Vol.:(0123456789)
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G ae e's A chi e o Clinical and Expe imen al Oph halmology
h ps://doi.o g/10.1007/s00417-021-05415-6
CORNEA
E icacy o hyalu onic acid 0.3%, cyanocobalamin, elec oly es,
andP‑Plus inmenopause pa ien s wi hmode a e d y eye disease
ConcepciónDe‑Hi a‑Can alejo1 · Ma íaCa menSánchez‑González1· Ca menSil a‑Vigue a1·
Ma aC.Ga cía‑Rome a1· Rica doFe ia‑Man e o1· José‑Ma íaSánchez‑González1
Recei ed: 31 Janua y 2021 / Re ised: 8 July 2021 / Accep ed: 10 Sep embe 2021
© The Au ho (s) 2021
Abs ac
Pu pose To s udy he ea men e icacy o hyalu onic acid 0.3%, cyanocobalamin ( i amin B12), elec oly es, and P-Plus
in menopausal pa ien s wi h mode a e d y eye disease.
Me hods Thi y emale pa ien s o mean age 53.06 ± 5.20 yea s (45–65) we e en olled in his p ospec i e longi udinal s udy.
Meibomian gland loss assessmen was de e mined using a scale wi h ou le els. The Ocula Su ace Disease Index (OSDI)
ques ionnai e, phenol ed h ead (PRT) es , and ea ilm b eak-up ime (TFBUT) we e also comple ed by he pa ien s.
Tea eye d ops we e o mula ed wi h 0.3 g o sodium hyalu ona e, P-Plus ™, i amin B12, sodium chlo ide, po assium
chlo ide, calcium chlo ide, magnesium chlo ide, and SCO® (s abilized complex oxychlo ide). A e 30 days, he pa ien s
we e e-e alua ed.
Resul s The mean meibomian gland loss pe cen age was 37.97 ± 19.02 % (7.20 o 88.30%). Be o e ea men , he OSDI was
22.53 ± 14.03 sco e poin s (6.25 o 77.08). Pos e io OSDI dec eased o 16.26 ± 13.69 sco e poin s (0.00 o 70.83) (W =
58.00, P < 0.01). Be o e ea men , PRT was 10.31 ± 4.48 mm (4.00 o 21.00). Pos e io PRT inc eased o 15.41 ± 6.27 mm
(4.00 o 21.00) (W = 1520.50, P < 0.01). Be o e ea men , TFBUT was 6.23 ± 1.75 s (3.00 o 9.00). The pos e io TFBUT
inc eased o 8.10 ± 2.06 s (4.00 o 14.00) (W= 1382.50, P < 0.01).
Conclusion The hyalu onic acid 0.3% and i amin B12 eye d ops e ec i ely dec eased d y eye symp oms in menopausal
women and imp o ed ea s abili y and olume.
Key messages
Wha was known
Hyalu onic acid has been shown an e ec i e ea men o he con ol o he symp oms o d y eye disease, in
addi ion, i amin B12 is a powe ul an ioxidan .
New in o ma ion
Hyalu onic acid 0.3% and i amin B12 dec eased d y eye symp oms in menopausal women. The combina ion o
Hyalu onic acid and P-Plus ™ imp o ed ea s abili y and olume.
Keywo ds Hyalu onic acid· Vi amin B12· D y eye disease· Menopause· A i icial ea s
In oduc ion
Menopause is associa ed wi h he physiological in e up ion
o he o a ian ho monal sec e ion o es ogen and p oges-
e one. Consequen ly, pa hological p ocesses can de elop
in di e en loca ions, such as he u ogeni al sys em [1],
* Concepción De-Hi a-Can alejo
[email p o ec ed]
1 Depa men o Physics o Condensed Ma e , Op ics A ea,
Pha macy Facul y, Uni e si y o Se ille, Reina Me cedes
S ee , 41012Se ille, Spain
G ae e's A chi e o Clinical and Expe imen al Oph halmology
1 3
ca dio ascula sys em [2], and bones [3]. Addi ionally, some
ocula s uc u es may be al e ed. As a consequence o physi-
cal and psychological de e io a ion, he quali y o li e o
menopausal women may be educed [4]. D y eye synd ome
is a disease cha ac e ized by he pa hological es uc u ing
o ea s and lesions on he co neal su ace, which esul in
symp oms, such as isual discom o and dis u bance, bu n-
ing, i ching, edness, pain, and ocula a igue, wi hou uni-
o m diagnos ic c i e ia [5]. Main aining physiological le els
o ho mones, such as es ogens, is essen ial o ob ain s able
ea quali y. Es ogen and and ogen le els a ec he h ee
componen s o he ea ilm, he aqueous laye , lipids, and
mucin. Du ing menopause, he e is a dec ease in he le el
o many sex ho mones ha subsequen ly esul s in d y eye
disease (DED) [6].
Fu he , a posi i e co ela ion has been demons a ed
be ween age and d y eye synd ome symp oms [7], and a
syne gis ic e ec be ween physiological ac o s linked o age
and ho monal changes in menopause is possible. The p e a-
lence o ocula su ace disease symp oms in menopausal
women was 64% (45–79 yea s), wi h a mean age o 49.45
± 4.02 yea s a menopause [8]. Tea ac s as he subs i u e o
inc ease humidi y a he ocula su ace and imp o e lub i-
ca ion, consequen ly educing symp oms in mos cases [9].
Cu en ly, he e a e se e al s a egies o he ea men o d y
eyes, whe eby au ologous se um [10], su gical in e en ions
[11] o combina ions o lub ica ion and an i-in lamma o y
agen s [12] ha e been used. In many cases, nu i ional sup-
plemen a ion [13], such as ha wi h omega-3 and omega-6
a y acids, and empo a y occlusion o he d y eye [14] a e
conside ed easonable ecommenda ions. The cu en unde -
s anding o he ocula su ace changes in pa ien s wi h d y
eye synd ome esul s om hype osmola i y o he ea ilm,
in lamma o y p ocesses, and oxida i e s ess. We s udied
an a i icial ea he apy o mula ed wi h hyalu onic acid,
a compound widely used as an ocula lub ican in isola ion
o in combina ion wi h o he subs ances [15]. P-Plus™ p o-
ides iscosi y and adhe ence o he ea s, and cyanocobala-
min ( i amin B12) has an ioxidan and an i-in lamma o y
p ope ies [16].
The p ima y pu pose o his s udy was o de e mine he
ea men e icacy o 0.3% hyalu onic acid, cyanocobalamin,
elec oly es, and P-Plus in menopausal pa ien s wi h mode -
a e d y eye disease.
Me hods
Design andsubjec s
Thi y emale pa ien s we e en olled in his p ospec i e
longi udinal s udy ha was de eloped in he op ome y
cabine s o he Facul y o Pha macy a he Uni e si y o
Se ille (Spain) be ween Janua y 2019 and Ma ch 2019. This
s udy was app o ed by he E hics Commi ee o Andalu-
sia and conduc ed ollowing he p inciples o he Helsinki
Decla a ion.
The inclusion c i e ia we e as ollows: (1) women in men-
opause o pe imenopause; (2) age be ween 45 and 65 yea s;
(3) a b eak-up ime o <10 s; (4) comple ion o all exami-
na ions; and (5) a ull unde s anding o he meaning o he
s udy and a signed in o med consen o m be o e he s a
o measu emen s. The exclusion c i e ia we e as ollows: (1)
any p e ious eye su ge y, (2) any sys emic diseases, (3) any
pha macological ea men (including ho mone eplacemen
he apy o meibomian gland d ain ins umen s as lipi low),
and (4) con ac lens wea e s. Ou o a o al o 36 women who
me he inclusion bu no he exclusion c i e ia, wo decided
no o ake ejec ion es s, wo o he s did no comple e he
ull s udy, and wo o he s did no show up.
Ma e ial
Non-con ac in a ed meibog aphy (CSO Non-myd ia ic
Fundus Came a Cob a HD, I aly) was used o he meibo-
mian gland (MG) s uc u e and heal h analysis using Ana
Eyes so wa e (Essilo Ins umen s, USA). A scale de e -
mined MG loss assessmen (meibosco e) wi h ou le els;
g ade 0 exhibi ed no loss, and g ades 1, 2, and 3 exhib-
i ed < 33%, 33–66%, and > 66% loss [17, 18]. Pa ien s
also comple ed he Ocula Su ace Disease Index (OSDI)
ques ionnai e. The ques ionnai e was used o assess DED
symp oma ology pe cei ed by he pa ien du ing he p e-
ious mon h. The ques ionnai e consis ed o h ee blocks,
each wi h ou ques ions (12 issues in o al). The o al OSDI
sco e was ob ained om he o al sum o he alue answe ed
o each ques ion, measu ed om 0 o 4, mul iplied by a
ixed alue o 25, and di ided by he numbe o ques ions
answe ed, esul ing in a pe cen age ha measu ed he p ob-
abili y o p esen ing d y eye be ween 0 and 50% [19, 20].
The phenol ed h ead es (PRT) (Tianjin Jingming New
Technological De elopmen Co., L d., China) was used o
measu e ea ilm sec e ion. I consis ed o a co on h ead
placemen imp egna ed wi h phenol ed on o he empo al
one- hi d o he lowe eyelid. The h ead is yellow when
d y and changes o ed when mois ened by ea s because i
is sensi i e o pH. A e 15 s, he h ead was emo ed, and
he pe iod when i changed o ed was measu ed [19, 20].
The p ocedu e was pe o med i s in he igh eye ollowed
by he le eye. The ea ilm quali y was measu ed by he
ea ilm b eak-up ime es (TBUT) using a luo escein s ip
(Bio 62 Glo Con aCa e Oph halmic & Diagnos ics, Guja-
a , India) imp egna ed wi h saline solu ion d ops and a sli
lamp (TOPCON SL-6E, Japan). The s ip was used o dye
he uppe bulba conjunc i a. The pa ien was ins uc ed o
blink na u ally h ee imes and s op blinking un il ins uc ed,
G ae e's A chi e o Clinical and Expe imen al Oph halmology
1 3
and he ea ilm was obse ed wi h cobal blue illumina ion
o a sli lamp. The in e al o ime in seconds be ween he
las comple e blink and he appea ance o he i s b eak
in he ea ilm was epo ed as he ea ilm b eak-up ime
(TFBUT)[19, 20]. The a e age alue o h ee consecu i e
measu emen s was used o analysis.
Tea eyed ops (VISIONLUX® PLUS, No ax® Pha ma,
Monaco, F ance) we e o mula ed wi h 0.3 g o sodium hya-
lu ona e, P-plusTM, i amin B12, sodium chlo ide, po as-
sium chlo ide, calcium chlo ide, magnesium chlo ide, and
SCO® (s abilized complex oxychlo ide). This p ese a i e
when exposed o sunligh b eaks down in o na u al compo-
nen s ha a e no oxic o he ocula su ace. All componen s
we e dissol ed in a bu e ed iso onic solu ion. Hyalu ona e
sodium 0.3% was ob ained by e men a ion and was no o
animal o igin. Sodium hyalu ona e ac i i y was op imized
wi h he syne gis ic ac ion o P-plus™. P-Plus™ is a wa e -
soluble polyme wi h phylogenic p ope ies and lub ican s.
The hyalu ona e associa ion o sodium and P-Plus™ no only
inc eased he iscosi y o he solu ion bu also imp o ed
i s mucoadhesi e p ope ies. The p esence o elec oly es
(Cl–, Na+, K+, Ca++, and Mg++) essen ial o he cellu-
la biochemical p ocess helped main ain he eye su ace in
good physiological condi ions. Vi amin B12 has an ioxidan
p ope ies, he eby p o ec ing he eye su ace om damage
induced by eac i e oxygen species (ROS). The e o e, i was
an essen ial ac o in main aining a heal hy eye su ace. I
was packaged in a 10-ml mul idose bo le. Labo a o y ec-
ommended dosage was wice a day.
Examina ions p ocedu e
The s udy consis ed o wo phases. In he i s phase, pa ien s
we e selec ed, and a biomic oscope examina ion was pe -
o med o assess hei sui abili y o inclusion in he s udy.
The pa ien s comple ed he OSDI ques ionnai e. Tea ol-
ume was e alua ed using he PRT es and ea quali y wi h
he TBUT es using luo escein and he cobal blue ligh o
he sli lamp. MG loss assessmen was e alua ed by mei-
bog aphy (meibosco e). A e a ze o ime o 15 days wi h-
ou ea ea men , pa ien s we e ins uc ed on he co ec
ins illa ion echnique and he dose o ea eye d ops ( wice
ins illa ion pe day). A e 30 days, in he second phase,
pa ien s we e e-e alua ed and es ed using he OSDI, PRT,
and TFBUT. To a oid he subjec i e bias o he esea che ,
he esul s o he measu emen s ob ained du ing he second
isi we e eco ded in a di e en documen om ha o he
i s measu emen s. Finally, he da a collec ed in bo h phases
we e compa ed o ob ain he esul s o he s udy. All exami-
na ions we e conduc ed by an expe ienced op ome is , a he
same loca ion, unde he same ime and humidi y condi ions,
and using he same ins umen a ion.
S a is ical analysis
The sample size was assessed wi h he GRANMO® cal-
cula o (Ins i u Municipal d’In es igació Mèdica, Ba ce-
lona, Spain, Ve sion 7.12). Accep ing an alpha isk o 12:05
and a be a isk o 0.2 in a wo-sided es , 21 subjec s mus
ecognize a s a is ically signi ican di e ence consis ing o
an ini ial p opo ion o 0.8 and a inal p opo ion o 0.2. A
d op-ou a e o 10% was an icipa ed. S a is ical analysis
was pe o med using SPSS s a is ical so wa e ( e sion 26.0,
IBM Co p, A monk, New Yo k, USA). The no mali y o he
da a dis ibu ion was assessed using he Shapi o-Wilk es .
Desc ip i e analysis was pe o med using he mean ± SD
(s anda d de ia ion; a iabili y alue). Di e ences be ween
p e ious and pos e io ea men a iables we e assessed
using he Wilcoxon es . E ec size calcula ion was assessed
wi hin D o he Cohen es . Quali a i e di e ences we e
assessed using he chi-squa ed es o McNema es . The
co ela ion s udy was assessed using he Spea man Rho es .
The le el o signi icance was se a 95% (P- alue < 0.05).
Resul s
Thi y women we e en olled in his longi udinal s udy. The
mean age o he women included in he s udy was 53.06
± 5.20 yea s (45–65). The mean MG loss pe cen age was
37.97 ± 19.02% (7.20 o 88.30), and he mean MG loss
g ade acco ding o A i a e al. [17, 18], measu ed by he
meibomian sco e ank, was 1.70 ± 0.67 (g ade 1 o g ade
3). Rega ding he MG loss g ade equency, 25 pa ien s
achie ed g ade 1 (41.7%), 28 pa ien s achie ed g ade 2
(46.7%), and only se en pa ien s achie ed g ade 3 (11.7%).
Fou ep esen a i e MG images o di e en deg ees and pe -
cen ages o MG loss a e shown in Fig.1. MG loss assess-
men was no pe o med a e eyed op ea men because
i has been shown ha a i icial ea s do no al e he MG
pa e n [21]. Acco ding o he McNema es (P<0.01).
OSDI, PRT and TFBUT box and plo g aph we e p esen ed
in Fig.2.
OSDI
A quan i a i e analysis was pe o med be o e he ea men ;
he Ocula Su ace Disease Index (OSDI) was 22.53 ± 14.03
sco e poin s (6.25 o 77.08). Pos e io OSDI dec eased o
16.26 ± 13.69 sco e poin s (0.00 o 70.83). Signi ican s a is-
ical di e ences occu ed be ween he p e ious and pos e io
OSDI alues (W = 58.00, P < 0.01). Posi i e di e ences
(OSDI inc eased) we e ound only in ou eyes, nega i e
di e ences (OSDI dec eased) in 52 eyes, and ies (same
OSDI) only in ou eyes. The e ec size was 0.4523, and
acco ding o Cohen’s D esul s, i was a medium e ec size.
G ae e's A chi e o Clinical and Expe imen al Oph halmology
1 3
Spea man’s ho be ween he p e ious and pos e io OSDI
was 0.824 (P < 0.01).
Addi ionally, a quali a i e analysis was pe o med. Acco d-
ing o he Tea Film and Ocula Su ace In e na ional D y Eye
Wo kshop (DEWS II) [19, 20], he OSDI es was classi ied
in o ou anks (no mal < 13 sco e poin s, mild be ween 13
and 22, mode a e be ween 23 and 32, and se e e ≥ 33). In he
p e ious OSDI, 14 eyes eached no mal sco e poin s (23.3%),
26 eyes a ained mild sco e poin s (43.3%), 12 eyes achie ed
mode a e sco e poin s (20.0%), and only eigh eyes achie ed
se e e sco e poin s (13.3). In he pos e io OSDI, 26 eyes
eached no mal sco e poin s (43.3%), 20 eyes a ained mild
sco e poin s (33.3%), 10 eyes achie ed mode a e sco e poin s
(16.7%), and only ou eyes achie ed se e e sco e poin s
(6.7%). Acco ding o he chi-squa e es , his ep esen ed a
s a is ically signi ican di e ence (χ2 = 47.37, P < 0.01).
PRT
A quan i a i e analysis was pe o med be o e he ea men .
The PRT was 10.31 ± 4.48 mm (4.00 o 21.00). Pos e io
PRT inc eased o 15.41 ± 6.27 mm (4.00 o 21.00). Signi i-
can s a is ical di e ences occu ed be ween he p e ious and
pos e io PRT (W = 1520.50, P < 0.01). Posi i e di e ences
(PRT inc eased) occu ed in 48 eyes, nega i e di e ences
(PRT dec eased) in 10 eyes, and ies (same PRT) only in wo
eyes. The e ec size was 0.9360, and acco ding o Cohen’s
D esul s, i was a conside able e ec size. Spea man’s ho
be ween p e ious and pos e io OSDI was 0.295 (P < 0.05).
Addi ionally, a quali a i e analysis was pe o med.
Acco ding o DEWS II [19, 20], PRT es cu -o poin was
10 mm. In he p e ious PRT, 26 eyes we e unde he cu -
o poin (43.3%), and 34 eyes we e abo e he cu -o poin
(56.7%). Only eigh eyes we e unde 10 mm (13.3%) in he
pos e io PRT, and 52 eyes we e abo e 10 mm (86.7%). This
ep esen ed a s a is ically signi ican di e ence, acco ding
o he McNema es (P < 0.01).
TFBUT
A quan i a i e analysis was pe o med be o e he ea men .
TFBUT was 6.23 ± 1.75 s (3.00 o 9.00). The pos e io
TFBUT inc eased o 8.10 ± 2.06 s (4.00 o 14.00). Signi i-
can s a is ical di e ences we e ound be ween he p e ious
and pos e io TFBUT (W = 1382.50, P < 0.01). Posi i e di -
e ences (TFBUT inc eased) we e ound in 49 eyes, nega i e
di e ences (TFBUT dec eased) in ou eyes, and ies (same
TFBUT) in only se en eyes. The e ec size was 0.9941,
and acco ding o Cohen’s D esul s, i was a conside able
e ec size. Spea man’s ho be ween p e ious and pos e io
TFBUT was 0.694 (P < 0.01).
Addi ionally, a quali a i e analysis was pe o med.
Acco ding o DEWS II [19, 20], TFBUT es cu -o poin
was 10 s. In he p e ious TFBUT, all eyes we e unde 10 s
(100%). In he pos e io TFBUT, only 41 eyes we e unde
10 s (68.3%), and 19 eyes we e abo e 10 s (31.7%). This
ep esen ed a s a is ically signi ican di e ence, acco ding
o he McNema es (P < 0.01).
Discussion
This p ospec i e longi udinal s udy aimed o s udy he e i-
cacy o eye d ops wi h 0.3% hyalu onic acid and i amin
B12 in menopausal women a e 1 mon h o use. Hyalu onic
acid is conside ed an e ec i e ea men o he con ol o
Figu e1 Meibomian gland
dys unc ion (MGD) models
acco ding o he meibomian
sco e ank desc ibed by A i a
e al. [17, 18], which was based
on he pe cen age o meibomian
gland loss de e mined using
image p ocessing so wa e. All
cap ions we e om an uppe
lid. A Meibomian gland loss
o 22.8%, achie ing g ade 1 o
MGD. B Meibomian gland loss
o 45.8%, achie ing g ade 2 o
MGD. C Meibomian gland loss
o 73.5%, achie ing g ade 3 o
MGD. D Meibomian gland loss
o 87.5%, achie ing g ade 3 o
MGD
G ae e's A chi e o Clinical and Expe imen al Oph halmology
1 3
he symp oms o DED [22–25]. On he o he hand, i amin
B12 is a powe ul an ioxidan , obse ing ha ce ain hyalu-
onic acid eye d ops wi h i amin B12 can educe oxida i e
s ess and imp o e d y eye symp oms [26]. MG assessmen
was pe o med on all pa ien s, showing he d y eye symp-
oms cha ac e is ic o gland loss [27]. Addi ionally, some
s udies show d y eyes in women o his age. Ga cía-Al a o
e al. [8] conduc ed a s udy in pe imenopausal and pos -
menopausal women o e alua e he symp oms o d y eye
using he OSDI ques ionnai e, concluding ha his symp-
oma ology exis s in bo h g oups and may a ec ac i i ies
ela ed o ision along wi h a dec ease in quali y o li e.
Simila ly, Ca eba e al. [28] conduc ed a s udy wi h 66
pos menopausal women in which ocula d yness was e alu-
a ed using he OSDI, TBUT, and non-in asi e TFBUT, in
which hey ound ha he g oup o women wi h symp oms
o ocula d yness was ela ed o da a om he highe OSDI
es s, sho e TBUTs, and non-in asi e TFBUT. Addi ion-
ally, a ious s udies ha e conside ed his es eliable o he
measu emen o his symp oma ology[29, 30].
Acco ding o he es s pe o med, ou esul s indica ed
ha all women exhibi ed imp o ed d y eye symp oms a e
ea men (OSDI, PRT, and TFBUT). The dec ease in OSDI
in 52 eyes indica ed pa ien sa is ac ion wi h he use o d ops
o elie ing symp oms. Se ano-Mo ales e al. [31] con-
duc ed a s udy in menopausal women o demons a e he
e icacy o hyalu onic acid, concluding ha a e 2 mon hs
o ea men , he OSDI es sco e dec eased, coinciding wi h
he da a om ou s udy. In he PRT es , conside ing he cu -
o poin a 10 mm, 86.7% had mo e han 10 mm a e he
mon h o ea men , esul ing in a highe esul in 48 eyes.
Saeed e al.[32] conduc ed a s udy o he e icacy o hyalu-
onic acid in d y eyes in which h ee measu emen s (baseline
4–8 weeks) o he Schi me ’s es we e pe o med, showing
how in each case he e was an inc ease in he esul s, which
co obo a ed ou e icacy da a using his es . Al hough
Schi me ’s es was pe o med in his s udy, some s udies
equalize he e icacy o bo h es s o he diagnosis o ea
quan i y [33, 34].
In he TFBUT es , posi i e s a is ically signi ican di -
e ences we e ound in 49 eyes and he same esul in only
se en eyes. Cheo e al. [24] conduc ed a s udy compa ing
he e icacy o 0.1%, 0.18%, and 0.3% hyalu onic acid eye
d ops in mice and obse ed ha he TBUT inc eased a e
28 days o ea men . They concluded ha d ops wi h a con-
cen a ion o 0.3% we e mo e use ul o he ea men o
d y eye, he eby suppo ing ou esul s and indica ing ha
hese d ops a e mo e e ec i e han hose wi h a lowe con-
cen a ion o hyalu onic acid. The e o e, i was concluded
ha i amin B12 is an essen ial componen o hese a i i-
cial ea s, wi h an ioxidan p ope ies ha p o ec he ocu-
la su ace. Mac i e al. [26] conduc ed a s udy wi h 0.15%
hyalu onic acid eye d ops and i amin B12 o e alua e he
e ec s on oxida i e s ess and d y eye and concluded ha
bo h we e ela ed and ha he combined composi ion o he
d ops educed s ess and in lamma ion and imp o ed all
d y eye symp oms. P e iously, we men ioned he g ea e
e icacy o 0.3% hyalu onic acid p esen in ou ea s, and
his along wi h he an ioxidan e ec s o i amin B12 con-
i med he e icacy o he da a om all he es s conduc ed.
Addi ionally, i should be no ed ha he ea s used a e
composed o a wa e -soluble polyme , P-Plus ™, which,
oge he wi h hyalu onic acid, ends o inc ease iscosi y and
imp o e mucoadhesi e p ope ies. A agona e al. [35] con-
duc ed a s udy in which hey analyzed he physicochemical
Figu e2 Box and plo g aphs o longi udinal di e ences wi hin h ee
main a iables s udied. A Ocula Su ace Disease Index (OSDI),
measu ed in sco e poin s. B Phenol ed es (PRT), measu ed in mil-
lime e s. C Tea ilm b eak up ime (TFBUT), measu ed in s

G ae e's A chi e o Clinical and Expe imen al Oph halmology
1 3
p ope ies o 18 d ops wi h hyalu onic acid and wi h di -
e en polyme s and concluded ha ea s in he p esence
o polyme s inc eased iscosi y we e mo e bene icial o
pa ien s and inc eased he p ope ies o hyalu onic acid in
he ea men o d y eyes; composi ion o he d ops used
in ou s udy demons a ed simila e ec s. Ou s udy had
some limi a ions. Fi s , he sample consis ed o 30 pa ien s,
and highe pa ien olume should include in u u e esea ch.
Addi ionally, he s udy was designed as a longi udinal one-
a m s udy, and a longe ollow-up is needed o con i m he
achie ed esul s.
In conclusion, 0.3% hyalu onic acid and i amin B12 eye
d ops e ec i ely dec eased d y eye symp oms in menopau-
sal women and imp o ed ea s abili y and olume.
Acknowledgemen s The au ho s app ecia e he suppo o e ed by
he Depa men o Physics o Condensed Ma e , Facul y o Physics,
Uni e si y o Se ille, wi h special hanks o Ja ie Rome o-Landa and
Cla a Conde-Amiano. Addi ionally, he au ho s also app ecia e he
echnical suppo o e ed by he membe s and acili ies o he Fac-
ul y o Pha macy, Uni e si y o Se ille, wi h special hanks o Ma ía
Ál a ez-de-So omayo .
Da a a ailabili y Da a a e a ailable om he co esponding au ho
upon easonable eques .
Decla a ions
E hics app o al All p ocedu es pe o med in s udies in ol ing human
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and/o na ional esea ch commi ee and wi h he ene s o he 1964
Helsinki Decla a ion and i s la e amendmen s o compa able e hical
s anda ds.
Consen o pa icipa e All subjec s included in his s udy we e ade-
qua ely in o med e bally and in w i ing ega ding he bene i s, cha ac-
e is ics, and isks o he s udy. All subjec s p o ided w i en in o med
consen be o e he s udy.
Consen o publica ion All he au ho s consen o he publica ion
o his a icle.
Con lic o in e es The au ho s decla e no compe ing in e es s.
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Publishe 's no e Sp inge Na u e emains neu al wi h ega d o
ju isdic ional claims in published maps and ins i u ional a ilia ions.