57

Jurnal Oftalmologi Indonesia

JOI
Vol. 7. No. 2 Desember 2009
The Effectiveness of Lipofilm Microemulsion Eye Drops in Dry
Eye Syndrome by Enhancing The Tear Film Quality
enry !arou"# $etno E%antini# Tri !ahyu !idayanti
Department of Opthalmology
Shool of !ediine" #ad$ah !ada %ni&ersity'Dr.Sard$ito #eneral (ospital
)ogya*arta
&'ST$&(T
The aim of this study was to evaluate the effectiveness of lipofilm microemulsion as ocular lubricant in dry eye syndrome. It was
prospective randomized clinical trial design with single blind masked study. Sixty eyes were enrolled according to the inclusion and
exclusion criteria. Two weeks and four weeks of follow-up were documented. Obective parameters were Schirmer I test and break
up time test. Subective symptoms were assessed by means of !-!" scale of visual analogic score. Thirty eyes were enrolled to
lipofilm group and #" eyes to sodium hyaluronate ".!$% group. &oth groups had improvement in mean Schirmer test 'p ( ".""!)
but there was no statistically difference between two groups after two weeks 'p * ".#+!) and four weeks 'p * ".",!). &oth groups
induced a significant increase of break up time test 'p ( ".""!) and there was statistically significant difference in lipofilm group
after two weeks 'p * "."#-) and four weeks 'p * "."".). Symptoms improved in all groups but statistically significant different in
lipofilm group in foreign body sensation 'p * ".""!) and blurred vision 'p * ".".!) after two weeks. /ipofilm tends to show a faster
improvement than sodium hyaluronate in patients with dry eye syndrome.
)ey "ords* lipofilm microemulsion0 sodium hyaluronate0 Schirmer test0 break up time test0 visual analogic score0 dry eye syndrome.
+orrespondene, (enry -arou." 'o, /agian !ata 0S Dr. Sard$ito'1a*ultas 2edo*teran %ni&ersitas #ad$ah !ada. Jalan 2esehatan
I" Se*ip %tara. 3elp., 0274552650. 78mail, sinyo997:;yahoo.om
+,T$-D.(T+-,
Dry eye is a multifatorial disease of the tears and
oular surfae that results in symptoms of disomfort"
&isual disturbane" and tear film instability .ith potential
damage to the oular surfae. It is aompanied by
inreased osmolarity of the tear film and inflammation of
the oular surfae.
9
3ear replaement by topial artifiial
tears and lubriants is urrently the most .idely used
therapy for dry eye" and a &ariety of omponents are used
to formulate a onsiderable number of ommerially
a&ailable preparations.
2
Oular lubriant replae tear
&olume" and though only paliati&e" are fre<uently
effeti&e in mild dry eye syndrome.
=
3he tear lipid layer has the important funtion of
delaying the .ater e&aporation thus maintaining tear film
stability and osmolarity.
4"5
3he preser&ation of a stable
preorneal tear film is essential for oular surfae health.
:
Se&eral studies indiated that there is a orrelation
bet.een lipid defiieny in the preorneal tear film"
inreased e&aporation and dry eye syndrome.
7
!iroemulsion lipofilm is a thermodynamially stable
miroemulsion of oil in .ater ontaining lipids and
ha&ing a physiologial funtion &ery lose to that of lipid
layer present in natural tears. 3he hemo8physial
struture of the miroemulsion" in partiular the presene
of oil droplet of sub8miron si>e and its stability gi&e to
?ipofilm the apability of impro&ing the tear lipid barrier
funtion by restoring the lipid layer as .ell as a
.ettability similar to that of natural tears.
6
3he purpose of this study is to e&aluate the
effeti&eness of ?ipofilm miroemulsion ompared to
Sodium hyaluronate
0.95@ in dry eye syndrome by enhaning the tear film
<uality.
Table /0 Demographi and baseline harateristi
#ender
Variable Lipofilm group Sodium hyaluronate
group P
!ale AN"@B : A50@B : A50@B 9.00
1emale AN"@B 24 A50@B 24 A50@B 9.00
Cge, years AmeanDSDB 70.4= D 7.:9 :6.47 D 6.5: 0.=5
Shirmer I test, mm. AmeanDSDB :.20 D 2.25 7.2= D =.59 0.45
/%3 test, seonds AmeanDSDB :.90 D 9.45 5.9= D 9.20 0.52
/urning, VCS AmeanDSDB 9.6= D 2.4: 2.07 D 2.45 0.79
1oreign body sensation, VCS AmeanDSDB 2.:0 D 9.60 2.77 D 9.40 0.:9
Ithing, VCS AmeanDSDB =.0= D 2.24 =.97 D 9.90 0.60
/lurred &ision, VCS AmeanDSDB 9.7= D 2.06 2.2= D 2.=4 0.=9
Table 10 +hanges in Shirmer I test bet.een baseline and follo.8up
2ariable Lipofilm group Sodium hyaluronate group p
Shirmer I test, mm AmeanDSDB
/aseline :.20 D 2.25 7.2= D =.59
Cfter 2 .ee*s
+hanges
9.27 D =.95
=.07 D 2.2:
9.77 D =.:9
2.5= D 9.60
0.905E
0.=:9E
Cfter 4 .ee*s 99.20 D =.27 99.00 D =.69 0.575E
+hanges 5.00 D 2.64 =.77 D 2.:9 0.069E
E!ann8-hitney 3est
M&TE$+&L &,D MET-DS
3he study follo.ed the design of single mas*ed
randomised parallel group linial trial. 3he treatment
duration .as 4 .ee*s. 3he study inluded :0 patients
A:0 eyesB" 46 A60@B females dan 92 A20@B males" mean
age :9.45 years" range 52F96 yearsB .ith dry eye
syndrome defined by t.o linial test, brea* up time test"
G 90 seonds in eah eye" ShirmerHs I test G 7 mm
.etting'5 min in eah eye and at least one of the
follo.ing symptoms of dry eye, burning" foreign body
sensation" ithing and blurred &ision. Only one eye of the
patients" that suffered the .orst symptoms of dry eye .as
used for the analysis.
Inlusion riteria .ere patients aged I 29 years"
suffered from dry eye syndrome" informed onsent
.ritten. 7Jlusion riteria .ere any ati&e inflammation
of the eye" latation and pregnanyK history of systemi
ontraeptionK history of eye trauma" infetion and oular
surgery .ithin the past : months before inlusion"
.earing ontat lens" ha&ing oular surgery due to dry
eye syndrome" suh li*e puntum auterisation and use of
topial and'or systemi treatments potentially interfering
.ith tear produtions.
Natural tear prodution .as assessed by the
ShirmerHs test" in .hih the eJtent of tear flo. do.n a
piee of filter paper inserted into the lateral part of the
inferior forniJ of the eye is measured o&er a 5 minute
period. 3he tear film brea*8up time Atime bet.een last
blin* and first disturbane
of the orneal tear film" /%3B .as assessed as a measure
of the stability of the preoular tear film.
Sub$eti&e symptoms Ai.e. burning'painK foreign body
sensationK ithingK blurred &isionB .ere assessed by
means of 9F90 sale of &isual analogi sore AVCSB.
Cbsene of any pain onstituted a sore of 0 points on the
&isual analog pain sales" and intense" unbearable pain
.as onsidered a full pain sore of 90 points and the
patients .ere as*ed to he* a point on the line
orresponding to their degree of pain. ?ipofilm
miroemulsion .as administered into the on$unti&al
sa" at least = times'day. Cs referene drug a
ommerially a&ailable multidose ophthalmi solution
ontaining 0.95@ Sodium (yaluronate .as used.
Similarly to ?ipofilm it .as administered into the
on$unti&al sa at least = times'day. 7ah patient .as
assigned to one of the treatments" aording to a
randomisation list" and under.ent to = &isits" as reported
in the follo.ing study plan, visit
! AbaselineBK visit . Aafter 2 .ee*s of treatmentBK visit
= Aafter 4 .ee*s of treatmentB. In eah &isit the follo.ing
&ariables .ere olleted in the follo.ing order, Shirmer
I test" brea* up time test and sub$eti&e symptoms. 3hese
parameters .ere ompared before" t.o .ee*s and four
.ee*s after treatment.
Sine the sample si>e .as small and" therefore" the
distribution .as not normal" non parametri tests .ere
applied Ai.e. -iloJonHs test and !ann8-hitneyHs testB.
-arou." d**., 3he 7ffeti&eness of ?ipofilm !iroemulsion 7ye Drops 53
Table 40 +hanges in brea* up time test bet.een baseline and follo.8up
2ariable Lipofilm group Sodium hyaluronate group 5
/rea* up time test, seonds A!eanDSDB
/aseline :.90 D 9.45 5.9= D 9.20
Cfter 2 .ee*s
+hanges
90.=7 D 2.=4
4.27 D 2.05
9.90 D 9.65
=.97 D 9.9=
0.0=4E
0.0=7
0
Cfter 4 .ee*s 92.:7 D 2.49 90.:= D 9.5: 0.009E
+hanges :.57 D 2.25 4.70 D 9.7= 0.002E
E!ann8-hitney 3estK
0
383est
Tabel 6. Sub$eti&e symptoms on &isual analogi sore bet.een baseline and follo.8up
2ariable Lipofilm group Sodium hyaluronate group p
/urning, VCS AmeanDSDB
/aseline 9.6= D 2.4: 2.07 D 2.45 0.556
Cfter 2 .ee*s 0.=0 D 0.66 0.77 D 9.52 0.999
Cfter 4 .ee*s 0.00 D =.:6 0.07 D 0.=7 0.=97
1oreign body sensation, VCS Amean D SDB
/aseline 2.:0 D 9.79 2.77 D 9.49 0.==:
Cfter 2 .ee*s 0.9= D 0.57 0.77 D 9.90 0.009E
Cfter 4 .ee*s 0 0 9
Ithing, VCS Amean D SDB
/aseline =.0= D 2.24 =.97 D 9.69 0.494
Cfter 2 .ee*s 0.=0 D 0.59 0.70 D 9.2: 0.=00
Cfter 4 .ee*s 0 0 9
/lurred &ision, VCS Amean D SDB
/aseline 9.7= D 2.06 2.2= D 2.=4 0.4=4
Cfter 2 .ee*s 0 0.20 D 0.46 0.029E
Cfter 4 .ee*s 0 0 9
E!ann8-hitney 3est
$ES.LTS
C total :0 eyes .ere enrolled in this study" of .hih
=0 eyes .ere enrolled to ?ipofilm miroemulsion group
and =0 eyes to Sodium hyaluronate 0.95@ group. 3able
9 summari>es demographi and baseline harateristis
inluding gender" age" mean Shirmer test" mean brea*
up time test" and sub$eti&e symptoms that assessed .ith
&isual analogi sore. 3here .ere no signifiant
differenes bet.een t.o groups .ith regard to these
baseline harateristis. 3he ma$ority of the sub$ets in
both groups .ere female A60@B.
Cfter 2 .ee*s of follo.8up both groups had ahie&ed
suessful in mean Shirmer I test &ersus baseline
Ap G 0.009B A3able 2B but no statistially different
bet.een ?ipofilm miroemulsion group" ompared to
Sodium hyaluronate 0"95@ group Ap L 0.905B. /oth
treatments also sho.ed a statistially signifiant
impro&ement &ersus baseline of mean Shirmer I test test
after 4 .ee*s of follo.8up Ap G 0.009B A3able 2B" but there
.ere no statisally signifiant differene bet.een
?ipofilm miroemulsion ompared to sodium
hyaluronate 0.95@ Ap L 0.069B.
Cfter 2 .ee*s and 4 .ee*s after treatment both
groups indued a signifiant impro&ement of brea* up
time test &ersus baseline Ap G 0.009B" there .ere also
statistially signifiant effet at 2 .ee*s Ap L 0.0=7B
and 4 .ee*s Ap L 0.002B after treatment in ?ipofilm
miroemulsion group" ompared to Sodium hyaluronate
0.95@ group. A3able =B
Sub$eti&e symptoms A3able 4B impro&ed on the
&isual analogue sale .ith all treatments and there .ere
statistially signifiant different bet.een t.o groups in
foreign body sensation Ap L 0.009B and blurred &ision
Ap L 0.029B after t.o .ee*s of study in ?ipofilm
miroemulsion group.
In terms of relief from burning sensation" 90.:=@
reported relief after 2 .ee*s .hile using ?ipofilm
miroemulsion ompared .ith 7 :.65@ on Sodium
hyaluronate 0"95@" but there .ere no signifiant
differene Ap L 0.064B. Cfter 4 .ee*s" 900@ relief from
burning sensation had been reported in ?ipofilm
miroemulsion group" ompared .ith 96.69@ on
Sodium hyaluronate
0.95@" but there .ere no statistially signifiant differene
Ap L 0.=67B. Its about 96.99@ in ?ipofilm miroemulsion
Table 50 +hanges of sub$eti&e symptoms bet.een baseline and follo.8up
2ariable Lipofilm group Sodium hyaluronate group p
/urning A@B
Cfter 2 .ee*s 90.:= 7:.65 0.064
Cfter 4 .ee*s 900 96.69 0.=67
1oreign body sensation A@B
Cfter 2 .ee*s 96.99 69.0: G 0.009E
Cfter 4 .ee*s 900 900
Ithing A@B
Cfter 2 .ee*s 94.=6 67.95 0.095
Cfter 4 .ee*s 900 900
/lurred &ision A@B
Cfter 2 .ee*s 900 94.29 0.0==E
Cfter 4 .ee*s 900 900
E!ann8-hitney 3est
group had statistially signifiant impro&ement from
foreign body sensation after 2 .ee*s of follo.8up
ompared to 69.0:@ on Sodium hyaluronate group Ap G
0.009B. /oth groups had ahie&ed 900@ relief from
foreign body sensation after 4 .ee*s of study.
3here .ere 94.=6@ relief from ithing sensation in
?ipofilm miroemulsion group ompared .ith 67.95@ on
Sodium hyaluronate group" but there .ere no statistially
signifiant differene Ap L 0.095B. /oth ?ipofilm and
Sodium hyaluronate 0.95@ group had ahie&ed 900@
relief from ithing sensation after 4 .ee*s.
/lurred &ision also statistially signifiant differene
in ?ipofilm miroemulsion group" 900@ impro&ed
ompared .ith 94.29@ on Sodium hyaluronate group
Ap L 0.0==B. Cfter 4 .ee*s" 900@ relief from blurred
&ision had been seen on both groups. No ad&erse e&ent in
any group .as obser&ed by the in&estigator or reported
by the patient throughout the study. /oth treatments .ere
.ell tolerated" eJept temporally blurred &ision
immediately after instillation on 9 sub$ets in ?ipofilm
miroemulsion group.
D+S(.SS+-,
In this study" dry8eye symptoms .ere &ery ommon
in .omen A60@B than men A20@B" mean age :9.45 years"
range
52F96 years. 3he pre&ious study that performed in
Custralia by !+arty et al.
9
indiated that .omen .ere
more li*ely to report symptoms of dry eye. 3he study
performed in Cmeria by !oss et al.
90
indiated that the
age8ad$usted pre&alene in men .as 99.4@" .hih .as
signifiantly lo.er than the 9:.7@ pre&alene in .omen.
3able 9 summari>es demographi and baseline
harateristis inluding gender" age" mean Shirmer test"
mean brea* up time test" and sub$eti&e symptoms that
assess .ith &isual analogi sore. 3here .ere no
signifiant differenes bet.een t.o groups .ith regard to
these baseline harateristis. 3his study indiates that
ompared .ith men" .omen are more
li*ely to ha&e dry8eye symptoms and positi&e dry8eye
tests" inluding the Shirmer test and the tear film
brea*up test" but not statistially signifiant differene.
3he apparent impro&ement in tear prodution in
patients reei&ing sodium hyaluronate 0.95@" as
determined by the ShirmersHs test" may reflet the .ater
retenti&e property of sodium hyaluronate resulting in an
inreased preorneal residene time of the artifiial tear
and inreased orneal .ettability
99
and redued tear
e&aporation from the oular surfae.
92
+ompared .ith
?ipofim" the hemo8physial struture of the
miroemulsion" in partiular the presene of oil droplet of
sub8miron si>e and its stability gi&e to ?ipofilm the
apability of impro&ing the tear lipid barrier funtion by
restoring the lipid layer as .ell as a .ettability similar to
that of natural tears.
6
+ondon et al.
9=
had reported the results of the
ShirmerHs test sho. a highly signifiant differene
bet.een hyaluronan and saline" also study that onduted
by Cragona et al.
94
had reported impro&ement of the
ShirmerHs test but no statistially signifiant differene
bet.een hypotoni 0.4@ sodium hyaluronate and isotoni
0.4@ sodium hyaluronate. In this study both ?ipofilm and
Sodium (yaluronate 0.95@ groups statistially
signifiant effet in impro&ing the ShirmerHs test Ap G
0.009B" but there .ere no statistially signifiant
differene bet.een both group after 2 .ee*s Ap L 0.905B
and 4 .ee*s Ap L 0.575B.
Cn unstable tear film is one of the most ommon
findings in patients .ith oular irritation aused either
by redued a<ueous tear prodution or an inrease in tear
e&aporation. 3he method most fre<uently used to assess
tear film stability is to measure the tear brea*8up time
A3/%3B" ie" the time inter&al bet.een a omplete blin*
and the first appearane of a dry spot in the preorneal
tear film after fluoresein instillation.
95"9:
Cragona et al.
94
reported that the omparison of
sodium hyaluronate hypotoni 0.4@ A950mOsm'?B to
isotoni 0.4@ after 90 days administration" there .ere not
statistially signifiant different of /%3 test Ap G 0.05B
in eah groups. 3he study onduted by Cragona et al.
6
had reported the results of the /%3 test that sho.ed no
signifiant differene bet.een ?ipofilm miroemulsion
and sodium hyaluronate 0.2@ groups. In this study" there
.ere signifiant impro&ement of brea* up time test
&ersus baseline Ap G 0.009B after 2 .ee*s and 4 .ee*s in
both groups" there .ere also statistially signifiant effet
at 2 .ee*s Ap L 0.0=7B and 4 .ee*s Ap L 0.002B after
treatment in ?ipofilm miroemulsion group" ompared to
Sodium hyaluronate 0.95@ group.
!Donalds et al.
97
reported signifiant symptoms
impro&ement in sodium hyaluronate 9.4@ group
ompared to poly&inyl alohol. 3he study by Cragona
et al.
6
had reported signifiant relief of burning sensation
and foreign body sensation in /ipofilm microemulsion
group ompared to sodium hyaluronate 0.2@ group. In
this study sub$eti&e symptoms impro&ed on the &isual
analogue sale .ith all treatments and there .ere
statistially signifiant different bet.een t.o groups in
foreign body sensation Ap L 0.009B and blurred &ision Ap
L 0.029B after t.o .ee*s of study in ?ipofilm
miroemulsion group" but there .as no signifiant
differene in the symptom of burning sensation and
ithing bet.een t.o study groups.
3he foremost ob$eti&es in aring for patients .ith
dry eye disease are to impro&e the patientHs oular
omfort and <uality of life" and to return the oular
surfae and tear film to the normal homeostati state.
Clthough symptoms an rarely be eliminated" they an
often be impro&ed" leading to an impro&ement in the
<uality of life. It is more diffiult to demonstrate that
topial lubriants impro&e the oular surfae and the tear
film abnormalities assoiated .ith dry eye.
9
!ost linial
studies fail to demonstrate signifiant orrelation bet.een
symptoms and linial test &alues or bet.een the linial
test &alues themsel&es.
96"99
In this study /ipofilm microemulsion does not ontain
any preser&ati&e" unli*e Sodium hyaluronate in this
study" it ontain of oJidati&e preser&ati&e that *no.n as
stabili>ed oJyhloro ompleJ ASO+B. -hen SO+ is
administered in the eye" it is on&erted into natural tear
omponents" suh as sodium and hloride ions" oJygen"
and .ater.
20"29
Impro&ement at lo. onentrations A0.005@ .'&B that
are benign to the eye ma*es SO+ an ideal ophthalmi
preser&ati&e. Safety and tolerability .ere established in
a study of :2 patients .ith mild to moderate dry eye .ho
.ere treated .ith an SO+8ontaining produt four to
eight times per day for 4 .ee*s.
22
No ad&erse e&ent in any group .as obser&ed by the
in&estigator or reported by the patient throughout the
study. /oth treatments .ere .ell tolerated" eJept
temporally blurred &ision immediately after instillation
on 9 sub$ets in ?ipofilm miroemulsion group. ?ipofilm
miroemulsion tended to sho. a faster impro&ement than
did the Sodium hyaluronate in patients .ith dry eye
syndrome.
(-,(L.S+-,
3he results of the study sho. a signifiant linial
benefit in /%3 test and impro&ement of the symptom of
foreign body sensation and blurred &ision in those dry eye
patients reei&ing ?ipofilm miroemulsion.
$EFE$E,(ES
9. 2007 0eport of the International Dry 7ye -or*shop AD7-SB. The
Ocular Surface. 2007K 5, :5F204.
2. +alonge !, 3he treatment of dry eye. Surv Ophthalmol 45 ASuppl
2B, 2009K S227F=9"
=. Johnson" !.7." !urphy" M.J." +hanges In 3he 3ears 1ilm and
Oular Surfae 1rom Dry 7ye SyndromeK In 1rogress in 2etinal
and 3ye 2esearch. 2004K 2=, 449F474
4. +raig J.M." 3omlinson C. Importane of lipid layer in human tear
film stability and e&aporation. Optom 4is Sci. 9997K 74, 6F9=.
5. !athers -. 7&aporation from the oular surfae. 3xp eye 2es. 200=K
76, =69F=94.
:. 3seng S+#" 3subota 2. Important onepts for treating oular
surfae and tear disorders. 5m 6 Ophthalmol 9997K 924, 625F6=5.
7. )o*oi N" 3a*ehisa )" 2inoshita S. +orrelation of tear lipid layer
interferene patterns .ith diagnosis and se&erity of dry eye. 5m 6
Ophthalmol. 999:K 922, 696F624"
6. Cragona" M." 0olando !." /onini S." /aro>>i +." 1alhetti 0." De
#regorio 1. Impro&ement and Safety of an Ophthalmi
Mhospholipid8 based !iroemulsion A?ipofilmB in Matients
Suffering from 2eratoon$unti&itis Sia, Single8!as*ed
0andomised +linial 3rial. +th International Symposium on
Ocular 1harmacology and Therapeutics. 200:.
9. !+arty" +.C." /ansal" C.2." ?i&ingston" M.!. 3he 7pidemiology
of Dry 7ye In !elbourne" Custralia. Ophthalmology. 9996K 905,
9994F9996.
90. !oss" S.+." 2lein" 0." 2lein" /. Inidene of Dry 7ye In Cn Older
Mopulation.Invest Ophthalmol 4is SciK 200=K 5s.
99. Na*amura !" (i*ida !" Na*ano 3" et al. +harateri>ation of .ater
retenti&e properties of hyaluronan. 7ornea 999=K 92, 4==F:.
92. 3subota 2" )amada !. 3ear e&aporation from the oular surfae.
Invest Ophthalmol 4is Sci. 9992K ==, 2942F50.
9=. +ondon MI" !7.an +#" -right !" !a*intosh #" Mresott 0J"
!Donald ++. Double blind" randomised" plaebo ontrolled"
rosso&er" multientre study to determine the impro&ement of a
0.9@ A.'&B sodium hyaluronate solution A1erma&isB in the
treatment of dry eye syndrome. &r 6 Ophthalmol. 9999K 6=, 9929F
9924.
94. Cragona M" Di Stefano #" 1erreri 1" Spinella 0" Stilo C. Sodium
hyaluronate eyedrops of different osmolarity for the treatment of
dry eye in S$ogrenHs syndrome patients. &r 6 Ophthalmol. 2002K 6:,
679F664.
95. Norn" !.S. Desiation of the preorneal fi lm. I. +orneal .etting8
time. 5cta Ophthalmol '7openh). 99:9K 47, 6:5F60.
9:. ?emp" !.C. /rea*up of the tear film. Int Ophthalmol 7lin. 97=K 9=,
97F902.
97. !Donald" +.+." 2aye" S./." 1igueiredo" 1.+." !aintosh" #."
?o*ett" +. C randomised" rosso&er" multientre study to ompare
the performane of 0.9@ A.'&B sodium hyaluronate .ith 9.4@
A.'&B poly&inyl alohol in the alle&iation of symptoms assoiated
.ith dry eye syndrome. 3ye. 2002K 9:, :09F:07.
96. Shein O" 3ielsh J" !uno> /. 0elation bet.een signs and
symptoms of dry eye in the elderly. Ophthalmology. 9997K 904,
9=95F9400.
99. Nelson JD" #ordon J1. 3opial fibronetin in the treatment of
*eratoon$unti&itis sia. +hiron 2eratoon$unti&itis Sia Study
#roup. 5m 6 Ophthalmol. 9992K 994, 449F7.
20. #rant 0." C$ello !." Vlass 7. Salt .ater or high tehN C loo* at
t.o ne. rinsing solutions for ontat lenses. Optiian. 999:K 292,
=6F49.
29. !asshelein -.J." 0ie 0.#. 9979. +hlorine DioJide. 7hemistry
and 3nvironmental Impact of Oxychlorine 7ompounds. Cnn Crbor"
!ih, Cnn Crbor Siene Mublishers.
22. 0o>en S" Cbelson !" #io&anoni C" -elh D. Cssessment of the
omfort and tolerane of 0.5@ arboJymethylellulose preser&ed
.ith Murite A0efresh 3earsB in dry eye sufferers. Invest Ophthalmol
4is Sci. 9996K =9 A4B, S459.