Randomized, Controlled Trial to Evaluate the Safety and Effectiveness of the TearCare® System in the Treatment of the Signs and Symptoms of Dry Eye Disease
Phase: NA
Conditions: Dry Eye Syndromes
Sponsor: Sight Sciences, Inc.

C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 of 8 4  
 
 
 
R A N D O MI Z E D , C O N T R OLL E D  T RI AL  T O E V AL U A T E  T H E S A F E T Y A N D 
E F F E C TI V E N E S S O F T H E  T E A R C A R E ®  S Y S T E M  I N T H E T R E A T M E N T O F T H E 
S I G N S A N D S Y M P T O M S O F D R Y E Y E D I S E A S E ( OL Y M PI A) 
 
P R O T O C OL I D #:  
 
0 5 4 7 4  
C U R R E N T R E VI SI O N : 
 
 
R E VI SI O N D A T E : 
 
M arc h 1 6 , 2 0 1 8 
S P O N S O R : 
Si g ht Sci e nc es, I nc.  
3 0 0 0 S a n d Hill R o a d  
B uil di n g 3, S uit e 1 0 5  
M e nl o P ar k, C A  9 4 0 2 5  
8 7 7 -2 6 6 -1 1 4 4  
 
 
A gr e e m e nt of Pri nci p al I n v esti g at or  
I,   
  
  
  
  
 
  a gr e e t o c o n d uct t his tri al i n acc or d a nc e 
wit h t his cli nic al pr ot oc ol a n d a n y a m e n d m e nts.  
  
  
  
  
  
  
  
  
  
  
 
Si g n at ur e   
  
  
  
  
 
D at e  
 
  
  
  
  
  
  
  
  
  
  
 
C e nt er N a m e     
  
  
  
 
Cit y, St at e, C o u ntr y  
 
T his pr ot oc ol c o nt ai ns c o nfi d e nti al i nf or m ati o n f or us e b y t h e I n v esti g at ors a n d t h eir 
d esi g n at e d r e pr es e nt ati v es p artici p ati n g i n t his cli nic al i n v esti g ati o n.  It m ust b e h el d 
c o nfi d e nti al a n d m ai nt ai n e d i n a s ec ur e l oc ati o n. 
D o n ot c o p y or distri b ut e wit h o ut writt e n p er missi o n.  
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 of 8 4  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 3 of 8 4  
T A BL E O F C O N T E N T S  
1  
P R O T O C OL S Y N O P SI S  ...................................................................................................................... 6 
2  
S T U D Y O BJ E C TI V E  ......................................................................................................................... 1 1  
3  
B A C K G R O U N D A N D J U S TI FI C A TI O N F O R T H E S T U D Y  .................................................................... 1 1  
4  
D E S C RI P TI O N O F D E VI C E  ............................................................................................................... 1 5  
4. 1  
C U R R E N T IN DI C A TI O N F O R U S E .............................................................................................................. 1 5  
4. 2  
P R O P O S E D IN DI C A TI O N F O R U S E ............................................................................................................ 1 5  
4. 3  
D E VI C E D E S C RI P TI O N  ........................................................................................................................... 1 5  
4. 4  
IN S T R U C TI O N S F O R U S E ........................................................................................................................ 1 8  
4. 5  
T R AI NI N G  .......................................................................................................................................... 1 8  
5  
P RI O R I N V E S TI G A TI O N S  ................................................................................................................ 1 9  
5. 1  
P R E CLI NI C AL T E S TI N G ........................................................................................................................... 1 9  
5. 2  
P R E VI O U S C LI NI C AL E X P E RI E N C E  ............................................................................................................ 1 9  
 
Cli nic al St u d y of t h e Pr ot oty p e T e ar C ar e S yst e m ( 2 0 1 3)  ...................................................... 2 0  
 
Cli nic al St u d y of t h e T e ar C ar e S yst e m ( 2 0 1 7)  ....................................................................... 2 1  
 
S u m m ary  ............................................................................................................................... 2 2  
6  
S T U D Y E N D P OI N T S ........................................................................................................................ 2 3  
6. 1  
E F F E C TI V E N E S S E N D P OI N T S  ................................................................................................................... 2 3  
6. 2  
S A F E T Y E N D P OI N TS .............................................................................................................................. 2 4  
7  
S T U D Y D E SI G N  .............................................................................................................................. 2 4  
7. 1  
S T U D Y D E VI C E A N D C O N T R OL A R M  ........................................................................................................ 2 4  
7. 2  
C O N T R OL G R O U P C R O S S O V E R A T 6  M O N T H S  ........................................................................................... 2 5  
7. 3  
S T U D Y C E N T E R S .................................................................................................................................. 2 5  
8  
S T U D Y S EL E C TI O N C RI T E RI A  .......................................................................................................... 2 5  
8. 1  
IN CL U SI O N C RI T E RI A  ............................................................................................................................ 2 5  
8. 2  
E X CL USI O N C RI T E RI A  ............................................................................................................................ 2 6  
9  
S T U D Y P R O C E D U R E S  ..................................................................................................................... 2 7  
9. 1  
S T U D Y S C H E D UL E  ................................................................................................................................ 2 7  
9. 2  
N U M B E R O F S U BJ E C TS , D U R A TI O N O F F OLL O W -U P A N D S T U D Y D U R A TI O N  .................................................... 2 9  
9. 3  
M A T E RI AL A N D E Q UI P M E N T  .................................................................................................................. 2 9  
9. 4  
IN F O R M E D C O N S E N T A N D P OI N T O F E N R OLL M E N T  .................................................................................... 3 0  
9. 5  
B A S ELI N E V ISI T ................................................................................................................................... 3 0  
 
Sc h e d uli n g t h e B as eli n e Visit  ................................................................................................ 3 0  
 
B as eli n e Ex a ms a n d Q u esti o n n air es  ..................................................................................... 3 1  
 
R a n d o miz ati o n  ...................................................................................................................... 3 1  
 
Tr e at m e nt f or T e ar C ar e Gr o u p  ............................................................................................. 3 2  
 
Tr e at m e nt f or W ar m C o m pr ess a n d Li d m ass a g e Gr o u p  ..................................................... 3 3  
9. 6  
F OLL O W - UP V I SI T S .............................................................................................................................. 3 4  
 
F oll o w -U p Visit R o uti n e Pr oc e d ur es  ...................................................................................... 3 4  
 
6 M o nt h F oll o w -u p Visit:  R e -Tr e at m e nt/ Cr oss ov er  ............................................................. 3 5  
9. 7  
M A S K E D A SS ES S O R ............................................................................................................................. 3 6  
9. 8  
M A N A G E M E N T O F D R Y E Y E S Y M P T O M S D U RI N G F OLL O W - UP  ..................................................................... 3 6  
9. 9  
W I T H D R A W AL A N D D I S C O N TI N U A TI O N .................................................................................................... 3 7  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 4 of 8 4  
9. 1 0  
S U BJ E C T S L O S T T O F OLL O W -U P  ......................................................................................................... 3 7  
1 0  
A D V E R S E E V E N T S ( A E S)  ................................................................................................................. 3 7  
1 0. 1  
D E FI NI TI O N S O F A E,  S A E,  S A D E,  U S A D E  .......................................................................................... 3 8  
1 0. 2  
L I S T O F A N TI CI P A T E D P O T E N TI AL A D V E R S E E V E N T S  ............................................................................... 3 8  
1 0. 3  
R E P O R TI N G A D V E R S E E V E N TS A N D U N A N TI CI P A T E D A D V E RS E D E VI C E E F F E C TS ........................................... 3 9  
1 1  
RI S K -B E N E FI T A N AL Y SI S  ................................................................................................................ 3 9  
1 1. 1  
A N TI CI P A T E D CLI NI C AL B E N E FI TS  ........................................................................................................ 3 9  
1 1. 2  
A N TI CI P A T E D A D V E R S E D E VI C E E F F E C T S  ............................................................................................... 4 0  
1 1. 3  
R E SI D U AL RIS K S A S S O CI A T E D WI T H T H E T E S T D E VI C E , A S I D E N TIFI E D I N T H E RI S K A N AL Y SIS R E P O R T  .................. 4 0  
1 1. 4  
R I S K S AS S O CI A T E D WI T H P A R TI CI P A TI O N I N T H E CLI NI C AL I N V E S TI G A TI O N ................................................... 4 0  
1 1. 5  
P O S SI BL E I N T E R A C TI O NS WI T H C O N C O MI T A N T M E DI C AL T R E A T M E N TS  ....................................................... 4 0  
1 1. 6  
S T E PS T H A T WILL B E T A K E N T O C O N T R OL O R MI TI G A T E T H E RI S KS  ............................................................. 4 0  
1 2  
S T A TI S TI C AL C O N SI D E R A TI O N S  ..................................................................................................... 4 2  
1 2. 1  
E V AL U A BILI T Y  ................................................................................................................................ 4 2  
1 2. 2  
A N AL Y SIS P O P UL A TI O N S  .................................................................................................................. 4 2  
1 2. 3  
S U BJ E C T A C C O U N T A BILI T Y  ................................................................................................................ 4 2  
1 2. 4  
D E M O G R A P HI C S A N D B A S ELI N E C H A R A C T E RI S TI CS  ................................................................................ 4 2  
1 2. 5  
E N D P OI N TS A N D A N AL Y SIS M E T H O D S  ................................................................................................ 4 2  
 
D escri ptiv e A n alys es ......................................................................................................... 4 3  
 
Pri m ary Eff ectiv e n ess E n d p oi nt  ........................................................................................ 4 3  
 
P o ol a bility  ........................................................................................................................ 4 3  
 
Missi n g D at a  .................................................................................................................... 4 3  
 
S ec o n d ary Eff ectiv e n ess E n d p oi nts  .................................................................................. 4 3  
 
E v al u ati o n of Tr e at m e nt D ur ati o n  ................................................................................... 4 4  
 
A d diti o n al Ex pl or at ory A n alys es  ...................................................................................... 4 5  
 
M o d eli n g of Ext e n d e d F oll o w -u p R es ults  ......................................................................... 4 5  
 
S af ety A n alysis  ................................................................................................................. 4 6  
1 2. 6  
H Y P O T H ES ES ................................................................................................................................. 4 6  
1 2. 7  
S A M PL E S I Z E C AL C UL A TI O N  .............................................................................................................. 4 7  
1 2. 8  
IN T E RI M A N AL YSI S  .......................................................................................................................... 4 7  
1 2. 9  
D E VI A TI O N F R O M T H E S T A TI S TI C AL P L A N ............................................................................................ 4 7  
1 3  
M O NI T O RI N G P R O C E D U R E S  ......................................................................................................... 4 7  
1 4  
D A T A A N D Q U ALI T Y M A N A G E M E N T  ............................................................................................. 4 8  
1 4. 1  
D A T A B AS E M A N A G E M E N T  ............................................................................................................... 4 8  
1 4. 2  
S U BJ E C T ID E N TI FI C A TI O N  ................................................................................................................. 4 9  
1 4. 3  
S U BJ E C T A C C O U N T A BILI T Y  ................................................................................................................ 4 9  
1 4. 4  
C O N FI D E N TI ALI T Y  ........................................................................................................................... 4 9  
1 4. 5  
S O U R C E D A T A A N D C A S E R E P O R T F O R M S  ........................................................................................... 4 9  
1 4. 6  
R E T E N TI O N P E RI O D......................................................................................................................... 5 0  
1 5  
P R O T O C OL M O DI FI C A TI O N S A N D D E VI A TI O N S  ............................................................................. 5 0  
1 6  
D E VI C E F AIL U R E S A N D M AL F U N C TI O N S  ........................................................................................ 5 0  
1 7  
E T HI C AL C O N SI D E R A TI O N S  ........................................................................................................... 5 0  
1 7. 1  
D E CL A R A TI O N O F H ELSI N KI ............................................................................................................... 5 0  
1 7. 2  
IN S TI T U TI O N AL R E VI E W B O A R D S (I R B) ............................................................................................... 5 1  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 5 of 8 4  
1 7. 3  
IN F O R M E D C O N S E N T F O R M (I C F) ..................................................................................................... 5 1  
1 7. 4  
P U BLI C L I S TI N G O F S T U D Y ................................................................................................................ 5 1  
1 8  
S T U D Y A D MI NI S T R A TI O N  ............................................................................................................. 5 1  
1 8. 1  
D E VI C E A C C O U N T A BILI T Y  ................................................................................................................. 5 1  
1 8. 2  
E A RL Y T E R MI N A TI O N O R S U S P E NSI O N O F A N IN V E S TI G A TI O N  .................................................................. 5 2  
1 8. 3  
IN V E S TI G A T O R R E S P O N SI BILI TI E S  ....................................................................................................... 5 2  
 
G e n er al R es p o nsi biliti es of I nv esti g at ors  ......................................................................... 5 2  
 
S p ecific R es p o nsi biliti es of I nv esti g at ors  .......................................................................... 5 3  
 
I nv esti g at or R ec or ds ........................................................................................................ 5 3  
 
I nv esti g at or R e p orts ......................................................................................................... 5 3  
1 8. 4  
IN V E S TI G A T O R A G R E E M E N T  .............................................................................................................. 5 4  
1 9  
P U BLI C A TI O N P OLI C Y  .................................................................................................................... 5 4  
2 0  
BI BLI O G R A P H Y  .............................................................................................................................. 5 6  
2 1  
A P P E N DI X A – M E T H O D S F O R E X A M S, T E S T S A N D Q U E S TI O N N AI R E S  ........................................... 5 9  
2 1. 1  
M E DI C A TI O N S ................................................................................................................................ 5 9  
2 1. 2  
M A NI F ES T R EF R A C TI O N A N D V I S U AL A C UI T Y  ....................................................................................... 5 9  
2 1. 3  
S LI T L A M P E X A M  ............................................................................................................................ 6 1  
2 1. 4  
T E A R B R E A K U P T I M E ( T B U T) ........................................................................................................... 6 1  
2 1. 5  
C O R N E AL S T AI NI N G ........................................................................................................................ 6 2  
2 1. 6  
C O NJ U N C TI V AL S T AI NI N G ................................................................................................................. 6 2  
2 1. 7  
S C HI R M E R 1  T E S T ........................................................................................................................... 6 4  
2 1. 8  
M EI B O MI A N G L A N D S E C R E TI O N S C O RI N G  ........................................................................................... 6 4  
2 1. 9  
IN T R A O C UL A R P R E S S U R E  .................................................................................................................. 6 5  
2 1. 1 0  
Q U E S TI O N N AI R ES  ........................................................................................................................... 6 5  
 
G e n er al I nstr ucti o ns f or Q u esti o n n air es  .......................................................................... 6 5  
 
OS DI Q u esti o n n air e  .......................................................................................................... 6 6  
 
S A N D E Q u esti o n n air e a n d E y e Dry n ess V AS  .................................................................... 6 6  
 
Disc o mf ort/ P ai n Q u esti o n n air e  ....................................................................................... 6 6  
2 2  
A P P E N DI X B – I N S T R U C TI O N S F O R W A R M C O M P R E S S A N D LI D M A S S A G E ................................... 6 8  
2 3  
A P P E N DI X C – S T A TI S TI C AL A N AL Y SI S PL A N  .................................................................................. 6 9  
2 3. 1  
E N D P OI N TS A N D A N AL Y SIS M E T H O D S  ................................................................................................ 6 9  
 
Pri m ary Eff ectiv e n ess E n d p oi nt  ........................................................................................ 6 9  
 
P o ol a bility  ........................................................................................................................ 7 0  
 
Missi n g D at a  .................................................................................................................... 7 0  
 
S ec o n d ary Eff ectiv e n ess E n d p oi nts  .................................................................................. 7 1  
 
E v al u ati o n of Tr e at m e nt D ur ati o n  ................................................................................... 7 1  
 
M o d eli n g of Ext e n d e d F oll o w -u p R es ults  ......................................................................... 7 1  
2 3. 2  
S A M PL E S I Z E C AL C UL A TI O N S  ............................................................................................................. 7 2  
 
T e ar Br e a k u p Ti m e  ........................................................................................................... 7 2  
 
OS DI  ................................................................................................................................. 7 4  
 
S af ety  ............................................................................................................................... 7 5  
 
S a m pl e Siz e S u m m ary  ...................................................................................................... 7 6  
2 4  
A P P E N DI X D - D E CL A R A TI O N O F H EL SI N KI  .................................................................................... 7 7  
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 7 of 8 4  
I ncl usi o n Crit eri a 
1.  At l e ast 2 2  y e ars of a g e  
2.  R e p orts dr y e y e s y m pt o ms 
 
3.  R e p orts h a vi n g t o us e artifici al t e ars or l u bric a nts 
r e g ul arl y 
 
 
4.  O S DI Sc or e 
  
5.  T B U T 
  
6.  M ei b o mi a n gl a n d o bstr ucti o n i n b ot h e y es 
 
.  
7.  B est c orr ect e d vis u al ac uit y of 2 0/ 1 0 0 or b ett er i n b ot h 
e y es.  
8.  Willi n g a n d a bl e t o c o m pl y wit h t h e st u d y  pr oc e d ur es 
a n d f oll o w -u p  
9.  Willi n g a n d a bl e t o pr o vi d e i nf or m e d c o ns e nt 
1 0.  E n glis h -s p e a ki n g 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
Pr ot oc ol 0 5 4 7 4 R e v B 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 8 of 8 4  
E xcl usi o n Crit eri a  
1.  A n y acti v e , cli nic all y si g nific a nt oc ul ar or p eri -oc ul ar 
i nf ecti o n or i nfl a m m ati o n 
2.  R ec urr e nt cli nic all y si g nific a nt e y e i nfl a m m ati o n , 
ot h er t h a n dr y e y e,  
 
 
3.  Hist or y of e y eli d, c o nj u ncti v a or c or n e al s ur g er y 
(i ncl u di n g r efr acti v e s ur g er y) wit hi n t h e p ast y e ar .  I n 
a d diti o n, s u bj ects wit h a n y hist or y of t h e f oll o wi n g 
ar e excl u d e d:  c h al azio n s ur g er y, s ur g er y o n t h e t ars al 
c o nj u ncti v a, r a di al k er at ot o m y ( R K), c o m plic at e d 
bl e p h ar o pl ast y, li d r ec o nstr ucti o n, or si g nific a nt 
c o m plic ati o ns p ost-r efr acti v e s ur g er y. 
4.  A n y o ffic e-b as e d dr y e y e tr e at m e nt  ( e. g. I PL, t h er m al 
p uls ati o n  [Li pifl o w], etc.)
 
. 
5.  M ei b o mi a n gl a n d ex pr essi o n wit hi n 6 m o nt hs pri or t o 
e nr oll m e nt . 
 
. 
6.  I n t h e cli nic al j u d g e m e nt of t h e i n v esti g at or, 
m ei b o mi a n gl a n ds h a v e si g nific a nt c a p pi n g, atr o p h y, 
or ar e u n a bl e t o b e di git all y ex pr ess e d.   
7.  C o nt act l e ns us e
 
8.  
 
 
 
9.  Hist or y of Oc ul ar H er p es Si m pl ex or Oc ul ar H er p e s 
Z ost er  
1 0.  Cli nic all y si g nific a nt o c ul ar s urf ac e a b n or m aliti es t h at 
m a y aff ect t e ar fil m distri b uti o n or tr e at m e nt  ( e. g. 
pt er y gi u m, a nt eri or m e m br a n e d ystr o p h y, etc.)  
1 1.  Cli nic all y si g nific a nt e y eli d a b n or m aliti es  i n eit h er e y e 
( e. g. e ntr o pi o n/ ectr o pi o n, bl e p h ar os p as m, 
a p o n e ur otic pt osis, l a g o p ht h al m os, n otc hi n g of li d 
m ar gi n, distic hi asis, tric hi asis).  
1 2.  Cli nic all y si g nific a nt a nt eri or bl e p h aritis.  I n a d diti o n, 
coll ar ett es or fl a k es of m or e t h a n o n e q u art er of t h e 
e y eli d ar e excl u d e d.  
1 3.  Cli nic all y si g nific a nt d er m at ol o gic or c ut a n e o us 
dis e as e of t h e e y eli d or p eri oc ul ar ar e a.  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 9 of 8 4  
1 4.  Oc ul ar tr a u m a 
. 
1 5.  A n y acti v e, cli nic all y si g nific a nt  all er gic, v er n al, or 
gi a nt p a pill ar y c o nj u ncti vitis.  
1 6.  K n o w n hist or y of d i mi nis h e d or a b n or m al f aci al, 
p eri oc ul ar, oc ul ar or c or n e al s e ns ati o n  
1 7.  C or n e al  s urf ac e a b n or m aliti es s uc h as c or n e al 
e pit h eli al d ef ects  ( ot h er t h a n p u nct at e st ai ni n g), 
ulc ers, c or n e al e pit h eli al d ystr o p hi es , k er at oc o n us, 
a n d ect atic dis e as e of t h e c or n e a  
1 8.  P u nct al occl usi o n or p u nct al pl u g pl ac e m e nt  
 
   
1 9.  S yst e mic dis e as es r es ulti n g i n dr y e y e ( e. g. 
a ut oi m m u n e dis e as es s uc h as Sj o gr e n’s s y n dr o m e , 
r h e u m at oi d art hritis, l u p us, Gr a v es’ dis e as e, 
s arc oi d osis, etc.) 
2 0.  All er gi es t o silic o n e tiss u e a d h esi v es  
2 1.  
 
 
 
2 2.  Us e of a nti hist a mi n es ( or al or t o pic al) 
 
 
2 3.  S u bj ect is c urr e ntl y o n a s yst e mic m e dic ati o n(s) ( ot h er 
t h a n a nti-hist a mi n es) t h at is k n o w n t o c a us e oc ul ar 
dr y n ess 1 a n d w h os e d os e of t his m e dic ati o n(s) h as 
n ot b e e n st a bl e 
  
 
 
2 4.  S u bj ect h as t a k e n or is c urr e ntl y t a ki n g Acc ut a n e.  
2 5.  S u bj ect r e q uir es c hr o nic us e (i. e. f or a n y p orti o n of 
t h e st u d y) of t o pic al o p ht h al mic a nti bi otics, a nti -
gl a uc o m a m e dic ati o ns, st er oi ds, n o n -st er oi d al a nti-
i nfl a m m at or y m e dic ati o ns or w h o h as b e e n o n a n y of 
t h es e m e dic ati o ns 
. 
2 6.  S u bj ect is c urr e ntl y usi n g R eti n A or L atiss e.  
2 7.  P artici p ati o n i n a n ot h er o p ht h al mic cli nic al tri al 
wit hi n 3 0 d a ys  pri or t o e nr oll m e nt. 
 
 
   
2 8.  C o -existi n g c o n diti o ns t h at c o ul d i nt erf er e wit h t h e 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
Pr ot oc ol 0 5 4 7 4 R e v B 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 0  of 8 4  
ass ess m e nt of s af et y or eff ecti v e n ess of tr e at m e nt 
( e. g. m ac ul ar dis e as e, pr e g n a ncy, n ursi n g, etc.). 
 
N u m b er of S u bj ects  
E nr oll e d a n d R a n d o miz e d  
2 0 0  
R a n d o miz ati o n  
1: 1  
N u m b er of C e nt ers  
U p t o 1 5  
St u d y D ur ati o n f or E ac h 
S u bj ect  
1 2  m o nt hs  
T ot al St u d y D ur ati o n  
A p pr oxi m at el y 1 8 m o nt hs  
Sc h e d ul e of Visits  
B as eli n e, D a y 1, W e e k 1, 1 M o nt h, 3 M o nt h, 6 M o nt h, 7 
m o nt h, 9 M o nt h, 1 2 M o nt h   
Tr e at m e nts  
T e ar C ar e Gr o u p:  T e ar C ar e pr oc e d ur e at B as eli n e a n d r e -
tr e at m e nt at 6 m o nt hs 
W ar m C o m pr ess & Li d M ass a g e:  
 
  
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 1  of 8 4  
2  S T U D Y O BJ E C TI V E  
T h e o bj ecti v e of t his st u dy is t o d e m o nstr at e  t h e s af et y a n d eff ecti v e n ess of a si n gl e 
T e ar C ar e ® tr e at m e nt  c o m p ar e d t o a d ail y r e gi m e n of c o m bi n e d w ar m c o m pr ess t h er a p y 
a n d li d m ass a g e  t o tr e at t h e si g ns a n d s y m pt o ms of dr y e y e dis e as e i n a d ult p ati e nts. 
 
T his st u d y is  b ei n g c o n d uct e d t o c oll ect d at a t o s u p p ort a m o dific ati o n t o t h e T e ar C ar e 
i n dic ati o n f or us e t o r e a d as f oll o ws, “T h e T e ar C ar e ® S yst e m is i n dic at e d f or t h e 
tr e at m e nt of t h e si g ns a n d s y m pt o ms of d r y e y e d is e as e ( D E D).” 
3  B A C K G R O U N D A N D JU S TI FI C A TI O N F O R T H E S T U D Y  
Dr y E y e Dis e as e ( D E D)  is a c hr o nic e y e c o n diti o n t h at c a n c a us e a n arr a y of s y m pt o ms i n 
p ati e nts, r a n gi n g fr o m p eri o dic oc ul ar disc o mf ort t o s e v er e c or n e al i nfl a m m ati o n, 
sc arri n g, a n d visi o n l oss. 2 ,3  A p pr oxi m at el y 1/ 3 of p ati e nts visiti n g t h eir e y e d oct or s uff er 
fr o m dr y e y e.  T h e pr e v al e nc e of dr y e y e dis e as e i ncr e as es wit h a g e, es p eci all y i n 
p ost m e n o p a us al w o m e n.  It is esti m at e d t h at dr y e y e dis e as e aff ects m or e t h a n 7 
milli o n A m eric a ns ol d er 4 0 y e ars of a g e 2, a n d a p pr oxi m at el y 1 milli o n t o 4 milli o n 
A m eric a ns b et w e e n 6 5 t o 8 4 y e ars of a g e. 4   
 
E ac h y e ar i n t h e U. S., billi o ns of d oll ars ar e s p e nt o n t o pic al l u bric a nts, m e dic ati o ns, t e ar 
d uct occl usi o ns, a n d ot h er tr e at m e nts t o c o ntr ol t h e c hr o nic c o n diti o n  of dr y e y e 
dis e as e .  Y u et al r e p ort e d t h at t h e a v er a g e a n n u al c ost of m a n a gi n g a p ati e nt wit h dr y 
e y e w as $ 7 8 3 (r a n g e $ 7 5 7 – 8 0 9) fr o m t h e p a y ers’ p ers p ecti v e. 5  W h e n a dj ust e d t o t h e 
pr e v al e nc e of D E D n ati o n wi d e, t h e o v er all b ur d e n of D E D o n t h e U S h e alt hc ar e s yst e m 
w as esti m at e d t o b e $ 3. 8 4 billi o n.  M or e o v er, t h er e is a gr e at c ost t o s oci et y i n t er ms of 
d ecr e as e d pr o d ucti vit y d u e t o t h e s y m pt o ms of dr y e y e.   Y u, et al esti m at e d t h e s oci et al 
c ost t o b e $ 1 1, 3 0 2 p er p ati e nt a n d $ 5 5. 4 billi o n t o t h e U S s oci et y o v er all. 5  Ess e nti all y, 
n ot o nl y d o dr y e y e p ati e nts dir ectl y s uff er, b ut t h er e is als o a b ur d e n t o h e alt hc ar e, 
e m pl o y ers, a n d s oci et y.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 2  of 8 4  
Hist oric all y, dr y e y e dis e as e h as b e e n c at e g oriz e d i nt o o n e of t w o f or ms, a q u e o us t e ar 
d efici e ncy a n d e v a p or ativ e t e ar d efici e ncy.  T h e c urr e nt u n d erst a n di n g is t h at 
e v a p or ati v e dr y e y e is m or e c o m m o n t h a n a q u e o us d efici e nt dr y e y e. 6  H o w e v er, 
b ec a us e t h e s y m pt o ms of a q u e o us -d efici e nt dr y ey e ar e diffic ult t o diff er e nti at e fr o m 
t h os e of e v a p or ati v e dr y e y e, it is oft e n i m p ossi bl e t o tr ul y s e p ar at e p ati e nts i nt o 
disti nct gr o u ps. 7  I n f act, A A O g ui d eli n es st at e t h at t h es e c o n diti o ns c o exist i n t h e 
m aj orit y of t h e p ati e nts wit h t h e dis e as e.
8   
 
I n t er ms of t h e m ec h a nis m of acti o n f or dr y e y e dis e as e, th e  I nt er n ati o n al Dr y E y e 
W or ks h o p  ( D E W S)2 ex pl ai n e d  t h at t e ar h y p er os m ol arit y a n d t h e s y m pt o ms of dr y e y e 
r es ult fr o m w at er e v a p or ati o n c a us e d b y l o w a q u e o us t e ar fl o w a n d/ or  exc essi v e 
e v a p or ati o n.  T his  r e d uc e d, c o nc e ntr at e d t e ar v ol u m e, i n t ur n r es ults i n f urt h er 
i nfl a m m ati o n a n d t e ar fil m i nst a bilit y cr e ati n g a vici o us cycl e.  T h e D E W S r e p ort 
c o ncl u d ed t h e f oll o wi n g:  “Si nc e b ot h a q u e o us t e ar d efici e ncy a n d  i ncr e as e d 
e v a p or ati v e t e ar l oss occ ur i n m ost c as es of dr y ey e dis e as e a n d ar e li n k e d  b y c o m m o n 
p at h o g e n etic m ec h a nis ms, ex p ert cli nici a ns ar e i ncr e asi n gl y b asi n g  tr e at m e nt d ecisi o ns 
o n a n ass ess m e nt of s e v erit y r at h er t h a n discr et e d efici e nci es. ” 9 
 
N or m al t e ars c o at t h e oc ul ar s urf ac e a n d p erf or m m a n y f u ncti o ns, i ncl u di n g l u bric ati o n 
of t h e oc ul ar s urf ac e, pr ot ecti o n fr o m i nf ecti o n, n o uris hi n g t h e oc ul ar s urf ac e c ells, a n d 
pr o vi di n g a n o ptic all y cl e ar s urf ac e t o pr o p erl y r efr act li g ht. T e ars c o nsist of t hr e e l a y ers:  
 
1.  A n u n d erl yi n g m uci n l a y er w hic h acts as a w etti n g a g e nt t o s pr e a d t e ars 
u nif or ml y o n t h e oc ul ar s urf ac e t o pr e v e nt b e a di n g or irr e g ul arit y ; 
2.  A n a q u e o us l a y er t o m ai nt ai n a n o ptic all y cl e ar m e di u m a n d t o k e e p t h e oc ul ar 
s urf ac e m oist a n d h e alt hy; a n d 
3.  A s u p erfici al li pi d l a y er t o r et ar d e v a p or ati o n of t h e a q u e o us l a y er. 
W h e n a n y of t h es e l a y ers is dist ur b e d, t e ars m a y l os e t h eir pr ot ecti v e a n d o ptic al 
pr o p erti es l e a di n g t o a c o nst ell ati o n of s y m pt o ms, a c asc a d e of i nfl a m m at or y pr oc ess es, 
a n d t h e vici o us cycl e of dr y e y e.  
 
Wit h t h e m ost r ec e nt eti ol o gi es of dr y e y e dis e as e i n mi n d, m ulti pl e  st a n d ar d-of -c ar e, 
t h er a p e utic a p pr o ac h es ar e e m pl o y e d: 
 
 
 
 
 
 
 
 
 
  
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 3  of 8 4  
 
1.  S u p pl e m e nt ati o n of t h e t e ar fil m wit h artifici al t e ars t o a d dr ess e v a p or ati o n  a n d 
m ai nt ai n t e ar v ol u m e  
2.  Us e of w ar m c o m pr ess a n d li d m ass a g e t o i m pr o v e li pi d pr o d ucti o n a n d fl o w o n 
t h e t e ar fil m 
3.  Us e of i m m u n os u p pr essi v es (cycl os p ori n e, c ortic ost er oi ds, lifit e gr ast) t o r e d uc e 
i nfl a m m ati o n  
4.  Pl ac e m e nt of p u nct al pl u gs t o a d dr ess e v a p or ati o n  a n d m ai nt ai n t e ar v ol u m e  
 
R ec e ntl y, a gr e at d e al of e vi d e nc e s u g g ests t h at o bstr ucti o n of t h e m ei b o mi a n gl a n ds, 
w hic h ar e t h e gl a n ds o n t h e e y eli d t h at pr o d uc e t h e li pi d l a y er of t e ars, is str o n gl y 
ass oci at e d wit h dr y e y e dis e as e .1 0 ,1 1 ,1 2 ,1 3    T h e D E W S II r e p ort st at es t h at m ei b o mi a n 
gl a n d dis e as e is c o nsi d er e d t h e l e a di n g c a us e of dr y e y e i n cli nic a n d p o p ul ati o n b as e d 
st u di es. 1 4  As t h es e gl a n ds b ec o m e eit h er i nfl a m e d or o bstr uct e d, t h eir a bility t o s u p pl y 
t h e ess e nti al li pi ds t o t h e oc ul ar s urf ac e is di mi nis h e d. T his, i n t ur n, l e a ds t o r a pi d 
e v a p or ati o n of t e ars a n d t h us t o  t h e si g ns a n d s y m pt o ms of dr y e y e  dis e as e .1 5  W h e n 
t his occ urs, it c a n r es ult i n oc ul ar disc o mf ort a n d, i n m a n y c as es, oc ul ar s urf ac e 
dis or d ers t h at c a n aff ect visi o n.   
 
T o a d dr ess t his, u s e of w ar m c o m pr ess es a n d li d m ass a g e ar e  r ec o m m e n d e d f or t h e 
tr e at m e nt of dr y e y e b y t h e A O A, A A O , a n d t h e I nt er n ati o n al W or ks h o p o n M ei b o mi a n 
Gl a n d D ysf u ncti o n .1 6 ,1 7 ,1 8  It is b eli e v e d t h at t h e h e at h el ps m elt t h e oil y o bstr ucti o ns i n 
t h e m ei b o mi a n gl a n ds a n d h el ps r e d uc e gl a n d i nfl a m m ati o n, t h er e b y h el pi n g t o r est or e 
t h e a bilit y of t h e m ei b o mi an gl a n ds t o eff ecti v ely s ecr et e oil o nt o t h e t e ar fil m a n d 
pr e v e nt r a pi d t e ar e v a p or ati o n.    
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 4  of 8 4  
It h as b e e n s h o w n t h at w ar m c o m pr ess t h er a p y c a n l e a d t o i m pr o v e d li pi d pr o d uctio n 
a n d fl o w o n t o t h e t e ar fil m .1 9 ,2 0 ,2 1   T his i m pr o v e d li pi d d eli v er y is ass oci at e d n ot o nl y 
wit h a n i m pr o v e m e nt i n t h e pr ofil e of t h e t e ar fil m b ut als o a n i m pr o v e m e nt i n p ati e nt 
s y m pt o ms. 2 2 ,2 3 ,2 4  T h e t e ar fil m is d e m o nstr a bl y t hic k er a n d m or e st a bl e wit h a n 
i ncr e as e d c o ntri b uti o n of li pi d t o its s urf ac e.2 5 ,2 6 ,2 7     
 
I n a d diti o n t o w ar m c o m pr ess es, vari o us alt er n ativ e a p pr o ac h es t o h e ati n g  t h e e y eli ds 
h a v e b e e n pr o p os e d.  2 8 ,2 9 ,3 0 ,3 1 ,3 2  Wi d es pr e a d a d o pti o n of t h es e a p pr o ac h es h as b e e n 
li mit e d d u e t o a v ari et y of f act ors i ncl u di n g q u esti o ns a b o ut d ur ati o n of  eff ecti v e n ess, 
iss u es r el at e d t o e as e of us e, l ac k of r ei m b urs e m e nt, a n d t h e  o ut -of -p oc k et  c ost of t h e 
tr e at m e nt t o t h e p ati e nts. 
 
Si g ht Sci e nc es h as d e v el o p e d t h e T e ar C ar e ™ S yst e m  t o pr o vi d e a s af e a n d eff ecti v e 
tr e at m e nt f or t h e si g ns a n d s y m pt o ms of dr y e y e dis e as e .  T h e S yst e m is d esi g n e d t o 
c o nf or m t o t h e e y eli ds t o d eli v er c o ntr oll e d, pr ecis e h e at t o t h e t ars al pl at es a n d 
u n d erl yi n g m ei b o mi a n gl a n ds of t h e e y eli ds f or 15 mi n ut es i n t h e m o nit or e d s etti n g of 
a n o p ht h al m ol o gist or o pt o m etrist offic e. I n a d diti o n t o bli n ki n g d uri n g T e ar C ar e™ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 5  of 8 4  
tr e at m e nt t o n at ur all y ex pr ess m elt e d m ei b u m, th e p h ysici a n t h e n us es t h e Ex pr ess T M 
F orc e ps t o f urt h er ex pr ess t h e m ei b o mi a n gl a n ds  m a n u all y i m m e di at el y f oll o wi n g t h e 
e y eli d h e at tr e at m e nt .   
 
I n t his st u d y, t h e T e ar C ar e S yst e m will b e c o m p ar e d wit h st a n d ar d-of -c ar e w ar m 
c o m pr ess tr e at m e nt a n d li d m ass a g e  i n p ati e nts wit h dr y e y e dis e as e .  T h e o bj ecti v e is 
t o d e m o nstr at e t h at t h e T e ar C ar e S yst e m is s af e a n d eff ecti v e i n r eli e vi n g t h e si g ns a n d 
s y m pt o ms of dr y e y e dis e as e  a n d t h at it is s u p eri or t o a c o m m o nl y pr escri b e d, st a n d ar d 
tr e at m e nt of w ar m c o m pr ess a n d li d m ass a g e.   
 
T h e T e ar C ar e S yst e m is a Cl ass II -ex e m pt d e vic e t h at is c urr e ntl y list e d a n d c o m m erci all y 
a v ail a bl e i n t h e U S.  T his st u d y is b ei n g c o n d uct e d t o c oll ect d at a t o u p d at e t h e 
i n dic ati o n f or us e f or t h e T e ar C ar e S yst e m t o r e a d as f oll o ws, “T h e T e ar C ar e ® S yst e m is 
i n dic at e d f or t h e tr e at m e nt of t h e si g ns a n d s y m pt o ms of d r y e y e d is e as e ( D E D). 
4  D E S C RI P TI O N O F D E VI C E  
4. 1  C U R R E N T IN DI C A TI O N F O R U S E  
T h e T e ar C ar e S yst e m is a Cl ass II ex e m pt d e vic e t h at is list e d wit h t h e F D A.  It is 
c o m m erci all y a v ail a bl e i n t h e U S.  It is c urr e ntl y l a b el e d wit h t h e f oll o wi n g i n dic ati o n f or 
us e:   
“T h e T e ar C ar e ® S yst e m is i n dic at e d f or t h e a p plic ati o n of l oc aliz e d h e at w h e n t h e 
c urr e nt m e dic al c o m m u nit y r ec o m m e n ds t h e a p plic ati o n of a w ar m c o m pr ess t o 
t h e e y eli ds. S uc h a p plic ati o ns w o ul d i ncl u d e M ei b o mi a n Gl a n d D ysf u ncti o n 
( M G D), Dr y E y e, or Bl e p h aritis.” 
4. 2  P R O P O S E D IN DI C A TI O N F O R U S E 
T his st u d y is b ei n g c o n d uct e d t o c oll ect d at a t o s u p p ort a m o dific ati o n t o t h e T e ar C ar e 
i n dic ati o n f or us e t o r e a d as f oll o ws: 
 
“T h e T e ar C ar e ® S yst e m is i n dic at e d f or t h e tr e at m e nt of t h e si g ns a n d s y m pt o ms 
of d r y e y e d is e as e ( D E D).”   
4. 3  D E VI C E D E S C RI P TI O N   
T h e T e ar C ar e S yst e m is d esi g n e d t o d eli v er c o ntr oll e d, pr ecis e h e at t o t h e t ars al pl at es 
a n d u n d erl yi n g m ei b o mi a n gl a n ds of t h e e y eli ds f or 1 5 mi n ut es , f oll o w e d i m m e di at el y 
b y m a n u al m ec h a nic al m ei b o mi a n gl a n d ex pr essi o n .  T h e T e ar C ar e pr oc e d ur e t a k es 
pl ac e i n t h e m o nit or e d s etti n g of a n o p ht h al m ol o gist or o pt o m etrist offic e. 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 6  of 8 4  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 7  of 8 4  
 
 
 
 
 
  
 
 
 
 
Ti m e r e m ai ni n g 
i n dic at or 
O n/ Off b utt o n  
# S essi o ns 
r e m ai ni n g o n t h e 
b att er y  
T e m p er at ur e 
s etti n g i n dic at or 
a n d a dj ust m e nt 
b utt o ns ( + a n d -) 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 8  of 8 4  
 
T o us e t h e S yst e m, t h e fl exi bl e iLi d d e vic es ar e a p pli e d t o t h e ext er n al s urf ac e of t h e 
u p p er a n d l o w er e y eli ds of t h e p ati e nt ( Fi g ur e 1 ).   T h e iLi d d e vic es ar e t h e n c o n n ect e d 
t o t h e T e ar C ar e S m art H u b .  W h e n t h e S m art H u b  is t ur n e d o n a n d t h e p h ysici a n i niti at es 
t h e pr oc e d ur e, t h e T e ar C ar e S yst e m b e gi ns d eli v eri n g h e at t o t h e e y eli ds.  T h e s yst e m 
a ut o m atic all y a n d gr a d u all y i ncr e as es t h e t e m p er at ur e o v er 2 -3 mi n ut es u ntil it r e ac h es 
t h e m axi m u m s et p oi nt t e m p er at ur e of 4 5 °C.  A c o m pl et e T e ar C ar e s essi o n l asts 1 5  
mi n ut es.    
 
 
 
 
 
 
 
  
 
 
 
 
I m m e di at el y f oll o wi n g t h e T e ar C ar e s essi o n, t h e cli nici a n us es t h e Ex pr ess F orc e ps t o 
m a n u all y ex pr ess t h e m ei b o mi a n gl a n ds i n all f o ur e y eli ds.     
4. 4  IN S T R U C TI O N S F O R U S E 
I nstr ucti o ns f or Us e ar e pr o vi d e d wit h e ac h T e ar C ar e S yst e m. 
4. 5  T R AI NI N G  
Pri or t o t h e st art of t h e st u d y, i n v esti g at ors a n d st u d y st aff w h o h a v e n ot b e e n 
pr e vi o usl y tr ai n e d i n t h e pr o p er us e of t h e T e ar C ar e S yst e m will b e tr ai n e d i n its us e.  
W hil e m ost i n v esti g at ors s h o ul d h a v e ex p eri e nc e i n p erf or mi n g m a n u al ex pr essi o n of 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 1 9  of 8 4  
t h e m ei b o mi a n gl a n ds, w hic h is a st a n d ar d pr oc e d ur e f or dr y e y e p ati e nts, i n v esti g at ors 
will b e tr ai n e d  i n t h e pr ot oc ol m et h o d f or p erf or mi n g m ei b o mi a n gl a n d ex pr essi o n usi n g 
t h e Ex pr ess  Ex pr essi o n F orc e ps .  All st u d y st aff will r ec ei v e tr ai ni n g o n t h e pr ot oc ol a n d 
ex ec uti o n of t h e st u d y acc or di n g t o a p plic a bl e r e g ul ati o ns a n d G o o d Cli nic al Pr actic es.  
5  P RI O R  IN V E S TI G A TI O N S  
 
T h e T e ar C ar e S yst e m h as b e e n t est e d ext e nsi v el y o n t h e b e nc h  a n d i n cli nic al v ali d ati o n 
t esti n g t o d e m o nstr at e t h at it m e ets all s p ecifi e d s af et y a n d p erf or m a nc e r e q uir e m e nts.  
T h e f oll o wi n g t esti n g a n d a n al ys es w as p erf or m e d:  
 
 
 
 
 
  
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 2  P R E VI O U S C LI NI C AL E X P E RI E N C E  
T h e T e ar C ar e S yst e m h as b e e n st u di e d i n t w o pil ot st u di es.  T h e first st u d y w as 
c o n d uct e d i n 2 0 1 3 as a n I n v esti g at or -s p o ns or e d st u d y wit h a pr ot ot y p e v ersi o n of t h e 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 0  of 8 4  
T e ar C ar e S yst e m.  T h e s ec o n d st u d y w as i niti at e d i n 2 0 1 7 wit h a c o m m erci al v ersi o n of 
t h e T e ar C ar e S yst e m ( Si g ht Sci e nc es pr ot oc ol # 0 5 4 2 9).   T h es e t w o st u di es ar e 
s u m m ariz e d b el o w. 
 
C LI NI C AL S T U D Y O F T H E  P R O T O T Y P E T E A R C A R E S Y S T E M  ( 2 0 1 3) 
A pr ot ot y p e v ersi o n of t h e T e ar C ar e S yst e m w as t est e d i n a si n gl e c e nt er, pr os p ecti v e, 
r a n d o miz e d st u d y.  T h e st u d y e nr oll e d 1 8  s u bj ects w h o w er e r a n d o miz e d t o  t w o 
tr e at m e nt ar ms:  ( a) P r ot ot y p e T e ar C ar e S yst e m, or  ( b) w ar m c o m pr ess tr e at m e nt.  
S u bj ects r a n d o miz e d t o t h e T e ar C ar e ar m ( n = 1 0 s u bj ects) r ec ei v e d o n e, 1 0-mi n ut e 
s essi o n wit h t h e pr ot ot y p e d e vic e  f oll o we d b y m a n u al ex pr essi o n of t h e m ei b o mi a n 
gl a n ds.  S u bj ects r a n d o miz e d t o t h e w ar m c o m pr ess ar m  ( n = 8 s u bj ects) r ec ei v e d 
st a n d ar d w ar m c o m pr ess t h er ap y  ( Fir e & Ic e M ask, R h ei n M e dic al, I nc.) f or 5 mi n ut es  
p er d a y f or 2 w e e ks .  S u bj ects w er e f oll o w e d f or 4 w e e ks, wit h f oll o w -u p visits at 1 d a y, 
2 w e e ks, a n d 4 w e e ks.   
 
N o a d v ers e e v e nts w er e r e p ort e d i n t his st u d y.  T a bl e 1  pr es e nts t h e eff ecti v e n ess 
o utc o m es fr o m  t his st u dy. 
 
T his st u d y d e m o nstr at e d t h e s af et y of t h e T e ar C ar e S yst e m a n d pr o vi d e d e vi d e nc e t h at 
T e ar C ar e S yst e m pr o vi d es st atistic all y si g nific a nt i m pr o v e m e nt i n m ei b o mi a n gl a n d 
s ecr eti o n, t e ar br e a k-u p ti m e, a n d dr y e y e s y m pt o ms.  R es ults fr o m t his st u d y i nf or m e d 
t h e d ecisi o n t o c o nti n u e d e v el o p m e nt o n t h e T e ar C ar e S yst e m. 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 1  of 8 4  
 
C LI NI C AL S T U D Y O F T H E T E A R C A R E S Y S T E M ( 2 0 1 7) 
F oll o wi n g c o m pl eti o n of t h e d esi g n a n d d e v el o p m e nt of t h e c o m m erci al v ersi o n of t h e 
T e ar C ar e S yst e m, a si n gl e c e nt er pil ot st u d y w as i niti at e d t o c oll ect a d diti o n al cli nic al 
d at a.   
 
O bj ecti v es  
T h e o bj ecti v e of t his st u dy w as  t o e v al u at e t h e cli nic al utilit y, s af et y, a n d eff ecti v e n ess 
of t h e T e ar C ar e ™ S yst e m c o m p ar e d t o st a n d ar diz e d w ar m c o m pr ess t h er a p y . 
 
S u bj ects  
T w e nt y -f o ur ( 2 4) s u bj ects wit h s y m pt o ms of dr y ey e i n t h e p ast 3 m o nt hs w er e e nr oll e d.  
T h e a v er a g e a g e w as 6 7. 6 ± 1 3. 5 y e ars (r a n g e 2 9. 7 – 8 9. 8 y e ars).  All s u bj ects w er e 
f e m al e, w hit e a n d n ot His p a nic or L ati n o.  All s u bj ects h a d a S P E E D sc or e ≥6 at t h e 
B as eli n e visit.  All s u bj ects h a d a T e ar Br e a k -u p Ti m e ( T B U T ) of < 1 0 s ec o n ds i n at l e ast 
o n e e y e  at b as eli n e a n d 7 2 % ( 1 7/ 2 4) h a d a Sc hir m er 1 sc or e ( n o n-a n est h etiz e d) of  ≤1 0 
m m i n at l e ast o n e e y e at t h e B as eli n e visit .   
 
M et h o ds  
T his w as a pr os p ecti v e, si n gl e -c e nt er, r a n d o miz e d, p ar all el-gr o u p, cli nic al tri al. S u bj ects 
wit h D E D w er e r a n d o miz e d t o eit h er a si n gl e T e ar C ar e tr e at m e nt c o n d uct e d at t h e cli nic 
or 4 w e e ks of d ail y w ar m c o m pr ess t h er a p y. T h e T e ar C ar e pr oc e d ur e c o nsist e d o f 1 2 
mi n ut es of t h er m al e y eli d tr e at m e nt i m m e di at el y f oll o w e d b y m a n u al ex pr essi o n of t h e 
m ei b o mi a n gl a n ds.  W ar m c o m pr ess t h er a p y c o nsist e d of o nc e d ail y a p plic ati o n of t h e 
c o m pr ess es t o t h e e y eli ds f or 5 mi n ut es. S u bj ects w er e f oll o w e d t o 6 m o nt hs p ost -
tr e at m e nt. T h e pri m ar y eff ecti v e n ess e n d p oi nt w as d efi n e d as c h a n g e fr o m b as eli n e t o 
4 w e e ks f or T e ar Br e a k -u p Ti m e ( T B U T).  S ec o n d ar y eff ecti v e n ess e n d p oi nts i ncl u d e d 
m ei b o mi a n gl a n d ass ess m e nt, c or n e al a n d c o nj u ncti v al st ai ni n g sc or es, a n d ass ess m e nt 
of d r y e y e s y m pt o ms usi n g v ali d at e d q u esti o n n air es.  S af et y w as e v al u at e d b y c oll ecti n g 
d e vic e -r el at e d a d v ers e ev e nts, i ntr a oc ul ar pr ess ur e, a n d b est s p ect acl e-c orr ect e d 
S n ell e n Vis u al ac uit y.  
 
R es ults  
T w e nt y -f o ur s u bj ects w er e e nr oll e d a n d c o m pl et e d 6 m o nt hs f oll o w -u p .  D at a ar e 
s u m m ariz e d i n T a bl e 2  b el o w.  
 
At 1 m o nt h f oll o w -u p, T e ar C ar e s u bj ects d e m o nstr at e d a n i m pr o v e m e nt fr o m b as eli n e 
i n m e a n ( ± S D) T B U T of 1 1. 7 ± 2. 6 s ec o n ds c o m p ar e d wit h a n a v er a g e w ors e ni n g of -0. 3 
± 1. 1 s ec o n ds f or s u bj ects i n t h e w ar m c o m pr ess gr o u p ( p < 0. 0 0 0 1). Si g nific a ntl y gr e at er 
im pr o v e m e nts i n t h e c h a n g e fr o m b as eli n e i n m ei b o mi a n gl a n d sc or es, as w ell as 
c or n e al a n d c o nj u ncti v al st ai ni n g sc or es w er e o bs er v e d i n t h e T e ar C ar e gr o u p. S u bj ects 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 2  of 8 4  
i n t h e T e ar C ar e gr o u p als o s h o w e d si g nific a ntl y gr e at er i m pr o v e m e nt i n dry e y e 
s y m pt o ms as m e as ur e d b y t h e t hr e e q u esti o n n air es.  
   
N o a d v ers e e v e nts w er e r e p ort e d i n eit h er gr o u p.     
 
 
C o ncl us i o ns 
T h e T e ar C ar e Gr o u p c o nsist e ntl y s h o w e d a si g nific a nt i m pr o v e m e nt b et w e e n t h e 
b as eli n e a n d 4 w e e ks f oll o w -u p f or all o utc o m e m e as ur es, w h er e as t h e W ar m C o m pr ess 
gr o u p di d n ot.  F or all o utc o m e m e as ur es, t h e T e ar C ar e Gr o u p’s m e a n c h a n g e b et w e e n 
b as eli n e a n d 4 w e e ks f oll o w -u p w as b ett er t h a n t h e W ar m C o m pr ess gr o u p.  T h es e 
r es ults w er e m ai nt ai n e d o ut t o 6 m o nt hs. 
 
T his pil ot st u d y pr o vi d e d pr eli mi n ar y e vi d e nc e of t h e s af et y a n d eff ecti v e n ess of t h e 
T e ar C ar e d e vic e i n r eli e vi n g t h e si g ns a n d s y m pt o ms of dr y e y e.   
 
S U M M A R Y  
T h e t w o pri or cli nic al st u di es pr o vi d e d pr eli mi n ary cli nic al d at a wit h t h e T e ar C ar e 
S yst e m.  B ot h of t h es e st u di es w er e s m all, si n gl e -c e nt er pil ot st u di es. 
 
T his c urr e nt tri al is b ei n g u n d ert a k e n t o e v al u at e t h e s af et y a n d effic acy of t h e T e ar C ar e 
s yst e m v ers us st a n d ar d-of -c ar e w ar m c o m pr ess a n d li d m ass a g e i n a pr os p ecti v e, m ulti -
c e nt er, h y p ot h esis -dri v e n, r a n d o miz e d, c o ntr oll e d tri al.  T h e st u d y is i nt e n d e d t o 
d e m o nstr at e t h at t h e T e ar C ar e S yst e m i n dic at e d i n t h e tr e at m e nt of si g ns a n d 
s y m pt o ms of dr y e y e dis e as e. 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 3  of 8 4  
6  S T U D Y E N D P OI N T S  
6. 1  E F F E C TI V E N E S S  E N D P OI N T S  
T his st u d y will c oll ect d at a t o ass ess t h e i m p act of e ac h tr e at m e nt o n t h e si g ns a n d 
s y m pt o ms of dr y e y e dis e as e.  T e ar Br e a k-U p Ti m e, w hic h m e as ur es t h e tr e at m e nt 
eff ect of t h e d e vic e o n t h e si g ns of dr y e y e dis e as e, is t h e pri m ar y e n d p oi nt.  T h e Oc ul ar 
S urf ac e Dis e as e I n d ex ( O S DI) q u esti o n n air e, w hic h is a v ali d at e d i nstr u m e nt f or 
m e as uri n g t h e s e v erit y of s y m pt o ms o f dr y e y e dis e as e, is t h e k e y s ec o n d ar y e n d p oi nt.  
T h e f oll o wi n g ot h er s ec o n d ar y e n d p oi nts h a v e b e e n c h os e n t o c oll ect a d diti o n al d at a 
r e g ar di n g c h a n g es i n t h e si g ns a n d s y m pt o ms of dr y e y e dis e as e i n st u d y s u bj ects:  
M ei b o mi a n Gl a n d  S ecr eti o n  Sc or e , C or n e al a n d C o nj u ncti v al St ai ni n g, t h e S y m pt o m 
Ass ess m e nt i N Dr y E y e  (S A N D E ) q u esti o n n air e , a n d t h e E y e Dr y n ess Sc or e. 
 
F or e ac h o utc o m e m e as ur e, r es ults fr o m t h e T e ar C ar e s u bj ects will b e c o m p ar e d wit h 
r es ults fr o m t h e W ar m C o m pr ess a n d Li d M ass a g e  s u bj ects.   All t h e pri m ar y a n d 
s ec o n d ar y e n d p oi nts will b e at 1 m o nt h . 
 
•  P ri m ar y eff ecti v e n ess e n d p oi nt    
o  M e a n C h a n g e  fr o m b as eli n e i n T e ar Br e a k -U p Ti m e ( T B U T) 
•  S ec o n d ar y eff ecti v e n ess e n d p oi nts    
o  M e a n C h a n g e fr o m b as eli n e i n O S DI  sc or e 3 9 
o  M e a n C h a n g e fr o m b as eli n e i n t h e t ot al M ei b o mi a n Gl a n d S ecr eti o n 
Sc or e 4 0  
o  M e a n C h a n g e fr o m b as eli n e i n cor n e al  st ai ni n g sc or es 
o  M e a n C h a n g e fr o m b as eli n e i n c o nj u ncti v al st ai ni n g sc or es  
o  M e a n C h a n g e fr o m b as eli n e i n S A N D E  sc or es 4 1 ,4 2  
o  E y e Dr y n ess Sc or e  
•  Tr e at m e nt D ur ati o n E n d p oi nts  
o  M e a n 3- a n d 6 -m o nt h C h a n g e fr o m b as eli n e f or s ucc essf ul pri m ar y a n d 
s ec o n d ar y e n d p oi nts 
•  A d diti o n al E x pl or at or y  E n d p oi nts  
 
 
 
 
 
 
 
 
  
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 4  of 8 4  
o  N u m b er of m ei b o mi a n gl a n ds yi el di n g cl e ar li q ui d s ecr eti o ns  
o  N u m b er of m ei b o mi a n gl a n ds s ecr eti n g a n y li q ui d (cl e ar or cl o u d y)  
o  U s e of dr y e y e l u bric a nt s 
o  Ass ess m e nt of a ll eff ectiv e n ess e n d p oi nts at  7, 9 a n d 1 2  m o nt hs.  
6. 2  S A F E T Y E N D P OI N T S  
S af et y will b e ass ess e d  by e v al u ati n g t h e f oll o wi n g m e as ur es  o v er ti m e : 
 
•  D e vic e -r el at e d a d v ers e ev e nts ( all a d v ers e e v e nts  will b e r ec or d e d)  
•  B est c orr ect e d vis u al ac uit y  ( E T D R S) 
•  I ntr a oc ul ar pr ess ur e (I O P)  
•  Disc o mf ort/ p ai n d uri n g tr e at m e nt  
7  S T U D Y D E SI G N 
T his is a pr os p ecti v e, r a n d o miz e d, c o ntr oll e d, si n gl e-m as k e d, m ulti -c e nt er tr e at m e nt 
st u d y.  T his is a p ost -m ark et st u d y i nt e n d e d t o c oll ect d at a t o u p d at e t h e i n dic ati o n f or 
us e f or t h e T e ar C ar e S yst e m.  T o r e d uc e p ot e nti al bi as i n t h e st u d y, st u d y st aff 
p erf or mi n g t h e e n d p oi nt ass ess m e nts will b e m ask e d as t o t h e s u bj ect’s tr e at m e nt ar m.  
S u bj ects c a n n ot b e m as k e d as it will b e o b vi o us t o t h e m w hic h tr e at m e nt t h e y ar e 
r ec ei vi n g. 
 
7. 1  S T U D Y  D E VI C E A N D C O N T R OL A R M  
I n t his st u d y, T e ar C ar e tr e at m e nt will b e c o m p ar e d wit h st a n d ar d -of -c ar e w ar m 
c o m pr ess tr e at m e nt pl us li d m ass a g e.  W ar m c o m pr ess tr e at m e nt pl us li d m ass a g e , 
o nc e a d a y,  w as c h os e n f or t h e c o ntr ol ar m  si nc e it is on e of t h e m ost c o m m o nl y 
pr escri b e d tr e at m e nts f or dr y e y e dis e as e .4 3 ,4 4 
 
T e ar C ar e tr e at m e nt i ncl u d es a n  i n-offic e 1 5 mi n ut e tr e at m e nt s essi o n wit h t h e T e ar C ar e 
S yst e m i m m e di at el y f oll o w e d b y m a n u al ex pr essi o n of t h e m ei b o mi a n gl a n ds usi n g t h e 
Ex pr ess  Ex pr essi o n F orc e ps.  S u bj ects r a n d o miz e d t o T e ar C ar e will r ec ei v e o n e i n -offic e 
tr e at m e nt s essi o n at t h e b as eli n e visit a n d o n e  r e-tr e at m e nt at 6 m o nt hs.   
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
Pr ot oc ol 0 5 4 7 4 R e v B 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 5  of 8 4  
S u bj ects r a n d o miz e d t o t h e W ar m C o m pr ess a n d Li d M ass a g e Gr o u p will b e i nstr uct e d 
t o us e a m oist  w ar m c o m pr ess f or 5 mi n ut es a n d t h e n p erf or m li d m ass a g e.  T h e y will 
b e i nstr uct e d t o p erf or m t his  at h o m e  o n ce p er d a y d uri n g t h e f oll o w -u p p eri o d .  T his 
r e gi m e n is c o nsist e nt wit h t h e r ec o m m e n d ati o ns of t h e I nt er n ati o n al W orks h o p o n 
M ei b o mi a n Gl a n d D ysf u ncti o n.
4 5  S u bj ects i n t h e w ar m c o m pr ess a n d li d m ass a g e gr o u p 
will p erf or m t h eir first d ail y s essi o n i n t h e i n v esti g at or’s offic e s o t h at t h e cli nici a n c a n 
i ns ur e t h e s u bj ect is p erf or mi n g t h e tr e at m e nt pr o p erl y.    
  
 
 
 
 
 
7. 3  S T U D Y C E N T E R S  
T his st u d y will b e c o n d uct e d at u p t o 1 5 c e nt ers i n t h e U nit e d St at es.  N o c e nt er will 
h a v e m or e t h a n 2 0 % of t h e t ar g et e nr oll m e nt.  
8  S T U D Y S EL E C TI O N C RI T E RI A  
8. 1  IN CL U SI O N C RI T E RI A  
F or i ncl usi o n i n t his st u dy, s u bj ects m ust m e et all of t h e f oll o wi n g crit eri a:  
 
1.  At l e ast 2 2  y e ars of a g e  
2.  R e p orts dr y e y e s y m pt o ms 
 
3.  R e p orts h a vi n g t o us e artifici al t e ars or l u bric a nts r e g ul arl y 
 
 
4.  O S DI Sc or e 
  
5.  T B U T 
  
6.  M ei b o mi a n gl a n d o bstr ucti o n i n b ot h e y es 
 
 
7.  B est c orr ect e d vis u al ac uit y of 2 0/ 1 0 0 or b ett er i n b ot h e y es.  
8.  Willi n g a n d a bl e t o c o m pl y wit h t h e st u d y  pr oc e d ur es a n d f oll o w -u p  
9.  Willi n g a n d a bl e t o pr o vi d e i nf or m e d c o ns e nt 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 6  of 8 4  
1 0.  E n glis h -s p e a ki n g 
8. 2  E X CL U SI O N C RI T E RI A  
A s u bj ect w h o m e ets a n y of t h e crit eri a list e d b el o w  (i n eit h er e y e) will b e excl u d e d fr o m 
t h e st u d y: 
 
1.  A n y acti v e, cli nic all y si g nific a nt oc ul ar or p eri -oc ul ar i nf ecti o n or i nfl a m m ati o n  
2.  R ec urr e nt cli nic all y si g nific a nt e y e i nfl a m m ati o n, ot h er t h a n dr y e y e,  
 
t 
3.  Hist or y of e y eli d, c o nj u ncti v a or c or n e al s ur g er y (i ncl u di n g r efr acti v e s ur g er y) 
wit hi n t h e p ast y e ar.  I n a d diti o n, s u bj ects wit h a n y hist or y of t h e f oll o wi n g ar e 
excl u d e d: c h al azi o n s ur g er y, s ur g er y o n t h e t ars al c o nj u ncti v a, r a di al k er at ot o m y 
( R K), c o m plic at e d bl e p h ar o pl ast y, li d r ec o nstr ucti o n, or si g nific a nt c o m plic ati o ns 
p ost -r efr acti v e s ur g er y. 
4.  
 
 
5.  M ei b o mi a n gl a n d ex pr essi o n wit hi n 6 m o nt hs pri or t o e nr oll m e nt .   
 
. 
6.  I n t h e cli nic al j u d g e m e nt of t h e i n v esti g at or, m ei b o mi a n gl a n ds h a v e si g nific a nt 
c a p pi n g, atr o p h y, or ar e u n a bl e t o b e di git all y ex pr ess e d.  
7.  C o nt act l e ns us e wit hi n t h e p ast 2 w e e ks.  (
 
8.  
 
9.  Hist or y of Oc ul ar H er p es Si m pl ex or Oc ul ar H er p e s Z ost er  
1 0.  Cli nic all y si g nific a nt o c ul ar s urf ac e a b n or m aliti es t h at m a y aff ect t e ar fil m 
distri b uti o n or tr e at m e nt  ( e. g. pt er y gi u m, a nt eri or m e m br a n e d ystr o p h y, etc.) 
1 1.  Cli nic all y si g nific a nt e y eli d a b n or m aliti es  i n eit h er e y e ( e. g. e ntr o pi o n/ ectr o pi o n, 
bl e p h ar os p as m, a p o n e ur otic pt osis, l a g o p ht h al m os, n otc hi n g of li d m ar gi n, 
distic hi asis, tric hi asis).  
1 2.  Cli nic all y si g nific a nt a nt eri or bl e p h aritis.  I n a d diti o n, c oll ar ett es or fl a k es of m or e 
t h a n o n e q u art er of t h e e y eli d ar e excl u d e d. 
1 3.  Cli nic all y si g nific a nt d er m at ol o gic or c ut a n e o us dis e as e of t h e e y eli d or 
p eri oc ul ar ar e a.  
1 4.  Oc ul ar tr a u m a 
 
1 5.  A n y acti v e, cli nic all y si g nific a nt  all er gic, v er n al, or gi a nt p a pill ar y c o nj u ncti vitis.  
1 6.  K n o w n hist or y of d i mi nis h e d or a b n or m al f aci al, p eri oc ul ar, oc ul ar or c or n e al 
s e ns ati o n 
1 7.  C or n e al  s urf ac e a b n or m aliti es s uc h as c or n e al e pit h eli al d ef ects ( ot h er t h a n 
p u nct at e st ai ni n g) , ulc ers, c or n e al e pit h eli al d ystr o p hi es , k er at oc o n us, a n d 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 7  of 8 4  
ect atic dis e as e of t h e c or n e a  
1 8.  P u nct al occl usi o n or p u nct al pl u g pl ac e m e nt 
   
1 9.  S yst e mic dis e as es r es ulti n g i n dr y e y e ( e. g. a ut oi m m u n e dis e as es s uc h as 
Sj o gr e n’s s y n dr o m e, r h e u m at oi d art hritis, l u p us, Gr a v es’ dis e as e, s arc oi d osis, 
etc. ) 
2 0.  All er gi es t o silic o n e tiss u e a d h esi v es  
2 1.  
 
2 2.  Us e of a nti hist a mi n es ( or al or t o pic al) wit hi n 1 0 d a ys pri or t o e nr oll m e nt.  
 
2 3.  S u bj ect is c urr e ntl y o n a s yst e mic m e dic ati o n(s) ( ot h er t h a n a nti -hist a mi n es) t h at 
is k n o w n t o c a us e oc ul ar dr y n ess4 6 a n d w h os e d os e of t his m e dic ati o n(s) h as n ot 
b e e n st a bl e wit hi n 3 0 d ays pri or t o e nr oll m e nt. 
 
 
2 4.  S u bj ect h as t a k e n or is c urr e ntl y t a ki n g Acc ut a n e.  
2 5.  S u bj ect r e q uir es c hr o nic us e (i. e. f or a n y p orti o n of t h e st u d y) of t o pic al 
o p ht h al mic a nti bi otics, a nti -gl a uc o m a m e dic ati o ns, st er oi ds, n o n-st er oi d al a nti-
i nfl a m m at or y m e dic ati o ns 
 
 
2 6.  S u bj ect is c urr e ntl y usi n g R eti n A or L atiss e.  
2 7.  P artici p ati o n i n a n ot h er o p ht h al mic cli nic al tri al wit hi n 3 0 d a ys  pri or t o 
e nr oll m e nt.  S u bj ect m ust als o b e willi n g t o r efr ai n fr o m a n ot h er o p ht h al mic 
st u d y f or t h e d ur ati o n of t h e st u d y.   
2 8.  C o -existi n g c o n diti o ns t h at c o ul d i nt erf er e wit h t h e ass ess m e nt of s af et y or 
eff ecti v e n ess of tr e at m e nt ( e. g. m ac ul ar dis e as e, pr e g n a ncy, n ursi n g, etc.).  
9  S T U D Y P R O C E D U R E S  
9. 1  S T U D Y S C H E D UL E  
T h e St u d y Sc h e d ul e is s h o w n b el o w i n T a bl e 3 . 
 
 
 
 
 
 
 

 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m ( OL Y M PI A)  
  
C O N FI D E N TI AL  
Si g ht Sci e nc es, I nc.  
 
P a g e 2 8  of 8 4  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 2 9  of 8 4  
9. 2  N U M B E R O F S U BJ E C T S , D U R A TI O N O F F OLL O W -U P  A N D S T U D Y 
D U R A TI O N  
A t ot al of 2 0 0  s u bj ects will b e e nr oll e d a n d r a n d o miz e d  i n t h e st u d y.  Ass u mi n g a 1 5 % 
scr e e n f ail ur e r at e,  a p pr oxi m at el y 2 3 0 s u bj ects will b e e nr oll e d  a n d scr e e n e d t o o bt ai n 
2 0 0 r a n d o miz e d s u bj ects .  All s u bj ects will b e f oll o w e d f or 1 2  m o nt hs.  
 
It is a ntici p at e d t h at e nr oll m e nt i n t h e st u d y will t a k e 3- 6 m o nt hs.  I ncl u di n g t h e 1 2 -
m o nt h f oll o w -u p p eri o d, t h e st u d y is ex p ect e d t o l ast 1 5 -1 8  m o nt hs.  
 
A n al ysis of t h e pri m ar y o utc o m e will occ ur w h e n t h e l ast s u bj ect h as r e ac h e d t h e 1 
m o nt h f oll o w u p. I n or d er t o e v al u at e l o n g -t er m r es ults of t h e T e ar C ar e tr e at m e nt, d at a 
will b e r e -a n al yz e d aft er t h e l ast s u bj ect r e ac h es t h e 6 m o nt h f oll o w -u p  a n d t h e n a g ai n 
aft er t h e l ast s u bj ect r e ac h es t h e 1 2 m o nt h f oll o w u p.  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 0  of 8 4  
 
 
9. 4  IN F O R M E D C O N S E N T A N D P OI N T O F E N R OLL M E N T  
T h e I R B -a p pr o v e d i nf or m e d c o ns e nt will b e pr es e nt e d a n d ex pl ai n e d t o e ac h 
pr os p ecti v e s u bj ect b y t h e i n v esti g at or or a tr ai n e d cli nic al pr of essi o n al.  O nc e t h e 
s u bj ect h as h a d a m pl e ti m e t o r e a d t h e c o ns e nt f or m, h as b e e n i nf or m e d of all as p ects 
of t h e st u d y , a n d h as h a d a n o p p ort u nit y t o as k q u esti o ns, t h e s u bj ect will b e gi v e n a 
c h oic e t o v ol u nt aril y c o nfir m his or h er p artici p ati o n i n t h e st u d y as d oc u m e nt e d b y 
c o m pl eti o n of t h e I nf or m e d C o ns e nt.  Aft er si g ni n g t h e I nf or m e d C o ns e nt a n d t h e HI P A A 
( H e alt h I ns ur a nc e P ort a bilit y a n d Acc o u nt a bilit y Act) aut h oriz ati o n, t h e s u bj ect c a n t h e n 
pr oc e e d wit h t h e b as eli n e visit .  T h e s u bj ect h as t h e ri g ht t o wit h dr a w fr o m t h e st u d y at 
a n y ti m e wit h o ut c o ns e q u e nc es, as i n dic at e d i n t h e I nf or m e d C o ns e nt D oc u m e nt.  
 
T h e s u bj ect’s si g n e d a n d d at e d i nf or m e d c o ns e nt m ust b e o bt ai n e d b ef or e c o n d ucti n g 
a n y pr oc e d ur e s p ecific ally f or t h e st u d y.  S u bj ects ar e e nr oll e d u p o n si g ni n g t h e I C D 
e v e n if t h e y s u bs e q u e ntly f ail t o m e et t h e eli gi bilit y crit eri a.    
 
T h e pri nci p al i n v esti g at or(s) m ust r et ai n t h e ori gi n al, si g n e d writt e n I nf or m e d C o ns e nt 
D oc u m e nt.  A c o p y of t h e writt e n I nf or m e d C o ns e nt D oc u m e nt m ust b e gi v e n t o t h e 
s u bj ect. 
9. 5  B A S ELI N E V I SI T 
 
S C H E D ULI N G T H E B A S ELI N E V I SI T 
T h e b as eli n e visit m a y b e p erf or m e d o v er t w o s e p ar at e visits.  If t h e visit is p erf or m e d 
o v er t w o visits, t h e n all b as eli n e ex a ms a n d q u esti o n n air es ( S ecti o n 9. 5. 2 ) a n d 
r a n d o miz ati o n ( S ecti o n 9. 5. 3 ) s h o ul d b e p erf or m e d i n t h e first visit.  If t h e s u bj ect is 
r a n d o miz e d t o t h e w ar m c o m pr ess a n d li d m ass a g e gr o u p, t h e tr e at m e nt f or w ar m 
c o m pr ess a n d li d m ass a g e ( S ecti o n 9. 5. 5 ), a n d t h e ass oci at e d disc o mf ort/ p ai n 
q u esti o n n air e a n d A E ass ess m e nt s h o ul d b e p erf or m e d at t h e first visit. If t h e s u bj ect is 
r a n d o miz e d t o T e ar C ar e, t h e n t h e T e ar C ar e pr oc e d ur e ( S ecti o n 9. 5. 4 ) a n d t h e 
ass oci at e d Disc o mf ort/ p ai n q u esti o n n air e  a n d A E ass ess m e nt  m a y b e p erf or m e d o n a 
s e p ar at e visit, as l o n g as it is p erf or m e d wit hi n 7 d a ys of t h e first visit.  If t h e T e ar C ar e 
pr oc e d ur e is p erf or m e d o n a s ec o n d visit, t h e n t h e d at e of t h e s ec o n d visit will b e D a y 0 
of t h e st u d y  f or sc h e d uli n g p ur p os es. 
 
E n d p oi nt ass ess m e nts p erf or m e d d uri n g t h e B as eli n e visit m ust b e p erf or m e d b y t h e 
M as k e d Ass ess or  ( S e e S ecti o n 9. 7 ). 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 1  of 8 4  
Si nc e dr y e y e dr o ps a n d l u bric a nts c a n aff ect t h e e n d p oi nt ass ess m e nts, i nstr uct 
s u bj ects n ot t o us e a n y of t h es e pr o d ucts wit hi n 2 h o urs of t h e B as eli n e visit. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
R A N D O MI Z A TI O N  
S u bj ects will b e r a n d o miz e d t o eit h er t h e T e ar C ar e (i. e. “tr e at m e nt gr o u p”) or W ar m 
C o m pr ess  a n d Li d M ass a g e   (i. e. “c o ntr ol gr o u p”) usi n g a ps e u d o-r a n d o m n u m b er 
g e n er at or wit h s u bj ects e nr oll e d acc or di n g t o a pr e d et er mi n e d list. R a n d o miz ati o n will 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 2  of 8 4  
us e p er m ut e d bl oc ks wit h r a n d o m bl oc k siz es of 2 or 4.  T h e i n v esti g ati o n al sit e will b e 
pr o vi d e d a s et of e n v el o p es wit h r a n d o miz ati o n assi g n m e nts. F oll o wi n g r a n d o miz ati o n, 
t h e s u bj ect s h o ul d i m m e di at el y u n d er g o t h e a p plic a bl e  pr oc e d ur es  d escri b e d  i n t h e 
s ecti o ns b el o w.   
 
T R E A T M E N T F O R T E A R C A R E G R O U P  
S u bj ects r a n d o miz e d t o t h e T e ar C ar e Gr o u p will u n d er g o t h e f oll o wi n g pr oc e d ur e .  
R ef er t o t h e T e ar C ar e I nstr ucti o ns f or Us e f or d et ail e d i nstr ucti o ns f or o p er ati n g t h e 
T e ar C ar e S yst e m.  
 
 
  
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 3  of 8 4  
 
 
 
 
  
 
 
   
 
 
 
 
   
 
 
 
 
 
 
T R E A T M E N T F O R W A R M C O M P R E S S  A N D L I D M A S S A G E G R O U P  
1.  S u bj ects r a n d o miz e d t o t h e W ar m C o m pr ess a n d Li d M ass a g e Gr o u p s h o ul d b e 
pr o vi d e d wit h t h e writt e n i nstr ucti o ns f or h o w t o p erf or m t h e d ail y w ar m 
c o m pr ess a n d li d m ass a g e  ( p er t h e m et h o d d escri b e d b y Fi nis, et al4 7) at h o m e .  
T h es e i nstr ucti o ns ar e pr o vi d e d i n A p p e n dix B.    
2.  G o o v er t h e i nstr ucti o ns pr o vi d e d i n A p p e n dix B  a n d h a v e t h e s u bj ect p erf or m 
e ac h st e p i n t h e pr es e nc e of st u d y st aff.  T his is t o e ns ur e t h e s u bj ect pr o p erl y 
u n d erst a n ds t h e i nstr ucti o ns.     
3.  I m m e di at el y f oll o wi n g t h e w ar m c o m pr ess tr e at m e nt, as k t h e s u bj ect t o ass ess 
w h et h er s/ h e ex p eri e nc e d a n y oc ul ar disc o mf ort or p ai n d uri n g or i m m e di at el y 
aft er t h e tr e at m e nt usi n g t h e sc al e s pr o vi d e d o n t h e c as e r e p ort f or m.  
4.  I nstr uct t h e s u bj ect t o p erf or m t h e w ar m c o m pr ess/li d m ass a g e o nc e  e v er y d a y.  
5.  Pr o vi d e t h e s u bj ect wit h a c o p y of t h e W ar m C o m pr ess Us e L o g a n d i nstr uct 
t h e m t o r ec or d e ac h ti m e t h e y p erf or m t h e w ar m c o m pr ess/li d m ass a g e 
tr e at m e nt. 
6.  I nstr uct t h e s u bj ect t h at if t h e y r e q uir e l u bric a nt dr o ps t o r eli e v e dr y e y e 
s y m pt o ms d uri n g t h e f oll o w-u p p eri o d, t h e y s h o ul d o nl y us e R efr es h Pl us ® dr o ps 
w hic h will b e s u p pli e d t o t h e m i n si n gl e -us e vi als b y t h e i n v esti g at or.  Pr o vi d e t h e 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 4  of 8 4  
s u bj ect wit h a s u p pl y of t h es e si n gl e-us e vi als.  R ec or d o n t h e R efr es h Pl us Vi als 
w or ks h e et h o w m uc h is pr o vi d e d t o t h e s u bj ect.   
7.  I nstr uct t h e s u bj ect t h at t h e y s h o ul d n ot r e us e t h e vi al.  O nc e o p e n e d, t h ey 
s h o ul d disc ar d t h e vi al.  I nstr uct t h e s u bj ect t o bri n g t h e u n us e d vi als b ac k at t h e 
n ext f oll o w -u p visit s o t h at t h e y c a n b e c o u nt e d.  
9. 6  F OLL O W - UP V I SI T S 
 
F OLL O W - UP V I SI T R O U TI N E P R O C E D U R E S  
Pri or t o t h e Visit:  R e mi n d er C all  
 
A f e w d a ys b ef or e t h e f oll o w -u p visit,  it is r ec o m m e n d e d t h at t h e c o or di n at or c o nt act 
t h e s u bj ect t o r e mi n d t h e m t o bri n g t h eir u n us e d R efr es h Pl us vi als  a n d, if t h e y ar e i n 
t h e w ar m c o m pr ess gr o u p, t h eir W ar m C o m pr ess L o g.   
 
Als o, si nc e dr y e y e dr o ps a n d l u bric a nts c a n aff ect t h e e n d p oi nt ass ess m e nts, it is 
i m p ort a nt t o r e mi n d s u bj ects, o n t h e d a y of t h e F oll o w -u p visit, n ot t o us e a n y of t h es e 
pr o d ucts b ef or e  t h e F oll o w -u p visit. 
 
At t h e B e gi n ni n g of t h e F oll o w -u p Visit :  M ai nt ai ni n g M as ki n g of St u d y P ers o n n el 
 
E n d p oi nt ass ess m e nts p erf or m e d d uri n g t h e F oll o w -u p visit m ust b e p erf or m e d b y t h e 
M as k e d Ass ess or  ( S e e S ecti o n 9. 7 ). 
 
At t h e b e gi n ni n g of t h e f oll o w -u p visit, t h e c o or di n at or s h o ul d r e mi n d t h e s u bj ect t o n ot 
r e v e al t h eir r a n d o miz ati o n gr o u p t o t h e st u d y p ers o n n el w h o will b e p erf or mi n g t h e 
f oll o w-u p ex a ms.  
 
Or d er of Pr oc e d ur es  D uri n g t h e F oll o w -U p  Visit  
 
F oll o w -u p pr oc e d ur es will b e p erf or m e d p er t h e St u d y Sc h e d ul e pr o vi d e d i n T a bl e 3  
( p a g e 2 8 ) a n d t h e m et h o ds i ncl u d e d i n A p p e n dix A.  Si nc e c ert ai n t ests/ ex a ms c a n 
i m p act t h e a bilit y t o p erf or m ot h er t ests/ ex a ms, th e f oll o wi n g t ests a n d ex a ms s h o ul d 
b e p erf or m e d i n t his or d er:  
 
1.  Q u esti o n n air es  
2.  M a nif est r efr acti o n a n d E T D R S B est -c orr ect e d vis u al ac uit y 
3.  Slit L a m p Ex a m  
4.  T e ar Br e a k u p Ti m e  
5.  C or n e al a n d c o nj u ncti v al st ai ni n g sc or e  
6.  M ei b o mi a n Gl a n d S ecr eti o n Sc ori n g  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 5  of 8 4  
7.  I OP 
8.  Ass ess m e nt of a d v ers e ev e nts  
T h e f oll o wi n g acti viti es c a n b e p erf or m e d i n a n y ord er:  
•  M e dic ati o n Us e  
•  C oll ecti o n of W ar m C o m pr ess L o g  
•  C o u nt u n us e d R efr es h Pl us Vi als  
At t h e E n d of t h e F oll o w -U p Visit  
 
At t h e e n d of t h e f oll o w -u p visit, pr o vi d e s u bj ects wit h a n e w s u p pl y of R efr es h Pl us 
vi als , if n e e d e d.  R ec or d h o w m a n y vi als ar e  pr o vi d e d t o t h e s u bj ect.  
 
F or s u bj ects i n t h e W ar m C o m pr ess  a n d Li d M ass a g e  gr o u p, pr o vi d e t h e m wit h a n e w 
W ar m C o m pr ess L o g f or us e i n t h e n ext f oll o w -u p p eri o d.  
 
 
6  M O N T H F OLL O W -U P V I SI T:  R E- TR E A T M E N T
 
Sc h e d uli n g t h e 6 M o nt h Visit  
 
Li k e t h e B as eli n e visit, t h e 6 m o nt h visit m a y b e p erf or m e d o v er t w o s e p ar at e visits.  If 
t h e visit is p erf or m e d o v er t w o visits, t h e n all r e q uir e d visit el e m e nts exc e pt t h e 
T e ar C ar e pr oc e d ur e a n d Disc o mf ort q u esti o n n air e s h o ul d b e p erf or m e d i n t h e first visit.  
T h e T e ar C ar e pr oc e d ur e a n d t h e ass oci at e d Disc o mf ort/ p ai n q u esti o n n air e m a y b e 
p erf or m e d o n a s e p ar at e visit, as l o n g as it is p erf or m e d wit hi n 7 d a ys of t h e first visit.  If 
t h e T e ar C ar e pr oc e d ur e is p erf or m e d o n a s ec o n d visit, t h e n t h e d at e of t h e s ec o n d visit 
will b e c o nsi d er e d t h e d at e of t h e 6 M o nt h visit f or s u bs e q u e nt visit sc h e d uli n g 
p ur p os es.  
 
At t h e 6 m o nt h f oll o w -u p visit, all s u bj ects will u n d er g o t h e t ests a n d ex a ms list e d i n 
T a bl e 3  ( p a g e 2 8 ).   
 
T e ar C ar e Gr o u p:  R e -Tr e at m e nt  
 
Aft er  c o m pl eti o n of t h e f oll o w-u p t ests a n d ex a ms, s u bj ects i n t h e T e ar C ar e gr o u p will 
u n d er g o r e -tr e at m e nt wit h t h e T e ar C ar e S yst e m, f oll o wi n g t h e i nstr ucti o ns pr o vi d e d i n 
S ecti o n 9. 5. 4 . 
 
 
 
, 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 6  of 8 4  
 
 
9. 7  M A S K E D A S S E S S O R  
T o r e d uc e p ot e nti al bi as i n t h e st u d y, st u d y st aff p erf or mi n g e n d p oi nt ass ess m e nts will 
b e m as k e d as t o t h e s u bj ect’s tr e at m e nt ar m.  I n a d diti o n, t o e ns ur e c o nsist e ncy i n 
p erf or mi n g t h e e n d p oi nt ass ess m e nts t h e st u d y st aff m e m b er w h o p erf or ms t h e 
b as eli n e  ass ess m e nts s h o ul d als o p erf or m t h e f oll o w -u p ass ess m e nts.  A n alt er n at e 
M as k e d A ss ess or m a y b e a p p oi nt e d t o h a n dl e sc h e d uli n g c o nflicts, b ut e v er y eff ort 
s h o ul d b e m a d e t o h a v e t h e s a m e p ers o n p erf or mi n g all e n d p oi nt ass ess m e nts 
t hr o u g h o ut t h e st u d y.  T he M as k e d A ss ess or s h o ul d n ot p erf or m t h e r a n d o miz ati o n, i n-
offic e T e ar C ar e Tr e at m e nt, gl a n d ex pr essi o n or t h e i n -offic e w ar m c o m pr ess tr e at m e nt 
pri or t o h o m e us e.  M as ki n g will b e m ai nt ai n e d u ntil all s u bj ects at t h e sit e h a v e p ass e d 
t h e 6- m o nt h f oll o w u p ti m e.  
 
T h e f oll o wi n g ass ess m e nts m ust b e p erf or m e d b y M as k e d A ss ess or: 
 
•  M a nif est r efr acti o n a n d B C V A  
•  Slit l a m p ex a m  
•  T e ar Br e a k -u p Ti m e  
•  C or n e al a n d c o nj u ncti v al st ai ni n g  
•  M ei b o mi a n gl a n d s ecr eti o n sc ori n g 
•  I O P 
•  A E ass ess m e nt  
 
T h e st u d y c o or di n at or s h o ul d c oll ect t h e W ar m C o m pr ess L o g fr o m t h e s u bj ect.  
9. 8  
M A N A G E M E N T O F D R Y E Y E S Y M P T O M S D U RI N G  F OLL O W - UP  
D uri n g f oll o w -u p, if s u bj ects r e q uir e dr o ps t o r eli e v e t h eir dr y e y e s y m pt o ms, t h e y m a y 
us e R efr es h ® Pl us l u bric a nt vi als w hic h h a v e b e e n s u p pli e d b y t h e i n v esti g at or .  Ot h er 
t y p es of o v er-t h e-c o u nt er l u bric a nts s h o ul d n ot b e us e d .  S u bj ects s h o ul d bri n g t h e 
u n us e d vi als t o e ac h f oll o w-u p visit s o t h at t h e y c a n b e c o u nt e d.  
 
S u bj ects s h o ul d  n ot us e R est asis or Xii dr a d uri n g t h e st u d y.   Us e of t h es e dr u gs will 
r es ult i n t h e s u bj ect b ei n g excl u d e d fr o m t h e “ P er Pr ot oc ol” a n al ysis fr o m t h e ti m e of 
i niti ati o n of t h es e dr u gs f or w ar d. 
 
S u bj ect s h o ul d n ot b e tr e at e d wit h ot h er dr y e y e tr e at m e nts ( e. g. Li pi Fl o w, p u nct al 
pl u gs, etc.) d uri n g t h e c o urs e of t h e st u d y.  A d mi nistr ati o n of t h es e tr e at m e nts will 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 7  of 8 4  
r es ult i n t h e s u bj ect b ei n g excl u d e d fr o m t h e “ P er Pr ot oc ol” a n al ysis fr o m t h e ti m e of 
i niti ati o n of t h es e tr e at m e nts f or w ar d. 
 
N O T E:  If a s u bj ect  h a d a p u nct al pl u g at t h e b as eli n e visit a n d it f alls o ut d uri n g t h e 
st u d y, it s h o ul d b e r e pl ac e d. 
9. 9  W I T H D R A W AL A N D D I S C O N TI N U A TI O N 
All s u bj ects h a v e t h e ri g ht t o wit h dr a w at a n y p oi nt d uri n g t h e tr e at m e nt wit h o ut 
pr ej u dic e.  T h e i n v esti g at or c a n disc o nti n u e a n y s u bj ect at a n y ti m e if c o nti n u e d 
p artici p ati o n i n t h e st u d y w o ul d r es ult i n h ar m t o t h e s u bj ect.  All eff orts s h o ul d b e 
m a d e b y t h e i n v esti g at or t o r et ai n t h e s u bj ect i n t h e st u d y.  If a s u bj ect wit h dr a ws 
pr e m at ur el y fr o m t h e st u d y, a g e n ui n e eff ort m ust b e m a d e t o d et er mi n e t h e r e as o n(s) 
t h e s u bj ect disc o nti n u e d t h e st u d y.  T h e r e as o n m ust b e r ec or d e d i n t h e s u bj ect’s fil e 
a n d o n t h e St u d y Exit  F or m.    
 
If a s u bj ect wit h dr a ws fr o m t h e st u d y p ost -r a n d o miz ati o n b ut pri or t o r ec ei vi n g t h e 
T e ar C ar e or W ar m C o m pr ess tr e at m e nt, t h e n t h at s u bj ect m a y b e r e pl ac e d i n t h e st u d y 
b y a n e wl y e nr oll e d s u bj ect.  
9. 1 0  S U BJ E C T S LO S T T O F OLL O W -U P  
S u bj ects w h o d o n ot s h o w u p f or a f oll o w -u p m ust b e c o nt act e d t o att e m pt t o h a v e 
t h e m c o m e f or t h e f oll o w-u p.  F or t h os e s u bj ects w h o c a n n ot b e r e ac h e d, at l e ast 3 
p h o n e c all att e m pts s h o ul d b e m a d e a n d d oc u m e nt e d.  If still n o r es p o ns e, a r e gist er e d 
l ett er s h all b e s e nt t o t h e a d dr ess o n fil e f or t h e s u bj ect i n a n att e m pt t o m a k e c o nt act.  
If a s u bj ect miss es t w o c o ns ec uti v e f oll o w-u p visits wit h o ut a n y c o nt act wit h t h e st u d y 
st aff, t h e s u bj ect will b e c o nsi d er e d l ost-t o-f oll o w-u p u nl ess t h er e is a f urt h er  
c o m m u nic ati o n b y t h e s u bj ect. 
1 0  A D V E R S E E V E N T S ( A ES) 
A d v ers e E v e nts ar e d efi n e d b el o w.  A d v ers e e v e nts t h at occ ur i n t h e e y e d uri n g t h e tri al, 
w h et h er t h e y ar e c o nsi d er e d t o b e d e vic e r el at e d or n ot, m ust b e d oc u m e nt e d i n t h e 
s u bj ect’s r ec or ds.  D at e of t h e e v e nt, its s e v erit y, tr e at m e nt (if a n y) a n d t h e assess e d 
r el ati o ns hi p of t h e e v e nt t o t h e st u d y d e vic e will b e r ec or d e d o n t h e A d v ers e E v e nt 
F or m.  C o n diti o ns w hic h exist at t h e ti m e t h e s u bj ect is e nr oll e d d o n ot n e e d t o b e 
r ec or d e d as a d v ers e e v e nts u nl ess t h e y i ncr e as e i n s e v erit y d uri n g t h e st u d y. 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 8  of 8 4  
1 0. 1  D E FI NI TI O N S O F A E,  S A E,  S A D E,  U S A D E  
A d v ers e E v e nt  
A n y u nt o w ar d m e dic al occ urr e nc e i n a s u bj ect w h o h as b e e n 
tr e at e d wit h t h e d e vic e t h at d o es n ot n ec ess aril y h a v e c a us al 
r el ati o ns hi p wit h t h e tr e at m e nt. 
A d v ers e D e vic e 
Eff ect  
A n y u nf a v or a bl e a n d u ni nt e n d e d si g n (i ncl u di n g a n a b n or m al 
l a b or at or y fi n di n g), s y m pt o m, or dis e as e t h at is p ossi bl y r el at e d 
t o t h e st u d y d e vic e. 
S eri o us A d v ers e 
E v e nt ( S A E)  
A n y u nt o w ar d m e dic al occ urr e nc e t h at:  
•  R es ults i n d e at h  
•  Is lif e-t hr e at e ni n g 
•  R e q uir es i n -p ati e nt h os pit aliz ati o n or pr ol o n gs existi n g 
h os pit aliz ati o n  
•  N ec essit at es m e dic al or s ur gic al i nt er v e nti o n t o pr ecl u d e 
p er m a n e nt i m p air m e nt of a b o d y f u ncti o n or p er m a n e nt 
d a m a g e t o a b o d y str uct ur e  
•  Si g ht t hr e at e ni n g  
U n a ntici p at e d 
A d v ers e D e vic e 
Eff ect  
A n y s eri o us a d v ers e eff ect o n h e alt h or s af et y, a ny lif e -
t hr e at e ni n g pr o bl e m or d e at h c a us e d b y, or ass oci at e d wit h a 
d e vic e if t h at eff ect, pr o bl e m, or d e at h w as n ot pr e vi o usl y 
i d e ntifi e d i n n at ur e, s e v erit y, or d e gr e e of i nci d e nc e i n t h e 
cli nic al i n v esti g ati o n al pl a n; or a n y ot h er s eri o us pr o bl e m 
ass oci at e d wit h a d e vic e t h at r el at es t o t h e ri g hts, s af et y, or 
w elf ar e of s u bj ects ( 2 1 C F R 8 1 2. 3(s)).  A n y si g ht -t hr e at e ni n g 
e v e nt, w h et h er list e d i n t h e pr ot oc ol or n ot, is c o nsi d er e d t o b e 
r e p ort a bl e as a U A D E 
 
1 0. 2  LI S T O F A N TI CI P A T E D P O T E N TI AL  A D V E R S E E V E N T S  
A ntici p at e d p ot e nti al a dv ers e e v e nts i ncl u d e t h os e t h at mi g ht r e as o n a bl y b e ex p ect e d t o 
occ ur i n t his st u d y b ec a us e t h e y ar e ass oci at e d wit h dr y e y e dis e as e , t h e ris k a n al ysis f or 
T e ar C ar e S yst e m  ( al b eit r e m ot e li k eli h o o d), st u d y t esti n g m et h o ds or p ot e nti al ris ks 
ass oci at e d wit h w ar m c o m pr ess es  a n d li d m ass a g e .  
•  B ur n, er yt h e m a, or s w elli n g of t h e e y eli ds  
•  C o nj u ncti v al i nj ecti o n  ( M o d er at e or s e v er e) 
•  C o nj u ncti v al a br asi o n  
•  C or n e al a br asi o n  
•  C or n e al d ef or m ati o n  
•  All er gic or i nfl a m m at or y r e acti o n t o m e dic al a d h esi v e o n t h e iLi d d e vic e  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 3 9  of 8 4  
•  F or m ati o n of a c h al azi o n or st y e  
•  L oss i n B C V A of 2 li n es or gr e at er  
•  W ors e n i n g of dr y e y e s y m pt o m 
•  I ncr e as e d d isc o mf ort or p ai n of oc ul ar s urf ac e ( gritti n ess, f or ei g n b o d y s e ns ati o n, 
etc.)  
•  Disc o mf ort or p ai n  of e y eli ds or or bit  
1 0. 3  R E P O R TI N G A D V E R S E E V E N T S A N D U N A N TI CI P A T E D A D V E R S E D E VI C E 
E F F E C T S 
I d e ntific ati o n, c oll ecti o n a n d r e p orti n g of a d v ers e e v e nt i nf or m ati o n is t h e r es p o nsi bilit y 
of t h e pri nci p al i n v esti g at or.  T h e i n v esti g at or r ec or ds t h e d at e of t h e e v e nt, its s e v erit y, 
tr e at m e nt (if a n y) a n d t h e ass ess e d r el ati o ns hi p of t h e e v e nt t o t h e st u d y d e vic e o n t h e 
A d v ers e E v e nt C as e R e p ort F or m  ( A E C R F).   
A n y oc ul ar -r el at e d s eri o us a d v ers e e v e nt ( S A E) s h o ul d b e r e p ort e d t o t h e st u d y s p o ns or 
wit hi n o n e w or ki n g d a y of l e ar ni n g of t h e e v e nt .  N o n -oc ul ar -r el at e d S A Es s h o ul d b e 
r e p ort e d t o t h e st u d y s p o ns or wit hi n t w o w or ki n g d a ys of l e ar ni n g of t h e e v e nt.  E m ail 
t h e A E C R F t o T Cs af et y @si g htsci e nc es.c o m. 
A n y  u n a ntici p at e d a d v ers e d e vic e eff ects ( U A D E)  m ust b e r e p ort e d  t o t h e f oll o wi n g 
t w o e ntiti es: 
1.  T h e st u d y s p o ns or  – Wit hi n o n e w or ki n g d a y of t h e i n v esti g at or first l e ar ni n g of 
t h e e v e nt, e-m ail  t h e A E C R F t o T Cs af et y @si g htsci e nc es.c o m; a n d  
2.  T h e r e vi e wi n g I R B – As s o o n as p ossi bl e, b ut n o l at er t h a n 1 0 w or ki n g d a ys aft er 
t h e i n v esti g at or first l e ar ns of t h e e v e nt, r e p ort p er t h e I R B’s i nstr ucti o ns .  
T h e s p o ns or will c o n d uct a n e v al u ati o n of u n a ntici p at e d a d v ers e d e vic e eff ects.  If t h e 
s p o ns or d et er mi n es t h at a n u n a ntici p at e d a d v ers e d e vic e eff ect pr es e nts a n 
u nr e as o n a bl e ris k t o s u bj ects, p arts of t h e i n v esti g ati o n pr es e nti n g ris ks will b e 
t er mi n at e d.  T er mi n ati o n will occ ur n o l at er t h a n 5 w or ki n g d a ys aft er t h e s p o ns or 
m a k es s uc h a d et er mi n ati o n a n d n o l at er t h a n 1 5 w or ki n g d a ys aft er t h e s p o ns or first 
r ec ei v e d n otic e of t h e eff ect. 
1 1  R I S K- BE N E FI T A N AL Y SI S  
1 1. 1  A N TI CI P A T E D CLI NI C AL B E N E FI T S  
T h e T e ar C ar e ™ pr oc e d ur e will b e p erf or m e d wit h t h e ai m of r e d uci n g t h e si g ns a n d 
s y m pt o ms of dr y e y e.   T h e g o al of t h e pr oc e d ur e is t o pr o vi d e a s af e, r e pr o d uci bl e, a n d 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 0  of 8 4  
eff ecti v e tr e at m e nt f or dr y e y e dis e as e, a dis e as e f or w hic h t h er e is a n u n m et n e e d f or 
eff ecti v e t h er a pi es.  
1 1. 2  A N T I CI P A T E D A D V E R S E D E VI C E E F F E C T S 
A ntici p at e d a d v ers e eff ects ass oci at e d wit h t h e T e ar C ar e S yst e m h a v e b e e n d escri b e d 
a b o v e i n S ecti o n 1 0. 2 . 
1 1. 3  R E SI D U AL RI S K S A S S O CI A T E D WI T H T H E T E S T  D E VI C E , A S I D E N TI FI E D I N 
T H E RI S K A N AL Y SI S R E P O R T  
Si g ht Sci e nc es b eli e v es t h at t h er e ar e n o I nt ol er a bl e r esi d u al ris ks fr o m t his n o n -
i n v asi v e, c o ntr oll e d h e at tr e at m e nt d e vic e t h at c a n b e e asil y a n d q uic kl y r e m o v e d b y t h e 
s u bj ect or b y t h e s u p er visi n g o p ht h al m ol o gist , i n t h e e v e nt of a c o m plic ati o n d uri n g a 
T e ar C ar e tr e at m e nt s essi o n . 
1 1. 4  R I S K S A S S O CI A T E D WI T H P A R TI CI P A TI O N I N T H E CLI NI C AL 
I N V E S TI G A TI O N 
All a ntici p at e d st u d y ris ks ar e list e d i n S ecti o n 1 0. 2 . 
1 1. 5  P O S SI BL E I N T E R A C TI O N S WI T H  C O N C O MI T A N T M E DI C AL T R E A T M E N T S  
It is a ntici p at e d t h at t h er e will b e n o i nt er acti o ns wit h c o nc o mit a nt m e dic al tr e at m e nts.   
1 1. 6  S T E P S T H A T WILL B E T A K E N T O C O N T R OL O R MI TI G A T E T H E RI S K S  
T h e m aj or ris ks t o t h e s u bj ects a n d t h e st e ps t a k e n t o c o ntr ol or miti g at e t h e m ar e 
d escri b e d b el o w:  
 
1.  Ov er h e ati n g of t h e e y eli d s: All T e ar C ar e tr e at m e nts will b e d o n e i n t h e 
i n v esti g at or’s offic e u n d er dir ect s u p er visi o n of t h e i n v esti g at or. T h e d e vic e 
d eli v ers h e at t o t h e e y eli ds at a t e m p er at ur e r a n gi n g fr o m 4 1-4 5 °C.  T his 
t e m p er at ur e r a n g e w as s el ect e d b ec a us e it is b ot h s af e f or e y eli d h e ati n g a n d 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 1  of 8 4  
eff ecti v e f or m elti n g o bstr ucti o ns i n t h e m ei b o mi a n gl a n ds. 4 8 ,4 9 ,5 0 ,5 1  T h e us er  
c a n a dj ust t h e t e m p er at ur e u p or d o w n  t o a l e v el t h at is c o mf ort a bl e, a n d m a y 
als o s h ut off t h e S yst e m at a n y ti m e if it is t o o u nc o mf ort a bl e or p ai nf ul.  I n 
a d diti o n, t h e T e ar C ar e Syst e m c o nti n u o usl y m o nit ors a n d r e g ul at es t h e 
t e m p er at ur e at t h e tiss u e-c o nt acti n g s urf ac e of t h e iLi d d e vic es a n d h as b e e n 
d esi g n e d t o  n ot exc e e d t h e  m axi m u m all o w a bl e t e m p er at ur e .    
 
2.  C or n e al a br asi o n : If t h e iLi d d e vic es ar e n ot p ositi o n e d pr o p erl y or c o m e l o os e 
d uri n g t h e tr e at m e nt, t h er e is t h e p ot e nti al f or a c or n e al a br asi o n. T o miti g at e 
t his, t h e s u p er visi n g p h ysici a n will a p pl y t h e stri ps t o t h e s u bj ect a n d will m o nit or 
t h eir p ositi o n d uri n g  t h e tr e at m e nt t o e ns ur e t h ey r e m ai n i n pl ac e a n d s ec ur e. 
 
I n a d diti o n, t h er e is t h e p ossi bilit y of c or n e al a br asi o n or a br asi o n of t h e e y eli d 
s urf ac e d uri n g ex pr essi o n of t h e m ei b o mi a n gl a n ds.  T o r e d uc e t h e c h a nc e of 
a br asi o n, t h e f orc e ps h av e b e e n d esi g n e d wi t h s m o ot h s urf ac es (i. e. n o r o u g h 
e d g es)  a n d o nl y tr ai n e d us ers will p erf or m ex pr essi o n . 
 
3.  W ors e ni n g of dr y e y e  s y m pt o ms:  It is p ossi bl e t h at s u bj ects will ex p eri e nc e a 
w ors e ni n g of dr y e y e s y m pt o ms d uri n g t h e st u dy .  S u bj ects will u n d er g o a 
c o m pl et e e y e ex a m at e ac h  visit a n d if a n y u nt o w ar d or w ors e ni n g si g ns of 
oc ul ar s urf ac e dis e as e  ar e o bs er v e d, t h e y will b e tr e at e d a p pr o pri at el y.  
 
I n a d diti o n t o t h e a b o v e, t h e f oll o wi n g miti g ati o n st e ps h a v e als o b e e n t a k e n t o r e d uc e 
t h e ris ks i n t his st u d y: 
 
•  T h e d e vic e h as b e e n t est e d t o d e m o nstr at e t h at it m e ets p erf or m a nc e a n d 
s af et y s p ecific ati o ns, as d escri b e d i n S ecti o n 5. 1 . 
•  I nstr ucti o ns f or Us e ar e pr o vi d e d wit h e ac h d e vic e. 
•  T h e cli nici a n usi n g t h e d evic e will b e tr ai n e d i n h o w t o s af el y a n d c orr ectl y a p pl y 
a n d r e m o v e t h e iLi d d e vic es, a n d o p er at e t h e T e ar C ar e S yst e m.  
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 2  of 8 4  
1 2  S T A TI S TI C AL C O N SI D E R A TI O N S  
1 2. 1  E V AL U A BILI T Y  
All s u bj ects o n  w h o m t h e T e ar C ar e d e vic e is att e m pt e d will b e c o nsi d er e d e v al u a bl e f or 
t h e s af et y a n al ysis. All e y es t h at h a v e at l e ast o n e p ost o p er ati v e visit a n d h a v e n o m aj or 
pr ot oc ol d e vi ati o ns will b e e v al u a bl e f or t h e p er pr ot oc ol a n al ysis.  
1 2. 2  A N AL Y SI S P O P UL A TI O N S  
T h e p er -pr ot oc ol a n al ysis p o p ul ati o n i ncl u d es all s u bj ects w h o h a v e at l e ast o n e p ost -
tr e at m e nt visit a n d h a v e n o m aj or pr ot oc ol d e vi ati o ns , i ncl u di n g s p ecific ally n o us e of 
dr y -e y e m e dic ati o ns ( Xii dr a, R est asis) . T h e pri m ar y a n d s ec o n d ar y e n d p oi nt a n al ys es will 
b e c arri e d o ut o n t h e p er -pr ot oc ol p o p ul ati o n.  T h e pri m ar y a n al ysis p o p ul ati o n will b e 
p er -pr ot oc ol.   
T h e i nt e nt -t o-tr e at (I T T) a n al ysis p o p ul ati o n i ncl u d es all s u bj ects w h o ar e r a n d o miz e d t o 
eit h er ar m, r e g ar dl ess of tr e at m e nt r ec ei v e d. T h e pri m ar y a n d s ec o n d ar y e n d p oi nt 
a n al ys es will als o b e c arri e d o ut o n  t h e I T T p o p ul ati o n as w ell . 
1 2. 3  S U BJ E C T  A C C O U N T A BILI T Y  
A c o m pl et e acc o u nti n g of s u bj ects b y visit will b e pr o vi d e d, i ncl u di n g r e as o ns f or 
dr o p o ut, if k n o w n.  
1 2. 4  D E M O G R A P HI C S A N D B A S ELI N E C H A R A C T E RI S TI C S  
D e m o gr a p hic v ari a bl es g e n d er, r ac e, et h nicit y, a n d a g e will b e s u m m ariz e d f or all 
e nr oll e d s u bj ects, al o n g wit h m e dic al hist or y.  D escri pti v e st atistic al s u m m ari es of pr e -
tr e at m e nt p ar a m et ers ( mi n, m ax, m e di a n, m e a n, st a n d ar d d e vi ati o n) will als o b e 
pr o vi d e d  f or e ac h tr e at m e nt ar m. T his i ncl u d es b as eli n e m e as ur e m e nts f or e ac h of t h e 
st u d y e n d p oi nts: T B U T, M ei b o mi a n Gl a n d  S ecr eti o n  Sc or e, C or n e al S t ai ni n g, 
C o nj u ncti v al St ai ni n g, O S DI Sc or e,  S A N D E Sc or e, a n d E y e Dr y n ess Sc or e . 
All b as eli n e m e as ur e m e nts will b e e v al u at e d f or a d e q u at e b al a nc e b et w e e n t h e t w o 
tr e at m e nt ar ms. 
1 2. 5  E N D P OI N T S A N D A N AL Y SI S M E T H O D S  
All pri m ar y a n d s ec o n d ary e n d p oi nts will b e e v al u at e d at 1 m o nt h  f or s u b missi o n f or 
r e g ul at or y a p pr o v al.  O utc o m es m e as ur e d o n a p er -e y e b asis will b e a n al yz e d usi n g 
li n e ar mix e d eff ect m o d els t o acc o u nt f or wit hi n-p ers o n c orr el ati o n (c orr el ati o n 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 3  of 8 4  
b et w e e n ri g ht a n d l eft ey es).  If t h e pri m ar y e n d p oi nt is s ucc essf ul at 1 m o nt h, a n d f or 
all s ucc essf ul s ec o n d ar y e n d p oi nts, tr e at m e nt d ur ati o n will b e f urt h er e v al u at e d at 3 
a n d 6 m o nt hs.  
 D E S C RI P TI V E A N AL Y S E S  
All o utc o m e m e as ur es, I O P o utc o m es, a n d Us e of dr y e y e l u bric a nts, will b e t a b ul at e d b y 
visit a n d tr e at m e nt gr o u p.  
 P RI M A R Y E F F E C TI V E N E S S E N D P OI N T  
T h e pri m ar y eff ecti v e n ess o utc o m e is t h e c h a n g e fr o m b as eli n e i n T e ar Br e a k -U p Ti m e 
( T B U T) at t h e 1 m o nt h f oll o w u p.  T B U T will b e a n al yz e d usi n g a li n e ar mix e d eff ects 
(L M E) m o d el.  T his will all o w f or t h e pr o p er i nc or p or ati o n of wit hi n-p ers o n c orr el ati o n  
i nt o t h e st atistic al m o d el, a n d will als o all o w f or a dj ust m e nt f or b as eli n e m e as ur e m e nts.  
D et ails of t h e L M E m o d el ar e pr o vi d e d i n t h e St atistic al A n al ysis Pl a n ( S A P) pr o vi d e d i n 
A p p e n dix C.  Hy p ot h es es r e g ar di n g t h e pri m ar y a n d s ec o n d ar y eff ecti v e n ess o utc o m es 
ar e d escri b e d b el o w i n S ecti o n 1 2. 6 . 
 P O OL A BILI T Y  
Usi n g t h e L M E m o d eli n g a p pr o ac h o utli n e d a b o v e, p o ol a bilit y will b e e v al u at e d acr oss 
c e nt ers b y t esti n g a Tr e at m e nt -b y -C e nt er i nt er acti o n  ( Tx C).  If t h e Tx C i nt er acti o n is 
si g nific a nt at α = 0. 1 5 a C e nt er eff ect will b e i ncl u d e d i n t h e fi n al m o d el a n d r es ults will 
b e r e p ort e d  s e p ar at el y by C e nt er. F or t his a n al ysis, C e nt ers wit h l ess t h a n 5 e nr oll e d 
s u bj ects will b e c o m bi n e d i nt o a si n gl e virt u al c e nt er.  
 M I S SI N G D A T A  
As a s e nsiti vit y a n al ysis, m ulti pl e i m p ut ati o n s f or t h e pri m ar y o utc o m e at t h e 1 m o nt h  
ti m e p oi nt will b e c arri e d o ut usi n g b as eli n e c h ar act eristics a n d 1 -w e e k o utc o m es  as 
pr e dict ors .  D et ails ar e pr o vi d e d i n t h e S A P  ( A p p e n dix C).  
 S E C O N D A R Y E F F E C TI V E N E S S E N D P OI N T S  
T h e s ec o n d ar y eff ecti v e n ess e n d p oi nts i ncl u d e c h a n g e fr o m b as eli n e f or t h e f oll o wi n g 
o utc o m es:  
1.  Oc ul ar S urf ac e Dis e as e I n d ex ( O S DI) sc or e,  
2.  T ot al M ei b o mi a n Gl a n d  S ecr eti o n S c or e,  
3.  C or n e al st ai ni n g sc or e,  
4.  C o nj u ncti v al st ai ni n g sc or e,  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 4  of 8 4  
5.  S y m pt o m Ass ess m e nt i N Dr y E y e ( S A N D E) Fr e q u e ncy sc or e, S e v erit y Sc or e a n d 
T ot al sc or e. 
6.  E y e Dr y n ess Sc or e ( E D S)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 E V AL U A TI O N O F T R E A T M E N T D U R A TI O N  
If t h e pri m ar y e n d p oi nt is s ucc essf ul at t h e o n e m o nt h pri m ar y ti m e p oi nt, t h e n 
tr e at m e nt d ur ati o n will b e e v al u at e d usi n g a hi er arc hic al t esti n g pr oc e d ur e.  Usi n g d at a 
t h at ar e o bt ai n e d at t h e 3- a n d 6 -m o nt h f oll o w -u p visits w e will a g ai n t est t h e pri m ar y 
h y p ot h esis c o m p ari n g c h a n g e fr o m b as eli n e T e ar Br e a k -U p Ti m e ( T B U T) b et w e e n t h e 
tr e at m e nt a n d c o ntr ol.  W e will us e t h e s a m e li n e ar mix e d eff ects (L M E) m o d el as i n t h e 
pri m ar y a n al ysis, e v al u ati n g e ac h ti m e p oi nt s e p ar at el y.  T h e t w o ti m e p oi nts will b e 
t est e d s e q u e nti all y, st o p pi n g at 3 m o nt hs if t h e t est f ails at t h at p oi nt.  Tr e at m e nt 
d ur ati o n will b e t h e m axi m u m ti m e p oi nt at w hic h t his tr e at m e nt d ur ati o n t esti n g 
s ucc e e ds, eit h er 1, 3, or 6 m o nt hs.  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 5  of 8 4  
T his a n al ysis will n ot b e c arri e d o ut if t h e pri m ar y 1 -m o nt h e n d p oi nt f ails, it is n ot 
i nt e n d e d t o est a blis h pri m ar y eff ecti v e n ess i n t h e e v e nt of st u d y f ail ur e at o n e m o nt h. 
N ot e t h at t his a n al ysis will b e c arri e d o ut usi n g d at a t h at will b e at l e ast p arti all y 
o bt ai n e d aft er t h e pri m ar y d at a b as e l oc k.  H o w e v er e v er y eff ort will b e m a d e t o 
m ai nt ai n t h e m as ki n g of ass ess ors t hr o u g h t h e 6 -m o nt h f oll o w -u p as d escri b e d i n 
s ecti o n 9. 7. 
T his a n al ysis d o es n ot aff ect t h e t y p e I err or f or t h e pri m ar y e n d p oi nt.  T h e 1 - 3- a n d 6 -  
m o nt h T B U T o utc o m es will li k el y b e hi g hl y c orr el at e d, h o w e v er t h e s e q u e nti al t esti n g 
will a p pr o pri at el y c o ntr ol t h e ti m e -wis e t y p e I err or r at e.  
F or e ac h s ec o n d ar y e n d p oi nt t h at is s ucc essf ul at t h e o n e m o nt h ti m e p oi nt usi n g t h e 
hi er arc hic al t esti n g pr oc e d ur e d escri b e d i n 1 2. 5. 5, tr e at m e nt d ur ati o n will b e e v al u at e d 
at t h e 3 - a n d 6 -m o nt h f oll o w u p.  E v al u ati o n of tr e at m e nt d ur ati o n f or t h e s ec o n d a r y 
e n d p oi nts will b e b as e d o n s e q u e nti al t esti n g of 3 - a n d 6 -m o nt h f oll o w u p ti m es 
s e p ar at el y, i n t h e s a m e m a n n er as f or t h e pri m ary e n d p oi nt. S ec o n d ar y e n d p oi nts t h at 
f ail at t h e 1-m o nt h ti m e p oi nt will n ot b e e v al u at e d f or tr e at m e nt d ur ati o n.  
 A D DI TI O N AL E X PL O R A T O R Y  A N AL Y S E S  
T h e f oll o wi n g a d diti o n al eff ecti v e n ess a n al ys es will b e pr o vi d e d at t h e ti m e of r e g ul at or y 
s u b missi o n: 
 
•  N u m b er of m ei b o mi a n gl a n ds yi el di n g cl e ar li q ui d s ecr eti o ns  
•  N u m b er of m ei b o mi a n gl a n ds s ecr eti n g a n y li q ui d (cl e ar or cl o u d y)  
•  Us e of dr y e y e l u bric a nts, c oll ect e d t hr o u g h c o u nti n g u n us e d vi als of R efr es h Pl us   
 
T h e m ei b o mi a n gl a n d -r el at e d m e as ur e m e nts will b e a n al yz e d i n t h e s a m e m a n n er as 
t h e p er-e y e s ec o n d ar y e n d p oi nts.   
L u bric a nt us e will b e s u m m ariz e d b y Tr e at m e nt gr o u p at e ac h f oll o w -u p visit.  
 M O D ELI N G O F E X T E N D E D F OLL O W -U P R E S UL T S 
Aft er t h e i niti al 1 m o nt h  pri m ar y a n al ysis, s u bj ects will b e f oll o w e d u p t o 1 2 m o nt hs t o 
e v al u at e d ur a bilit y of t h e tr e at m e nt eff ect.  Aft er t h e 6 m o nt h visit, s u bj ects i n t h e 
W ar m C o m pr ess gr o u p will cr oss o v er i nt o t h e T e ar C ar e ar m.   Tr e at m e nt d ur ati o n will 
b e e v al u at e d pri m aril y vi a c o m p aris o ns of tr e at m e nt v ers us c o ntr ol c h a n g e i n T B U T at 
e ac h of t h e 3 - a n d 6 -m o nt h ti m e p oi nts s e p ar at el y as d escri b e d i n 1 2. 5. 6.  
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 8  of 8 4  
t h e n e e ds of t h e st u d y, a n d t o f a mili ariz e t h e i n v esti g at or wit h t h e st u d y 
pr ot oc ol.    
•  Sit e I niti ati o n :  Si g ht Sci e nc es or C R O p ers o n n el will m e et wit h t h e 
i n v esti g at or(s) a n d cli nic al st u d y st aff w h e n t h e sit e is r e a d y t o b e gi n  e nr olli n g 
s u bj ects in or d er t o tr ai n t h e m i n h o w t o pr o p erl y s el ect s u bj ects, p erf or m  t h e 
st u d y pr oc e d ur e, a n d r ec or d st u d y d at a.  T his visit will i ncl u d e, b ut n ot b e 
li mit e d t o a r e vi e w of t h e f oll o wi n g: 
o  D et ail e d r e vi e w of t h e pr ot oc ol  
o  I nf or m e d c o ns e nt pr oc e d ur es 
o  R a n d o miz ati o n pr oc e d ur es  
o  I nstr ucti o n i n h o w t o us e t h e T e ar C ar e S yst e m 
o  G ui d a nc e i n h o w t o i nstr uct s u bj ects t o us e t h e w ar m c o m pr ess at h o m e 
a n d p erf or m li d m ass a g e at h o m e.  
o  G ui d a nc e i n h o w t o a d mi nist er q u esti o n n air es t o s u bj ects  
o  Pr oc e d ur es f or m ai nt ai ni n g m as ki n g of st u d y p ers o n n el  
o  R ec or ds a n d r e p orts  
•  I nt eri m M o nit ori n g:  Si g ht Sci e nc es or C R O p ers o n n el  will  visit t h e cli nic al sit e 
r o uti n el y d uri n g t h e st u dy t o r e vi e w c h arts a n d t o p erf or m s o urc e d oc u m e nt 
v erific ati o n, t o e ns ur e pr o p er a d h er e nc e t o t h e st u d y pr ot oc ol, a n d t o r e vi e w 
r e g ul at or y d oc u m e nts.  I nt eri m m o nit ori n g visits a n d t el e p h o n e c o ns ult ati o n 
will occ ur as n ec ess ar y d uri n g t h e c o urs e of t h e st u d y t o e ns ur e t h e pr o p er 
pr o gr ess a n d d oc u m e nt ati o n of t h e st u d y fi n di n gs.  
•  St u d y Cl os ur e :  At t h e c o ncl usi o n of t h e tri al t h er e will b e a st u d y cl os ur e visit  
d uri n g w hic h s e v er al acti o ns, i ncl u di n g b ut n ot li mit e d t o t h e f oll o wi n g, will b e  
p erf or m e d:  
o  A fi n al i ns p ecti o n of t h e st u d y bi n d er  
o  Acc o u nt a bilit y a n d r et ur n of all d e vic es a n d st u d y m at eri als t o t h e 
s p o ns or 
o  Disc ussi o n of r ec or d r et e nti o n r e q uir e m e nts wit h t h e i n v esti g at or  
o  Cl os e -o ut n otific ati o n t o t h e I R B   
1 4  D A T A A N D Q U ALI T Y M A N A G E M E N T  
1 4. 1  D A T A B A S E M A N A G E M E N T  
T h e st u d y d at a b as e will b e d esi g n e d usi n g a n el ectric d at a c a pt ur e ( E D C) s yst e m t h at is 
c o m pli a nt wit h 2 1 C F R P art 1 1 a n d r el e v a nt g ui d a nc e d oc u m e nts.  T h e E D C  will b e 
d e v el o p e d a n d m ai nt ai n e d b y a n i n d e p e n d e nt , q u alifi e d d at a m a n a g e m e nt fir m. 
 
T h e d at a b as e will i nc or p or at e ti m e -st a m p e d a u dit tr ails, pr ot ecti o n of h u m a n s u bj ects, 
r estrict e d acc ess, a n d d at a s ec urit y at t h e c o m p o n e nt l e v el.  E ac h d at a b as e m o d ul e, 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 4 9  of 8 4  
i ncl u di n g e ac h i n di vi d u al e C R F, will b e v ali d at e d by c o n d ucti n g a s eri es of st a n d ar d t ests 
t h at d e m o nstr at e us a bilit y a n d c orr ect n ess of t h e d at a b as e s yst e m.  T h e d at a b as e will 
b e m ai nt ai n e d o n a n o n g oi n g b asis a n d will b e r o uti n el y b ac k e d u p.  
1 4. 2  S U BJ E C T ID E N TI FI C A TI O N  
T h e s u bj ects will b e i d e ntifi e d b y a fi v e di git s u bj ect n u m b er c o m p os e d of a o n e -di git 
st u d y i d e ntific ati o n n u m b er, a t w o di git c e nt er i d e ntific ati o n n u m b er f oll o w e d b y a t w o 
di git s e q u e nti al s u bj ect n u m b er.  T h e s u bj ect i d e ntific ati o n will b e assi g n e d w h e n 
i nf or m e d c o ns e nt is o bt ai n e d.  I n t his w a y, i nf or m ati o n c o nt ai n e d i n t h e st u d y r ec or ds 
will b e k e pt as c o nfi d e nti al as p ossi bl e.  
1 4. 3  S U BJ E C T A C C O U N T A BILI T Y  
All s u bj ects r a n d o miz e d  a n d tr e at e d  i n t his cli nic al i n v esti g ati o n s h all b e m o nit or e d f or 
t h e d ur ati o n of t h e i n v esti g ati o n. T h e cli nic al i n v esti g ati o n s h all b e c o nsi d er e d 
c o m pl et e d w h e n all s u bj ects t h at h a v e b e e n e nr oll e d i n t h e i n v esti g ati o n  h a v e r e ac h e d 
t h e fi n al r e p orti n g p eri o d, excl u di n g s u bj ects w h o w er e wit h dr a w n .   
1 4. 4  C O N FI D E N TI ALI T Y  
All m e dic al r ec or ds ass oci at e d wit h t h e cli nic al i n v esti g ati o n will b e m a d e av ail a bl e f or 
r e vi e w b y Si g ht Sci e nc es p ers o n n el, its c o ntr act r es e arc h or g a niz ati o n ( C R O) a n d 
g o v er n m e nt al/r e g ul at ory a g e nci es i n v ol v e d.  T h e r es ults of t h e st u d y m a y b e p u blis h e d  
i n t h e f ut ur e f or sci e ntific a n d m ar k eti n g p ur p os es, b ut t h e i d e ntit y ( n a m e) of e ac h 
s u bj ect will n ot b e r e v e al e d.  All r ec or ds will b e st or e d i n a s ec ur e ar e a at t h e 
i n v esti g at or’s f acilit y, t h e C R O, t h e d at a m a n a g e m e nt fir m a n d at Si g ht Sci e nc es, I nc.  
1 4. 5  S O U R C E D A T A A N D C A S E R E P O R T F O R M S  
S o urc e d at a will b e e nt er e d i nt o a v ali d at e d el ectr o nic s yst e m at e ac h sit e b y tr ai n e d 
p ers o n n el i n acc or d a nc e wit h 2 1 C F R P art 1 1 r e q uir e m e nts.  El ectr o nic e ntri es will b e 
1 0 0 % v erifi e d a g ai nst c orr es p o n di n g s o urc e d at a at t h e sit es a n d q u eri e d/c orr ect e d if 
n e e d e d t o t h e ext e nt p ossi bl e.  M e dic al sit e r ec or ds s er v e as s o urc e d at a.  I n a d diti o n, 
d at a t h at ar e c oll ect e d excl usi v el y f or t h e p ur p os e of t his st u d y a n d n ot n or m all y 
r ec or d e d i n t h e s u bj ects’ m e dic al r ec or ds c a n b e c oll ect e d dir ectl y o n t h e st u d y 
w or ks h e ets pr o vi d e d b y t h e s p o ns or  a n d t h es e st u d y w or ks h e ets will s er v e as t h e 
s o urc e d at a.   
 
S o urc e d at a a n d st u d y w or ks h e ets ar e t o b e m ai nt ai n e d at t h e sit e i n t h e s u bj ect 
r ec or ds or i n t h e m e dic al r ec or ds.  All e ntri es m ust b e m a d e i n bl ac k or bl u e i n k a n d 
c h a n g es m ust b e m a d e by stri k e-t hr o u g h o nl y wit h d at e a n d i niti als or si g n at ur e.  All 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 0  of 8 4  
s o urc e d oc u m e nts m ust b e c o m pl et e d a n d si g n e d b y t h e a ut h oriz e d st u d y p ers o n n el 
( e. g., st u d y c o or di n at or).    N o “ w hit e-o ut” is t o b e us e d o n t h e s o urc e d oc u m e nts.  
1 4. 6  R E T E N TI O N P E RI O D  
Cli nic al sit es ar e t o r et ai n a n y a n d all cli nic al tri al m at eri al ( d oc u m e nt ati o n, p h ot o gr a p hs, 
etc.) f or a p eri o d of t w o y e ars fr o m t h e d at e t h e m ar k eti n g a p plic ati o n is a p pr o v e d or 
t w o y e ars aft er t h e i n v esti g ati o n h as b e e n disc o nti n u e d, or as dir ect e d b y t h eir 
i nstit uti o n al d oc u m e nt r et e nti o n r e q uir e m e nts, w hic h e v er is t h e l o n g est.  Aft er t h at 
ti m e, t h e it e ms m ust b e r et ur n e d t o Si g ht Sci e nc es f or arc hi vi n g.  U n us e d m e dic al 
d e vic es ar e t o b e r et ur n e d t o t h e s p o ns or at t h e c o ncl usi o n of t h e e nr oll m e nt p eri o d.  
1 5  P R O T O C OL M O DI FI C A TI O N S A N D D E VI A TI O N S  
Pr ot oc ol m o dific ati o ns m a y occ ur d uri n g t h e st u dy.   E ac h will b e a p pr o v e d b y t h e 
s p o ns or b ef or e i m pl e m e nt ati o n. E ac h will u n d er g o I nstit uti o n al R e vi e w B o ar d (I R B) 
r e vi e w a n d a p pr o v al, as n ec ess ar y. 
 
A n y d e vi ati o ns fr o m t his pr ot oc ol i nt e n d e d t o pr ot ect t h e lif e or p h ysic al w ell -b ei n g of a 
s u bj ect i n a n e m er g e ncy ar e t o b e r e p ort e d t o Si g ht Sci e nc es, I nc. as w ell as t h e I R B as 
s o o n as p ossi bl e, a n d n o l at er t h a n 5 w or ki n g d a ys aft er t h e e m er g e ncy occ urr e d. 
 
All pr ot oc ol d e vi ati o ns will b e d oc u m e nt e d usi n g t h e Pr ot oc ol D e vi ati o n f or m.  
1 6  D E VI C E F AIL U R E S A N D M AL F U N C TI O N S  
All d e vic e f ail ur es or m alf u ncti o ns s h o ul d b e r ec or d e d o n t h e D e vic e D efici e ncy  F or m 
a n d r e p ort e d t o Si g ht Sci e nc es C ust o m er S er vic e ( 8 7 7 -2 6 6 -1 1 4 4).  
1 7  E T HI C AL C O N SI D E R A TI O N S  
1 7. 1  D E CL A R A TI O N O F H EL SI N KI  
T his st u d y s h all b e c o n d uct e d i n acc or d a nc e wit h t h e D ec l ar ati o n of H elsi n ki ( A p p e n dix 
D ).   

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 1  of 8 4  
1 7. 2  IN S TI T U TI O N AL R E VI E W B O A R D S (I R B) 
T h e st u d y s h all n ot b e gi n at a sit e u ntil a p pr o v al h as b e e n o bt ai n e d fr o m t h e r e vi e wi n g 
I R B.  It is t h e I n v esti g at ors’ r es p o nsi bilit y t o o bt ai n a n d m ai nt ai n writt e n a p pr o v al of t h e 
st u d y pr ot oc ol a n d I nf or m e d C o ns e nt d oc u m e nts fr o m t h e a p pr o pri at e I R B.  It is als o t h e 
I n v esti g at ors’ r es p o nsi bilit y t o n otif y t h at b o d y a b o ut a n y a m e n d m e nts t o t h es e 
d oc u m e nts  a n d t o f oll o w t h e I R Bs r ul es r e g ar di n g t h e r e p orti n g of A d v ers e E v e nts a n d 
Pr ot oc ol D e vi ati o ns r el at e d t o t h e d e vic e a n d/ or t his st u d y.  C o p i es of all  writt e n 
a p pr o v al s (i d e ntif yi n g t h e st u d y, t h e s u b mitt e d a n d a p pr o v e d d oc u m e nts a n d t h e d at e 
r e vi e w e d) a n d t h e a p pr ov e d v ersi o ns of t h e d oc u m e nts m ust b e pr o vi d e d  t o Si g ht 
Sci e nc es or its C R O .  
 
T h e I n v esti g at ors m ust fil e all c orr es p o n d e nc e wit h t h e I R B a n d f or w ar d c o pi es of s uc h 
c orr es p o n d e nc e t o Si g ht Sci e nc es.  
1 7. 3  IN F O R M E D C O N S E N T F O R M (I C F) 
A n I nf or m e d C o ns e nt t e m pl at e t h at c o v ers all pr ot oc ol pr oc e d ur es a n d f oll o ws G C P 
G ui d eli n es will b e pr e p ar e d b y Si g ht Sci e nc es a n d m a d e a v ail a bl e t o e ac h I n v esti g at or.  
T h e  I n v esti g at or m a y  a d a pt t h es e t e m pl at es t o t h e r e q uir e m e nts of t h e l oc al I R B a n d of 
t h e i nstit uti o n w h er e t h e st u d y is c o n d uct e d, b ut a n y r e visi o ns m a d e t o t h e I C F m ust b e 
s u b mitt e d t o t h e s p o ns or f or r e vi e w pri or t o s u b missi o n t o t h e I R B.  A c o p y of e ac h I R B-
a p pr o v e d I C F v ersi o n is t o b e m a d e a v ail a bl e t o Si g ht Sci e nc es a n d its C R O.  T h e  
a p pr o v e d, I R B -st a m p e d I C F is t o b e k e pt i n its f ull l e n gt h i n t h e st u d y R e g ul at or y Bi n d er.  
Ori gi n al, si g n e d I C Fs ar e t o b e m ai nt ai n e d i n t h e s u bj ect’s st u d y r ec or ds a n d m ust b e 
m a d e a v ail a bl e f or m o nit ori n g r e vi e w.  
1 7. 4  P U BLI C LI S TI N G O F S T U D Y  
T h e st u d y will b e list e d o n t h e NI H w e bsit e w w w.cli nic altri als. g o v.  
1 8  S T U D Y A D MI NI S T R A TI O N  
1 8. 1  D E VI C E A C C O U N T A BILI T Y  
Wit h e ac h s hi p m e nt of st u d y d e vic es, Si g ht Sci e nc es will i ncl u d e a P ac ki n g List t h at will 
gi v e t h e a m o u nt s hi p p e d a n d t h e l ot n u m b ers. T his p ac ki n g list m ust b e r ec o ncil e d b y 
t h e i n v esti g ati o n al sit e wit h t h e c o nt e nts of t h e s hi p m e nt a n d t h e n r ec or d e d o n t h e 
D e vic e Acc o u nt a bilit y  L o gs (t h es e l o gs ar e c o nt ai n e d wit hi n t h e r e g ul at ory bi n d er at t h e 
sit e).  All st u d y pr o d ucts at t h e sit e m ust b e st or e d i n a s ec ur e d/l oc k e d ar e a.  W h e n 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 2  of 8 4  
st u d y d e vic es ar e us e d, r et ur n e d or dis p os e d of, t h eir dis p ositi o n (i ncl u di n g t h e 
dis p ositi o n a n d d at e of dis p ositi o n) m ust b e r ec or d e d o n t h e D e vic e Acc o u nt a bilit y l o g.  
 
D e vic e r ec o ncili ati o n activiti es will als o b e c o n d uct e d p eri o dic all y i n c o nj u ncti o n wit h 
sit e m o nit ori n g visits. T h e i n v esti g at or m ust m ai nt ai n acc ur at e r ec or ds of t h e r ec ei pt 
a n d dis p ositi o n of all d e vic es s hi p p e d b y Si g ht Sci e nc es.   
1 8. 2  E A RL Y T E R MI N A TI O N O R S U S P E N SI O N O F A N IN V E S TI G A TI O N  
Si g ht Sci e nc es m a y t er mi n at e t h e st u d y , i n w hic h c as e t h e i n v esti g at ors a n d ass oci at e d 
I R Bs will b e n otifi e d i n writi n g.   P ossi bl e r e as o ns f or st u d y t er mi n ati o n i ncl u d e  b ut ar e 
n ot li mit e d t o : 
 
• 
T h e disc o v er y of a n u n ex p ect e d, si g nific a nt, or u n acc e pt a bl e ris k t o t h e st u d y 
s u bj ects i m pl a nt e d wit h t h e d e vic e 
• 
Wit h dr a w al of F D A listi n g of t h e T e ar C ar e pr o d uct.  
 
Si g ht Sci e nc es r es er v es t h e ri g ht t o st o p t h e st u dy at a c e nt er a n y ti m e aft er t h e 
i niti ati o n visit if t h er e h av e b e e n n o s u bj ect e nr ol lm e nts.     
 
Li k e wis e, a pri nci p al i n v esti g at or m a y t er mi n at e t h e st u d y at his/ h er i nstit uti o n.  T his 
d ecisi o n m ust b e f oll o w e d b y writt e n n otific ati o n t o Si g ht Sci e nc es  wit hi n fi v e w or ki n g 
d a ys, st ati n g t h e r e as o ns f or t er mi n ati o n.  
 
If t h e st u d y is t er mi n at e d, e v er y eff ort s h o ul d b e m a d e t o o bt ai n fi n al f oll o w -u p fr o m all 
s u bj ects.   
 
I n t h e e v e nt t h at t h er e ar e si g nific a nt h u m a n us e iss u es wit h t h e d e vic e, t h e i n v esti g at or 
will b e c o ns ult e d t o m a k e a d et er mi n ati o n of w h et h er t h e st u d y s h o ul d b e t er mi n at e d 
or n ot.  
1 8. 3  IN V E S TI G A T O R R E S P O N SI BILI TI E S  
 G E N E R AL R E S P O N SI BILI TI E S O F IN V E S TI G A T O R S  
A n I n v esti g at or is r es p o nsi bl e f or e ns uri n g t h at a n i n v esti g ati o n is c o n d uct e d acc or di n g 
t o t h e si g n e d a gr e e m e nt, t h e i n v esti g ati o n al pl a n a n d a p plic a bl e F D A r e g ul ati o ns, f or 
pr ot ecti n g t h e ri g hts, s af et y, a n d w elf ar e of s u bj ects u n d er t h e I n v esti g at or’s c ar e, a n d 
f or t h e c o ntr ol of d e vic es u n d er i n v esti g ati o n. A n I n v esti g at or als o is r es p o nsi bl e f or 
e ns uri n g t h at i nf or m e d c o ns e nt is o bt ai n e d i n acc or d a nc e wit h 2 1 C F R p art 5 0.  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 3  of 8 4  
 S P E CI FI C R E S P O N SI BILI TI E S O F IN V E S TI G A T O R S  
1.  
A w aiti n g a p pr o v al - A n I nv esti g at or m a y d et er mi n e w h et h er p ot e nti al s u bj ects 
w o ul d b e i nt er est e d i n p artici p ati n g i n a n i n v esti g ati o n, b ut s h all n ot r e q u est t h e 
writt e n i nf or m e d c o ns e nt of a n y s u bj ect t o p artici p at e, a n d s h all n ot all o w a n y 
s u bj ect t o p artici p at e b ef or e o bt ai ni n g I R B a p pr o v al. 
2.  
S u bj ect Q u alific ati o n -T h e I n v esti g at or is r es p o nsi bl e f or e ns uri n g t h at all s u bj ects 
e nt eri n g t h e st u d y c o nf or m t o t h e p ati e nt s el ecti o n crit eri a.  
3.  
C o m pli a nc e - A n I n v esti g at or s h all c o n d uct a n i n v esti g ati o n i n acc or d a nc e wit h t h e 
si g n e d a gr e e m e nt wit h t h e S p o ns or, t h e i n v esti g ati o n al pl a n, all a p plic a bl e F D A 
r e g ul ati o ns, a n d a n y c o n diti o ns of a p pr o v al i m p os e d b y a n I R B. 
 IN V E S TI G A T O R R E C O R D S 
A p artici p ati n g I n v esti g at or s h all m ai nt ai n t h e f oll o wi n g acc ur at e, c o m pl et e, a n d c urr e nt 
r ec or ds r el ati n g t o t h e I nv esti g at or’s p artici p ati o n i n a n i n v esti g ati o n f or t h e p eri o d 
s p ecifi e d i n S ecti o n 1 4. 6 :  
1.  
All c orr es p o n d e nc e wit h a n ot h er I n v esti g at or, a n I R B, t h e S p o ns or, a m o nit or, or 
F D A, i ncl u di n g r e q uir e d r e p orts.  
2.  
R ec or ds of e ac h s u bj ect’s c as e hist or y a n d ex p os ur e t o t h e d e vic e. C as e hist ori es 
i ncl u d e t h e st u d y C R F’s/ w or ks h e ets a n d s u p p orti n g d at a i ncl u di n g, f or ex a m pl e, 
si g n e d a n d d at e d c o ns e nt f or ms a n d m e dic al r ec or ds.  S uc h r ec or ds s h all i ncl u d e: 
a)  
D oc u m e nts e vi d e nci n g i nf or m e d c o ns e nt.  
b)  All r el e v a nt o bs er v ati o ns, i ncl u di n g r ec or ds c o nc er ni n g a d v ers e d e vic e eff ects 
( w h et h er a ntici p at e d or u n a ntici p at e d), i nf or m ati o n a n d d at a o n t h e c o n diti o n 
of e ac h s u bj ect u p o n e nt eri n g, a n d d uri n g t h e c o urs e of, t h e i n v esti g ati o n, 
i ncl u di n g i nf or m ati o n a b o ut r el e v a nt pr e vi o us m e dic al hist or y a n d t h e r es ults 
of all di a g n ostic t ests.  
3.  
T h e pr ot oc ol, wit h d oc u m e nts s h o wi n g t h e d at es a n d r e as o ns f or e ac h d evi ati o n 
fr o m t h e pr ot oc ol. 
4.  
A n y ot h er r ec or ds t h at F D A r e q uir es t o b e m ai nt ai n e d b y r e g ul ati o n or b y s p ecific 
r e q uir e m e nt f or a c at e g or y of i n v esti g ati o ns or a p artic ul ar i n v esti g ati o n. 
 IN V E S TI G A T O R R E P O R T S 
A n I n v esti g at or s h all pr e p ar e a n d s u b mit t h e f oll o wi n g c o m pl et e, acc ur at e, a n d ti m el y 
r e p orts: 
1.  
U n a ntici p at e d A d v ers e D e vic e Eff ects - A n I n v esti g at or s h all s u b mit t o t h e S p o ns or 
a n d t o t h e r e vi e wi n g I R B a r e p ort of a n y u n a ntici p at e d a d v ers e d e vic e eff ect 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 4  of 8 4  
occ urri n g d uri n g a n i n v esti g ati o n as s o o n as p ossi bl e, b ut i n n o e v e nt l at er t h a n 1 0 
w or ki n g d a ys aft er t h e I nv esti g at or first l e ar ns of t h e eff ect.  
2.  
Wit h dr a w al of I R B A p pr ov al - A n I n v esti g at or s h all r e p ort t o t h e S p o ns or, wit hi n 5 
w or ki n g d a ys, a wit h dr a w al of a p pr o v al b y t h e r evi e wi n g I R B of t h e I n v esti g at or’s 
p art of a n i n v esti g ati o n.  
3.  
Pr o gr ess - A n I n v esti g at or s h all s u b mit pr o gr ess r e p orts o n t h e i n v esti g ati o n t o t h e 
S p o ns or, t h e m o nit or, a n d t h e r e vi e wi n g I R B at r e g ul ar i nt er v als, b ut i n n o e v e nt 
l ess oft e n t h a n y e arl y. 
4.  
D e vi ati o ns fr o m t h e I n v esti g ati o n al Pl a n - A n I n v esti g at or s h all d oc u m e nt a n d 
r e p ort t o t h e S p o ns or a ny d e vi ati o n fr o m t h e i n v esti g ati o n al pl a n.  
5.  
I nf or m e d C o ns e nt - If a n I n v esti g at or e nr olls a s u bj ect wit h o ut o bt ai ni n g i nf or m e d 
c o ns e nt, t h e I n v esti g at or s h all r e p ort s uc h us e t o t h e S p o ns or a n d t h e r e vi e wi n g 
I R B wit hi n 5 w or ki n g d a ys aft er t h e us e occ urs. 
6.  
Fi n al R e p ort - A n I n v esti g at or s h all, wit hi n 3 m o nt hs aft er t er mi n ati o n or 
c o m pl eti o n of t h e i n v esti g ati o n or t h e I n v esti g at or’s p art of t h e i n v esti g ati o n, 
s u b mit a fi n al r e p ort t o t h e S p o ns or a n d t h e r e vi e wi n g I R B. 
7.  
Ot h er - A n I n v esti g at or s h all, u p o n r e q u est b y a r e vi e wi n g I R B or F D A, pr ovi d e 
acc ur at e, c o m pl et e, a n d c urr e nt i nf or m ati o n a b o ut a n y as p ect of t h e i n v esti g ati o n.  
 
1 8. 4  IN V E S TI G A T O R A G R E E M E N T  
T h e pri nci p al i n v esti g at ors i n e ac h c e nt er s h all a gr e e t o t h e cli nic al pr ot oc ol a n d a n y 
a m e n d m e nts a n d i n dic at e t h eir a p pr o v al a n d a gr e e m e nt b y si g ni n g a n d d ati n g t h e c o v er 
p a g e of t h e st u d y pr ot oc ol a n d t h e I n v esti g at or R es p o nsi bilit y A gr e e m e nt . 
1 9  P U BLI C A TI O N P OLI C Y  
Si g ht Sci e nc es r ec o g niz es t h e v al u e of diss e mi n ati n g r es e arc h r es ults.  It is u n d erst o o d 
t h at t h e St u d y is p art of t h e M ulti-C e nt er Cli nic al Tri al  a n d p u blic ati o n of r es ults is 
ex p ect e d.  T his p u blic ati o ns p olicy a p pli es t o j o ur n al articl es, c o nf er e nc e a bstr acts, a n d 
c o nf er e nc e pr es e nt ati o ns ( p ost ers a n d sli d es) c o v eri n g Si g ht Sci e nc es -s p o ns or e d cli nic al 
st u di es.  T his p olicy is i n a d diti o n t o a n y arr a n g e m e nt c o nt ai n e d i n t h e Cli nic al Tri al 
A gr e e m e nt b et w e e n Si g ht Sci e nc es a n d t h e i n v esti g at or.  
 
M ulti -Sit e D at a  
Cli nic al sit e i n v esti g at ors ar e e nc o ur a g e d t o pr o p os e p u blic ati o ns a n d a bstr acts t h at 
i ncl u d e cli nic al or r es e arc h d at a fr o m m ulti pl e cli nic al sit es; s uc h pr oj ects will b e 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 5  of 8 4  
c o or di n at e d b y Si g ht Sci e nc es.  A ut h ors hi p  of p a p ers a n d a bstr acts r es ulti n g fr o m t h es e 
pr oj ects will b e d et er mi n e d c oll a b or ati v el y acc or di n g t o t h e f oll o wi n g g ui d eli n es:  
 
•  T h e first a ut h or o n s uc h p u blic ati o ns will b e t h e p ers o n w h o pri m aril y wr ot e t h e 
p a p er a n d t o o k t h e l e a d o n t h e r es e arc h.  I n t h e c as e of cli nic al tri al p a p ers 
w h er e all a ut h ors c o ntri b ut e d e q u all y, a ut h ors hi p or d er m a y b e b as e d o n sit e 
e nr oll m e nt or ot h er  crit eri a at Si g ht Sci e nc es’ discr eti o n.  
•  Ot h er a ut h ors i ncl u d e t h os e w h o si g nific a ntl y c o ntri b ut e d t o t h e s p ecific w or k.   
•  At l e ast o n e p ers o n fr o m e ac h cli nic al sit e w h os e st u d y s u bj ects a p p e ar i n t h e 
w or k will b e ac k n o wl e d g e d i n t h e m a n uscri pt/ pr es e nt ati o n i n s o m e w a y, eit h er 
as a n a ut h or gr o u p m e m b er, a n o n -a ut h or c o ntri b ut or, or list e d i n t h e 
ac k n o wl e d g e m e nts, d e p e n di n g o n  t h e p artic ul ar p olici es of t h e j o ur n al or 
c o nf er e nc e. 
 
Si n gl e Sit e D at a  
Aft er p u b lic ati o n of t h e m ulti-c e nt er st u d y r es ults i n a p e er-r e vi e w e d j o ur n al, or if 
S p o ns or h as n ot s u b mitt e d a m a n uscri pt f or p u blic ati o n i n a p e er -r e vi e w e d j o ur n al 
wit hi n t w el v e ( 1 2) m o nt hs aft er t h e st u d y h as b e e n c o m pl et e d, w hic h e v er occ urs first, 
I n v esti g at ors m a y p u blis h t h e r es ults of t h e St u d y g e n er at e d b y t h e I n v esti g at or, s u bj ect 
t o t h e o bli g ati o ns of t h e Cli nic al Tri al A gr e e m e nt b et w e e n Si g ht Sci e nc es a n d t h e 
I n v esti g at or, a n d t h e pri or a p pr o v al of S p o ns or i n writi n g.   
 
P u blic ati o ns R e vi e w P olicy  
I n v esti g at ors m ust s u b mit all pr es e nt ati o ns, p ost ers, a bstr acts a n d m a n uscri pts 
p ert ai ni n g t o  t his st u d y t o Si g ht Sci e nc es f or r e vi e w i n a d v a nc e of t h eir s u b missi o n.  
Si g ht Sci e nc es c o n d ucts t his r e vi e w  t o pr ot ect its  pr o pri et ar y ri g hts t o i nf or m ati o n, 
i n v e nti o ns, or pr o d ucts d e v el o p e d u n d er t h e St u dy.  Pl eas e us e t h e f oll o wi n g g ui d eli n e 
t o d et er mi n e t h e a bs ol ut e mi ni m u m a d v a nc e ti m e f or s u b mitti n g a n it e m t o Si g ht 
Sci e nc es f or r e vi e w: 
 
•  Pr es e nt ati o ns/ P ost ers: 5 b usi n ess d a ys i n a d v a nc e of pr es e nt ati o n  
•  A bstr acts: 5 b usi n ess d a ys i n a d v a nc e of s u b missi o n  
•  M a n uscri pts: 3 0 c al e n d ar d a ys i n a d v a nc e of s u b missi o n f or p u blic ati o n  
 
I n acc or d a nc e wit h t h e Cli nic al Tri al A gr e e m e nt, th es e it e ms m ust r ec ei v e writt e n 
a p pr o v al fr o m Si g ht Sci e nc es  i n or d er f or t h e m t o b e s u b mitt e d or pr es e nt e d.  If a n it e m 
is n ot r ec ei v e d i n t h e ti m efr a m e list e d a b o v e, a p pr o v al m a y n ot b e gr a nt e d d u e t o 
i ns uffici e nt ti m e f or c o nsi d er e d r e vi e w. I n a d diti o n, si nc e m ost of o ur Cli nic al Tri al 
A gr e e m e nts r e q uir e t h at Si g ht Sci e nc es  h as 6 0 d ays t o r e vi e w p u blic ati o ns, Si g ht 
Sci e nc es r es er v es t h e ri g hts gr a nt e d i n t h os e A gr e e m e nts if circ u mst a nc es r e q uir e a 
l o n g er r e vi e w. 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 6  of 8 4  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 7  of 8 4  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 8  of 8 4  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 5 9  of 8 4  
2 1  A P P E N DI X A  –  M E T H O D S F O R E X A M S , T E S T S A N D 
Q U E S TI O N N AI R E S  
2 1. 1  M E DI C A TI O N S  
W h e n r ec or di n g m e dic ati o ns t h at t h e s u bj ect is t aki n g, b e s ur e t o as k t h e s u bj ect t o list 
a n y  o v er -t h e-c o u nt er m e dic ati o ns a n d s u p pl e m e nts t h e y ar e t a ki n g t h at c o ul d aff ect dr y 
e y e dis e as e i ncl u di n g , f or ex a m pl e, c ol d m e dici n es, B e n a dr yl, fis h oil s u p pl e m e nts a n d 
O m e g a 3 pr o d ucts , r eti n ol pr o d ucts, L atiss e, etc. 
2 1. 2  M A NI F E S T R E F R A C TI O N A N D V I S U AL A C UI T Y  
M as k e d ass ess m e nt:  T his ass ess m e nt s h o ul d b e p erf or m e d b y t h e m as k e d ass ess or.   
 
B est -c orr ect e d vis u al ac uit y will b e m e as ur e d usi n g t h e E T D R S  m et h o d.   S u bj ects s h o ul d 
u n d er g o m a nif est r efr acti o n pri or t o t h e E T D R S t es t, wit h t h e exc e pti o n of t h e D a y 1 
f oll o w-u p visit.  O n D a y 1, s u bj ects’ b est s p ect acl e  c orr ect e d vis u al ac uit y  ( B S C V A) (i. e., 
wit h o ut m a nif est r efr acti o n)  will b e m e as ur e d usi n g t h e E T D R S m et h o d.  If t h e s u bj ect’s 
vis u al ac uit y h as w ors e n e d b y ≥ 2 li n es fr o m b as eli n e, t h e n m a nif est r efr acti o n s h o ul d 
b e p erf or m e d a n d t h e E T D R S m e as ur e m e nt s h o ul d b e r e p e at e d.  
 
M a nif est R efr acti o n  
 
R efr acti o n will b e p erf or m e d b y t h e I n v esti g at or or st aff usi n g st a n d ar d  cli nic al pr actic e.   
 
 
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 1  of 8 4  
 
 
 
 
 
2 1. 3  S LI T LA M P  E X A M  
M as k e d ass ess m e nt:  T his ass ess m e nt s h o ul d b e p erf or m e d b y t h e m as k e d ass ess or.   
 
A st a n d ar d slit-l a m p ex a mi n ati o n s h all b e p erf or m e d i ncl u di n g i ns p ecti o n of t h e c or n e a 
at a m a g nific ati o n of 1 0 X a n d 1 6 x f or t h e pr es e nc e or acti v e i nfl a m m ati o n or str uct ur al 
c h a n g e, t h e iris a n d a nt eri or c h a m b er f or i nfl a m m ati o n, a n d t h e e y eli ds f or cr usts, 
c oll ar ett es, or sc al es. 
 
2 1. 4  T E A R B R E A K U P T I M E ( T B U T) 
M as k e d ass ess m e nt:  T his ass ess m e nt s h o ul d b e p erf or m e d b y t h e m as k e d ass ess or.   
 
T B U T is a n i n dic at or of t e ar fil m i nst a bilit y.   T h e Dry E y e T est ( D E T) m et h o d s h o ul d b e 
f oll o w e d usi n g D E T t est stri ps ( A mc o n L a b or at ori es).  W hil e h ol di n g a fl u or esc ei n 
i m pr e g n at e d D E T stri p s us p e n d e d i n air, us e a micr o pi p ett e t o a p pl y 1 0 uL of st eril e 
s ali n e o nt o t h e d y e d e n d of t h e stri p. D o n ot all o w t h e s ali n e t o dri p off a n d d o n ot 
s h a k e t h e stri p. I nstill t h e d y e d ti p of stri p i nt o t h e l ow er c o nj u ncti v al f or nix . 
 
U n d er t h e c o b alt bl u e ill u mi n ati o n of t h e slit l a m p, t e ar br e a k -u p ti m e s h o ul d b e 
 
  
 
 
 
  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 2  of 8 4  
2 1. 5  C O R N E AL S T AI NI N G  
M as k e d ass ess m e nt:  T his ass ess m e nt s h o ul d b e p erf or m e d b y t h e m as k e d ass ess or.  
 
C or n e al st ai ni n g  s h o ul d b e ass ess e d i m m e di at el y f oll o wi n g T B U T m e as ur e m e nts (i. e. 
wit hi n 1 -4 mi n ut es aft er i nstill ati o n of fl u or esc ei n d y e) t o ass ur e t h e d y e d o es n ot 
diff us e i nt o str o m a, bl urri n g t h e discr et e m ar gi n of a n y st ai ni n g d ef ects .  A y ell o w 
Wr att e n filt er s h o ul d b e us e d  t o i m pr o v e a n y vis u aliz ati o n of c or n e al st ai ni n g.  Gr a d e 
t h e c or n e al st ai ni n g usi n g t h e N EI/I n d ustr y Gr a di n g S yst e m pr o vi d e d i n Fi g ur e 4  b el o w.  
5 2 
Fi g ur e 4 :  N EI/I n d ustr y Gr a di n g S yst e m f or C or n e al a n d C o nj u ncti v al St ai ni n g 
 
 
 
2 1. 6  C O NJ U N C TI V AL  S T AI NI N G  
M as k e d ass ess m e nt:  T his ass ess m e nt s h o ul d b e p erf or m e d b y t h e m as k e d ass ess or.  
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 4  of 8 4  
 
 
 
2 1. 7  S C HI R M E R 1  T E S T  
T h e Sc hir m er 1 T est m e as ur es a q u e o us t e ar q u a ntit y a n d is a n i n dic ati o n of a q u e o us -
d efici e nt dr y e y e.  T h e Sc hir m er 1 t est, wit h o ut a n est h esi a, s h o ul d b e p erf or m e d b y 
pl aci n g t h e filt er stri p i n t h e i nf eri or f or nix f or 5 mi n ut es.  R e m o v e t h e stri ps a n d 
m e as ur e w etti n g i n milli m et ers.   
2 1. 8  M EI B O MI A N G L A N D S E C R E TI O N S C O RI N G  
M as k e d ass ess m e nt:  T his ass ess m e nt s h o ul d b e p erf or m e d b y t h e m as k e d ass ess or.  
 
T h e M ei b o mi a n Gl a n d S ecr eti o n Sc ori n g  is a n ass ess m e nt of t h e q u alit y of t h e s ecr eti o ns 
pr o d uc e d b y t h e m ei b o mi a n gl a n ds  i n t h e l o w er e y eli ds.  T h e M ei b o mi a n Gl a n d  
S ecr eti o n  Sc ori n g  s h o ul d b e p erf or m e d usi n g t h e M ei b o mi a n Gl a n d E v al u at or 
( T e ar Sci e nc e, I nc.).  E ns ur e t h at t h e i nstr u m e nt h as b e e n cl e a n e d usi n g alc o h ol pri or t o 
e ac h us e.   
 
Gr a d e t h e q u alit y of s ecr eti o ns i n t h e l at er al, c e ntr al a n d t e m p or al t hir ds of t h e l o w er 
e y eli ds.  Gr a d e t h e 5 c e ntr al gl a n ds i n e ac h r e gi o n, f or a t ot al of 1 5 gl a n ds p er e y e.  
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 5  of 8 4  
 
o  0 = n ot hi n g  
o  1 = t o ot h p ast e  
o  2 = cl o u d y  
o  3 = cl e ar  
 
Fr o m t his ass ess m e nt  t h e f oll o wi n g e n d p oi nts will b e c alc ul at e d: 
•  T ot al M ei b o mi a n Gl a n d S ecr eti o n Sc or e :  S u m of t h e gr a d e ( 0 – 3) f or e ac h of t h e 
1 5 gl a n ds.  R a n g e f or t his sc or e is 0 -4 5.  
•  C o u nt of t h e n u m b er of M ei b o mi a n gl a n ds yi el di n g cl e ar li q ui d s ecr eti o ns .  
R a n g e f or t his c o u nt is 0-1 5.  
•  C o u nt of t h e n u m b er of gl a n ds s ecr eti n g a n y li q ui d (cl e ar or cl o u d y).  R a n g e f or 
t his c o u nt is 0-1 5.  
2 1. 9  IN T R A O C UL A R P R E S S U R E  
M as k e d ass ess m e nt:  T his ass ess m e nt s h o ul d b e p erf or m e d b y t h e m as k e d ass ess or.  
 
T h e s a m e m et h o d of m e as uri n g i ntr a oc ul ar pr ess ur e s h o ul d b e us e d at e ac h visit.  
I ntr a oc ul ar pr ess ur e s h o ul d b e m e as ur e d wit h a G ol d m a n n t o n o m et er, if a v ail a bl e.   
2 1. 1 0  
Q U E S TI O N N AI R E S  
 G E N E R AL IN S T R U C TI O N S  F O R Q U E S TI O N N AI R E S  
T h e s u bj ect s h o ul d c o m pl et e all r e q uir e d q u esti o n n air es at t h e b e gi n ni n g of e ac h visit 
b ef or e c o n d ucti n g ot h er cli nic al t esti n g.  T h e o nl y exc e pti o n t o t his g ui d eli n e is t h e 
Disc o mf ort/ P ai n Q u esti o n n air e a d mi nist er e d o n D a y 0 , w hic h is c o m pl et e d b y t h e 
s u bj ect j ust f oll o wi n g t h e st u d y tr e at m e nt (r ef er t o i nstr ucti o ns pr o vi d e d i n S ecti o ns 
9. 5. 4  a n d 9. 5. 5 ).   
 
Pr o vi d e a p a p er c o p y of t h e q u esti o n n air e s a n d a bl u e or bl ac k  i n k p e n t o t h e 
s u bj ect.  R e vi e w t h e i nstr ucti o ns f or e ac h q u esti o n n air e wit h t h e s u bj ect a n d a ns w er a n y 
q u esti o ns t h e y h a v e a b o ut h o w t o c o m pl et e t h e m.  T h e n all o w t h e s u bj ect t o c o m pl et e 
t h e q u esti o n n air es o n t h eir o w n (i. e. s elf-a d mi nist er e d).   
 
St u d y st aff s h o ul d r e vi e w t h e q u esti o n n air e s b ef or e t h e s u bj ect l e a v es t h e offic e t o 
c h ec k f or missi n g or m ulti pl e a ns w ers o n a gi v e n q u esti o n.   If t h es e ar e f o u n d, pl e as e 
p oi nt t his o ut t o t h e s u bj ect a n d all o w t h e m t o r evis e t h eir r es p o ns e(s) t o t h e s p ecific 
q u esti o n(s).   Pl e as e c o nfir m i niti als a n d d at e of t h e s u bj ect o n t h e l ast p a g e of t h e 
q u esti o n n air e.   D o n ot all o w t h e s u bj ect t o t a k e t h e q u esti o n n air es h o m e. 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 6  of 8 4  
 O S DI  Q U E S TI O N N AI R E  
T h e O S DI h as 1 2 q u esti o ns.  B as e d o n t h e a ns w ers  pr o vi d e d b y t h e s u bj ect, st u d y st aff 
c alc ul at e th e o v er all O S DI T ot al sc or e (fr o m 0 -1 0 0) a n d sc or es f or t h e t hr e e s u bsc al es 
acc or di n g t o t h e O S DI i nstr ucti o ns.  B as e d o n t h e r ec o m m e n d e d c ut off s f or O S DI T ot al 
sc or e, t h e s e v erit y of t h e s u bj ect’s dr y e y e s y m pt o ms will b e c at e g oriz e d as f oll o ws:  
 
o  N or m al – 0- 1 2  
o  Mil d – 1 3 -2 2  
o  M o d er at e – 2 3 -3 2  
o  S e v er e – 3 3 or hi g h er  
 S A N D E  Q U E S TI O N N AI R E  A N D E Y E D R Y N E S S V A S  
T h e S A N D E is a si m pl e dry e y e i nstr u m e nt c o nt ai ni n g t w o it e ms m e as uri n g t h e  
fr e q u e ncy a n d s e v erit y of s y m pt o ms, e ac h  is ass ess e d o n a 1 0 0 m m vis u al a n al o g sc al e 
( V A S) r a n gi n g fr o m ‘ N e v er/ V er y c o mf ort a bl e’ t o ‘ All t h e ti m e/ V er y s e v er e’ a n d sc or e d 
fr o m 0 t o 1 0 0.   T h e E y e Dr y n ess Vis u al A n al o g Sc al e m e as ur es s u bj ect’s l ev el of 
disc o mf ort r el at e d t o e y e dr y n ess  r a n gi n g fr o m “ N o disc o mf ort/ m axi m al disc o mf ort.”   
 
T hr e e sc or es will b e o bt ai n e d fr o m t h e S A N D E:  
 
•  Fr e q u e ncy sc or e (r a n gi n g fr o m 0 t o 1 0 0):  T h e dist a nc e (i n m m) b et w e e n t h e l eft 
e n d of t h e sc al e a n d t h e s u bj ect’s r es p o ns e.  
•  S e v erit y sc or e (r a n gi n g fr o m 0 t o 1 0 0):  T h e dist a nc e (i n m m) b et w e e n t h e l eft 
e n d of t h e sc al e a n d t h e s u bj ect’s r es p o ns e.  
•  A S A N D E T ot al sc or e ( als o r a n gi n g fr o m 0 t o 1 0 0) :  T his is c alc ul at e d as t h e 
s q u ar e-r o ot of t h e pr o d uct of t h e Fr e q u e ncy a n d S e v erit y  sc or es.  
 
T h e E y e Dr y n ess Sc or e is d eri v e d fr o m t h e E y e Dr y n ess Vis u al A n al o g Sc al e.  T h e E y e 
Dr y n ess Sc or e (r a n gi n g fr o m 0 t o 1 0 0) is t h e dist a nc e (i n m m) b et w e e n t h e l eft e n d of 
t h e sc al e a n d t h e s u bj ect’s r es p o ns e. 
 
St u d y st aff s h o ul d i nstr uct s u bj ects t o r ec or d t h eir r es p o ns e t o e ac h q u esti o n b y pl aci n g  
a v ertic al li n e ( n ot a n “ X”) acr oss t h e h oriz o nt al li n e of t h e vis u al a n al o g sc al e.  
 
 D I S C O M F O R T/ P AI N Q U E S TI O N N AI R E  
T h e Disc o mf ort/ P ai n Q u esti o n n air e is d esi g n e d t o ass ess t h e d e gr e e of disc o mf ort or 
p ai n t h at t h e s u bj ect ex p eri e nc es d uri n g a n d i m m e di at el y aft er t h e st u d y tr e at m e nt o n 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 7  of 8 4  
D a y 0  a n d p ost -tr e at m e nt ( D a y 1).  S u bj ects ar e as k e d t o i n dic at e t h eir l e v el of 
disc o mf ort a n d p ai n usi n g a Vis u al A n al o g Sc al e pr o vi d e d i n t h e c as e r e p ort f or ms . 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
Pr ot oc ol 0 5 4 7 4 R e v B 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 8  of 8 4  
2 2  A P P E N DI X B  –  IN S T R U C TI O N S F O R W A R M C O M P R E S S A N D LI D 
M A S S A G E  
P erf or m t h e w ar m c o m pr ess a n d li d m ass a g e at h o m e o nc e  e ac h  d a y.   
 
I nstr ucti o ns 
 
1.  Pr e p ar e  t h e w ar m c o m pr ess 
a.  Usi n g a cl e a n w as h cl ot h, r u n it u n d er w ar m, s h o w er t e m p er at ur e t a p w at er 
t o s at ur at e it. It is i m p ort a nt t h at t h e w at er b e w ar m, or s h o w er-
t e m p er at ur e, b ut n ot s o h ot t h at it c a us es p ai n or i nj ur y. 
b.  S q u e ez e t h e w as h cl ot h t o r e m o v e exc ess w at er.  
c. F ol d t h e w as hcl ot h i n t hir ds.  
 
2.  A p pl y  t h e W ar m C o m pr ess es 
a.  T est t h e w as hcl ot h t o m a k e s ur e it is n ot t o o h ot.  If it is t o o h ot, w ait a b o ut 
1 0 s ec o n ds b ef or e t esti n g a g ai n.  
b.  Wit h e y es cl os e d, a p pl y t h e w ar m c o m pr ess o v er y o ur cl os e d e y eli ds f or 5 
mi n ut es . 
 
3.  Li d M ass a g e 
a.  Li d m ass a g e s h o ul d b e p erf or m e d i m m e di at el y aft er c o m pl eti n g  t h e 5 
mi n ut es wit h t h e w ar m c o m pr ess.  
b.  D o n ot vi g or o usl y r u b y o ur e y eli ds.  A v oi d c o nt acti n g or scr atc hi n g y o ur e y e.  
c. T o m ass a g e t h e u p p er e y eli ds, pl ac e o n e fi n g er at t h e o ut er e d g e of y o ur 
e y eli d t o h ol d it cl os e d a n d sli g htl y t a ut.  Usi n g t h e o p p osit e h a n d, pl ac e a 
fi n g er o n t h e u p p er e y eli d b y t h e n os e a n d, usi n g mil d pr ess ur e, r u n t h e 
fi n g er al o n g t h e l o w er e d g e of t h e u p p er e y e li d t o w ar d t h e o utsi d e of t h e 
e y e.  R e p e at o n t h e o p p osit e e y e.  
d.  T o m ass a g e t h e l o w er e y eli d, pl ac e o n e fi n g er at t h e o ut er e d g e of y o ur 
e y eli d t o h ol d it sli g htl y t a ut.  L o o k u p.  Usi n g t h e o p p osit e h a n d, pl e as e a 
fi n g er o n t h e l o w er e y eli d b y t h e n os e a n d, usi n g mil d pr ess ur e, r u n t h e 
fi n g er al o n g t h e u p p er e d g e of t h e l o w er li d t o w ar d t h e o utsi d e of t h e e y e.  
R e p e at o n t h e o p p osit e si d e.  
 
4.  W ar m C o m pr ess L o g  
a.  Us e t h e W ar m C o m pr ess L o g s h e et t o r ec or d t h e d at e a n d ti m e t h at y o u 
p erf or m t h e w ar m c o m pr ess a n d li d m ass a g e.  Bri n g t his l o g wit h y o u t o e ac h 
f oll o w-u p visit.  
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 6 9  of 8 4  
2 3  A P P E N DI X C  –  S T A TI S TI C AL A N AL Y SI S P L A N 
2 3. 1  E N D P OI N T S A N D A N AL Y SI S M E T H O D S  
 P RI M A R Y E F F E C TI V E N E S S E N D P OI N T  
T h e pri m ar y eff ecti v e n ess o utc o m e is t h e c h a n g e fr o m b as eli n e i n T e ar Br e a k -U p Ti m e 
( T B U T) at t h e 1 m o nt h f oll o w u p.  T B U T will b e a n al yz e d usi n g a li n e ar mix e d eff ects 
(L M E) m o d el.  T his will all o w f or t h e pr o p er i nc or p or ati o n of wit hi n-p ers o n c orr el ati o n 
i nt o t h e st atistic al t ests, a n d will als o all o w f or a dj ust m e nt f or b as eli n e m e as ur e m e nts.  
 
T h e  li n e ar mix e d eff ects m o d el f or T B U T c a n b e writt e n as f oll o ws:  
 
𝑦𝑦𝑖𝑖𝑖𝑖=  𝛽𝛽0 +  𝛽𝛽1 𝑇𝑇𝑖𝑖+ 𝛽𝛽2 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑖𝑖𝑖𝑖,0 + 𝑏𝑏0𝑖𝑖+ 𝜖𝜖𝑖𝑖𝑖𝑖 
 
W h er e 
•  𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑖𝑖𝑖𝑖,0  is t h e b as eli n e T B U T v al u e f or s u bj ect i, e y e j, w e e k 0. 
•  𝑦𝑦𝑖𝑖𝑖𝑖 is t h e 1 m o nt h  c h a n g e fr o m b as eli n e T B U T f or s u bj ect i, e y e j. 
𝑦𝑦𝑖𝑖𝑖𝑖= 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑖𝑖𝑖𝑖,4 −𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑖𝑖𝑖𝑖,0  
•  𝑇𝑇𝑖𝑖 is t h e 0, 1 tr e at m e nt i n dic at or f or s u bj ect i 
•  𝛽𝛽0 ,𝛽𝛽1 ,𝑎𝑎𝑎𝑎𝑎𝑎 𝛽𝛽2  ar e t h e fix e d eff ect p ar a m et ers  
•  𝑏𝑏0𝑖𝑖is t h e r a n d o m eff ect (r a n d o m i nt erc e pt t er m) f or s u bj ect i 
𝑏𝑏0𝑖𝑖~ 𝑁𝑁( 0, 𝜎𝜎𝑎𝑎
2 ) 
•  𝜖𝜖𝑖𝑖𝑖𝑖 is t h e n or m all y-distri b ut e d err or t er m  
𝜖𝜖𝑖𝑖𝑖𝑖~ 𝑁𝑁( 0, 𝜎𝜎𝑒𝑒
2 ) 
•  {𝑏𝑏0𝑖𝑖} a n d �𝜖𝜖𝑖𝑖𝑖𝑖� ar e i n d e p e n d e nt  
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 1  of 8 4  
   
 S E C O N D A R Y E F F E C TI V E N E S S E N D P OI N T S  
If t h e pri m ar y e n d p oi nt is s ucc essf ul (if t h e n ull hy p ot h esis f or t h e pri m ary e n d p oi nt is 
r ej ect e d) t h e n t h e s ec o n d ar y e n d p oi nts will b e t est e d usi n g a hi er arc hic al t esti n g 
pr oc e d ur e as d escri b e d i n 1 2. 5. 5.  
 E V AL U A TI O N O F T R E A T M E N T D U R A TI O N  
If t h e pri m ar y e n d p oi nt is s ucc essf ul at t h e o n e m o nt h pri m ar y ti m e p oi nt, t h e n 
tr e at m e nt d ur ati o n will b e e v al u at e d vi a c o m p aris o ns of tr e at m e nt v ers us c o ntr ol 
c h a n g e i n T B U T at e ac h of t h e 3- a n d 6 -m o nt h ti m e p oi nts s e p ar at el y as d escri b e d i n 
1 2. 5. 6.  
F or e ac h s ec o n d ar y e n d p oi nt t h at is s ucc essf ul at t h e o n e m o nt h ti m e p oi nt usi n g t h e 
hi er arc hic al t esti n g pr oc e d ur e d escri b e d i n 1 2. 5. 5, tr e at m e nt d ur ati o n will b e e v al u at e d 
at t h e 3 - a n d 6 -m o nt h f oll o w u p.  E v al u ati o n of tr e at m e nt d ur ati o n f or t h e s ec o n d a r y 
e n d p oi nts will b e b as e d o n s e q u e nti al t esti n g of 3 - a n d 6 -m o nt h f oll o w u p ti m es 
s e p ar at el y, i n t h e s a m e m a n n er as f or t h e pri m ary e n d p oi nt. S ec o n d ar y e n d p oi nts t h at 
f ail at t h e 1-m o nt h ti m e p oi nt will n ot b e e v al u at e d f or tr e at m e nt d ur ati o n  
 M O D ELI N G O F E X T E N D E D F OLL O W -U P R E S UL T S 
If t h e pri m ar y e n d p oi nt is s ucc essf ul at o n e m o nt h, t h e n as a s u p pl e m e nt al a n al ysis w e 
will fit li n e ar mix e d eff ects m o d els t o t h e 1 - 3- a n d 6 -m o nt h l o n git u di n al r es ults.  
 
 
 
 
 
 
 
 
 
 
T h e c h os e n m o d el will all o w us t o e v al u at e t h e f oll o wi n g:  
•  M ai nt e n a nc e of t h e Tr e at m e nt eff ect usi n g t h e f ull l o n git u di n al d at a o n e ac h 
s u bj ect, pr o vi di n g s o m e g ui d e as t o a n a p pr o pri at e r etr e at m e nt sc h e d ul e, 
•  A m or e d et ail e d e v al u ati o n of t h e b as eli n e eff ects, if a n y.  
A s u m m ar y of a n y m o d el s el ecti o n pr oc ess, as w ell as m or e d et ail e d o ut p ut fr o m t h e 
s el ect e d m o d el, will b e pr o vi d e d i n t h e fi n al r e p ort. 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 2  of 8 4  
F or t h e T e ar C ar e s u bj ects o nl y, t h e d at a fr o m all visits o ut t o 1 2 m o nt hs will b e us e d t o 
f urt h er i n v esti g at e t h e d ur a bilit y of t h e tr e at m e nt eff ect.  Si mil ar L M E m o d eli n g will 
all o w us t o e v al u at e t h eir c h a n g e fr o m b as eli n e o ut t o 1 2 m o nt hs.  H o w e v er  si nc e t h e 
W ar m C o m pr ess gr o u p will cr oss o v er t o T e ar C ar e at 6 m o nt hs, t h er e will b e n o c o ntr ol 
gr o u p t o pr o vi d e a n u n bi as e d c o m p aris o n at t h e 7, 9 or 1 2 m o nt h p oi nts.  
F or t h e W ar m C o m pr ess s u bj ects w h o cr oss o v er, t h eir c o m bi n e d 6 t hr o u g h 1 2 -m o nt h 
d at a  will b e a n al yz e d s e p ar at el y  ( a g ai n, usi n g a p pr o pri at e L M E m o d eli n g) t o e v al u at e 
t h eir r es p o ns e t o t h e cr oss o v er T e ar C ar e tr e at m e nt.  I n t his a n al ysis t h eir 6-m o nt h ( pr e -
cr oss o v er) m e as ur e m e nts will b e us e d as t h e n e w “ b as eli n e” t h at will b e us e d t o 
c o m p ar e wit h t h eir 7- , 9- a n d 1 2 -m o nt h o utc o m es.  A g ai n, t h er e will b e n o c o ntr ol gr o u p 
f or c o m p aris o n. 
2 3. 2  S A M PL E S I Z E C AL C UL A TI O N S  
 T E A R B R E A K U P T I M E 
T h e pri m ar y T e ar Br e a k u p Ti m e ( T B U T) e n d p oi nt is m e as ur e d o n a p er -e y e b asis.  I n 
or d er t o acc o u nt f or t h e c orr el ati o n b et w e e n e y es t h e s a m pl e siz e is c alc ul at e d i n t w o 
st e ps.  T h e first st e p is t o c arr y o ut a st a n d ar d s a m pl e siz e c alc ul ati o n f or t h e n u m b er of 
e y es b as e d o n a t w o -s a m pl e t-t est wit h u n e q u al v ari a nc es.  T his t est is a p pr o pri at e f or a 
s a m pl e of i n d e p e n d e nt ey es fr o m t h e t w o gr o u ps, t h at is, a st u d y i n w hic h o nl y o n e e y e 
p er s u bj ect is e nr oll e d. T h e s ec o n d st e p is t o all o w f or t w o e y es p er s u bject  b y a dj usti n g 
t h e i n d e p e n d e nt s a m pl e siz e t o acc o u nt f or t h e c orr el ati o n b et w e e n e y es. 5 7  T his is 
d o n e b y m ulti pl yi n g b y a  “ d esi g n eff ect” ( D E F F) t h at c a n b e c alc ul at ed fr o m t h e pil ot 
st u d y d at a ( pr o vi d e d i n S ecti o n 5. 2. 2 ).  Fi n all y w e all o w f or s o m e l oss t o f oll o w u p a n d 
t h e n di vi d e b y 2 ( e y es p er s u bj ect) t o arri v e at a fi n al e nr oll e d s a m pl e siz e i n t er ms of 
n u m b er of s u bj ects. 
T his s a m pl e siz e c alc ul ati o n d o es n ot acc o u nt f or t h e a dj ust m e nt f or b as eli n e T B U T i n 
t h e a n al ysis m o d el. T h at a dj ust m e nt s h o ul d o nl y s er v e t o i ncr e as e t h e p o w er of t h e t est, 
s o t his si m pl er c alc ul ati o n is c o ns er v ati v e i n t h at s e ns e. 
F or t h e s a m pl e siz e c alc ul ati o n, a p ositi v e tr e at m e nt eff ect f or t h e w ar m c o m pr ess 
c o ntr ol w as ass u m e d , r e d uci n g t h e T B U T ti m e p er e y e b y 4 s ec o n ds, wit h a st a n d ar d 
d e vi ati o n of 2.  T his is s o m e w h at c o ns er v ati v e b as e d o n t h e pil ot st u d y d at a (t his is o n 
t h e u p p er e n d of w h at w e ex p ect t o s e e f or t h e W ar m C o m pr ess gr o u p). 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 3  of 8 4  
F or t h e T e ar C ar e d e vic e a tr e at m e nt eff ect  of 6 s ec o n ds, wit h st a n d ar d d e vi ati o n 3  w as 
ass u m e d .  T his is als o s o m e w h at c o ns er v ati v e, as it is o n t h e l o w er e n d of w h at w e 
ex p ect t o s e e i n t h e T e ar C ar e gr o u p  b as e d o n t h e pil ot st u d y d at a . 
Fi n all y, w e will ass u m e t h at 1 0 % of t h e e nr oll e d s u bj ects will b e l ost t o f oll o w -u p. B as e d 
o n t h es e ass u m pti o ns, T a bl e 4  s h o ws s a m pl e siz es f or p o w ers of 8 0 %, 9 0 %, a n d 9 5 %.   
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 4  of 8 4  
 
 O S DI  
T h e m ost i m p ort a nt s ec o n d ar y eff ecti v e n ess e n d p oi nt, O S DI, m e as ur es s u bj ect-r e p ort e d 
s y m pt o ms.  T his e n d p oi nt is m e as ur e d o n a p er-s u bj ect b asis, s o n o a dj ust m e nt f or 
c orr el ati o n is n ec ess ar y. F or t his e n d p oi nt a mi ni m u m cli nic all y i m p ort a nt diff er e nc e 
r a n g es fr o m 7. 0 t o 9. 9 u nits. 5 9  B as e d o n d at a fr o m t h e T e ar C ar e pil ot st u d y,  w e 
c o ns er v ati v el y ass u m e d a 1 0-p oi nt O S DI i m pr o v e m e nt i n t h e W ar m C o m pr ess gr o u p a n d 
a n 1 8. 5 p oi nt i m pr o v e m e nt i n t h e T e ar C ar e gr o u p, a n d a st a n d ar d d e vi ati o n of 1 8 
 
 
 
 
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 5  of 8 4  
u nits.   Usi n g t h es e ass u m pti o ns, t h e f oll o wi n g T a bl e 5  s h o ws t h e p o w er f or a t w o-
s a m pl e t-t est wit h u n e q u al v ari a nc es f or a r a n g e of s a m pl e siz es. 
 S A F E T Y  
F or s af et y , t h e f oll o wi n g T a bl e 6  s h o ws  
•  t h e ex p ect e d n u m b er of e v e nts,  
•  t h e pr o b a bilit y of o bs er vi n g o n e or m or e e v e nts,  
•  t h e u p p er 9 5 % o n e-si d e d CI li mit if 0 e v e nts ar e o bs er v e d, a n d  
•  t h e u p p er 9 5 % o n e-si d e d CI li mit if t h e ex p ect e d n u m b er of e v e nts occ urs, 
f or s a m pl e siz es of 5 0, 1 0 0, a n d 2 0 0 a n d tr u e pr o p orti o ns of 0. 0 1, 0. 0 2, a n d 0. 0 5.  S o if 
t h e tr u e r at e of a n A E is 0. 0 1 t h e n i n a s a m pl e of 1 0 0 i n di vi d u als w e will o bs er v e o n e or 
m or e e v e nts wit h pr o b a bilit y 0. 6 3 4. If n o e v e nts ar e o bs er v e d i n t h e s a m pl e t h e n t h e 
u p p er 9 5 % o n e -si d e d CI li mit is 0. 0 2 6, a n d if 1 e v e nt is o bs er v e d (t h e ex p ect e d n u m b er 
i n t his c as e), t h e u p p er 9 5 % o n e-si d e d CI li mit is 0. 0 4 4. 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 6  of 8 4  
 S A M PL E S I Z E S U M M A R Y  
B as e d o n t h e c alc ul ati o ns o utli n e d a b o v e, a n o v er all s a m pl e of 2 0 0 i n di vi d u als, wit h 1 0 0 
i n t h e T e ar C ar e gr o u p, will pr o vi d e m or e t h a n 9 0 % p o w er f or t h e T B U T a n d O S DI 
eff ecti v e n ess e n d p oi nts a n d s uffici e nt pr ecisi o n ar o u n d t h e a d v ers e e v e nt esti m at es.  
 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 7  of 8 4  
2 4  A P P E N DI X D  - D E CL A R A TI O N O F H EL SI N KI  
I. 
P R E A M BL E  
 
1.  
T h e W orl d M e dic al Ass oci ati o n ( W M A) h as d e v el o p e d t h e D ecl ar ati o n of 
H elsi n ki as a st at e m e nt of et hic al pri nci pl es f or m e dic al r es e arc h i n v ol vi n g 
h u m a n s u bj ects, i ncl u di n g r es e arc h o n i d e ntifi a bl e h u m a n m at eri al a n d d at a.  
 
T h e D ecl ar ati o n is i nt e n d e d t o b e r e a d as a w h ol e a n d e ac h of its c o nstit u e nt 
p ar a gr a p hs s h o ul d b e a p pli e d wit h c o nsi d er ati o n of all ot h er r el e v a nt 
p ar a gr a p hs.  
 
2.  
C o nsist e nt wit h t h e m a n d at e of t h e W M A, t h e D ecl ar ati o n is a d dr ess e d 
pri m aril y t o p h ysici a ns. T h e W M A e nc o ur a g es ot h ers w h o ar e i n v ol v e d i n 
m e dic al r es e arc h i n v ol vi n g h u m a n s u bj ects t o a d o pt t h es e pri nci pl es.  
 
II. 
G E N E R AL P RI N CI PL E S  
 
1.  
T h e D ecl ar ati o n of G e n ev a of t h e W M A bi n ds t h e p h ysici a n wit h t h e w or ds, 
“ T h e h e alt h of m y p ati e nt will b e m y first c o nsi d er ati o n,” a n d t h e I nt er n ati o n al 
C o d e of M e dic al Et hics d ecl ar es t h at, “ A p h ysici a n s h all act i n t h e p ati e nt's b est 
i nt er est w h e n pr o vidi n g m e dic al c ar e.”  
 
2.  
It is t h e d ut y of t h e p h ysici a n t o pr o m ot e a n d s af e g u ar d t h e h e alt h, w ell-b ei n g 
a n d ri g hts of p ati e nts, i ncl u di n g t h os e w h o ar e i nv ol v e d i n m e dic al r es e arc h. 
T h e p h ysici a n's k n o wl e d g e a n d c o nsci e nc e ar e d e dic at e d t o t h e f ulfil m e nt of 
t his d ut y. 
 
3.  
M e dic al pr o gr ess is b as e d o n r es e arc h t h at ulti m at el y m ust i ncl u d e st u di es 
i n v ol vi n g h u m a n s u bj ects. 
 
4.  
T h e pri m ar y p ur p os e of m e dic al r es e arc h i n v ol vi n g h u m a n s u bj ects is t o 
u n d erst a n d t h e c a us es, d e v el o p m e nt a n d eff ects of dis e as es a n d i m pr o v e 
pr e v e nti v e, di a g n ostic a n d t h er a p e utic i nt er v e nti o ns ( m et h o ds, pr oc e d ur es 
a n d tr e at m e nts). E v e n t h e b est pr o v e n i n t er v e nti o ns m ust b e e v al u at e d 
c o nti n u all y t hr o u g h r es e arc h f or t h eir s af et y, eff ecti v e n ess, effici e ncy, 
acc essi bilit y a n d q u alit y.  
 
5.  
M e dic al r es e arc h is s u bj ect t o et hic al st a n d ar ds t h at pr o m ot e a n d e ns ur e 
r es p ect f or all h u m a n s u bj ects a n d pr ot ect t h eir h e alt h a n d ri g hts. 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 8  of 8 4  
6.  
W hil e t h e pri m ar y p ur p os e of m e dic al r es e arc h is t o g e n er at e n e w k n o wl e d g e, 
t his g o al c a n n e v er t a k e pr ec e d e nc e o v er t h e ri g hts a n d i nt er ests of i n di vi d u al 
r es e arc h s u bj ects. 
7.  
It is t h e d ut y of p h ysici a ns w h o ar e i n v ol v e d i n m e dic al r es e arc h t o pr ot ect t h e 
lif e, h e alt h, di g nit y, i nt e grit y, ri g ht t o s elf-d et er mi n ati o n, pri v acy, a n d 
c o nfi d e nti alit y of p ers o n al i nf or m ati o n of r es e arc h s u bj ects. T h e r es p o nsi bilit y 
f or t h e pr ot ecti o n of r es e arc h s u bj ects m ust al w ays r est wit h t h e p h ysici a n or 
ot h er h e alt h c ar e pr of essi o n als a n d n e v er wit h t h e r es e arc h s u bj ects, e v e n 
t h o u g h t h e y h a v e gi v e n c o ns e nt. 
 
8.  
P h ysici a ns m ust c o nsi d er t h e et hic al, l e g al a n d r e g ul at or y n or ms a n d st a n d ar ds 
f or r es e arc h i n v ol vi n g h u m a n s u bj ects i n t h eir o w n c o u ntri es as w ell as 
a p plic a bl e i nt er n ati o n al n or ms a n d st a n d ar ds. N o n ati o n al or i nt er n ati o n al 
et hic al, l e g al or r e g ul at ory r e q uir e m e nt s h o ul d r e d uc e or eli mi n at e a n y of t h e 
pr ot ecti o ns f or r es e arc h s u bj ects s et f ort h i n t his D ecl ar ati o n.  
 
9.  
M e dic al r es e arc h s h o ul d b e c o n d uct e d i n a m a n n er t h at mi ni miz es p ossi bl e 
h ar m t o t h e e n vir o n m e nt.  
 
1 0.  M e dic al r es e arc h i n v ol vi n g h u m a n s u bj ects m ust b e c o n d uct e d o nl y b y 
i n di vi d u als wit h t h e a p pr o pri at e et hics a n d sci e ntific e d uc ati o n, tr ai ni n g a n d 
q u alific ati o ns. R es e arc h o n p ati e nts or h e alt h y v ol u nt e ers r e q uir es t h e 
s u p er visi o n of a c o m p et e nt a n d a p pr o pri at el y q u alifi e d p h ysici a n or ot h er 
h e alt h c ar e pr of essi o n al.  
 
1 1.  Gr o u ps t h at ar e u n d err e pr es e nt e d i n m e dic al r es e arc h s h o ul d b e pr o vi d e d 
a p pr o pri at e acc ess t o p artici p ati o n i n r es e arc h.  
 
1 2.  P h ysici a ns w h o c o m bi n e m e dic al r es e arc h wit h m e dic al c ar e s h o ul d i n v ol v e 
t h eir p ati e nts i n r es e arc h o nl y t o t h e ext e nt t h at t his is j ustifi e d b y its p ot e nti al 
pr e v e nti v e, di a g n ostic or t h er a p e utic v al u e a n d if t h e p h ysici a n h as g o o d 
r e as o n t o b eli e v e t h at p artici p ati o n i n t h e r es e arc h st u d y will n ot a d v ers ely 
aff ect t h e h e alt h of t h e p ati e nts w h o s er v e as r es e arc h s u bj ects.  
 
1 3.  A p pr o pri at e c o m p e ns ati o n a n d tr e at m e nt f or s u bj ects w h o ar e h ar m e d as a 
r es ult of p artici p ati n g i n r es e arc h m ust b e e ns ur e d. 
 
III. 
RI S K S, B U R D E N S A N D B E N E FI T S  
 
•  
I n m e dic al pr actic e a n d i n m e dic al r es e arc h, m ost i nt er v e nti o ns i n v ol v e risks 
a n d b ur d e ns.  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 7 9  of 8 4  
 
M e dic al r es e arc h i n v ol vi n g h u m a n s u bj ects m a y o nl y b e c o n d uct e d if t h e 
i m p ort a nc e of t h e o bj ecti v e o ut w ei g hs t h e ris ks a n d b ur d e ns t o t h e r es e arc h 
s u bj ects. 
 
•  
All m e dic al r es e arc h i n v ol vi n g h u m a n s u bj ects m ust b e pr ec e d e d b y c ar ef ul 
ass ess m e nt of pr e dict a bl e ris ks a n d b ur d e ns t o t h e i n di vi d u als a n d gr o u ps 
i n v ol v e d i n t h e r es e arc h i n c o m p aris o n wit h f or es e e a bl e b e n efits t o t h e m a n d 
t o ot h er i n di vi d u als or gr o u ps aff ect e d b y t h e c o n diti o n u n d er i n v esti g ati o n. 
 
M e as ur es t o mi ni miz e t h e ris ks m ust b e i m pl e m e nt e d. T h e ris ks m ust b e 
c o nti n u o usl y m o nit or e d, ass ess e d a n d d oc u m e nt e d b y t h e r es e arc h er.  
 
•  
P h ysici a ns m a y n ot b e i nv ol v e d i n a r es e arc h st u dy i n v ol vi n g h u m a n s u bj ects 
u nl ess t h e y ar e c o nfi d e nt t h at t h e ris ks h a v e b e e n a d e q u at el y ass ess e d a n d c a n 
b e s atisf act oril y m a n a g e d.  
 
W h e n t h e ris ks ar e f o u n d t o o ut w ei g h t h e p ot e nti al b e n efits or w h e n t h er e is 
c o ncl usi v e pr o of of d efi niti v e o utc o m es, p h ysici a ns m ust ass ess w h et h er t o 
c o nti n u e, m o dif y or i m m e di at el y st o p t h e st u d y. 
 
I V. 
V UL N E R A BL E G R O U P S A N D I N DI VI D U AL S  
 
•  
S o m e gr o u ps a n d i n di vi d u als ar e p artic ul arl y v ul n er a bl e a n d m a y h a v e a n 
i ncr e as e d li k eli h o o d of b ei n g wr o n g e d or of i nc urri n g a d diti o n al h ar m. 
 
All v ul n er a bl e gr o u ps a n d i n di vi d u als s h o ul d r ec ei v e s p ecific all y c o nsi d er e d 
pr ot ecti o n.  
 
•  
M e dic al r es e arc h wit h a v ul n er a bl e gr o u p is o nl y j ustifi e d if t h e r es e arc h is 
r es p o nsi v e t o t h e h e alt h n e e ds or pri oriti es of t his gr o u p a n d t h e r es e arc h 
c a n n ot b e c arri e d o ut i n a n o n-v ul n er a bl e gr o u p. I n a d diti o n, t his gr o u p s h o ul d 
st a n d t o b e n efit fr o m t h e k n o wl e d g e, pr actic es or i nt er v e nti o ns t h at r es ult 
fr o m t h e r es e arc h. 
 
V.  
S CI E N TI FI C R E Q UI R E M E N T S A N D R E S E A R C H P R O T O C OL S  
 
•  
M e dic al r es e arc h i n v ol vi n g h u m a n s u bj ects m ust c o nf or m t o g e n er all y 
acc e pt e d sci e ntific pri nci pl es, b e b as e d o n a t h or o u g h k n o wl e d g e of t h e 
sci e ntific lit er at ur e, ot h er r el e v a nt s o urc es of i nf or m ati o n, a n d a d e q u at e 
l a b or at or y a n d, as a p pr o pri at e, a ni m al ex p eri m e nt ati o n. T h e w elf ar e of 
a ni m als us e d f or r es e arc h m ust b e r es p ect e d.  

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 8 0  of 8 4  
 
•  
T h e d esi g n a n d p erf or m a nc e of e ac h r es e arc h st u d y i n v ol vi n g h u m a n s u bj ects 
m ust b e cl e arl y d escri b e d a n d j ustifi e d i n a r es e arc h pr ot oc ol.  
 
T h e pr ot oc ol s h o ul d c o nt ai n a st at e m e nt of t h e et hic al c o nsi d er ati o ns i n v ol v e d 
a n d s h o ul d i n dic at e h o w t h e pri nci pl es i n t his D ecl ar ati o n h a v e b e e n 
a d dr ess e d. T h e pr ot oc ol s h o ul d i ncl u d e i nf or m ati o n r e g ar di n g f u n di n g, 
s p o ns ors, i nstit uti o n al affili ati o ns, p ot e nti al c o nflicts of i nt er est, i nc e nti v es f or 
s u bj ects a n d i nf or m ati o n r e g ar di n g pr o visi o ns f or tr e ati n g a n d/ or 
c o m p e ns ati n g s u bj ects w h o ar e h ar m e d as a c o ns e q u e nc e of p artici p ati o n i n 
t h e r es e arc h st u d y. 
 
I n cli nic al tri als, t h e pr ot oc ol m ust als o d escri b e a p pr o pri at e arr a n g e m e nts f or 
p ost -tri al pr o visi o ns. 
 
VI.  
R E S E A R C H E T HI C S C O M MI T T E E S  
 
•  
T h e r es e arc h pr ot oc ol m ust b e s u b mitt e d f or c o nsi d er ati o n, c o m m e nt, 
g ui d a nc e a n d a p pr o v al t o t h e c o nc er n e d r es e arc h et hics c o m mitt e e b ef or e t h e 
st u d y b e gi ns. T his c o m mitt e e m ust b e tr a ns p ar e nt i n its f u ncti o ni n g, m ust b e 
i n d e p e n d e nt of t h e r es e arc h er, t h e s p o ns or a n d a n y ot h er u n d u e i nfl u e nc e a n d 
m ust b e d ul y q u alifi e d. It m ust t a k e i nt o c o nsi d er ati o n t h e l a ws a n d r e g ul ati o ns 
of t h e c o u ntr y or c o u ntri es i n w hic h t h e r es e arc h is t o b e p erf or m e d as w ell as 
a p plic a bl e i nt er n ati o n al n or ms a n d st a n d ar ds b ut t h es e m ust n ot b e all o w e d t o 
r e d uc e or eli mi n at e a n y of t h e pr ot ecti o ns f or r es e arc h s u bj ects s et f ort h i n 
t his D ecl ar ati o n. 
 
T h e c o m mitt e e m ust h a v e t h e ri g ht t o m o nit or o n g oi n g st u di es. T h e r es e arc h er 
m ust pr o vi d e m o nit ori n g i nf or m ati o n t o t h e c o m mitt e e, es p eci all y i nf or m ati o n 
a b o ut a n y s eri o us a d v ers e e v e nts. N o a m e n d m e nt t o t h e pr ot oc ol m a y b e 
m a d e wit h o ut c o nsi d er ati o n a n d a p pr o v al b y t h e c o m mitt e e. Aft er t h e e n d of 
t h e st u d y, t h e r es e arc h ers m ust s u b mit a fi n al r e p ort t o t h e c o m mitt e e 
c o nt ai ni n g a s u m m ar y of t h e st u d y’s fi n di n gs a n d c o ncl usi o ns.  
 
VII.  P RI V A C Y A N D C O N FI D E N TI ALI T Y  
 
•  
E v er y pr ec a uti o n m ust b e t a k e n t o pr ot ect t h e pri v acy of r es e arc h s u bj ects a n d 
t h e c o nfi d e nti alit y of t h eir p ers o n al i nf or m ati o n. 
 
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 8 1  of 8 4  
VIII.  I N F O R M E D C O N S E N T 
 
•  
P artici p ati o n b y i n di vi d u als c a p a bl e of gi vi n g i nf or m e d c o ns e nt as s u bj ects i n 
m e dic al r es e arc h m ust b e v ol u nt ar y. Alt h o u g h it m a y b e a p pr o pri at e t o c o ns ult 
f a mil y m e m b ers or c o m m u nit y l e a d ers, n o i n di vi d u al c a p a bl e of gi vi n g 
i nf or m e d c o ns e nt m a y b e e nr oll e d i n a r es e arc h st u d y u nl ess h e or s h e fr e el y 
a gr e es.  
 
•  
I n m e dic al r es e arc h i n v olvi n g h u m a n s u bj ects c a p a bl e of gi vi n g i nf or m e d 
c o ns e nt, e ac h p ot e nti al s u bj ect m ust b e a d e q u at el y i nf or m e d of t h e ai ms, 
m et h o ds, s o urc es of f u n di n g, a n y p ossi bl e c o nflicts of i nt er est, i nstit uti o n al 
affili ati o ns of t h e r es e arc h er, t h e a ntici p at e d b e n efits a n d p ot e nti al ris ks of t h e 
st u d y a n d t h e disc o mf ort it m a y e nt ail, p ost-st u d y pr o visi o ns a n d a n y ot h er 
r el e v a nt as p ects of t h e st u d y. T h e p ot e nti al s u bj ect m ust b e i nf or m e d of t h e 
ri g ht t o r ef us e t o p artici p at e i n t h e st u d y or t o wit h dr a w c o ns e nt t o p artici p at e 
at a n y ti m e wit h o ut r e pris al. S p eci al att e nti o n s h o ul d b e gi v e n t o t h e s p ecific 
i nf or m ati o n n e e ds of i n di vi d u al p ot e nti al s u bj ects as w ell as t o t h e m et h o ds 
us e d t o d eli v er t h e i nf or m ati o n.  
 
Aft er e ns uri n g t h at t h e p ot e nti al s u bj ect h as u n d erst o o d t h e i nf or m ati o n, t h e 
p h ysici a n or a n ot h er a p pr o pri at el y q u alifi e d i n di vi d u al m ust t h e n s e e k t h e 
p ot e nti al s u bj ect’s fr e el y -gi v e n i nf or m e d c o ns e nt, pr ef er a bl y i n writi n g. If t h e 
c o ns e nt c a n n ot b e ex pr ess e d i n writi n g, t h e n o n -writt e n c o ns e nt m ust b e 
f or m all y d oc u m e nt e d a n d wit n ess e d. 
 
All m e dic al r es e arc h s u bj ects s h o ul d b e gi v e n t h e o pti o n of b ei n g i nf or m e d 
a b o ut t h e g e n er al o utc o m e a n d r es ults of t h e st u d y.  
 
•  
W h e n s e e ki n g i nf or m e d c o ns e nt f or p artici p ati o n i n a r es e arc h st u d y t h e 
p h ysici a n m ust b e p artic ul arl y c a uti o us if t h e p ot e nti al s u bj ect is i n a 
d e p e n d e nt r el ati o ns hi p wit h t h e p h ysici a n or m ay c o ns e nt u n d er d ur ess. I n 
s uc h sit u ati o ns t h e i nf or m e d c o ns e nt m ust b e s o u g ht b y a n a p pr o pri at el y 
q u alifi e d i n di vi d u al w h o is c o m pl et el y i n d e p e n d e nt of t his r el ati o ns hi p.  
 
•  
F or a p ot e nti al r es e arc h s u bj ect w h o is i nc a p a bl e of gi vi n g i nf or m e d c o ns e nt, 
t h e p h ysici a n m ust s e e k i nf or m e d c o ns e nt fr o m t h e l e g all y a ut h oriz e d 
r e pr es e nt ati v e. T h es e i n di vi d u als m ust n ot b e i ncl u d e d i n a r es e arc h st u d y t h at 
h as n o li k eli h o o d of b e n efit f or t h e m u nl ess it is i nt e n d e d t o pr o m ot e t h e 
h e alt h of t h e gr o u p r e pr es e nt e d b y t h e p ot e nti al s u bj ect, t h e r es e arc h c a n n ot 
i nst e a d b e p erf or m e d wit h p ers o ns c a p a bl e of pr o vi di n g i nf or m e d c o ns e nt, a n d 
t h e r es e arc h e nt ails o nl y mi ni m al ris k a n d mi ni m al b ur de n.  
 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 8 2  of 8 4  
•  
W h e n a p ot e nti al r es e arc h s u bj ect w h o is d e e m e d i nc a p a bl e of gi vi n g i nf or m e d 
c o ns e nt is a bl e t o gi v e ass e nt t o d ecisi o ns a b o ut p artici p ati o n i n r es e arc h, t h e 
p h ysici a n m ust s e e k t h at ass e nt i n a d diti o n t o t h e c o ns e nt of t h e l e g all y 
a ut h oriz e d r e pr es e nt ati v e. T h e p ot e nti al s u bj ect’s diss e nt s h o ul d b e r es p ect e d.  
 
•  
R es e arc h i n v ol vi n g s u bj ects w h o ar e p h ysic all y or m e nt all y i nc a p a bl e of gi vi n g 
c o ns e nt, f or ex a m pl e, u nc o nsci o us p ati e nts, m a y b e d o n e o nl y if t h e p h ysic al or 
m e nt al c o n diti o n t h at pr e v e nts gi vi n g i nf or m e d c o ns e nt is a n ec ess ar y 
c h ar act eristic of t h e r es e arc h gr o u p. I n s uc h circ u mst a nc es t h e p h ysici a n m ust 
s e e k i nf or m e d c o ns e nt fr o m t h e l e g all y a ut h oriz e d r e pr es e nt ati v e. If n o s uc h 
r e pr es e nt ati v e is a v ail a bl e a n d if t h e r es e arc h c a n n ot b e d el a y e d, t h e st u dy 
m a y pr oc e e d wit h o ut i nf or m e d c o ns e nt pr o vi d e d t h at  t h e s p ecific r e as o ns f or 
i n v ol vi n g s u bj ects wit h a c o n diti o n t h at r e n d ers t h e m u n a bl e t o gi v e i nf or m e d 
c o ns e nt h a v e b e e n st at e d i n t h e r es e arc h pr ot oc ol a n d t h e st u d y h as b e e n 
a p pr o v e d b y a r es e arc h et hics c o m mitt e e. C o ns e nt t o r e m ai n i n t h e r es e arc h 
m ust  b e o bt ai n e d as s o o n as p ossi bl e fr o m t h e s u bj ect or a l e g all y a ut h oriz e d 
r e pr es e nt ati v e. 
 
•  
T h e p h ysici a n m ust f ull y i nf or m t h e p ati e nt w hic h as p ects of t h eir c ar e ar e 
r el at e d t o t h e r es e arc h. T h e r ef us al of a p ati e nt t o p artici p at e i n a st u d y or t h e 
p ati e nt’s d ecisi o n t o wit h dr a w fr o m t h e st u d y m ust n e v er a d v ers el y aff ect t h e 
p ati e nt -p h ysici a n r el ati o ns hi p.  
 
•  
F or m e dic al r es e arc h usi n g i d e ntifi a bl e h u m a n m at eri al or d at a, s uc h as 
r es e arc h o n m at eri al or d at a c o nt ai n e d i n bi o b a nks or si mil ar r e p osit ori es, 
p h ysici a ns m ust s e e k i nf or m e d c o ns e nt f or its c oll ecti o n, st or a g e a n d/ or r e us e. 
T h er e m a y b e exc e pti o n al sit u ati o ns w h er e c o ns e nt w o ul d b e i m p ossi bl e or 
i m pr actic a bl e t o o bt ai n f or s uc h r es e arc h. I n s uc h sit u ati o ns t h e r es e arc h m a y 
b e d o n e o nl y aft er c o nsi d er ati o n a n d a p pr o v al of a r es e arc h et hics c o m mitt e e.  
 
I X. 
U S E O F PL A C E B O  
 
•  
T h e b e n efits, ris ks, b ur d e ns a n d eff ecti v e n ess of a n e w i nt er v e nti o n m ust b e 
t est e d a g ai nst t h os e of t h e b est pr o v e n i nt er v e nti o n(s), exc e pt i n t h e f oll o wi n g 
circ u mst a nc es: 
 
W h er e n o pr o v e n i nt er v e nti o n exists, t h e us e of pl ac e b o, or n o i nt er v e nti o n, is 
acc e pt a bl e; or  
 
W h er e f or c o m p elli n g a n d sci e ntific all y s o u n d m et h o d ol o gic al r e as o ns t h e us e 
of a n y i nt er v e nti o n l ess eff ecti v e t h a n t h e b est pr o v e n o n e, t h e us e of pl ac e b o, 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 8 3  of 8 4  
or n o i nt er v e nti o n is n ec ess ar y t o d et er mi n e t h e effic acy or s af et y of a n 
i nt er v e nti o n 
 
a n d t h e p ati e nts w h o r ec ei v e a n y i nt er v e nti o n l ess eff ecti v e t h a n t h e b est 
pr o v e n o n e, pl ac e b o, or n o i nt er v e nti o n will n ot b e s u bj ect t o a d diti o n al ris ks 
of s eri o us or irr e v ersi bl e h ar m as a r es ult of n ot r ec ei vi n g t h e b est pr o v e n 
i nt er v e nti o n. 
 
Extr e m e c ar e m ust b e t ak e n t o a v oi d a b us e of t his o pti o n.  
 
X.  
P O S T -T RI AL P R O VI SI O N S  
 
•  
I n a d v a nc e of a cli nic al tri al, s p o ns ors, r es e arc h ers a n d h ost c o u ntr y 
g o v er n m e nts s h o ul d m ak e pr o visi o ns f or p ost -tri al acc ess f or all p artici p a nts 
w h o still n e e d a n i nt er v e nti o n i d e ntifi e d as b e n efici al i n t h e tri al. T his 
i nf or m ati o n m ust als o b e discl ose d t o p artici p a nts d uri n g t h e i nf or m e d c o ns e nt 
pr oc ess.  
 
XI.  
R E S E A R C H R E GI S T R A TI O N A N D P U BLI C A TI O N A N D DI S S E MI N A TI O N O F R ES UL T S  
 
•  
E v er y r es e arc h st u d y i n v ol vi n g h u m a n s u bj ects m ust b e r e gist er e d i n a p u blicl y 
acc essi bl e d at a b as e b ef or e r ecr uit m e nt of t h e first s u bj ect.  
 
•  
R es e arc h ers, a ut h ors, s p o ns ors, e dit ors a n d p u blis h ers all h a v e et hic al 
o bli g ati o ns wit h r e g ar d t o t h e p u blic ati o n a n d diss e mi n ati o n of t h e r es ults of 
r es e arc h. R es e arc h ers h av e a d ut y t o m a k e p u blicly a v ail a bl e t h e r es ults of 
t h eir r es e arc h o n h u m a n s u bj ects a n d ar e acc o u nt a bl e f or t h e c o m pl et e n ess 
a n d acc ur acy of t h eir r e p orts. All p arti es s h o ul d a d h er e t o acc e pt e d g ui d eli n es 
f or et hic al r e p orti n g. N e g ati v e a n d i nc o ncl usi v e as w ell as p ositi v e r es ults m ust 
b e p u blis h e d or ot h er wis e m a d e p u blicl y a v ail a bl e . S o urc es of f u n di n g, 
i nstit uti o n al affili ati o ns a n d c o nflicts of i nt er est m ust b e d ecl ar e d i n t h e 
p u blic ati o n. R e p orts of r es e arc h n ot i n acc or d a nc e wit h t h e pri nci pl es of t his 
D ecl ar ati o n s h o ul d n ot b e acc e pt e d f or p u blic ati o n.  
 
XII.  U N P R O V E N I N T E R V E N TI O N S I N CLI NI C AL P R A C TI C E  
 
I n t h e tr e at m e nt of a n i n di vi d u al p ati e nt, w h er e pr o v e n i nt er v e nti o ns d o n ot exist 
or ot h er k n o w n i nt er v e nti o ns h a v e b e e n i n eff ectiv e, t h e p h ysici a n, aft er s e e ki n g 
ex p ert a d vic e, wit h i nf or m e d c o ns e nt fr o m t h e p ati e nt or a l e g all y a ut h oriz e d 
r e pr es e nt ati v e, m a y us e a n u n pr o v e n i nt er v e nti o n if i n t h e p h ysici a n's j u d g m e nt it 
off ers h o p e of s a vi n g lif e, r e -est a blis hi n g h e alt h or all e vi ati n g s uff eri n g. T his 
i nt er v e nti o n s h o ul d s u bs e q u e ntl y b e m a d e t h e o bj ect of r es e arc h, d esi g n e d t o 

 
 
R C T of t h e S af et y a n d Eff ecti v e n ess of t h e T e ar C ar e ® S yst e m
 
 
 
C O N FI D E N TI AL  
Si g ht Sci e nc es  
 
P a g e 8 4  of 8 4  
e v al u at e its s af et y a n d effic acy. I n all c as es, n e w i nf or m ati o n m ust b e r ec or d e d 
a n d, w h er e a p pr o pri at e, m a d e p u blicl y a v ail a bl e.