대한안과학회지 2018 년제 59 권제 2 호 J Korean Ophthalmol Soc 2018;59(2):117-122 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2018.59.2.117 Original Article 국내상품화된다양한인공눈물제품의오스몰농도비교 Comparison of Osmolarity of Various Artificial Tears Products Commercially Available in South Korea 우인호 1 홍준기 2 허정아 1 엄영섭 1 김효명 1 송종석 1 In Ho Woo, MD 1, Jun Gi Hong, MD 2, Jung Ah Huh, MD 1, Youngsub Eom, MD 1, Hyo Myung Kim, MD, PhD 1, Jong Suk Song, MD, PhD 1 고려대학교의과대학안과학교실 1, 대구파티마병원안과학교실 2 Department of Ophthalmology, Korea University College of Medicine 1, Seoul, Korea Department of Ophthalmology, Daegu Fatima Hospital 2, Daegu, Korea Purpose: To compare the osmolarity of various artificial tear products commercially available in the Republic of Korea. Methods: The osmolarity of the artificial tears was analyzed using TearLab and Multi-Osmette. We divided the artificial tear products into five groups, including hypo-osmolar 0.18% sodium hyaluronate (HA), iso-osmolar 0.1%, 0.15%, 0.3% HA, and 0.5% carboxymethylcellulose sodium (CMC), and measured three products per group. Results: Among the 12 products of iso-osmolar artificial tears, there were seven products (58.3%) < 300 mosm/l, and among the three products of hypo-osmolar artificial tears, there were two products (66.6%) < 150 mosm/l. A significant difference (p < 0.05) was observed between the iso-osmolar 0.3% HA group and the hypo-osmolar 0.18% HA group. In the iso-osmolar 0.1% HA and 0.15% HA, the difference between the products in each group was approximately 12 mosm/l, and the CMC group had the smallest deviation among products, which was close to 300 mosm/l. There was a significant difference of 305.57 ± 6.38 mosm/l in the iso-osmolar 0.15% HA group, 293.44 ± 8.71 mosm/l in the 0.1% HA group, and 285.67 ± 3.67 mosm/l in the 0.3% HA group (p < 0.001). There was no significant difference in osmolarity between the iso-osmolar products containing HA and CMC (p = 0.117). Conclusions: There was a difference in osmolarity between the published and actual measured values of commercial artificial tears, and there was a difference in osmolality depending on the content of HA and the manufacturer. J Korean Ophthalmol Soc 2018;59(2):117-122 Keywords: Artificial tears, Dry eye, Osmolarity, TearLab Received: 2017. 8. 10. Revised: 2017. 9. 21. Accepted: 2017. 10. 20. Address reprint requests to Jong Suk Song, MD, PhD Department of Ophthalmology, Korea University Guro Hospital, #148 Gurodong-ro, Guro-gu, Seoul 08308, Korea Tel: 82-2-2626-1260, Fax: 82-2-857-8580 E-mail: crisim@korea.ac.kr * This study was supported in part by Alumni of Department of Ophthalmology, Korea University College of Medicine. * Conflicts of Interest: The authors have no conflicts to disclose. 안구건조증은눈물과안구표면에관련된다양한요인에의해발생하는염증성질환으로안구의불편감, 시력저하, 안구표면의잠재적인손상을유발하는눈물층의불안정성등이나타난다. 1 2007년에 International Dry Eye Workshop 에서눈물의오스몰농도와눈물막의불안정성이안구건조증의중요한메커니즘으로보고하였다. 1 수성눈물층의생성이부족하거나또는눈물의증발과다에의해서발생하는눈물오스몰농도의증가는최근안구건조증의중요한병인으로인식되었다. 눈물오스몰농도의증가는각막세포의손상을유발하여눈물층의불안정성을만들고, 다양 c2018 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 117
- 대한안과학회지 2018 년제 59 권제 2 호 - 한염증인자들의발현이되는악순환이반복하게되며, 이로인해안구표면의손상이발생하게된다. 2-4 눈물오스몰농도와안구건조증에관한다양한연구들이이루어졌으며, 이연구들의결과에따르면 290-305 mosm/l를정상눈물오스몰농도로보고하였으며, 안구건조증에서의눈물오스몰농도는 308-400 mosm/l까지다양하게보고되었다. 5-8 Sullivan et al 9 의안구건조증과눈물오스몰농도사이의연관관계를평가한연구에서눈물막파괴시간, 각막염색정도, 쉬르머검사, Ocular Surface Disease Index (OSDI) 설문평가등으로확인된안구건조증의중등도는눈물오스몰농도와강한상관관계가있음을보고하였다. Lemp et al 6 은눈물오스몰농도가경증및중등도의안구건조증의진단에있어눈물막파괴시간, 쉬르머검사보다민감도및특이도가더높은검사임을보고하였으며, Suzuki et al 10 은눈물오스몰측정값이안구건조증의중등도와상관관계가있고진단적가치가있음을보고하였다. 현재시중에판매되고있는인공눈물은각제조사의발표에따라오스몰농도가 150 mosm/l인저장성오스몰제제와 300 mosm/l인등장성오스몰제제의두가지형태로상품화되어있다. 이전연구에서안구건조증의증상및중증도에따라저장성또는등장성오스몰제제를선택하여처방하는것이눈물오스몰농도에영향을주게되며, 안구건조증치료에효과적이라고발표하였다. 11 Bitton et al 12 은캐나다에서생산된점안제제를 vapor라는장비를이용하여연구를하였고, 그결과제조사에서알려진값과실제측정값사이에많은차이가있음을발표하였다. 반면우리나라에서처방되어사용되고있는인공눈물에대해오스몰농도를측정한연구는현재까지없는실정이다. 이에본저자들은 TearLab (TearLab Corporation, San Diego, CA, USA) 과 Multi-Osmette TM (PSI-2430; Precision Systems Inc., Natick, MA, USA) 장비를이용하여국내에서사용중인인공눈물의오스몰농도를직접측정하여각제조회사에서제품생산시발표한오스몰농도와차이가있는지비교해보고자하였다. 각각선정하여측정하였다. 먼저저장성오스몰농도의 0.18% 히알루론산 (sodium hyaluronate, HA) 이함유된군에서는카이닉스2 (KynexⅡ, Alcon, Seoul, Korea), 티어린에스 (Tearin S, DHP Korea, Seoul, Korea), 히알루미니 TM (Hyalu Mini TM, Hanmi, Seoul, Korea) 를선정하였고, 등장성오스몰농도의 0.1% 히알루론산이함유된군에서는히알유니 0.1% (Hyalyuni, Taejoon, Seoul, Korea), 티어린프리 (Terain Free, DHP Korea, Seoul, Korea), 히아루론 (Hyaluron, Hanlim, Seoul, Korea) 을, 등장성오스몰농도의 0.15% 히알루론산이함유된군에서는뉴히알유니 0.15% (New Hyalyuni 0.15%, Taejoon, Seoul, Korea), 티어린피 (Tearin P, DHP Korea, Seoul, Korea), 히아루론맥스 0.15% (Hyaluronmax 0.15%, Hanlim, Seoul, Korea) 를, 등장성오스몰농도의 0.3% 히알루론산이함유된군에서는히알유니 0.3% (Hyalyuni 0.3%, Taejoon, Seoul, Korea), 티어린에프 (Tearin F, DHP Korea, Seoul, Korea), 히아루론맥스 0.3% (Hyaluronmax 0.3%, Hanlim, Seoul, Korea) 를, 등장성오스몰농도의카복시메틸셀룰로스 (Carboxymethylcellulose sodium, CMC) 0.5% 가함유된군에서는리프레쉬플러스 TM (Refresh Plus TM, Allergan, Seoul, Korea), 디알후레쉬 (Dr. Fresh, DHP Korea, Seoul, Korea), 눈앤 0.5% (Nunen 0.5%, Hanmi, Seoul, Korea) 를각각선정하여실험하였다 (Fig. 1). TearLab 은약 50 nl의눈물량으로측정이가능하며수초이내에결과를확인할수있으며기기의휴대성이다른오스몰측정장비에비해뛰어나임상적으로사용하기에유용하다. 8 실험시주변온도와습도가결과값에영향을미칠수있어, 이에대한오차를최소화하기위해모든실험은같은시간같은장소에서진행되었으며, 같은장비, 같은실험자 (W.I.H) 가모든실험을진행하였다. 실험을진행하기전관리용액과, 전자칩카드를사용하여기기의오 대상과방법 이번연구에서는우리나라에서처방하여사용중인 6개회사의 15가지무보존제 1회용용기에담긴인공눈물제품을 TearLab 과 Multi-Osmette TM 을이용하여오스몰농도를분석하였다. 본연구는고려대학교구로병원연구윤리심의위원회로부터심의면제를받았다. 인공눈물제품은함유된성분의종류와오스몰농도에따라다섯가지의범주로나누었으며각범주마다제조회사가다른세가지제품을 Figure 1. TearLab osmometer and artificial tears used in this study. The artificial tears products were divided into five groups according to the type of ingredients and osmolality. For each group, three different products were selected and measured. 118
- 우인호외 : 인공눈물의오스몰농도비교 - 차를줄이기위한교정 (calibration) 을시행하였다. 실험의순서는무작위로선정하여진행하였으며 TearLab 의시스템펜에테스트카드를끼운후 1회용인공눈물의마개를벗겨약 50 nl가직접 Test card에수집되도록하였다. 인공눈물의수집이이루어진시스템펜을시스템에장착하여오스몰을확인하였다. TearLab 은임상적목적으로만들어진기계이므로측정할수있는눈물오스몰의범위는 270-400 mosm/l 범위의오스몰농도만측정이가능하기때문에 150 mosm/l의범위로알려진저장성오스몰농도인공눈물은 Multi-Osmette TM 을이용하여측정하였다. 13 이장비는오스몰활성화합물 (osmotically active compounds) 이용액의어는점을낮추는것을이용하여오스몰을측정하게되는데 0-2,000 mosm/l의범위의값을측정할수있다. 30 μl의양을마이크로피펫을이용하여, 수집한후오스몰농도를측정하였다. 모든제품은무작위로순서를정하여측정하였으며, 각제품마다세차례씩측정하여결과값을확인하였다. 통계분석은소프트웨어 SPSS 20.0 (IBM Corp., Armonk, NY, USA) 을사용하였다. 세군사이의비교는 Kruskal-Wallis U-test를사용하였으며, 필요한경우 Mann-Whitney test를실시하여사후검정을하였고, 포함된세군을각두군씩비교하는검사를총세번시행하였다. 유의수준은 Bonferroni s method 를이용하여 5%/3 = 1.7%, 즉 p값이 0.017 이하일때유의하다고하였다. 두군사이의비교에서는 Mann-Whitney U-test를사용하였다. 모든통계의 p값은 0.05 이하일때유의하다고하였다. 결과 연구에사용된안약은우리나라에서판매되는등장성오스몰농도인공눈물제품 12가지와저장성오스몰농도인공눈물제품 3가지였다. 등장성오스몰농도로알려진제품 12 가지중 300 mosm/l 이하로오스몰농도가측정된제품은 7가지 (58.3%) 였으며, 저장성오스몰농도로알려진제품중 150 mosm/l 이하인제품이 2가지 (66.6%) 였다. 측정된각인공눈물의제품별오스몰농도는 Table 1에기술하였다. 등장성오스몰농도에 0.3% 히알루론산을함유하고있는군과저장성오스몰농도에 0.18% 히알루론산을함유하고있는군에서는각군내에서제조회사별제품간측정된오스몰농도에통계적으로유의한차이가있었다 (p<0.05). 반면다른군에서는제조회사별제품간오스몰농도에유의한차이가없었다. 함유된성분의종류와, 그성분의함량에따라같은군내에서제품들사이의결과값가운데등장성오스몰농도에 0.1% 히알루론산함유제품군과등장성오스몰농도에 0.15% 히알루론산함유제품군에서제조회사에따른오스몰농도의차이가약 12 mosm/l 이상인것으로가장크게나타났으며, 상대적으로카복시메틸셀룰로즈군이제조회사에따른편차가가장작고 300 mosm/l 에근접한값으로나타났다 (Table 1). 등장성오스몰농도에함유된히알루론산이다른세군에서측정된오스몰농도는 0.15% 히알루론산이함유된군에서 305.67 ± 6.38 mosm/l로가장높았고, 0.1% 히알루론산함유된군이 293.44 ± 8.71 mosm/l로그다음으로높았으며, 0.3% 히알루론산함유군이 285.67 ± 3.67 mosm/l로유의하게가장낮았다 (p<0.001) (Table 2). 이러 Table 1. Artifical tear osmolarity Catagory Manufacturer Product Average Osmolarity (mosm/l) p-value * Iso-osmolar, 0.1% HA Taejoon Hyaluni 0.1% 287.67 ± 2.08 0.061 DHP Korea Tearin Free 298.00 ± 1.00 Hanlim Hyaluron 299.67 ± 4.93 Iso-osmolar, 0.15% HA Taejoon New Hyaluni 301.00 ± 2.64 0.063 DHP Korea Tearin P 302.67 ± 3.51 Hanlim Hyaluronmax 0.15% 313.33 ± 3.05 Iso-osmolar, 0.3% HA Taejoon Hyaluni 0.3% 284.67 ± 1.53 0.032 DHP Korea Tearin F 288.00 ± 1.00 Hanlim Hyaluronmax 0.3% 282.00 ± 1.00 Iso-osmolar, 0.5% CMC Allergan Refresh Plus 299.67 ± 2.52 0.630 DHP Korea Dr. Fresh 301.67 ± 2.52 Hanmi Nunen 300.33 ± 1.53 Hypo-osmolar, 0.18% HA Alcon Kynex2 141.00 ± 1.00 0.026 DHP Korea Tearin S 151.67 ± 1.15 Hanmi Hyalumini 144.33 ± 0.58 Values are presented as mean ± SD. HA = sodium hyaluronate; CMC = carboxymethylcellulose. * Statistically significant differences (p-value<0.05) in Kruskal-Wallis test. 119
- 대한안과학회지 2018 년제 59 권제 2 호 - Table 2. Comparison of artificial tears osmolarity grouped by composition Iso-Osmolar Hypo-osmolar 0.1% HA 0.15% HA 0.3% HA 0.5% CMC 0.18% HA Osmolarity (mosm/l) 293.44 ± 8.71 305.67 ± 6.38 285.67 ± 3.67 300.56 ± 2.13 145.67 ± 7.8 p-value <0.001 * 0.117 Values are presented as mean ± SD. HA = sodium hyaluronate; CMC = carboxymethylcellulose. * Statistically significant differences (p-value<0.05) in Kruskal-Wallis test; Statistically significant differences (p-value<0.05) in Mann-Whitney U-test. Figure 2. Graphs based on the content of sodium hyaluronate in iso-osmolarity products. Graphs showed the highest at 0.15% sodium hyaluronate and the lowest at 0.3% sodium hyaluronate, and this tendency was similar regardless of the manufacturer. HA = sodium hyaluronate. 한경향은제조회사별비교에서도동일하게각제조회사제품모두 0.15% 히알루론산함유제품에서오스몰농도가가장높고, 그다음이 0.1% 히알루론산함유제품, 그리고 0.3% 히알루론산함유제품이가장낮은것으로나타났다 (Fig. 2). 등장성오스몰농도에서히알루론산이함유된제품의오스몰농도와카복시메틸셀룰로즈가함유된제품의오스몰농도에대해비교한결과통계적으로유의한차이가없는것으로나타났다 (p=0.117) (Table 2). 고 찰 2006년에보고된 Delphi panel들토론에서합의된단계별치료지침 14 과, 이를바탕으로 2007년 International Dry Eye Workshop 15 에서발표된치료지침, 그리고가장최근에발표된안구건조증과마이봄샘염, 안검염등의개념을포괄적으로제시한눈물기능이상증 (dysfunctional tear syndrome) 16 에대해발표한치료지침에서공통적으로가장먼저사용하도록권하고있는것이인공눈물이다. 인공눈물을선택할때다양한조건들을고려하여처방하게된다. 함 유된성분과, 그성분의함유량정도, 그리고오스몰농도를고려하여환자의치료에최선이되는것을선택하게된다. 안구건조증의병태생리학적측면에서오스몰농도의증가가안구건조증의중요한기전으로생각되어왔고, 그에따라오스몰농도가다른인공눈물의효과를비교한연구도활발하게진행되어왔다. 17,18 또한 TearLab 의개발로환자의눈물오스몰농도의측정이이전보다쉽게되고, 5-7 오스몰농도의정보를얻는것이이전보다용이해져오스몰농도와안구건조증진단의유용성과치료효과의판정에유용하게사용되고있다. 8,19 우리나라에서생산되고있는인공눈물은크게오스몰농도 ( 저장성과등장성 ), 함유된성분 ( 히알루론산과카복시메틸셀룰로즈 ), 히알루론산의함유량 (0.1%, 0.15%, 0.18%, 0.3%) 으로제품군을분류하여생산되고있다. Bitton et al 12 은캐나다에서사용중인제품에대해서분석한결과 94.6% 의제품이 295 mmol/kg 이하로제조회사에서발표된값보다낮게측정된다는것을보고하였다. 본연구에서도등장성오스몰농도로알려진제품중 300 mosm/l 이하제품이약 60% 를차지하며, 이중 300 mosm/l로알려진제품들가운데서실제측정값이가장낮은것은 282.0 mosm/l로약 18 mosm/l의차이가나는것으로관찰되었다. 또한 Bitton et al 12 은인공눈물의성분에비교해본결과성분간오스몰농도의유의한차이가없다고하였고, 이러한결과는본연구에서도히알루론산과카복시메틸셀룰로즈의성분에따른비교에서유의한차이가없다는결과와일치한다. Cömez et al 20 은오스몰농도가다른인공눈물을환자에게점안후눈물오스몰농도의변화와눈물막파괴시간, 쉬르머검사, OSDI 설문평가의변화에대해연구하고발표하였다. 이연구에서저자들은 215 mosm/kg의저장성오스몰농도인공눈물제품하나와, 275, 302, 309 mosm/kg 의등장성오스몰농도제품세가지를비교하였는데그결과네가지약제모두눈물오스몰농도가사용전에비해약 12-33 mosm/kg으로유의하게감소하였고안구건조증상에대한지표가유의하게호전되었음을보고하였다. 이는오스몰농도의낮아짐이증상의호전과눈 120
- 우인호외 : 인공눈물의오스몰농도비교 - 물막파괴시간의증가, 쉬르머검사의증가로확인된안구건조증의호전과동반하는것으로생각된다. 일반적으로안구건조증이심할수록오스몰농도가증가하는데그증가정도가 10-30 mosm/l 정도가된다. 따라서, 인공눈물을통해일정값의오스몰농도만낮춰줘도오스몰농도와관련된염증반응을줄여안구건조증의치료로효과가있으리라생각된다. Dutescu et al 21 은오스몰농도가각막에미치는영향에대해오스몰농도가낮은제품일수록안구건조증의치료에보다효과가좋으며, 상대적으로오스몰농도가높은제품인경우각막부종관리에보다효과적이라고발표하였다. 안구건조증의치료효과측면에서는저장성오스몰농도가권유되나일부환자에서는점안시불편함을호소하는경우가있을수있어같은오스몰농도의같은성분의함량이라도제조회사에따라차이가있음을알고환자의각막상태와사용중인인공눈물에대한점안감의불편정도에따라적절한선택이필요할것으로보인다. 본연구의 Fig. 2에서제시하였듯이같은제조회사제품인경우등장성오스몰농도에서히알루론산의함유량에따라상대적인오스몰농도의측정값은 0.15% 일때높고, 0.3% 일때낮은것으로확인되었으며, 이는제조회사에관계없이같은경향을보였다. 따라서등장성오스몰농도인공눈물제품의히알루론산함량의차이를고려하여처방하고자할때히알루론산함량에따라오스몰농도의차이가있음을같이고려하여처방하는것이치료효과를증대시키는데도움이될것으로생각된다. 본연구의제한점으로는첫째, 현재우리나라에제품화되어있는더다양한종류의인공눈물을실험하지못하였으며, 또한측정의횟수도적었다는점이다. 이는결국연구비용의문제로연결되며이부분의지원이보완된다면추가적인연구가가능하리라생각된다. 둘째, TearLab 의제한된측정범위로인해저장성오스몰농도제제의경우다른방식의오스몰농도측정기를사용하였다는점이다. Tomlinson et al 22 의연구에따르면 TearLab 과어는점을이용한오스몰농도분석기사이에측정값을비교한결과차이는있으나그차이는전체의 1% 미만인 2 mosoml/l 이며, 두측정값사이의유의한상관관계와, 높은일치수준을보인다고발표하였다. 본연구에서는임상적으로빠른측정이가능하며, 눈물의수집이상대적으로쉬워최근들어임상적활용도가높아지고있는 TearLab 을이용하여측정값을확인하고자하였으며, 기계적한계점을극복하면서연구를지속하기위해저장성오스몰농도인공눈물제품에한해서만 Multi-Osmette TM 을사용하였다. 그러나연구의결과를비교할때는같은장비로측정된제품들사이에 만비교및분석을시행하여기계적차이에의한통계적오류가발생하지않도록하였다. 결론적으로본연구는현재우리나라에서사용되고있는안구건조증치료제인인공눈물의오스몰농도를직접측정해본것에큰의의를가지며, 안구건조증의치료제를선택할때오스몰농도를고려하여더나은치료효과를기대할수있는기본적인정보를제공하였으리라생각한다. REFERENCES 1) The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:75-92. 2) Luo L, Li DQ, Corrales RM, Pflugfelder SC. Hyperosmolar saline is a proinflammatory stress on the mouse ocular surface. Eye Contact Lens 2005;31:186-93. 3) Li DQ, Chen Z, Song XJ, et al. Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2004; 45:4302-11. 4) Luo L, Li DQ, Pflugfelder SC. Hyperosmolarity-induced apoptosis in human corneal epithelial cells is mediated by cytochrome c and MAPK pathways. Cornea 2007;26:452-60. 5) Tomlinson A, Khanal S, Ramaesh K, et al. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 2006;47:4309-15. 6) Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol 2011;151:792-8.e1. 7) Versura P, Profazio V, Campos EC. Performance of tear osmolarity compared to previous diagnostic teasts for dry eye diseases. Curr Eye Res 2010;35:553-64. 8) Versura P, Campos EC. TearLab(R) Osmolarity System for diagnosing dry eye. Expert Rev Mol Diagn 2013;13:119-29. 9) Sullivan BD, Whitmer D, Nichols KK, et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci 2010;51:6125-30. 10) Suzuki M, Massingale ML, Ye F, et al. Tear osmolarity as a biomarker for dry eye disease severity. Invest Ophthalmol Vis Sci 2010;51:4557-61 11) Aragona P, Di Stefano G, Ferreri F, et al. Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjögren's syndrome patients. Br J Ophthalmol 2002;86:879-84. 12) Bitton E, Perugino C, Charette S. Comparison of ocular lubricant osmolalities. Optom Vis Sci 2017;94:694-9. 13) Kim JH, Kim JH, Nam WH, et al. Oral alcohol administration disturbs tear film and ocular surface. Ophthalmology 2012;119:965-71. 14) Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea 2006;25: 900-7. 15) Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:163-78. 16) Milner MS, Beckman KA, Luchs JI, et al. Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new 121
- 대한안과학회지 2018 년제 59 권제 2 호 - strategies for diagnosis and treatment. Curr Opin Ophthalmol 2017;27 Suppl 1:3-47. 17) Papa V, Aragona P, Russo S, et al. Comparison of hypotonic and isotonic solutions containing sodium hyaluronate on the symptomatic treatment of dry eye patients. Ophthalmologica 2001;215:124-7. 18) Li Y, Cui L, Lee HS, et al. Comparison of 0.3% hypotonic and isotonic sodium hyaluronate eye drops in the treatment of experimental dry eye. Curr Eye Res 2017;42:1108-14. 19) Benelli U, Nardi M, Posarelli C, Albert TG. Tear osmolarity measurement using the TearLab Osmolarity System in the assessment of dry eye treatment effectiveness. Cont Lens Anterior Eye 2010;33:61-7. 20) Cömez AT, Tufan HA, Kocabıyık O, Gencer B. Effects of lubricating agents with different osmolalities on tear osmolarity and other tear function tests in patients with dry eye. Curr Eye Res 2013;38:1095-103. 21) Dutescu RM, Panfil C, Schrage N. Osmolarity of prevalent eye drops, side effects, and therapeutic approaches. Cornea 2015;34:560-6. 22) Tomlinson A, McCann LC, Pearce EI. Comparison of human tear film osmolarity measured by electrical impedance and freezing point depression techniques. Cornea 2010;29:1036-41. = 국문초록 = 국내상품화된다양한인공눈물제품의오스몰농도비교 목적 : 국내에서상품화된다양한인공눈물의오스몰농도를직접측정하여비교해보고자하였다. 대상과방법 : 국내에서사용중인인공눈물을 TearLab 과 Multi-Osmette TM 을이용하여오스몰농도를분석하였다. 저장성오스몰농도의 0.18% 히알루론산 (sodium hyaluronate, HA) 군, 등장성오스몰농도의 0.1%, 0.15%, 0.3% HA 군, 0.5% 카복시메틸셀룰로즈 (carboxymethylcellulose, CMC) 군으로 5 개군에군당 3 가지제품을측정하였다. 결과 : 등장성인공눈물 12 가지중 300 mosm/l 이하가 7 가지 (58.3%), 저장성인공눈물 3 가지중 150 mosm/l 이하가 2 가지 (66.6%) 였다. 등장성오스몰농도에 0.3% HA 군과저장성오스몰농도에 0.18% HA 군에서각군내제품간오스몰농도에유의한차이가있었다 (p<0.05). 등장성오스몰농도에 0.1% HA 와 0.15% HA 의두군에서각군내제품간차이가약 12 mosm/l 로나타났으며, CMC 군에서제품간편차가가장작고 300 mosm/l 에근접한값으로나타났다. 등장성오스몰농도에 0.15% HA 군이 305.67 ± 6.38 mosm/l, 0.1% HA 군이 293.44 ± 8.71 mosm/l, 0.3% HA 군이 285.67 ± 3.67 mosm/l 의순서로유의한차이가있었다 (p<0.001). HA 함유제품과 CMC 함유제품사이에오스몰농도는유의한차이가없었다 (p=0.117). 결론 : 상용화된인공눈물오스몰농도는제품생산시발표값과실제측정값사이에차이가있었으며, HA 의함량과제조회사에따라오스몰농도가차이가있었다. < 대한안과학회지 2018;59(2):117-122> 122