverse 
event estimates. The sample size also takes into account an estimated 10% dropout 
rate per 6 months. Details of the sample size calculation can  be found in Appendix B. 
In May of 2021, the study protocol was revised to update the appropriate Schirmer test 
parameters for inclusion.  Since the study treated some subjects that did not meet 
these parameters at baseline, the planned sample size of the study was increased to 
approximately 310 subjects, approximately 155 in the TearCare group and 155 in the 
Restasis group. 
In August of 2022, the sample size was increased to 350 subjects, with up to 175 in the 
TearCare group and up to 175 in the Restasis group in order to account for additional 
subjects (an estimated 10) not meeting all eligibility criteria and a possible slightly 
higher dropout rate per 6 months (~11%). 
 
12.8 DEVIATION FROM THE STATISTICAL PLAN 
Any deviations from the statistical plan will be noted in the final report. 
 
13 MONITORING PROCEDURES 
Sight Sciences or contract research organization (CRO) personnel will monitor the study 
in a manner consistent with FDA regulations, good clinical practices and the clinical 
research standards adopted by Sight Sciences. Study monitoring will consist of on-site 
and remote monitoring visits. Study monitoring will involve the following elements: 
• Site Qualification: Sight Sciences or CRO personnel will meet with investigators 
and clinical study staff prior to the initiation of the study in order to review the 
adequacy of the subject population, facilities, and equipment with respect to 
the needs of the study, and to familiarize the investigator with the study 
protocol. 
• Site Initiation: Sight Sciences or CRO personnel will meet with the 
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investigator(s) and clinical study staff when the site is ready to begin enrolling 
subjects in order to train them in how to properly select subjects, perform the 
study procedure, and record study data. This visit will include, but not be 
limited to a review of the following: 
o Detailed review of the protocol 
o Informed consent procedures 
o Randomization procedures 
o Instruction in how to use the TearCare System 
o Instruction in how to perform study procedures 
o Guidance in how to administer questionnaires to subjects 
o Procedures for maintaining masking of study personnel 
o Records and reports 
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• Interim Monitoring: Sight Sciences or CRO personnel will visit the clinical site 
routinely during the study to review charts and to perform source document 
verification, to ensure proper adherence to the study protocol, and to review 
regulatory documents. Interim monitoring visits and telephone consultation 
will occur as necessary during the course of the study to ensure the proper 
progress and documentation of the study findings. 
• Study Closure: At the conclusion of the trial there will be a study closure visit 
during which several actions, including but not limited to the following, will be 
performed: 
o A final inspection of the study binder 
o Accountability and return of all devices and study materials to the 
sponsor 
o Discussion of record retention requirements with the investigator 
o Close-out notification to the IRB 
 
 
14 DATA AND QUALITY MANAGEMENT 
 
14.1 DATABASE MANAGEMENT 
The study database will be designed using an electric data capture (EDC) system that is 
compliant with 21 CFR Part 11 and relevant guidance documents. The EDC will be 
developed and maintained by an independent, qualified data management firm. 
 
The database will incorporate time-stamped audit trails, protection of human subjects, 
restricted access, and data security at the component level. Each database module, 
including each individual eCRF, will be validated by conducting a series of standard tests 
that demonstrate usability and correctness of the database system. The database will 
be maintained on an ongoing basis and will be routinely backed up. 
 
14.2 SUBJECT IDENTIFICATION 
The subjects will be identified by a six-digit subject number composed of a two-digit 
study identification number, a two-digit center identification number followed by a two 
digit sequential subject number. The subject identification will be assigned when 
informed consent is obtained. In this way, information contained in the study records 
will be kept as confidential as possible. 
 
14.3 SUBJECT ACCOUNTABILITY 
All subjects who are randomized and treated in this clinical investigation shall be 
monitored for the duration of the investigation. The clinical investigation shall be 
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considered completed when all subjects that have been enrolled in the investigation 
have reached the final reporting period, excluding subjects who were withdrawn. 
 
14.4 CONFIDENTIALITY 
All medical records associated with the clinical investigation will be made available for 
review by Sight Sciences personnel, its contract research organization (CRO) and 
governmental/regulatory agencies involved. The results of the study may be published 
in the future for scientific and marketing purposes, but the identity (name) of each 
subject will not be revealed. All records will be stored in a secure area at the 
investigator’s facility, the CRO, the data management firm and at Sight Sciences, Inc. 
 
14.5 SOURCE DATA AND CASE REPORT FORMS 
Source data will be entered into a validated electronic system at each site by trained 
personnel in accordance with 21 CFR Part 11 requirements. Electronic entries will be 
100% verified against corresponding source data at the sites and queried/corrected if 
needed to the extent possible. Medical site records serve as source data. In addition, 
data that are collected exclusively for the purpose of this study and not normally 
recorded in the subjects’ medical records can be collected directly on the study 
worksheets provided by the sponsor and these study worksheets will serve as the 
source data. 
 
Source data and study worksheets are to be maintained at the site in the subject 
records or in the medical records. All entries must be made in black or blue ink and 
changes must be made by strike-through only with date and initials or signature. All 
source documents must be completed and signed by the authorized study personnel 
(e.g., study coordinator). No “white-out” is to be used on the source documents. 
 
14.6 RETENTION PERIOD 
Clinical sites are to retain any and all clinical trial material (documentation, photographs, 
etc.) for a period of two years from the date a marketing application is approved or two 
years after the investigation has been discontinued, or as directed by their institutional 
document retention requirements, whichever is the longest. After that time, the items 
must be returned to Sight Sciences for archiving. Unused medical devices are to be 
returned to the sponsor at the conclusion of the enrollment period. 
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15 PROTOCOL MODIFICATIONS AND DEVIATIONS 
 
Protocol modifications may occur during the study. Each will be approved by the 
sponsor before implementation. Each will undergo Institutional Review Board (IRB) 
review and approval, as necessary. 
 
Any deviations from this protocol intended to protect the life or physical well-being of a 
subject in an emergency are to be reported to Sight Sciences, Inc. as well as the IRB as 
soon as possible, and no later than 5 working days after the emergency occurred. 
 
All protocol deviations will be documented using the Protocol Deviation form. 
 
 
16 DEVICE FAILURES AND MALFUNCTIONS 
 
All device failures or malfunctions should be recorded on the Device Deficiency Form 
and reported to tcsafety@sightsciences.com. 
 
If the TearCare procedure cannot be completed due to a product failure or malfunction, 
the procedure may be rescheduled for a different day. Every effort should be made to 
reschedule the procedure within the next 7 calendar days of the Baseline visit. 
 
 
17 ETHICAL CONSIDERATIONS 
 
17.1 DECLARATION OF HELSINKI 
This study shall be conducted in accordance with the Declaration of Helsinki (Appendix 
D). 
 
17.2 INSTITUTIONAL REVIEW BOARDS (IRB) 
The study shall not begin at a site until approval has been obtained from the reviewing 
IRB. It is the Investigators’ responsibility to obtain and maintain written approval of the 
study protocol and Informed Consent documents from the appropriate IRB. It is also the 
Investigators’ responsibility to notify that body about any amendments to these 
documents and to follow the IRBs rules regarding the reporting of Adverse Events and 
Protocol Deviations related to the device and/or this study. Copies of all written 
approvals (identifying the study, the submitted and approved documents and the date 
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reviewed) and the approved versions of the documents must be provided to Sight 
Sciences or its CRO. 
 
The Investigators must file all correspondence with the IRB and forward copies of such 
correspondence to Sight Sciences. 
 
17.3 INFORMED CONSENT FORM (ICF) 
An Informed Consent template that covers all protocol procedures and follows GCP 
Guidelines will be prepared by Sight Sciences and made available to each Investigator. 
The Investigator may adapt these templates to the requirements of the local IRB and of 
the institution where the study is conducted, but any revisions made to the ICF must be 
submitted to the sponsor for review prior to submission to the IRB. A copy of each IRB- 
approved ICF version is to be made available to Sight Sciences and its CRO. The 
approved, IRB-stamped ICF is to be kept in its full length in the study Regulatory Binder. 
Original, signed ICFs are to be maintained in the subject’s study records and must be 
made available for monitoring review. 
 
17.4 PUBLIC LISTING OF STUDY 
The study will be listed on the NIH website www.clinicaltrials.gov. 
 
 
18 STUDY ADMINISTRATION 
 
18.1 DEVICE AND DRUG ACCOUNTABILITY 
With each shipment of study devices and drug (Restasis®), Sight Sciences will include a 
Packing List that will give the amount shipped and the lot numbers. This packing list 
must be reconciled by the investigational site with the contents of the shipment and 
then recorded on the Device and Drug Accountability Logs (these logs are contained 
within the regulatory binder at the site). All study products at the site must be stored in 
a secured/locked area. The drug (Restasis®) should be stored as per the storage 
recommendation between 15-25 °C (59-77 °F). When study devices or drug are used, 
returned or disposed of, their disposition (including the disposition and date of 
disposition) must be recorded on the Device and Drug Accountability log. 
 
Device and Drug reconciliation activities will also be conducted periodically in 
conjunction with site monitoring visits. The investigator must maintain accurate records 
of the receipt and disposition of all devices and drug shipped by Sight Sciences. 
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18.2 EARLY TERMINATION OR SUSPENSION OF AN INVESTIGATION 
Sight Sciences may terminate the study, in which case the investigators and associated 
IRBs will be notified in writing. Possible reasons for study termination include but are 
not limited to: 
 
• The discovery of an unexpected, significant, or unacceptable risk to the study 
subjects treated with the device 
• Insufficient enrollment in the study 
 
Sight Sciences reserves the right to stop the study at a center any time after the 
initiation visit if there have been no subject enrollments or if significant 
protocol/deviations are observed at the site. 
 
Likewise, a principal investigator may terminate the study at his/her institution. This 
decision must be followed by written notification to Sight Sciences within five working 
days, stating the reasons for termination. 
 
If the study is terminated, every effort should be made to obtain final follow-up from all 
subjects. 
 
In the event that there are significant human use issues with the device, the investigator 
will be consulted to make a determination of whether the study should be terminated 
or not. 
 
18.3 INVESTIGATOR RESPONSIBILITIES 
 
    GENERAL RESPONSIBILITIES OF INVESTIGATORS 
 
An Investigator is responsible for ensuring that an investigation is conducted according 
to the signed agreement, the investigational plan and applicable FDA regulations, for 
protecting the rights, safety, and welfare of subjects under the Investigator’s care, and 
for the control of devices under investigation. An Investigator also is responsible for 
ensuring that informed consent is obtained in accordance with 21 CFR part 50. 
 
    SPECIFIC RESPONSIBILITIES OF INVESTIGATORS 
 
1. 
Awaiting approval - An Investigator may determine whether potential subjects 
would be interested in participating in an investigation, but shall not request the 
written informed consent of any subject to participate, and shall not allow any 
subject to participate before obtaining IRB approval. 
2. 
Subject Qualification -The Investigator is responsible for ensuring that all subjects 
entering the study conform to the patient selection criteria. 
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3. 
Compliance - An Investigator shall conduct an investigation in accordance with the 
signed agreement with the Sponsor, the investigational plan, all applicable FDA 
regulations, and any conditions of approval imposed by an IRB. 
 
    INVESTIGATOR RECORDS 
 
A participating Investigator shall maintain the following accurate, complete, and current 
records relating to the Investigator’s participation in an investigation for the period 
specified in Section 14.6: 
1. 
All correspondence with another Investigator, an IRB, the Sponsor, a monitor, or 
FDA, including required reports. 
2. 
Records of each subject’s case history and exposure to the device. Case histories 
include the study CRF’s/worksheets and supporting data including, for example, 
signed and dated consent forms and medical records. Such records shall include: 
a) 
Documents evidencing informed consent. 
b) All relevant observations, including records concerning adverse device effects 
(whether anticipated or unanticipated), information and data on the condition 
of each subject upon entering, and during the course of, the investigation, 
including information about relevant previous medical history and the results 
of all diagnostic tests. 
3. 
The protocol, with documents showing the dates and reasons for each deviation 
from the protocol. 
4. 
Any other records that FDA requires to be maintained by regulation or by specific 
requirement for a category of investigations or a particular investigation. 
 
    INVESTIGATOR REPORTS 
 
An Investigator shall prepare and submit the following complete, accurate, and timely 
reports: 
1. 
Unanticipated Adverse Device Effects - An Investigator shall submit to the Sponsor 
and to the reviewing IRB a report of any unanticipated adverse device effect 
occurring during an investigation as soon as possible, but in no event later than 10 
working days after the Investigator first learns of the effect. 
2. 
Withdrawal of IRB Approval - An Investigator shall report to the Sponsor, within 5 
working days, a withdrawal of approval by the reviewing IRB of the Investigator’s 
part of an investigation. 
3. 
Progress - An Investigator shall submit progress reports on the investigation to the 
Sponsor, the monitor, and the reviewing IRB at regular intervals, but in no event 
less often than yearly. 
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4. 
Deviations from the Investigational Plan - An Investigator shall document and 
report to the Sponsor any deviation from the investigational plan. 
5. 
Informed Consent - If an Investigator enrolls a subject without obtaining informed 
consent, the Investigator shall report such use to the Sponsor and the reviewing 
IRB within 5 working days after the use occurs. 
6. 
Final Report - An Investigator shall, within 3 months after termination or 
completion of the investigation or the Investigator’s part of the investigation, 
submit a final report to the Sponsor and the reviewing IRB. 
7. 
Other - An Investigator shall, upon request by a reviewing IRB or FDA, provide 
accurate, complete, and current information about any aspect of the investigation. 
 
18.4 INVESTIGATOR AGREEMENT 
The principal investigators in each center shall agree to the clinical protocol and any 
amendments and indicate their approval and agreement by signing and dating the cover 
page of the study protocol and the Investigator Responsibility Agreement. 
 
 
19 PUBLICATION POLICY 
 
Sight Sciences recognizes the value of disseminating research results. It is understood 
that the Study is part of the Multi-Center Clinical Trial and publication of results is 
expected. This publications policy applies to journal articles, conference abstracts, and 
conference presentations (posters and slides) covering Sight Sciences-sponsored clinical 
studies. This policy is in addition to any arrangement contained in the Clinical Trial 
Agreement between Sight Sciences and the investigator. 
 
Multi-Site Data 
Clinical site investigators are encouraged to propose publications and abstracts that 
include clinical or research data from multiple clinical sites; such projects will be 
coordinated by Sight Sciences. Authorship of papers and abstracts resulting from these 
projects will be determined collaboratively according to the following guidelines: 
 
• The first author on such publications will be the person who primarily wrote the 
paper and took the lead on the research. In the case of clinical trial papers 
where all authors contributed equally, authorship order may be based on site 
enrollment or other criteria at Sight Sciences’ discretion. 
• Other authors include those who significantly contributed to the specific work. 
• At least one person from each clinical site whose study subjects appear in the 
work will be acknowledged in the manuscript/presentation in some way, either 
as an author group member, a non-author contributor, or listed in the 
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acknowledgements, depending on the particular policies of the journal or 
conference. 
 
Single Site Data 
After publication of the multi-center study results in a peer-reviewed journal, or if 
Sponsor has not submitted a manuscript for publication in a peer-reviewed journal 
within twelve (12) months after the study has been completed, whichever occurs first, 
Investigators may publish the results of the Study generated by the Investigator, subject 
to the obligations of the Clinical Trial Agreement between Sight Sciences and the 
Investigator, and the prior approval of Sponsor in writing. 
 
Publications Review Policy 
Investigators must submit all presentations, posters, abstracts and manuscripts 
pertaining to this study to Sight Sciences for review in advance of their submission. 
Sight Sciences conducts this review to protect its proprietary rights to information, 
inventions, or products developed under the Study. Please use the following guideline 
to determine the absolute minimum advance time for submitting an item to Sight 
Sciences for review: 
 
• Presentations/Posters: 5 business days in advance of presentation 
• Abstracts: 5 business days in advance of submission 
• Manuscripts: 30 calendar days in advance of submission for publication 
 
In accordance with the Clinical Trial Agreement, these items must receive written 
approval from Sight Sciences in order for them to be submitted or presented. If an item 
is not received in the timeframe listed above, approval may not be granted due to 
insufficient time for considered review. In addition, since most of our Clinical Trial 
Agreements require that Sight Sciences has 60 days to review publications, Sight 
Sciences reserves the rights granted in those Agreements if circumstances require a 
longer review. 
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20 BIBLIOGRAPHY 
 
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Fiscella RG. Understanding dry eye disease: a managed care perspective. Am J Manag Care 2011; 17 Suppl 
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Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision tree 
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Lemp M, Foulks, G. The Definition & Classification of Dry Eye Disease: Guidelines from the 2007 
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Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and 
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10. Korb DR, Henriquez AS. Meibomian gland dysfunction and contact lens intolerance. J Am Optom Assoc. 
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11. Blackie CA, Korb DR, Knop E, et al. Nonobvious obstructive meibomian gland dysfunction. Cornea. 
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12. Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland 
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14. Bron AJ, Tiffany JM. The contribution of meibomian disease to dry eye. Ocul Surf. 2004;2:149–165. 
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17. Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: report 
of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthal-mol 
Vis Sci 2011;52:2050-64 
18. Goto E, Monden Y, Takano Y, et al. Treatment of non-inflamed obstructive meibomian gland dysfunction by 
an infrared warm compression device. Br J Ophthalmol. 2002;86:1403–1407. 
19. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: 
executive summary. Invest Ophthalmol Vis Sci. 2011;52:1922–1929. 
20. Lemp MA. Report of the National Eye Institute/Industry workshop on clinical trials in dry eyes. CLAO J. 
1995;21:221–232. 
21. Korb DR, Blackie CA. Restoration of meibomian gland functionality with novel thermodynamic treatment 
device–a case report. Cornea. 2010;29:930–933. 
22. Friedland BR, Fleming CP, Blackie CA, et al. A novel thermodynamic treatment for meibomian gland 
dysfunction. Curr Eye Res. 2011;36: 79–87. 
23. Olson MC, Korb DR, Greiner JV. Increase in tear film lipid layer thickness following treatment with warm 
compresses in patients with meibomian gland dysfunction. Eye Contact Lens. 2003;29:96–99. 
24. Lemp MA, Bardfield L, Blackie CA, et al. Evaluation of a novel method of treatment of dry eye. Invest 
Ophthalmol Vis Sci. 2008; 127/A154. 
25. Majmudar PA. LipiFlow Study Group. A novel thermal pulsation treatment for obstructive meibomian gland 
dysfunction: applying heat to the inner eyelid surfaces. Invest Ophthalmol Vis Sci. 2010; 6281/D909. 
26. Mori A, Oguchi Y, Goto E, et al. Efficacy and safety of infrared warming of the eyelids. Cornea. 1999;18:188– 
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27. Matsumoto Y, Dogru M, Goto E, et al. Efficacy of a new warm moist air device on tear functions of patients 
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28. Lane SS, DuBiner H, Epstein RJ, et al; A New System, the LipiFlow, for the Treatment of Meibomian Gland 
Dysfunction. Cornea. 2012: 31 : 396-404. 
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treatment for superior limbic keratoconjunctivitis. Ophthalmology. 2003;110(8):1578-1581. 
doi:10.1016/S0161-6420(03)00538-4 
30. Stonecipher K, Perry HD, Gross RH, Kerney DL. The impact of topical cyclosporine A emulsion 0.05% on the 
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31. Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al., Efficacy of commercially available topical 
cyclosporine A 0.05% in the treatment of meibomian gland dysfunction. Cornea (2006);25:pp. 171–175. 
32. Bron AJ, Tiffany JM. The contribution of meibomian disease to dry eye.  Ocul Surf. 2004;2:149-165. 
33. Bron AJ, Tiffany JM, Gouveia SM, Yokoi N, Voon LW. Functional aspects of the tear film lipid layer. Exp Eye 
Res 2004;78:347–60. 
34. Jones et al. TFOS DEWS II Management and Therapy Report. The Ocular Surface 2017;15:575-628. 
35. Moritz AR, Henriques FC. Studies of thermal injury: the relative importance of time and surface temperature 
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36. Despa F, Orgill DP, Neuwalder J, Lee RC. The relative thermal stability of tissue macromolecules and cellular 
structure in burn injury. Burns 2005;31:568–77. 
37. Medical electrical equipment Part 1: General requirements for basic safety and essential performance (IEC 
60601-1). 
38. Badawi D. A novel system, TearCare®, for the treatment of the signs and symptoms of dry eye disease. 
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39. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. Classification and grading of lid changes. Eye 
1991;5: 395–411. 
40. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface 
Disease Index. Arch Ophthalmol 2000;118: 615-621. 
41. Schaumberg DA, Gulati A, Mathers WD, Clinch T, Lemp MA, Nelson JD, Foulks GN, Dana R. Development 
and Validation of a Short Global Dry Eye Symptom Index. Ocular Surface. 2007;5(1):50-57. 
42. Amparo F, Schaumberg DA, Dana R. Comparison of Two Questionnaires for Dry Eye Symptom Assessment: 
The Ocular Surface Disease Index and the Symptom Assessment iN Dry Eye. Ophthalmology. 
2015;122(7):1498-1503. 
43. Lane SS, DuBiner H, Epstein RJ, et al. A New System, the LipiFlow, for the Treatment of Meibomian Gland 
Dysfunction. Cornea. 2012: 31 : 396-404 
44. Blackie CA, Solomon JD, Greiner JV, Holmes M, Korb DR. Inner Eyelid Surface Temperature as a Function of 
Warm Compress Methodology. Optom Vis Sci 2008;85:675-683. 
45. Moritz AR, Henriques FC. Studies of thermal injury: the relative importance of time and surface temperature 
in the causation of cutaneous burns. Am J Pathol 1947;23:695–720. 
46. Medical electrical equipment Part 1: General requirements for basic safety and essential performance (IEC 
60601-1). 
47. Lane SS, DuBiner H, Epstein RJ, et al. A New System, the LipiFlow, for the Treatment of Meibomian Gland 
Dysfunction. Cornea. 2012: 31 : 396-404 
48. Blackie CA, Solomon JD, Greiner JV, Holmes M, Korb DR. Inner Eyelid Surface Temperature as a Function of 
Warm Compress Methodology. Optom Vis Sci 2008;85:675-683. 
49. Moritz AR, Henriques FC. Studies of thermal injury: the relative importance of time and surface temperature 
in the causation of cutaneous burns. Am J Pathol 1947;23:695–720. 
50. Medical electrical equipment Part 1: General requirements for basic safety and essential performance (IEC 
60601-1). 
51. DEWS. The definition and classification of dry eye disease: report of the Definition and Classification 
Subcommittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5:133. 
52. Lemp MA, Hamill JR. Factors affecting tear film break-up in normal eyes. Arch Ophthalmol. 1973;89:103– 
105. 
53. Norn MS. Desiccantion of the precorneal tear film. I. Corneal wetting time. Acta Ophthalmol (Copenh) 
1969;47:865–880. 
54. Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J 
1995;21: 221–232. 
55. Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and 
gland location. Cornea. 2008;27: 1142–1147. 
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56.  Lane SS, DuBiner H, Epstein RJ, et al; A New System, the LipiFlow, for the Treatment of Meibomian Gland 
Dysfunction. Cornea. 2012: 31 : 396-404 
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21 APPENDIX A – METHODS FOR EXAMS, TESTS AND 
QUESTIONNAIRES 
 
21.1 MEDICATIONS 
When recording medications that the subject is taking, be sure to ask the subject to list 
any over-the-counter medications and supplements they are taking that could affect 
dry eye disease including, for example, cold medicines, Benadryl, fish oil supplements 
and Omega 3 products, retinol products, Latisse, etc. Multivitamins and general health 
supplements do not need to be recorded. 
 
21.2 MANIFEST REFRACTION AND VISUAL ACUITY 
Masked assessment: This assessment should be performed by the masked assessor. 
 
Best-corrected visual acuity will be measured using the ETDRS method. Subjects 
should undergo manifest refraction prior to the ETDRS test, with the exception of the 
Day 1 and week 1 follow-up visit. On Day 1 and week 1, the subject’s best spectacle 
corrected visual acuity (BSCVA) (i.e., without manifest refraction) will be measured 
using the ETDRS method. If the subject’s visual acuity has worsened by ≥ 10 letters 
from baseline, then manifest refraction should be performed and the ETDRS 
measurement should be repeated. 
 
Manifest Refraction 
 
Refraction will be performed by the Investigator or staff using standard clinical practice. 
 
ETDRS Testing Methods 
 
Test Set-up 
Best-corrected visual acuity at Baseline and all scheduled follow-up visits will be 
measured using the ETDRS charts at 1 or 4 meters. 
 
The ETDRS chart must be placed at a distance of 4.00 meters (13 feet and 1.5 inches, or 
157.5 inches) from cornea to chart surface, when using a 4-meter chart. For testing at 1 
meter, the distance must be 1.00 (39 and 3/8 inches). A measuring tape or meter stick 
should always be available to verify the chart distance, even if the examining chair is 
supposed to be immovable or if reference marks are placed on the floor or walls. 
 
The 1-meter distance is measured from the eye of the participant, seated comfortably 
in a chair with his/her back firmly placed against the chair, to the center of the 2nd or 
4th letter of the 3rd line of the chart. 
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Note: If it is necessary to refract at the 1-meter distance, remember to add +0.75 
sphere to the trial frame. Subtract the +0.75 sphere from the final refraction obtained at 
the 1-meter distance before recording the refraction on the form. 
 
Methods 
Starting at 4 meters, the subject should attempt to read each letter, line-by-line, left to 
right, beginning with line 1 at the top of the chart. If the subject is unable to read line 1 
(20/200) at 4 meters, then visual acuity testing should be performed at 1 meter. 
 
The subjects should be told that the chart has letters only, no numbers. If the subject 
reads a number, he or she should be reminded that the chart contains no numbers, and 
the examiner should then request a letter in lieu of the number. The subject should be 
asked to read slowly, about one letter per second, so as to achieve the best 
identification of each letter. He/she is not to proceed to the next letter until he/she has 
given a definite response. 
 
A maximum effort should be made to identify each letter on the chart. When the 
subject says he/she cannot read a letter, the subject should be encouraged to guess. If 
the subject identified two (2) letters (e.g., A or B), the subject should be asked to choose 
one letter and, if necessary, to guess. When it becomes evident that no further 
meaningful readings can be made despite encouragement to read or guess, the 
examiner should stop the testing for that eye. However, all letters on the last line 
should be attempted as letter difficulties vary and the last letter may be the only one 
read correctly. The number of letters missed or read incorrectly should be noted. 
 
In order to provide standardized and well-controlled assessment of visual acuity, all 
visual acuity assessments for a subject should be performed consistently (e.g., the same 
lighting conditions, viewing distance, etc.) at each visit. 
 
Recording and Scoring Best-Corrected Visual Acuity 
Using the Visual Acuity Worksheet, circle each letter the subject identifies correctly, 
write total correct for each row in the place provided, and compute the total correct for 
all rows. Do not mark letters read incorrectly or not read at all. Each letter read 
correctly is recorded as one. Only move to the next line if 4 or more letters are read 
correctly. If 3 or more letters are read correctly in the final line, then that line is used for 
the Snellen equivalent and the visual acuity score. If 2 or fewer letters are read correctly 
in the final line, letters read from that line are added to the total visual acuity score and 
the previous line is used for the Snellen equivalent. 
 
The number of correct letters will be recorded on the study worksheets and entered into 
the EDC. For the Day 1 Visual Acuity measurement, if two measurements are made, 
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one BSCVA and one with manifest refraction, the latter VA obtained with manifest 
refraction should be entered into the EDC. 
 
21.3 SLIT LAMP EXAM 
Masked assessment: This assessment should be performed by the masked assessor. 
 
A standard slit-lamp examination shall be performed including inspection of the cornea 
at a magnification of 10X and/or 16X for the presence or active inflammation or 
structural change, the iris and anterior chamber for inflammation, and the eyelids for 
crusts, collarettes, or scales. 
 
 
21.4 TEAR BREAKUP TIME (TBUT) 
Masked assessment: This assessment should be performed by the masked assessor. 
 
Tear film stability is measured by a test of TBUT, defined as the time to initial breakup of 
the tear film after a blink. 
 
Measuring Tear Break-Up Time 
 
1. The fluorescein-impregnated strip is moistened with sterile saline and applied 
gently by touching against the superior bulbar conjunctiva. 
2. Measure TBUT approximately 30 seconds after instilling the fluorescein. Ask the 
subject to blink several times and to move the eyes, to mix the fluorescein in the 
tears. 
3. Use the cobalt blue illumination of the slit lamp and a Wratten filter. Use a beam 
width of approximately 4 mm, and full height. Move the beam slowly from side 
to side to cover the entire cornea.47,48,49 
4. Ask the subject to blink 3 times and then hold their eye open (e.g., “Blink, blink, 
blink, hold”). 
5. Using a stopwatch, record the time when the tear film breaks-up. The time from 
upstroke of the last blink to the first tear film break or dry spot formation is 
recorded as the TBUT measurement. 
6. Repeat the test 3 times per eye and take the average of the 3 measurements. 
 
 
47 DEWS. The definition and classification of dry eye disease: report of the Definition and Classification 
Subcommittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5:133. 
48 Lemp MA, Hamill JR. Factors affecting tear film break-up in normal eyes. Arch Ophthalmol. 
1973;89:103–105. 
49 Norn MS. Desiccantion of the precorneal tear film. I. Corneal wetting time. Acta Ophthalmol (Copenh) 
1969;47:865–880. 
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Tips for Tear Break-up Time 
 
• TBUT is the number of seconds between a blink and the appearance of a first 
dry spot or negative staining in the tear film. 
• TBUT measurements should be done quickly after installation of the dye 
because, in the presence of epithelial defects, the fluorescein will diffuse into 
the tissue and the borders of staining become indistinct, as does the intensity 
of staining of both tear film and cornea. 
• Clear instructions should be provided to subjects about the blink and hold 
sequence 
• Clear instructions should be provided to the study staff about when to start 
the stopwatch 
 
21.5 CORNEAL STAINING 
Masked assessment: This assessment should be performed by the masked assessor. 
 
Measuring Corneal staining 
 
1. Measure corneal staining within 3-4 minutes of installation of fluorescein dye to 
assure the dye does not diffuse into stroma, blurring the discrete margin of any 
staining defects. 
2. Use moderate illumination on the slit-lamp and use cobalt blue filter on with 
yellow Wratten filter to improve any visualization of corneal staining. Use 3 mm 
width and 10x magnification for assessing corneal staining. 
3. Grade the corneal staining using the NEI/Industry Grading System provided in 
Figure 7 below. 50 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
50 Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J 
1995;21: 221–232. 
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Figure 7: NEI/Industry Grading System for Corneal Staining 
 
 
Grade 0: No staining 
Grade 1: Scattered, micropunctate staining 
Grade 2: Grouped, micropunctate staining 
Grade 3: Diffuse micropunctate or macropunctate staining 
 
 
Tips for Corneal Staining 
• Ask subjects to blink several times to assure the uniform distribution of dye in 
cul-de-sac 
• Make sure to use moderate illumination to avoid hyper reflection from the spots 
of fluorescein uptake 
 
21.6 CONJUNCTIVAL STAINING 
Masked assessment: This assessment should be performed by the masked assessor. 
 
1. The lissamine green-impregnated strip is moistened with sterile saline and 
applied gently by touching against the superior bulbar conjunctiva. 
2. Wait at least 1 minute before grading the conjunctival staining. Perform grading 
within 4 minutes of instilling the dye. 
3. Start with a low illumination and increase the level until the lissamine green 
staining is most visible. 
4. Grade the conjunctival staining on moderate illumination per the NEI grading 
system shown below in Figure 8. 
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Figure 8: NEI/Industry Grading System for Conjunctival Staining 
 
 
Grade 0: No staining 
Grade 1: Scattered, micropunctate staining 
Grade 2: Grouped, micropunctate staining 
Grade 3: Diffuse micropunctate or macropunctate staining 
 
Tips for Conjunctival Staining 
• Ask subjects to blink several times to assure the uniform distribution of dye in 
cul-de-sac 
• Make sure to identify pooling or a stained mucus strand. Ask subjects to blink a 
couple of times when in doubt. 
 
21.7 SCHIRMER TEST 
The Schirmer Test measures aqueous tear quantity and is an indication of aqueous- 
deficient dry eye. 
 
Procedure 
1. The Schirmer test, with anesthesia, should be performed in a dimly lit room. 
2. Instill 1 drop of anesthetic into each eye and wait approximately 4 minutes. 
3. Gentle blotting of the corners of the eyelids with a facial tissue is allowed to 
catch the over spill. Any direct, active blotting of the cul-de-sac will not be 
allowed. 
4. Ask the patient to look up and draw the lower lid gently downward and 
temporally hook the rounded bent end of the sterile strip into the lower cul-de- 
sac at the temporal one-third of the lower eyelid margin. 
5. Start the timer 
6. To minimize artifacts from this test, ask subjects to gently close their eyelids until 
5 minutes have elapsed. Ask subjects to open their eyes and remove the strips. 
7. Because the tear front will continue advancing a few millimeters after it has 
been removed from the eyes, it is important to mark the tear front with a ball 
point pen at precisely 5 minutes. 
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Strip Measuring 
1. Write the letter “R” on the strip used in the right (OD) eye and the letter “L” on 
the strip used in the left (OS) eye. Each strip has graduated sections on it that will 
aid in capturing the appropriate measurement in millimeters. 
2. Record only whole numbers, rounding up to the nearest whole number if the 
tear front is at or greater than the half-millimeter mark. 
3. Once marked, each strip will be affixed to the source document (marked side 
up), in the space provided, and covered completely with transparent tape. The 
measurement is then to be captured on the source document and transcribed 
onto the EDC. 
 
21.8 MEIBOMIAN GLAND SECRETION SCORING 
Masked assessment: This assessment should be performed by the masked assessor. 
 
The Meibomian Gland Secretion Scoring is an assessment of the quality of the secretions 
produced by the meibomian glands in the lower eyelids. The Meibomian Gland 
Secretion Scoring should be performed using the Meibomian Gland Evaluator 
(TearScience, Inc.). Ensure that the instrument has been cleaned using alcohol prior to 
each use. 
 
Grade the quality of secretions in the lateral, central and temporal thirds of the lower 
eyelids. Grade the 5 central glands in each region, for a total of 15 glands per eye. 
 
Per the method described by Korb et al, 51 place the part of the instrument's contact 
surface onto the skin immediately inferior to the eyelashes of the lower eyelid so that 
the long dimension is parallel to the eyelid margin. Once full contact is achieved 
between the instrument and the skin immediately below the lash line of the lower lid, 
rotate the shaft of the instrument downward approximately 15 to 45 degrees. Then, 
depress the shaft midway (~3mm) and roll the lower eyelid margin slightly outward. 
Make sure to avoid contact with the ocular surface. 
 
Hold the instrument in place over each third of the lid for a minimum of 10 and a 
maximum of 15 seconds while grading the quality of secretion of the 5 glands in the 
center of the instrument (15 glands total per eye). Grade the quality of the secretions 
per the following scale described by Lane et al52: 
 
 
 
 
51 Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and 
gland location. Cornea. 2008;27: 1142–1147. 
52 Lane SS, DuBiner H, Epstein RJ, et al; A New System, the LipiFlow, for the Treatment of Meibomian 
Gland Dysfunction. Cornea. 2012: 31 : 396-404. 
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o 0 = nothing 
o 1 = toothpaste 
o 2 = cloudy 
o 3 = clear 
 
From this assessment the following endpoints will be calculated: 
• Total Meibomian Gland Secretion Score: Sum of the grade (0 – 3) for each of the 
15 glands. Range for this score is 0-45. 
• Count of the number of Meibomian glands yielding clear liquid secretions. 
Range for this count is 0-15. 
• Count of the number of glands secreting any liquid (clear or cloudy). Range for 
this count is 0-15. 
 
21.9 INTRAOCULAR PRESSURE 
Masked assessment: This assessment should be performed by the masked assessor. 
The same method of measuring intraocular pressure should be used at each visit. 
Intraocular pressure should be measured with applanation tonometry (e.g. Goldmann 
tonometer, if available). 
 
21.10 BLINK RATE 
Masked assessment: This assessment should be performed by the masked assessor. 
 
The blink rate of each subject will be measured over a three-minute period using a 
computer-based algorithm customized to count blinks per minute. Subjects will be 
instructed to look at a stimulus displayed on computer screen (while seated) and eyelid 
closure incidences will be collected. Make sure to record the start and stop time of 
when subject starts and stops viewing the stimulus displayed on the computer screen. 
Lighting that may cause squinting or minimizes the interpalpebral fissure will be directed 
away from a subject’s field of vision and the monitor brightness will be adjusted to a 
level which would not cause squinting or minimizes the interpalpebral fissure. Sites will 
be instructed with the specifications about the brightness, contrast, resolution and 
ambient light parameters while conducting the test. Blink rate will be utilized to 
calculate the inter-blink-interval (IBI) and ocular protection index (OPI). 
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21.11 QUESTIONNAIRES 
 
   GENERAL INSTRUCTIONS FOR QUESTIONNAIRES 
 
The subject should complete all required questionnaires at the beginning of each visit 
before conducting other clinical testing. 
 
Provide a paper copy of the questionnaires and a blue or black ink pen to the 
subject. Review the instructions for each questionnaire with the subject and answer any 
questions they have about how to complete them. Then allow the subject to complete 
the questionnaires on their own (i.e., self-administered) without any assistance. 
 
Study staff should review the questionnaires before the subject leaves the office to 
check for missing or multiple answers on a given question. If these are found, please 
point this out to the subject and allow them to revise their response(s) to the specific 
question(s). Please confirm initials and date of the subject on the last page of the 
questionnaire. Do not allow the subject to take the questionnaires home. 
 
    OSDI QUESTIONNAIRE 
 
The OSDI has 12 questions. Based on the answers provided by the subject, study staff 
calculate the overall OSDI Total score (from 0-100) and scores for the three subscales 
according to the OSDI instructions. Based on the recommended cutoffs for OSDI Total 
score, the severity of the subject’s dry eye symptoms will be categorized as follows: 
 
o Normal – 0-12 
o Mild – 13-22 
o Moderate – 23-32 
o Severe – 33 or higher 
 
     SANDE QUESTIONNAIRE AND EYE DRYNESS VAS 
 
The SANDE is a simple dry eye instrument containing two items measuring the 
frequency and severity of symptoms, each is assessed on a 100 mm visual analog scale 
(VAS) ranging from ‘Never/Very comfortable’ to ‘All the time/Very severe’ and scored 
from 0 to 100. The Eye Dryness Visual Analog Scale measures subject’s level of 
discomfort related to eye dryness ranging from “No discomfort/maximal discomfort.” 
 
Three scores will be obtained from the SANDE: 
 
• Frequency score (ranging from 0 to 100): The distance (in mm) between the left 
end of the scale and the subject’s response. 
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• Severity score (ranging from 0 to 100): The distance (in mm) between the left 
end of the scale and the subject’s response. 
• A SANDE Total score (also ranging from 0 to 100): This is calculated as the 
square-root of the product of the Frequency and Severity scores. 
 
The Eye Dryness Score is derived from the Eye Dryness Visual Analog Scale. The Eye 
Dryness Score (ranging from 0 to 100) is the distance (in mm) between the left end of 
the scale and the subject’s response. 
 
Study staff should instruct subjects to record their response to each question by placing 
a vertical line (not an “X”) across the horizontal line of the visual analog scale. 
 
 
            TREATMENT PREFERENCE QUESTIONNAIRE (RESTASIS GROUP ONLY) 
 
Treatment Preference Questionnaire will be administered in subjects randomized to 
Restasis group at their post TearCare 12M visit. Questionnaire completion guidelines 
described in Section 21.11.1 should be followed to administer this questionnaire. 
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22 APPENDIX B – STATISTICAL ANALYSIS PLAN 
 
22.1 ANALYSIS POPULATIONS 
• Intent-to-Treat Population - The intent-to-treat (ITT) population includes all 
randomized subjects. The primary and secondary efficacy analyses will be 
performed on the ITT population. Subjects will be analyzed as randomized. 
• Due to the inclusion criteria revision in May of 2021 for Schirmer’s test 
parameters, the modified ITT (mITT) population includes all ITT except for 
those subjects that did meet the revised eligibility at the baseline visit. 
• Per Protocol Population – The per protocol (PP) population (subset of mITT)  
includes all subjects who have at least one follow-up visit and have no major 
protocol deviations, including specifically no use of dry-eye medications 
(Doxycycline, Xiidra). Subjects will be analyzed as treated. The primary and 
secondary efficacy analyses will be performed on the per protocol population. 
• Safety Population – The safety population will include all subjects on whom the 
TearCare or Restasis is attempted. The safety population will be analyzed for all 
safety assessments. Subjects will be analyzed as treated. 
 
22.2 STATISTICAL HYPOTHESES 
The primary study hypotheses regard the superiority of the TearCare procedure as 
compared to Restasis, for Tear Break-Up Time (TBUT) and total OSDI. The primary 
endpoints will be tested for TearCare in a hierarchical fixed sequence. The statistical 
hypotheses are stated in terms of one-sided hypotheses, although statistical testing will 
be two-sided. 
 
To demonstrate superiority of the TearCare procedure to the Restasis control for TBUT 
we will test the following hypotheses: 
 
H01: There is no difference between TearCare and Restasis in the mean change from 
baseline in TBUT at 6 Months. 
 
H11: The mean change from baseline in TBUT at 6 Months is greater with TearCare than 
with Restasis. 
 
If H01 is rejected, then the study will be considered a success and we will test the 
following hypotheses to further demonstrate superiority of the TearCare procedure to 
the Restasis control for total OSDI: 
 
H02: There is no difference between TearCare and Restasis in the mean change from 
baseline in total OSDI at 6 Months. 
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H12: The mean change from baseline in total OSDI at 6 Months is less with TearCare than 
with Restasis. 
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22.3 MULTIPLICITY CONSIDERATIONS 
To address the multiple endpoints in this study, the primary and secondary effectiveness 
endpoints have been ordered in a hierarchical structure. Using this fixed sequence 
testing strategy, the family-wise Type I error rate will be maintained at the 0.05 
significance level for testing the two primary effectiveness endpoints and the secondary 
effectiveness endpoints. 
 
22.4 SAMPLE SIZE CALCULATIONS 
 
    TEAR BREAKUP TIME 
 
A minimum of 310 subjects, approximately 155 in the TearCare group and 155 in the 
Restasis group, will be enrolled and randomized in the study. With an estimated 10% 
drop out rate at 6 months, a minimum of 139 subjects in each group are expected to be 
available for the primary efficacy analysis. Assuming a common standard deviation of 2 
seconds for the change from baseline in TBUT at 6 months, a sample size of 139 
subjects per group will have 98% power to detect a mean difference of 1 second 
between TearCare and Restasis at a two-sided significance level of 0.05. Assuming an 
overall 15% drop out rate, a minimum of 100 subjects are expected to be available at 24 
months in each group to achieve 90% statistical power. This calculation is 
conservatively based  upon prior TearCare clinical trial data, published data on Restasis, 
and the use of a two-sample t-test. 
 
    SAFETY 
 
With an estimated 10% drop out rate per 6 months, a minimum of 98 subjects are 
expected to be available for analysis at 24 months in the TearCare group. For an AE 
that occurs at a rate of 5% within the TearCare group, this sample size would yield a 
95% confidence interval with a margin of error of 4.4%; for an AE that occurs at rate 
10%, the margin of error would be 6.0% and for an AE that occurs at rate 20%, the 
margin of error would be 8.1%.  
 
    SAMPLE SIZE SUMMARY 
 
With a minimum of 155 in the TearCare group and 155 in the Restasis group, the power  
for the primary efficacy analysis of TBUT exceeds 90% and provides sufficient precision 
around the adverse event estimates through 24 months. 
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22.5 STATISTICAL ANALYSIS 
 
    GENERAL CONSIDERATIONS 
 
The quantitative variables will be summarized using number of subjects (n), mean, 
median, standard deviation, minimum and maximum. The qualitative variables will be 
summarized using counts and percentages. 
Summaries of all endpoints will be presented by treatment group and visit. Summaries 
will also be provided for demographics, baseline medical history, concurrent therapies, 
and subject disposition. 
For the purpose of summarization, medical history, concurrent therapies, and adverse 
events will be coded to MedDRA and WHO Drug dictionaries, as appropriate. 
The number of subjects by center will be summarized in a table. Centers with less than 5 
enrolled subjects will be combined into a single virtual center for the purpose of 
statistical analyses. 
 
    UNIT OF ANALYSIS 
 
Safety endpoints will be analyzed for both eyes. For subject-level effectiveness 
endpoints, the unit of analysis will be the subject. For effectiveness endpoints assessed 
on each eye individually, the unit of analysis will be the eye. 
 
    MISSING DATA 
 
No missing data imputation will be carried out beyond what is built-in to the mixed-
effects modeling approach to be used in the primary effectiveness analysis. 
No secondary effectiveness endpoints or safety endpoints will be imputed. 
 
    PRIMARY EFFECTIVENESS ENDPOINTS 
 
22.5.4.1 
TEAR BREAKUP TIME 
Change from baseline in TBUT will be calculated as visit – baseline such that a positive 
difference indicates an improvement of dry eye signs. In addition, treatment 
comparisons between TearCare and Restasis will be calculated as TearCare – Restasis, 
such that a positive result indicates a better score for TearCare. 
Linear mixed effects models will be used to compare the change from baseline in 
TBUT at the 6 Month visit between TearCare and Restasis. Linear mixed effects models 
will include fixed terms for baseline TBUT and study site, and a random subject effect 
to account for within-person correlation (correlation between right and left eyes). The 
primary analysis will use MCMC imputation to have a full accounting of the ITT 
population at the 6 Month visit. As supportive analyses, multiple imputation assuming 
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that data are missing not at random and analyses of observed data only will also be 
conducted. Two-sample t-tests and Wilcoxon rank sum tests will also be conducted as 
supportive analyses. 
 
22.5.4.2 
TOTAL OSDI 
Change from baseline in total OSDI score will be calculated as visit – baseline such that a 
negative difference indicates an improvement of dry eye symptoms. In addition, 
treatment comparisons between TearCare and Restasis will be calculated as TearCare – 
Restasis, such that a negative result indicates a better score for TearCare. 
Change from baseline in total OSDI at the 6 Month visit will be analyzed using ANCOVA 
models adjusting for baseline and site. Two-sample t-tests and Wilcoxon rank sum tests 
will also be conducted as supportive analyses. 
 
22.5.4.3 
POOLABILITY OF CENTERS 
Poolability of the effectiveness outcomes across centers will be evaluated by testing a 
treatment-by-center interaction in a separate model using observed data only. If the 
interaction is significant at α=0.15 a center effect will be included in the final model and 
results will be reported separately by center. 
 
    SECONDARY EFFECTIVENESS ENDPOINTS 
 
The secondary effectiveness endpoints include change from baseline at 6 Months for 
the following outcomes: 
 
1. 
Meibomian Gland Secretion Score 
2. 
Symptom Assessment iN Dry Eye (SANDE) scores 
3. 
Eye Dryness Score 
4. 
Number of Meibomian Glands Yielding any liquid 
5. 
Number of Meibomian Glands Yielding clear liquid 
6. 
Corneal staining scores 
7. 
Conjunctival staining scores 
8. 
Schirmer Score 
9. 
Ocular protection index (OPI): Interblink interval (IBI)/TBUT 
 
All testing of the secondary endpoints will be done using a two-sided alpha of 0.05. We 
will test the secondary endpoints in the order listed, stopping at the point where a test 
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fails to reject. This sequential procedure controls the overall type I error rate for the 
secondary endpoints. 
 
The secondary endpoints can be divided into two groups, those which are measured on 
a per-eye basis (Corneal Staining, Conjunctival Staining, Meibomian gland scores, 
Number of Meibomian Glands Yielding any liquid, Number of Meibomian Glands 
Yielding clear liquid, Blink Rate, Schirmer Score) and those measured on a per-subject 
basis (OSDI Score, SANDE Scores, Eye Dryness Score). 
 
Endpoints assessed at the eye level will be analyzed with linear mixed effects models 
adjusting for baseline and site, and with a random subject effect. Two-sample t-tests 
and Wilcoxon rank sum tests will be conducted on the average of the two eyes as 
supportive analyses. Endpoints assessed at the subject level will be analyzed using 
ANCOVA models adjusting for baseline and site, with two-sample t-tests and Wilcoxon 
rank sum tests as supportive analyses. No imputation will be performed for secondary 
efficacy variables. 
All secondary effectiveness variables collected will be summarized descriptively (n, 
mean, standard deviation, median, min and max) by treatment group and visit. 
 
22.6 SAFETY ANALYSIS 
All adverse events will be reported by treatment group and AE category. Any serious 
adverse events will be completely described in the study report. The primary safety 
endpoint will be summarized for each treatment group. 
 
We will compute the incidence of ocular events in two ways: first as a simple 
proportion, counting the number of subjects with any event (that is, counting the first 
event per person in either eye), then as an incidence rate, counting all events including 
repeated events per subject. 
  INTERIM ANALYSES 
No interim analyses are planned for this study.  
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23 APPENDIX D - DECLARATION OF HELSINKI 
 
I. 
PREAMBLE 
 
1. 
The World Medical Association (WMA) has developed the Declaration of 
Helsinki as a statement of ethical principles for medical research involving 
human subjects, including research on identifiable human material and data. 
 
The Declaration is intended to be read as a whole and each of its constituent 
paragraphs should be applied with consideration of all other relevant 
paragraphs. 
 
2. 
Consistent with the mandate of the WMA, the Declaration is addressed 
primarily to physicians. The WMA encourages others who are involved in 
medical research involving human subjects to adopt these principles. 
 
II. 
GENERAL PRINCIPLES 
 
1. 
The Declaration of Geneva of the WMA binds the physician with the words, 
“The health of my patient will be my first consideration,” and the International 
Code of Medical Ethics declares that, “A physician shall act in the patient's best 
interest when providing medical care.” 
 
2. 
It is the duty of the physician to promote and safeguard the health, well-being 
and rights of patients, including those who are involved in medical research. 
The physician's knowledge and conscience are dedicated to the fulfilment of 
this duty. 
 
3. 
Medical progress is based on research that ultimately must include studies 
involving human subjects. 
 
4. 
The primary purpose of medical research involving human subjects is to 
understand the causes, development and effects of diseases and improve 
preventive, diagnostic and therapeutic interventions (methods, procedures 
and treatments). Even the best proven interventions must be evaluated 
continually through research for their safety, effectiveness, efficiency, 
accessibility and quality. 
 
5. 
Medical research is subject to ethical standards that promote and ensure 
respect for all human subjects and protect their health and rights. 
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6. 
While the primary purpose of medical research is to generate new knowledge, 
this goal can never take precedence over the rights and interests of individual 
research subjects. 
 
7. 
It is the duty of physicians who are involved in medical research to protect the 
life, health, dignity, integrity, right to self-determination, privacy, and 
confidentiality of personal information of research subjects. The responsibility 
for the protection of research subjects must always rest with the physician or 
other health care professionals and never with the research subjects, even 
though they have given consent. 
 
8. 
Physicians must consider the ethical, legal and regulatory norms and standards 
for research involving human subjects in their own countries as well as 
applicable international norms and standards. No national or international 
ethical, legal or regulatory requirement should reduce or eliminate any of the 
protections for research subjects set forth in this Declaration. 
 
9. 
Medical research should be conducted in a manner that minimizes possible 
harm to the environment. 
 
10. Medical research involving human subjects must be conducted only by 
individuals with the appropriate ethics and scientific education, training and 
qualifications. Research on patients or healthy volunteers requires the 
supervision of a competent and appropriately qualified physician or other 
health care professional. 
 
11. Groups that are underrepresented in medical research should be provided 
appropriate access to participation in research. 
 
12. Physicians who combine medical research with medical care should involve 
their patients in research only to the extent that this is justified by its potential 
preventive, diagnostic or therapeutic value and if the physician has good 
reason to believe that participation in the research study will not adversely 
affect the health of the patients who serve as research subjects. 
 
13. Appropriate compensation and treatment for subjects who are harmed as a 
result of participating in research must be ensured. 
 
III. 
RISKS, BURDENS AND BENEFITS 
 
• 
In medical practice and in medical research, most interventions involve risks 
and burdens. 
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Medical research involving human subjects may only be conducted if the 
importance of the objective outweighs the risks and burdens to the research 
subjects. 
 
• 
All medical research involving human subjects must be preceded by careful 
assessment of predictable risks and burdens to the individuals and groups 
involved in the research in comparison with foreseeable benefits to them and 
to other individuals or groups affected by the condition under investigation. 
 
Measures to minimize the risks must be implemented. The risks must be 
continuously monitored, assessed and documented by the researcher. 
 
• 
Physicians may not be involved in a research study involving human subjects 
unless they are confident that the risks have been adequately assessed and can 
be satisfactorily managed. 
 
When the risks are found to outweigh the potential benefits or when there is 
conclusive proof of definitive outcomes, physicians must assess whether to 
continue, modify or immediately stop the study. 
 
IV. 
VULNERABLE GROUPS AND INDIVIDUALS 
 
• 
Some groups and individuals are particularly vulnerable and may have an 
increased likelihood of being wronged or of incurring additional harm. 
 
All vulnerable groups and individuals should receive specifically considered 
protection. 
 
• 
Medical research with a vulnerable group is only justified if the research is 
responsive to the health needs or priorities of this group and the research 
cannot be carried out in a non-vulnerable group. In addition, this group should 
stand to benefit from the knowledge, practices or interventions that result 
from the research. 
 
V. 
SCIENTIFIC REQUIREMENTS AND RESEARCH PROTOCOLS 
 
• 
Medical research involving human subjects must conform to generally 
accepted scientific principles, be based on a thorough knowledge of the 
scientific literature, other relevant sources of information, and adequate 
laboratory and, as appropriate, animal experimentation. The welfare of 
animals used for research must be respected. 
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• 
The design and performance of each research study involving human subjects 
must be clearly described and justified in a research protocol. 
 
The protocol should contain a statement of the ethical considerations involved 
and should indicate how the principles in this Declaration have been 
addressed. The protocol should include information regarding funding, 
sponsors, institutional affiliations, potential conflicts of interest, incentives for 
subjects and information regarding provisions for treating and/or 
compensating subjects who are harmed as a consequence of participation in 
the research study. 
 
In clinical trials, the protocol must also describe appropriate arrangements for 
post-trial provisions. 
 
VI. 
RESEARCH ETHICS COMMITTEES 
 
• 
The research protocol must be submitted for consideration, comment, 
guidance and approval to the concerned research ethics committee before the 
study begins. This committee must be transparent in its functioning, must be 
independent of the researcher, the sponsor and any other undue influence and 
must be duly qualified. It must take into consideration the laws and regulations 
of the country or countries in which the research is to be performed as well as 
applicable international norms and standards but these must not be allowed to 
reduce or eliminate any of the protections for research subjects set forth in 
this Declaration. 
 
The committee must have the right to monitor ongoing studies. The researcher 
must provide monitoring information to the committee, especially information 
about any serious adverse events. No amendment to the protocol may be 
made without consideration and approval by the committee. After the end of 
the study, the researchers must submit a final report to the committee 
containing a summary of the study’s findings and conclusions. 
 
VII. PRIVACY AND CONFIDENTIALITY 
 
• 
Every precaution must be taken to protect the privacy of research subjects and 
the confidentiality of their personal information. 
 
 
VIII. INFORMED CONSENT 
 
• 
Participation by individuals capable of giving informed consent as subjects in 
medical research must be voluntary. Although it may be appropriate to consult 
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family members or community leaders, no individual capable of giving 
informed consent may be enrolled in a research study unless he or she freely 
agrees. 
 
• 
In medical research involving human subjects capable of giving informed 
consent, each potential subject must be adequately informed of the aims, 
methods, sources of funding, any possible conflicts of interest, institutional 
affiliations of the researcher, the anticipated benefits and potential risks of the 
study and the discomfort it may entail, post-study provisions and any other 
relevant aspects of the study. The potential subject must be informed of the 
right to refuse to participate in the study or to withdraw consent to participate 
at any time without reprisal. Special attention should be given to the specific 
information needs of individual potential subjects as well as to the methods 
used to deliver the information. 
 
After ensuring that the potential subject has understood the information, the 
physician or another appropriately qualified individual must then seek the 
potential subject’s freely-given informed consent, preferably in writing. If the 
consent cannot be expressed in writing, the non-written consent must be 
formally documented and witnessed. 
 
All medical research subjects should be given the option of being informed 
about the general outcome and results of the study. 
 
• 
When seeking informed consent for participation in a research study the 
physician must be particularly cautious if the potential subject is in a 
dependent relationship with the physician or may consent under duress. In 
such situations the informed consent must be sought by an appropriately 
qualified individual who is completely independent of this relationship. 
 
• 
For a potential research subject who is incapable of giving informed consent, 
the physician must seek informed consent from the legally authorized 
representative. These individuals must not be included in a research study that 
has no likelihood of benefit for them unless it is intended to promote the 
health of the group represented by the potential subject, the research cannot 
instead be performed with persons capable of providing informed consent, and 
the research entails only minimal risk and minimal burden. 
 
• 
When a potential research subject who is deemed incapable of giving informed 
consent is able to give assent to decisions about participation in research, the 
physician must seek that assent in addition to the consent of the legally 
authorized representative. The potential subject’s dissent should be respected. 
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• 
Research involving subjects who are physically or mentally incapable of giving 
consent, for example, unconscious patients, may be done only if the physical or 
mental condition that prevents giving informed consent is a necessary 
characteristic of the research group. In such circumstances the physician must 
seek informed consent from the legally authorized representative. If no such 
representative is available and if the research cannot be delayed, the study 
may proceed without informed consent provided that the specific reasons for 
involving subjects with a condition that renders them unable to give informed 
consent have been stated in the research protocol and the study has been 
approved by a research ethics committee. Consent to remain in the research 
must be obtained as soon as possible from the subject or a legally authorized 
representative. 
 
• 
The physician must fully inform the patient which aspects of their care are 
related to the research. The refusal of a patient to participate in a study or the 
patient’s decision to withdraw from the study must never adversely affect the 
patient-physician relationship. 
 
• 
For medical research using identifiable human material or data, such as 
research on material or data contained in biobanks or similar repositories, 
physicians must seek informed consent for its collection, storage and/or reuse. 
There may be exceptional situations where consent would be impossible or 
impracticable to obtain for such research. In such situations the research may 
be done only after consideration and approval of a research ethics committee. 
 
IX. 
USE OF PLACEBO 
 
• 
The benefits, risks, burdens and effectiveness of a new intervention must be 
tested against those of the best proven intervention(s), except in the following 
circumstances: 
 
Where no proven intervention exists, the use of placebo, or no intervention, is 
acceptable; or 
 
Where for compelling and scientifically sound methodological reasons the use 
of any intervention less effective than the best proven one, the use of placebo, 
or no intervention is necessary to determine the efficacy or safety of an 
intervention 
 
and the patients who receive any intervention less effective than the best 
proven one, placebo, or no intervention will not be subject to additional risks 
of serious or irreversible harm as a result of not receiving the best proven 
intervention. 
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Extreme care must be taken to avoid abuse of this option. 
 
X. 
POST-TRIAL PROVISIONS 
 
• 
In advance of a clinical trial, sponsors, researchers and host country 
governments should make provisions for post-trial access for all participants 
who still need an intervention identified as beneficial in the trial. This 
information must also be disclosed to participants during the informed consent 
process. 
 
XI. 
RESEARCH REGISTRATION AND PUBLICATION AND DISSEMINATION OF RESULTS 
 
• 
Every research study involving human subjects must be registered in a publicly 
accessible database before recruitment of the first subject. 
 
• 
Researchers, authors, sponsors, editors, and publishers all have ethical 
obligations with regard to the publication and dissemination of the results of 
research. Researchers have a duty to make publicly available the results of 
their research on human subjects and are accountable for the completeness 
and accuracy of their reports. All parties should adhere to accepted guidelines 
for ethical reporting. Negative and inconclusive as well as positive results must 
be published or otherwise made publicly available. Sources of funding, 
institutional affiliations and conflicts of interest must be declared in the 
publication. Reports of research not in accordance with the principles of this 
Declaration should not be accepted for publication. 
 
XII. UNPROVEN INTERVENTIONS IN CLINICAL PRACTICE 
 
In the treatment of an individual patient, where proven interventions do not exist 
or other known interventions have been ineffective, the physician, after seeking 
expert advice, with informed consent from the patient or a legally authorized 
representative, may use an unproven intervention if in the physician's judgment it 
offers hope of saving life, re-establishing health, or alleviating suffering. This 
intervention should subsequently be made the object of research, designed to 
evaluate its safety and efficacy. In all cases, new information must be recorded 
and, where appropriate, made publicly available. 
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