Improved Tear Film Stability in Patients with Dry Eye After Hyaluronic Acid and Galactoxyloglucan Use

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 Open Access Full Tex A icle submi you manusc ip | www.do ep ess.com Clinical Oph halmology 2020:14 1153–1159 1153 h p://doi.o g/10.2147/OPTH.S248949 Do eP ess © 2020 Molina-Solana e al. This wo k is published and licensed by Do e Medical P ess Limi ed. The ull e ms o his license a e a ailable a h ps://www.do ep ess.com/ e ms.php and inco po a e he C ea i e Commons A ibu ion –Non Comme cial (unpo ed, 3.0) License (h p://c ea i ecommons.o g/licenses/by-nc/3.0/). By accessing he wo k you he eby accep he Te ms. Non-comme cial uses o he wo k a e pe mi ed wi hou any u he pe mission om Do e Medical P ess Limi ed, p o ided he wo k is p ope ly a ibu ed. Fo pe mission o comme cial use o his wo k, please see pa ag aphs 4.2 and 5 o ou Te ms (h ps://www.do ep ess.com/ e ms.php). Clinical Oph halmology downloaded om h ps://www.do ep ess.com/ by 78.30.22.152 on 20-May-2021 Fo pe sonal use only. Powe ed by TCPDF (www. cpd .o g) 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 Molina-Solana e al Do ep ess submi you manusc ip | www.do ep ess.com Do eP ess Clinical Oph halmology 2020:14 1154 Clinical Oph halmology downloaded om h ps://www.do ep ess.com/ by 78.30.22.152 on 20-May-2021 Fo pe sonal use only. Powe ed by TCPDF (www. cpd .o g) 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 Do ep ess Molina-Solana e al Clinical Oph halmology 2020:14 submi you manusc ip | www.do ep ess.com Do eP ess 1155 Clinical Oph halmology downloaded om h ps://www.do ep ess.com/ by 78.30.22.152 on 20-May-2021 Fo pe sonal use only. Powe ed by TCPDF (www. cpd .o g) 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. Molina-Solana e al Do ep ess submi you manusc ip | www.do ep ess.com Do eP ess Clinical Oph halmology 2020:14 1156 Clinical Oph halmology downloaded om h ps://www.do ep ess.com/ by 78.30.22.152 on 20-May-2021 Fo pe sonal use only. Powe ed by TCPDF (www. cpd .o g) 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. Do ep ess Molina-Solana e al Clinical Oph halmology 2020:14 submi you manusc ip | www.do ep ess.com Do eP ess 1157 Clinical Oph halmology downloaded om h ps://www.do ep ess.com/ by 78.30.22.152 on 20-May-2021 Fo pe sonal use only. Powe ed by TCPDF (www. cpd .o g) 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. 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