ORIGINAL RESEARCH
Imp o ed Tea Film S abili y in Pa ien s wi h D y
Eye A e Hyalu onic Acid and
Galac oxyloglucan Use
This a icle was published in he ollowing Do e P ess jou nal:
Clinical Oph halmology
Ped o Molina-Solana
1
F ancisco de Bo ja
Domínguez-Se ano
1
An onio Manuel
Ga ido-He mosilla
1,2
Jesús Mon e o-I uzubie a
1,2
Ana Fe nández-Palacín
3
En ique Rod íguez-de-la-Rúa-
F anch
1,2
Manuel Ca o-Magdaleno
1,2
1
Oph halmology, Vi gen Maca ena
Hospi al Se ille, Se ille, Spain;
2
Su ge y
Depa men , Uni e si y o Se ille, Se ille,
Spain;
3
P e en i e Medicine and Public
Heal h Depa men , Uni e si y o Se ille,
Se ille, Spain
Pu pose: A ificial ea s only p o ide ansien elie o d y eye. To he bes o ou
knowledge, his is he fi s s udy o objec i ely compa e ea men wi h a ificial ea s wi h
Ke a og aph 5M, which allows accu a e and objec i e in es iga ion o d y eye and a ificial
ea ea men . We aimed o e alua e whe he a p ese a i e- ee combina ion o 0.4%
hyalu onic acid and 0.2% galac oxyloglucan can imp o e d y eye using he new opog aphe ,
Ke a og aph 5M.
Pa ien s and Me hods: This p ospec i e longi udinal, single-a m in e en ional coho
s udy was pe o med a a e ia y e e al cen e and in ol ed 20 pa ien s wi h d y eye (40
eyes). P ese a i e- ee a ificial ea s we e adminis e ed e e y 3 h. The pa icipan s unde -
wen clinical and ins umen al e alua ions a baseline, 15, 30, 60, 90 and 120 min a e
ins illa ion and 1 week and 1 mon h a e ea men . Baseline alues we e conside ed as he
con ols. All pa ien s we e assessed wi h Ke a og aph 5M o non-in asi e Ke a og aph fi s
b eak-up ime and non-in asi e Ke a og aph a e age b eak-up ime, conjunc i al hype emia,
and ea meniscus heigh . Ocula su ace s aining wi h fluo escein was e alua ed using he
sli -lamp and fluo escein b eak-up ime examina ions, and he Ocula Su ace Disease Index
sco e was eco ded o each pa ien .
Resul s: The signs and symp oms imp o ed a e 1 mon h o p ese a i e- ee 0.4%
hyalu onic acid and 0.2% galac oxyloglucan ea men . The e was a significan inc ease in
he non-in asi e Ke a og aph fi s b eak-up ime and non-in asi e Ke a og aph a e age
b eak-up ime a 15, 30, 60, and 90 min, and 1 week and 1 mon h (P < 0.05) and
a dec ease in hype emia, co neal s aining, and Ocula Su ace Disease Index sco es a e 1
week and 1 mon h (P < 0.05). No ea men - ela ed ad e se e en was obse ed.
Conclusion: A combina ion o 0.4% hyalu onic acid and 0.2% galac oxyloglucan a ificial
ea s seems e ec i e o ea ing d y eye. Ke a og aph 5M can objec i ely de ec hese
changes du ing he ollow-up pe iod.
Keywo ds: a ificial ea s, Ke a og aph, non-in asi e Ke a og aph b eak-up ime, Ocula
Su ace Disease Index, d y eye
In oduc ion
D y eye is one o he mos common pa hologies encoun e ed in oph halmologic
p ac ice and wi h an es ima ed p e alence o 14–35% in adul s.
1,2
A ificial ea s a e
used wo ldwide, o ea he signs and symp oms o d y eye, and he dosage depends
on he in ensi y o he symp oms. Howe e , hese ea men s only p o ide ansien
elie , as he a ificial ea s do no ea he unde lying condi ion.
Co espondence: Manuel Ca o-
Magdaleno
Calle Bogo á 7, Bloque 3, 1ºB, Se ille
41013, Spain
Tel +34 609030403
Email [email p o ec ed]
Clinical Oph halmology Do ep ess
open access o scien ific and medical esea ch
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h p://doi.o g/10.2147/OPTH.S248949
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The p ese a i e- ee combina ion o 0.4% hyalu onic
acid (a e age 8.5 × 10
5
Da) ob ained om bac e ial e -
men a ion and 0.2% galac oxyloglucan (6 × 10
5
Da),
which is bu e ed wi h sodium ci a e and ci ic monohy-
d a e acid, is a newly ma ke ed lac imal subs i u e. Bo h
he ac i e ing edien s a e highly mucoadhesi e polyme s
wi h no New onian heology and a high molecula weigh .
These p ope ies o he ing edien s ac syne gis ically o
p o ec he ocula su ace.
3,4
Hyalu onic acid allows o
he e en ion o wa e ha is up o 1000- old g ea e han
i s own weigh and has a be e p eco neal esidence ime
han low iscous solu ions.
5
Mo eo e , galac oxyloglucan
is a na u al polysaccha ide de i ed om ama ind seeds
wi h p o ec i e ba ie p ope ies. Mo eo e , i inc eases
he co neal wound healing a e and educes he in i o
oxici y o imolol, hiome sal, and fluo oquinolones in
human conjunc i al cells.
6
I can imp o e some ocula
su ace abno mali ies in pa ien s wi h glaucoma, caused
by exposu e o p os aglandins and benzalkonium chlo ide,
he eby, p o ec ing he ocula su ace.
7
The pu pose o ou s udy was o in es iga e he e ec
o hese a ificial ea s on d y eye by measu ing he ol-
lowing pa ame e s using he opog aphe , Ke a og aph 5M
(OculusOp ikge ä e GmbH, We zla , Ge many): P ima y,
non-in asi e Ke a og aph fi s ea b eak-up ime ( ime
elapsed in seconds om he las blink un il he fi s
b eak in he ea film) and non-in asi e Ke a og aph a e -
age b eak-up ime (a e age ime o all he ea film b eak-
ups) du ing he fi s 120 min a e ins illa ion and a e
1 mon h o ea men . The seconda y objec i e, was o
in es iga e he e ec o hese a ificial ea s aking mea-
su emen s o conjunc i al hype emia, ea meniscus heigh
and also he Ocula Su ace Disease Index and Ox o d
sco es using sli -lamp examina ion. The eliabili y and
epea abili y o he measu emen s ob ained by
Ke a og aph 5M ha e been alida ed by ea lie in es iga-
ions, pe o ming objec i e measu es.
8–10
Pa ien s and Me hods
h ps://dx.doi.o g/10.17504/p o ocols.io.bbx ipnn
Pa icipan Rec ui men
The sample size was de e mined by a s a is ically signifi-
can di e ence o 95% confidence in e als and wi h 80%
powe o non-in asi e Ke a og aph b eak-up ime based
on a pilo s udy. A o al o 34 eyes was equi ed, acco ding
o he p og am nQue y Ad iso Release 7.0 (S a is ical
Solu ions, B oadway, Saugus, Massachuse s, USA). The
s udy included 40 eyes om 20 pa icipan s (18 women
and 2 men; age ange, 36 o 79 yea s) wi h signs and
symp oms o d y eye, who isi ed ou hospi al be ween
No embe and Decembe 2017. The esul s o he
Schi me I es wi hou anes hesia and fluo escein b eak-
up ime es we e eco ded a he ime o he isi , and he
pa ien was en olled in he s udy i he esul was <10 mm
a 5 min o <10 s, espec i ely. Mo eo e , only pa ici-
pan s who we e olde han 18 yea s, did no ha e any
ac i e ocula su ace disease, who did no wea con ac
lenses o a leas 24 h p io o he isi , did no unde go
any ocula su ge y a leas 1 yea be o e he isi , who
we e no p egnan o lac a ing, and did no ha e any
known alle gy o any o he componen s o he ea supple-
men we e included. Pa ien s who ailed o mee hese
c i e ia we e excluded om he s udy. W i en in o med
consen was ob ained om all pa icipan s. This esea ch
was app o ed by he E hical Commi ee o Vi gen
Maca ena´s Hospi al and was conduc ed acco ding o he
ene s o he Decla a ion o Helsinki. The da a eco ded
was confiden ial.
All en olled pa ien s isi ed he hospi al h ice. They
isi ed he hospi al a app oxima ely he same hou du ing
he day and in he same examina ion oom. The empe a-
u e and humidi y o he examina ion oom we e main-
ained a a ound 22–25°C and 45–55% humidi y,
espec i ely. All pa ien s comple ed he s udy, and he e
we e no wi hd awals. Du ing he ollow-up mon h, all
pa ien s we e ea ed wi h a ificial ea s composed o
0.4% hyalu onic acid and 0.2% galac oxyloglucan e e y
3 h and we e allowed o es a nigh . The pa ien s we e
ques ioned abou compliance a e e y isi . The pa ien s
we e asked o con inue wi h any o he medica ion ( opical
s e oids o opical immunosupp essan s), o p e en mask-
ing he ue e ec o he a ificial ea s. Only pa ien s who
we e using o he a ificial ea s we e ins uc ed o swi ch
o he a ificial ea s used in ou s udy main aining p e-
ious ea men s.
Ocula Examina ions
De ails ega ding p e ious o cu en opical o sys emic
ea men we e eco ded du ing he fi s isi , and he
ollowing pa ame e s we e measu ed in each eye using
he opog aphe , Ke a og aph 5M (OculusOp ikge ä e
GmbH, We zla , Ge many): ea meniscus heigh (3 mea-
su emen s we e made manually along he leng h o he
lowe eyelid using he cu so s p o ided by he sys em, and
he a e age o he 3 alues was conside ed), conjunc i al
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hype emia (indica ed by he so wa e o he Ke a og aph
5M; ange, 0.1 o 4.0; accu acy, 0.1), non-in asi e
Ke a og aph fi s b eak-up ime (momen a which he
ea film b eaks o he fi s ime) and non-in asi e
Ke a og aph a e age b eak-up ime (a e age ime o he
fi s up u e a di e en loca ions o he 8-mm diame e o
he cen al co nea), and he Ocula Su ace Disease Index
ques ionnai e (Alle gan Inc, I ine, CA, USA). Co neal
s aining esul s (using he Ox o d schema)
11
and fluo es-
cein b eak-up ime we e e alua ed using sli -lamp exam-
ina ion. Baseline measu emen s we e used as con ols:
each pa ien was his/he own con ol. A e a 30-min
washou pe iod, a d op o he a ificial ea s was ins illed
in o he in e io palpeb al old o bo h eyes. The non-
in asi e Ke a og aph fi s b eak-up ime and non-
in asi e Ke a og aph a e age b eak-up ime alues we e
measu ed a 15 min, 30 min, 60 min, 90 min, and 120 min
a e a ificial ea ins illa ion o un il he non-in asi e
Ke a og aph a e age b eak-up ime alue was less han
he baseline alue. The objec i e o his assessmen was o
e i y he ime equi ed o he a ificial ea o b ing abou
an inc ease in he non-in asi e Ke a og aph b eak-up ime
pa ame e s in he pa ien s.
Du ing he second isi , which ook place 1 week a e
he fi s , and he hi d isi , which ook place 3 weeks a e
he second, he ea meniscus heigh , conjunc i al hype -
emia, non-in asi e Ke a og aph fi s b eak-up ime and
non-in asi e Ke a og aph a e age b eak-up ime, and
Ocula Su ace Disease Index sco e we e measu ed
again. Co neal s aining and fluo escein b eak-up ime
we e assessed using sli -lamp examina ion.
S a is ical Analysis
Da a we e analyzed using IBM SPSS S a is ics 24.0©.
S a is ical analyses included desc ip i e analysis, wi h
means, medians, s anda d de ia ions, and 25 h and 75 h
pe cen iles (in case o ma ked asymme y) o quan i a i e
a iables and pe cen ages o quali a i e a iables.
In e en ial analysis consis ed o a epea ed-measu es ana-
lysis o a iance (ANOVA) o es di e ences be ween he
a iables o conjunc i al hype emia, Ox o d and Ocula
Su ace Disease Index sco es, ea meniscus heigh , lac i-
mal s abili y le el, non-in asi e Ke a og aph fi s b eak-
up ime and non-in asi e Ke a og aph a e age b eak-up
ime eco ded du ing each ollow-up isi . The Bon e oni
es was used o de ec pa ame e s exhibi ing significan
di e ences. The leas significan di e ence es was used
in case o inconsis ency be ween he ANOVA and
Bon e oni alues. P- alues < 0.05 we e conside ed o be
indica i e o s a is ical significance, and he esul s we e
p esen ed as mean ± s anda d de ia ion.
Resul s
Twen y pa ien s we e en olled o he s udy. All he
en olled pa ien s ollowed ou ea men schedule. The
ad e se e ec s o he ea men included blu ed ision
a ew minu es a e ins illa ion [6 pa ien s (30%)] and
ocula s inging [3 pa ien s (15%)]. None o he pa ien s
expe ienced ad e se eac ions ha equi ed discon inua-
ion o ea men .
Thi y- wo eyes (80%) had a Schi me I es esul o
<10 mm, and he emaining 8 eyes (20%) had a ea b eak-up
ime o <10 s. Se en pa ien s (35%) had no unde gone any
p e ious ea men a he beginning o he s udy, 10 (50%)
we e being ea ed wi h di e en a ificial ea s, 2 (10%)
we e using a ificial ea s and opic s e oids, and 1 (5%)
was being ea ed wi h opical immunosupp essan s in addi-
ion o a ificial ea s and opical s e oids.
The baseline, 1-week, and 1-mon h demog aphic and clin-
ical da a o he pa ien s a e summa ized in Table 1.Non-
in asi e Ke a og aph fi s b eak-up ime and non-in asi e
Ke a og aph a e age b eak-up ime we e significan ly highe
a 1 week (P=0.01andP= 0.007, espec i ely) and 1 mon h
a e commencing ea men (P= 0.003 and P= 0.002, espec-
i ely) han hose a baseline (Figu e 1). Tea meniscus heigh
was significan ly highe a 1 week (P= 0.002) and a 1 mon h
(P= 0.001) han ha a baseline. Conjunc i al hype emia
educed significan lya 1mon h(P= 0.008) (Figu e 2), and
he Ox o d and Ocula Su ace Disease Index sco es we e
significan ly lowe a 1 week (P=0.03andP< 0.0001,
espec i ely) and 1 mon h (P<0.0001andP< 0.0001,
espec i ely), compa ed o hose a baseline (Figu e 3).
The analysis o he esul s showed a s a is ically sig-
nifican inc ease in non-in asi e Ke a og aph fi s b eak-
up ime du ing he fi s 60 min a e ins illa ion o he
a ificial ea s (P= 0.004 a 15 min, P= 0.03 a 30 min,
and P= 0.01 a 60 min).
Non-in asi e Ke a og aph a e age b eak-up ime was
significan ly inc eased ill 90 min a e ins illa ion (P= 0.01
a 15 min, P< 0.0001 a 30 min, P= 0.002 a 60 min, and
P= 0.03 a 90 min). (Figu e 4)
Discussion
The p esen s udy demons a ed he e ec i eness o p e-
se a i e- ee a ificial ea s con aining 0.4% hyalu onic
acid and 0.2% galac oxyloglucan in pa ien s wi h signs
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and symp oms o d y eye using he Ke a og aph 5M, as
he e we e imp o emen s in all o he d y-eye- ela ed
pa ame e s s udied.
While ea lie s udies ha e measu ed and compa ed ea
meniscus heigh using he Schi me es and an e io seg-
men swep -sou ce op ical cohe ence omog aphy,
12,13
he
measu emen o his pa ame e wi h he Ke a og aph
Table 1 Baseline, 1-Week, and 1-Mon h Clinical and
Demog aphic Cha ac e is ics o he Pa icipan s
Baseline 1 Week 1 Mon h
Age (yea s) 63.85 ± 13.15
Sex (M:F) 2:18
Schi me I es
(mm/5 min)
7.53 ± 4.69
FBUT (s) 4.80 ± 2.14 7.20 ± 2.51
P= 0.000
8.73 ± 2.26
P= 0.000
TMH (mm) 0.27 ± 0.10 0.33 ± 0.13
P=0.002
0.33 ± 0.15
P=0.001
NIKBUT-fi s (s) 6.20 ± 4.59 8.35 ± 5.26
P= 0.014
9.52 ± 5.92
P= 0.003
NIKBUT-a e age (s) 10.02 ± 5.72 12.12 ± 5.52
P= 0.007
13.22 ± 5.30
P= 0.002
Conjunc i al hype emia 1.36 ± 0.54 1.19 ± 0.45
P= 0.08
1.12 ± 0.48
P= 0.008
Ox o d sco e 2.68 ± 2.53 2.03 ± 1.76
P= 0.025
0.95 ± 1.78
P= 0.000
OSDI sco e 37.58 ± 17.66 29.69 ± 18.67
P= 0.000
16.41± 8.56
P= 0.000
No e: P- alues ep esen he di e ences be ween he baseline and he subsequen
imepoin s.
Abb e ia ions: M, male; F, emale; FBUT, fluo escein b eak-up ime; TMH, ea
meniscus heigh ; NIKBUT, non-in asi e Ke a og aph ea b eak-up ime; OSDI,
Ocula Su ace Disease Index.
0
5
10
15
20
Baseline 1 week 1 mon h
NIKBUT (seconds)
Time
NIKBUT- i s e sus NIKBUT-a e age
NIKBUT a e age NIKBUT i s
*
**
*
Figu e 1 Compa ison o he mean alues o non-in asi e Ke a og aph 5M fi s ea
b eak-up ime and non-in asi e Ke a og aph a e age b eak-up ime a he 3 isi s,
showing an inc ease a 1 week and 1 mon h om baseline. The as e isk (*) deno es
s a is ical significance.
Abb e ia ion: NIKBUT, non-in asi e Ke a og aph b eak-up ime.
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
Baseline 1 week 1 mon h
Hype emia sco e
Time
CONJUNCTIVAL HYPEREMIA
*
Figu e 2 Mean hype emia sco es o all pa ien s du ing he 3 isi s. The as e isk (*)
deno es s a is ical significance.
-2
-1
0
1
2
3
4
5
6
Baseline 1 week 1 mon h
e ocS
Time
OXFORD
*
0
10
20
30
40
50
60
Baseline 1 week 1 mon h
e ocS
Time
OSDI
*
Figu e 3 Mean alues o he Ox o d sco e measu ed du ing sli -lamp examina ion
( op panel) and he Ocula Su ace Disease Index sco es (bo om panel) eco ded
du ing he s udy, showing a dec ease a 1 week and 1 mon h om baseline. The
as e isk (*) deno es s a is ical significance.
Abb e ia ion: OSDI, Ocula Su ace Disease Index.
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exhibi s high eliabili y and epea abili y.
14
In ou s udy,
we obse ed a significan inc ease in ea meniscus heigh
a 1 week and 1 mon h.
T adi ionally, conjunc i al hype emia is assessed using
isual scales,
15
which a e subjec i e, while he analysis o
conjunc i al hype emia using he Ke a og aph, is a quick
and easy p ocess. Mo eo e , p e ious s udies ha e mea-
su ed conjunc i al hype emia using Ke a og aph in
pa ien s who we e ea ed wi h an iglaucoma eye d ops.
16
Ou esul s showed a s a is ically significan dec ease in
he bulba edness sco es a 1 mon h, while no significan
educ ion was obse ed a 1 week, sugges ing ha p o-
longed ea men is equi ed o achie e a significan
dec ease in bulba edness. This is simila o he finding
o an ea lie s udy on an iglaucoma d ops, which epo ed
a dec ease in he bulba edness sco es a 6 mon hs in
pa ien s who used p ese a i e- ee an iglaucoma d ops.
17
The p esen s udy in ol ed he measu emen o 2 ypes
o non-in asi e Ke a og aph b eak-up ime: non-in asi e
Ke a og aph fi s b eak-up ime and non-in asi e
Ke a og aph a e age b eak-up ime. The ac ha he non-
in asi e Ke a og aph fi s b eak-up ime and non-in asi e
Ke a og aph a e age b eak-up ime alues we e eco ded
du ing he fi s 120 min a e he ins illa ion o 1 d op o
he p ese a i e- ee a ificial ea ep esen s he signifi-
cance and no el y o ou s udy. The esul s showed ha
non-in asi e Ke a og aph fi s b eak-up ime was highe
when compa ed o he baseline alue ill 60 min a e
ins illa ion, and ha non-in asi e Ke a og aph a e age
b eak-up ime was highe , when compa ed o he baseline
alue ill 90 min a e ins illa ion.
The imp o emen in non-in asi e Ke a og aph b eak-
up ime alues ep esen s a c ucial aspec in he ea men
o d y-eye synd ome.
18
This imp o emen co ela es well
wi h he co neal s aining finding, as well as he Ox o d and
Ocula Su ace Disease Index sco es ob ained in he p e-
sen s udy, whe e a educ ion in he abo e-men ioned
pa ame e s was obse ed a 1 week. P e ious s udies on
pa ien s wi h e apo a i e d y eye epo ed ha he non-
in asi e Ke a og aph b eak-up ime was highe a 1 and 3
mon hs, and 4 weeks o ea men compa ed o ha a
baseline.
19,20
These esul s a e concu en wi h ou find-
ings a 1 mon h a e ea men .
The objec i e measu emen s ob ained wi h he
Ke a og aph 5M using in a ed ligh we e he s eng h o
ou s udy, hus, elimina ing he need o fluo escein s ain-
ing o opical anes hesia, which al e he lac imal film.
21
To he bes o ou knowledge, his is one o he fi s
s udies o compa e a ificial ea ea men objec i ely wi h
Ke a og aph 5M,
22
which enabled accu a e and objec i e
oph halmologic in es iga ions no being necessa y pho o-
g aphs and scales no subjec i e me hods like TBUT.
Howe e , u he in es iga ions a e needed o alida e
hese findings.
Fu he mo e, he absence o a placebo g oup is
a limi a ion o he s udy and i s inclusion should be
0
2
4
6
8
10
12
14
16
18
Baseline 15 min 30 min 60 min 90 min 120 min
NIKBUT (seconds)
Time (minu es)
NIKBUT- i s e sus NIKBUT-a e age
NIKBUT-a e age NIKBUT- i s
****
***
Figu e 4 Compa ison o he mean alues o non-in asi e Ke a og aph 5M fi s ea b eak-up ime and non-in asi e Ke a og aph a e age b eak-up ime measu ed du ing he
fi s 120 min a e ins illa ion o he d op. The e was an ini ial inc ease in bo h pa ame e s a 15 min, ollowed by a g adual dec ease a e 30 min. The as e isk (*) deno es
s a is ical significance.
Abb e ia ion: NIKBUT, Non-in asi e Ke a og aph b eak-up ime.
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conside ed in u u e s udies. Mo eo e , u u e s udies
could include la ge sample popula ions and s udy one
eye pe pa ien , o confi m he esul s. Mo eo e ,
a compliance o m filled no only by he in es iga o
du ing ollow-up isi s, bu also by pa ien s could educe
he a iabili y in he implemen a ion o he a ificial ea
egimen and should be conside ed in u u e s udies.
In conclusion, a ificial ea s composed o p ese a i e-
ee 0.4% hyalu onic acid and 0.2% galac oxyloglucan a e
use ul o he ea men o he signs and symp oms o d y
eye, imp o ing NIKBUT, conjunc i al hype emia, Ox o d
and OSDI sco es a e 1 mon h o ea men .
Acknowledgmen
The a ificial ea s used in he s udy we e dona ed by
Es e e Pha maceu icals.
Disclosu e
IATA and RETICS OFTARED ha e sponso ed he ansla-
ion o his manusc ip . AMG-H, JM-I, ER-d-l-R-F, and
MC-M a e membe s o RETICS OFTARED ‘RD16/0008/
0010ʹ,financed by Ins i u o de Salud Ca los III, as pa o
he Plan Nacional I+D+i 2013–2016 and co-financed by
he Eu opean Union (FEDER/FSE) “Una mane a de hace
Eu opa.”None o he unding agencies played an ac i e
ole in he s udy design and in he decision o submi his
manusc ip o publica ion, and hey do no ha e ul ima e
au ho i y o e any o hese ac i i ies. The au ho s epo
no o he possible conflic s o in e es in his wo k.
Re e ences
1. Moss SE, Klein R, Klein BE. P e alence o and isk ac o s o d y eye
synd ome. A ch Oph halmol.2000;118(9):1264–1268. doi:10.1001/
a choph .118.9.1264
2. Paulsen AJ, C uickshanks KJ, Fische ME, e al. D y eye in he bea e
dam o sp ing s udy: p e alence, isk ac o s, and heal h- ela ed qual-
i y o li e. Am J Oph halmol.2014;157(4):799–806. doi:10.1016/j.
ajo.2013.12.023
3. Uccello-Ba e a G, Nazzi S, Zambi o Y, Di Colo G, Balzano F,
Sansò M. Syne gis ic in e ac ion be ween TS-polysaccha ide and hya-
lu onic acid: implica ions in he o mula ion o eye d ops. In J Pha m.
2010;395(1–2):122–131. doi:10.1016/j.ijpha m.2010.05.031
4. Ve su a P, P o azio V, Balducci N, Campos EC. E ficacy o wo-mon h
ea men wi h Xiloial eyed ops o discom o om disposable so
con ac lenses. Clin Oph halmol.2010;4:1035–1041. doi:10.2147/
OPTH.S10448
5. Ma eo O obia AJ, Saa J, Olle o Lo enzo A, He e as JM. Combina ion
o hyalu onic acid, ca mellose, and osmop o ec an s o he ea men o
d y eye disease. Clin Oph halmol.2018;12:453–461. doi:10.2147/
OPTH.S157853
6. Soumend a S, Rashmi ekha S, Padma LN. Tama ind seed polysaccha -
ide: a e sa ile biopolyme o mucoadhesi e applica ions. JPha m
Biomed Sci.2010;8:20.
7. Ies e M, Oddone F, Fogagnolo P, F ezzo i P, Figus M. Con ocal
Mic oscopy S udy G oup. Changes in he mo phological and unc-
ional pa e ns o he ocula su ace in pa ien s ea ed wi h p os a-
glandin analogues a e he use o TSP 0.5%
®
p ese a i e- ee
eyed ops: a p ospec i e, mul icen e s udy. Oph halmic Res.
2014;51(3):146–152. doi:10.1159/000357100
8. Cox SM, Nichols KK, Nichols JJ. Ag eemen be ween au oma ed and
adi ional measu es o ea film b eakup. Op om Vis Sci.2015;92(9):
e257–63. doi:10.1097/OPX.0000000000000648
9. Wu S, Hong J, Tian L, Cui X, Sun X, Xu J. Assessmen o bulba
edness wi h a newly de eloped ke a og aph. Op om Vis Sci.2015;92
(8):892–899. doi:10.1097/OPX.0000000000000643
10. Ma koulli M, Duong TB, Lin M, Papas E. Imaging he ea film:
a compa ison be ween he subjec i e keele ea scope-plus™and
he objec i e oculus
®
ke a og aph 5M and LipiView
®
in e e om-
e e . Cu Eye Res.2018;43(2):155–162. doi:10.1080/0271
3683.2017.1393092
11. B on A, E ans VE, Smi h JA. G ading o co neal and conjunc i al
s aining in he con ex o o he d y eye es s. Co nea.2003;22
(7):640–650. doi:10.1097/00003226-200310000-00008
12. Akiyama-Fukuda R, Usui T, Yoshida T, Yamagami S. E alua ion
o ea meniscus dynamics using an e io segmen swep -sou ce
op ical cohe ence omog aphy a e opical solu ion ins illa ion o
d y eye. Co nea.2016;35(5):654–658. doi:10.1097/ICO.00000000
00000807
13. Baek J, Doh SH, Chung SK. Compa ison o ea meniscus heigh
measu emen s ob ained wi h he ke a og aph and ou ie domain
op ical cohe ence omog aphy in d y eye. Co nea.2015;34
(10):1209–1213. doi:10.1097/ICO.0000000000000575
14. López-de la Rosa A, Pin o-F aga J, Blázquez A auzo F, U bano
Rod íguez R, González-Ga cía MJ. Sa e y and e ficacy o an a ificial
ea con aining 0.3% hyalu onic acid in he managemen o
mode a e- o-se e e d y eye disease. Eye Con ac Lens.2017;43
(6):383–388. doi:10.1097/ICL.0000000000000284
15. Nagaha a Y, Koh S, Nishida K, e al. P olonged inc ease in ea
meniscus heigh by 3% diqua osol oph halmic solu ion in eyes wi h
con ac lenses. Clin Oph halmol.2015;9:1029–1031. doi:10.2147/
OPTH.S86173
16. Pé ez-Ba olomé F, Ma ínez-de-la-Casa JM, A iola-Villalobos P,
e al. Ocula edness measu ed wi h he ke a og aph 5m in pa ien s
using an i-glaucoma eye d ops. Semin Oph halmol.2018;33
(5):643–650. doi:10.1080/08820538.2017.1395891
17. El Ameen A, Vande mee G, Pisella PJ. E ficacy and pa ien ole -
abili y o p ese a i e- ee la anop os compa ed wi h p ese a i e
p os aglandin analogs in pa ien s wi h ocula hype ension o glau-
coma. Ac a Oph halmol.2016;94.
18. Abdel a ah NS, Das i idou A, Sadda SR, Lee OL. Nonin asi e
imaging o ea film dynamics in eyes wi h ocula su ace disease.
Co nea.2015;34:S48–52. doi:10.1097/ICO.0000000000000570
19. Kim YH, Kang YS, Lee HS, Choi W, You IC, Yoon KC.
E ec i eness o combined ea film he apy in pa ien s wi h e apo a-
i e d y eye wi h sho ea film b eakup ime. J Ocul Pha macol
The .2017;33(8):635–643. doi:10.1089/jop.2017.0019
20. Mun Y, Kwon JW, Oh JY. The apeu ic e ec s o 3% diqua osol
oph halmic solu ion in pa ien s wi h sho ea film b eak-up
ime- ype d y eye disease. BMC Oph halmol.2018;18(1):237.
doi:10.1186/s12886-018-0910-3
21. Koh S, Ikeda C, Wa anabe S, e al. E ec o non-in asi e ea
s abili y assessmen on ea meniscus heigh . Ac a Oph halmol.
2015;93(2):e135–139. doi:10.1111/aos.12516
22. Ma koulli M, Sobbizadeh A, Tan J, B iggs N, Co oneo M. The e ec
o op i e and op i e ad anced a ificial ea s on he heal hy ea film.
Cu Eye Res.2018;43(5):588–594. doi:10.1080/02713683.2018.
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