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1 대한안과학회지 2017 년제 58 권제 7 호 J Korean Ophthalmol Soc 2017;58(7): ISSN (Print) ISSN (Online) Original Article 눈물지질층두께와안구표면임상인자간의상관관계분석 Correlation Analysis of Tear Film Lipid Layer Thickness and Ocular Surface Disease Index 김래영 1 나경선 1,2 박율리 1,2 김현승 1,2 Rae Young Kim, MD 1, Kyung Sun Na, MD, PhD 1,2, Yu Li Park, MD 1,2, Hyun Seung Kim, MD, PhD 1,2 가톨릭대학교의과대학안과학교실 1, 가톨릭대학교여의도성모병원안과 2 Department of Ophthalmology, College of Medicine, The Catholic University of Korea 1, Seoul, Korea Department of Ophthalmology, The Catholic University of Korea Yeouido St. Mary s Hospital 2, Seoul, Korea Purpose: To analyze the relationship between ocular surface disease index and tear film lipid layer thickness (LLT) using a LipiView II (LipiView Ocular Surface Interferometer, TearScience, Morrisville, NC, USA) interferometer. Methods: Forty-nine patients diagnosed with dry eye syndrome were recruited for this prospective study. Patients completed ocular surface disease index questionnaires. We performed slit lamp examination, Schirmer test, corneal and conjunctival fluorescein staining, measured tear film break-up time, and graded meibomian gland dysfunction. Tear LLT, blinking time, and dynamic meibomian imaging were analyzed using a LipiView II ocular interferometer. To control for missing data, we analyzed four sets of imputated data via the multiple imputation method and performed Pearson correlation analysis. Patients were assigned to one of two LLT categories (LLT < 60 or LLT 60) and Chi-square test was performed. Results: Among ocular surface disease parameters, tear film break-up time (tbut) had a statistically significant correlation with average and maximum LLT (average LLT; p = 0.008, 0.035, 0.006, 0.049, maximum LLT; p = 0.006, 0.042, 0.020, 0.049, Pearson correlation analysis with multiple imputation) but there was no significant correlation with minimum LLT (minimum LLT; p = 0.048, 0.090, 0.079, 0.039). Of the patients with a relatively thick average LLT or maximum LLT (LLT 60 nm), 80% and 88% had a tbut < 10, respectively. Conversely, 39% and 47% of patients with relatively thin average LLT (LLT < 60 nm) had a tbut < 10 (average LLT; p = 0.013, maximum LLT; p = 0.039). Conclusions: Average LLT and maximum LLT were significantly correlated with tbut. Patients with a relatively thin average or maximum LLT tended to have a shorter tbut. Based on these results, measuring tear film LLT using a LipiView II interferometer may be useful in the diagnosis and follow-up of patients with evaporative dry eye. J Korean Ophthalmol Soc 2017;58(7): Keywords: Dry eye syndrome, Interferometry, Lipid layer thickness, Lipiview, Meibomian gland dysfunction Received: Revised: Accepted: Address reprint requests to Hyun Seung Kim, MD, PhD Department of Ophthalmology, The Catholic University of Korea Yeouido St. Mary s Hospital, #10, 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea Tel: , Fax: Sara514@catholic.ac.kr * This study was presented as a narration at the 115th Annual Meeting of the Korean Ophthalmological Society * Conflicts of Interest: The authors have no conflicts to disclose. 마이봄샘에서분비되는마이봄은눈물막의안정을유지하는역할을하며마이봄샘기능부전은마이봄샘의폐쇄혹은마이봄분비저하를일으켜마이봄의정상적인지질구성및분비량의변화를일으키게되어 1-4 눈물막증발건성안의주요원인으로보고되어있다. 5,6 따라서건성안환자에서마이봄샘기능부전의동반여부를적절히평가하는것이진단과치료및경과확인에도움이될수있다. 5,7 c2017 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 788

2 - 김래영외 : 눈물지질층두께와안구표면임상인자 - 임상적으로마이봄샘기능부전을진단하는방법으로마이봄샘및눈꺼풀테의형태적인변화를관찰하거나분비기능을측정하는방법이있다. 6 세극등현미경하에서눈꺼풀테및마이봄샘배출구를관찰하며물리적인압력을가하여분비되는마이봄의특성을평가하고, 8 마이봄샘촬영기를이용하여형태이상및탈락, 배출구의상태를관찰할수있다. 8,9 기존에는마이봄샘의기능부전을정량화하기위한노력으로증발계 (evapometry), 간섭계 (interferometry), 마이봄측정계 (meibometry) 등의방법이사용되었다. Foulks and Bron 6 의논문에소개된바와같이증발계는눈을뜬상태에서의안구표면의수분증발량을측정하는방법이며, 간섭계는빛의간섭현상을이용하여두께를측정하고, 마이봄측정계는하안검중심부에플라스틱테이프를부착하여마이봄을직접얻을수있고정량화할수있는방법이다. 10 LipiView II 간섭계 (LipiView Ocular Surface Inferometer, TearScience, Morrisville, NC, USA) 는눈물막지질층두께를자동화하여측정하는장비로서, 간섭계는위에서소개된것과같이광원에서나오는빛이눈물지질층의표면과후면에서반사되어발생하는빛의간섭현상을이용하여빛띠의우세한색을분석하여눈물막의지질두께를정량화할수있으며비침습적이라는장점이있다. 8,11,12 따라서최근이를이용하여마이봄샘기능장애를객관적으로평가하고자하는시도가있었다. 12 그러나아직 LipiView II 간섭계를통해도출하는수치의해석및임상적인적용에대한기준에대한합의가널리이루어지지않아임상적인적용에어려움이있다. 12 따라서본연구는 LipiView II 간섭계를이용하여측정한눈물지질층두께및눈깜박임횟수와임상적으로사용되는눈물막불안정성평가지표, 안구표면질환지표 (ocular surface disease index, OSDI) 와의상관성을분석하여기존연구들에서의결과와비교하고자하였다. 대상과방법 2015년 10월부터 2015년 11월까지본원에내원한건성안환자 49명총 49안을대상으로연구를진행하였다. 건성안은 International Dry Eye WorkShop (DEWS) 의 Definition and Classification Subcommittee에서 2007년에제시된기준에따라정의하였으며 13, DEWS 분류상중증도 2, 3, 4인환자를대상으로하였다. 각막, 결막, 눈꺼풀에알레르기성질환, 감염질환, 자가면역질환을동반한경우및각결막의염증질환이합병된경우, 안과적수술병력이있는환자의경우연구대상에서제외하였다. 대상환자들은헬싱키선언 (Declaration of Helsinki) 에입각한설명을 듣고자발적인동의하에시험에참여하였으며, 임상시험윤리위원회 (Institutional Review Board, IRB) 의승인을획득하였다 ( 승인번호 : SC15TISI0125). 모든환자에서의무기록을통한기본적인안과적, 전신적병력청취, 최대교정시력측정, 공기안압계측정및세극등현미경검사를시행하였다. LipiView II 간섭계를이용하여눈물지질층두께측정, 동적투과조명마이봄샘촬영및눈깜박임횟수를기록하였다. LipiView II 간섭계측정의경우, 본원에서는 20초간의측정을통해눈물지질층두께의평균, 최대, 최소치및표준편차, 총눈깜박임횟수 (total blinking) 및불완전눈깜박임 (partial blinking) 횟수, 이중조영마이봄샘촬영영상을얻었다. LipiView II 간섭계는최대수치를 100 nm까지만제공하기때문에본연구에서는최대치측정을위해최대눈물지질층두께의경우 Image J 프로그램을이용하여결괏값으로제공되는그래프를수치환산하여측정하였다. LipiView II 간섭계촬영은단일검사자에의해시행되었으며이미알려진건성안의임상적지표와의연관성을알아보기위해연구에참여한임상의두명중한사람이눈물막파괴시간측정, 쉬르머검사, 각막및결막형광염색검사, 또한마이봄샘기능부전의정도평가를시행하였다. 쉬르머검사및눈물막파괴시간측정, 각결막형광염색검사는 Jeon et al 14 의논문에서소개된바와같은방법으로측정하였으며마이봄샘기능부전은 Atria et al 15 에따른분류를참조하여평가하였다. 본연구는 49명의대상환자중 49명에서 LipiView II 간섭계검사를시행하였고 21명의환자에서 OSDI 설문조사, 38안에서눈물막파괴시간측정, 31안에서쉬르머검사를시행하였다. 통계적분석을위해각각의환자에서우안의검사결과만을선택하여검사결과를분석하였다. 측정값들이서로어떠한상관성을가지는지확인하기위해 Pearson 상관분석을시행하였으며눈물막파괴시간, 쉬르머검사와눈물지질층두께에서나이와성별을제한변수로설정한편상관분석을시행하였다. 또한본연구는눈물막증발건상안에서눈물지질층두께측정의진단적가치를알아보기위하여평균, 최소, 최대눈물지질층두께가상대적으로얇은환자군 (LLT < 60 nm) 과, 상대적으로두꺼운환자군 (LLT 60 nm) 으로나누어이들각각의군에서쉬르머검사가 5 mm 미만혹은이상인경우및 tear break-up time (tbut) 10초미만혹은 10 초이상인경우의비율이유의한차이를보이는지를카이제곱분석을이용하여확인하였다. 상관관계분석을위해눈물막파괴시간, 각결막형광염 789

3 - 대한안과학회지 2017 년제 58 권제 7 호 - 색, 쉬르머검사의경우결측값분석을통해이들의분포가임의적임을확인하였으며 (p=0.972, Estimate statistics of missing data analysis) 결측값다중대체 (multiple imputation) 를통해 4개의결측값대체모델을만들어분석을시행하였다. 4개모델모두에서 p값이 0.05 미만을나타내는경우만유의한상관관계를보이는것으로정의하였다. OSDI 검사의경우결측값비율이높았기때문에결측값대체를시행하지않고 OSDI 검사를시행한환자에한해서소집단분석을시행하였다. 결측값이없는측정값은대체를시행하지않고분석하였으며카이제곱분석은결측값대체를이용하지않고소집단분석을시행하였다. 통계분석은 IBM SPSS 24.0 software (IBM Corp., Armonk, NY, USA) 를이용하였으며, p값이 0.05 미만인경우를통계적으로의의가있는수치로정의하였다. 결과 건성안환자 49명, 총 49안을대상으로분석을시행하였다. 환자의평균연령은 ± 15.69세였으며남성이 18 명, 여성이 31명포함되었다. 49안에서측정된눈물지질층의두께는평균 ± nm, 최댓값 ± nm, 최솟값 ± nm ( 평균 ± 표준편차 ) 였다, 우선전체환자에서안구표면질환지표와 LipiView II 간섭계로측정한값을관찰하였다 (Table 1). Pearson 상관분석및편상관분석을통해각지표들의상관관계를분석하였다 (Table 2, 3). Table 2는쉬르머검사와눈물막파괴시간의결측값을대체한 4개의자료에서상관관계분석을보여주는것으로눈물막파괴시간의경우평균및최대눈물지질층두께와유의한양의상관관계를보였으나 (average LLT; r=0.376 [p=0.008], r=0.220 [p=0.035], r=0.390 [p=0.006], r=0.276 [p=0.049], maximum LLT; r=0.390 [p=0.006], r=0.178 [p=0.042], r=0.331 [p=0.020], r=0.279 [p=0.049]) 최소눈물지질층두께및최대와최소눈물지질층두께의차와는 4개의분석에서일정하게유의하지않았다 (minimum LLT; r=0.284 [p=0.048], r=0.179 [p=0.090], r=0.254 [p=0.079], r=0.297 [p=0.039], maximum LLT - minimum LLT; r= [p=0.024], r=0.199 [p=0.051], r=0.249 [p=0.096], r=0.035 [p=0.913]). 쉬르머검사와각결막염색등급, 하안검마이봄샘기능부전정도의경우평균, 최대, 최소눈물지질층두께모두와일정하게유의한상관관계를보이지않았다 (Table 2, Table 3). 나이및성별에따른영향을배제하기위하여나이및성별을보정한편상관분석을시행하였으며, 이에서도눈물막파괴시간과평균및최대눈물지질층두께와의유의한상관관계를보임을확인하였다 (Table 3, Fig. 1, 2). 총눈깜박임횟수의경우평균지질층두께와일정한음의상관관계를보였으나통계적으로유의한결과를보이지않았으며, 각결막염색등급은총눈깜박임과불완전눈깜박임횟수모두와일정한양의상관관계를나타내었으나통계적으로유의하지않았다 (Table 2). 또한평균, 최소, 최대눈물지질층두께를 60 nm 미만과 60 nm 이상으로나눈두군에서쉬르머검사와눈물막파괴시간값에따른분포를분석하였을때평균및최대눈물지질층두께가 60 nm 미만으로상대적으로얇은환자에서 tbut 값이 10초이하로단축된경우가각각 80%, 88% 로눈물지질층두께가 60 nm 이상인경우에서의 39%, 47% 보다유의하게높게나타났다 (Fig. 3, p=0.013, p=0.039). 쉬르머검사결과 (Schirmer test <5 mm, Schirmer test 5 mm) 의분포는평균및최대눈물지질층두께의값에따른유의한분포의차이를보이지않았다 (Fig. 3, p=0.619, p=0.606). OSDI를시행한환자만을대상으로, 눈물지질층두께가 60 nm 이상인경우와미만인두군으로나누고건성안증 Table 1. Clinical characteristics of patients Characteristics Value (range * ) Age (years) ± (18-72) Sex (male:female) 18:31 Schirmer s test (mm) 8.45 ± 7.80 (2-20) tbut (sec) 5.00 ± 3.43 (1-10) Average LLT (nm) ± (25-140) Maximum LLT (nm) ± (29-150) Minimum LLT (nm) ± (23-115) Total blinking (times/20 sec) 5.80 ± 3.24 (2-12) Partial blinking (times/20 sec) 3.30 ± 2.36 (0-9) Partial blinking/total blinking ratio 0.59 ± 0.31 (0-1) Values are presented as mean ± SD (range) unless otherwise indicated. tbut = tear break-up time; LLT = lipid layer thickness; sec = second. * Range: minimum value-maximum value. 790

4 - 김래영외 : 눈물지질층두께와안구표면임상인자 - Table 2. Correlation analysis among LLT and clinical factors using 4 sets of implantation data Data set Average LLT Maximum LLT Minimum LLT Difference Total blink Partial blink Schirmer test (0.307) (0.733) (0.114) * (0.011) * (0.007) (-0.554) (0.221) (0.646) (0.147) (0.005) (0.000) (0.009) (0.765) (0.933) (0.700) (0.199) * (0.012) (0.243) (0.297) (0.615) (0.128) * (0.043) (0.060) * (0.042) tbut (0.008) * (0.048) * (0.024) (0.435) (0.456) * (0.035) * (0.042) (0.090) (0.051) * (0.014) (0.499) * (0.020) (0.079) (0.096) (0.090) (0.765) * (0.049) * (0.049) * (0.039) (0.913) (0.177) (0.162) Staining grade (0.311) (0.202) (0.811) * (0.101) (0.582) (0.399) * (0.029) (0.069) * (0.012) * (0.042) (0.067) * (0.035) (0.129) (0.099) (0.211) (0.217) (0.152) (0.243) (0.129) * (0.044) (0.296) * (0.010) (0.247) (0.067) LL MGD grade (0.916) (0.959) (0.999) (0.906) (0.909) (0.465) Values are presented as correlation coefficient r (p-value) unless otherwise indicated. p-values were calculated by Pearson s correlation test. LLT = lipid layer thickness; tbut = tear break-up time; LL MGD grade = lower lid meibomian gland dysfunction grade. * p-value < 0.05; p-value < 0.01; Difference = Maximum LLT - Minimum LLT. Table 3. Partial correlation analysis controlling for age and sex of the subject using 4 sets of implantation data Data set Average LLT Maximum LLT Minimum LLT Difference Total blink Partial blink Schirmer test (0.171) (0.410) (0.066) * (0.031) * (-0.067) (0.198) (0.633) (0.144) * (0.030) (0.000) (0.003) (0.784) (0.743) (0.733) (0.108) * (0.014) * (0.041) (0.272) (0.469) (0.102) * (0.040) * (0.049) * (0.140) tbut (0.051) * (0.028) (0.445) (0.162) (0.002) * (0.007) (0.066) * (0.018) * (0.016) (0.505) (0.004) * (0.013) (0.074) (0.050) (0.097) (0.752) * (0.018) * (0.035) (0.050) (0.891) (0.162) (0.363) Values are presented as r (p-value) unless otherwise indicated. p-values were calculated by partial correlation analysis. LLT = lipid layer thickness; tbut = tear break-up time. * p-value < 0.05; p-value < 0.01; Difference = Maximum LLT - Minimum LLT. 상이거의없는경우 (OSDI 점수 13 미만 ), 증상이경미하 거나중등도인경우 (OSDI 점수 13 이상 33 미만인경우 ), 증상이심한경우 (33 이상 ) 에서각각두군의분포가차이 를보이는지를카이제곱분석을통해확인하였다. 평균, 최 대, 최소눈물지질층두께모두에서분포의유의한차이가 없었으며 (average LLT; p=0.052, maximum LLT; p=0.062, 791

5 - 대한안과학회지 2017 년제 58 권제 7 호 - A B C D Figure 1. Pearson correlation scatter plot of tear break-up time (tbut) and average lipid layer thickness (LLT) using implanted data set 1 (A), 2 (B), 3 (C), and 4 (D). (A) r = 0.376, p-value = (B) r = 0.220, p-value = (C) r = 0.390, p-value = (D) r = 0.276, p-value = p-values were calculated by Pearson correlation test. minimum; p=0.630, Chi-square test), 중등도에따른분포의경향성도보이지않았다 (average LLT; p=0.448, maximum LLT; p=0948, minimum; p=0.353, linear-by-linear association). 고찰 본연구에서는기존에마이봄샘기능부전이눈물막의불안정성을초래하여건성안의원인이된다고알려진것 16,17 을바탕으로건성안환자를대상으로 LipiView II 간섭계를이용하여측정한눈물지질층두께를임상적으로흔하게사용되는안구표면질환평가지표들과상관분석하였으며, tbut값이평균및최대눈물지질층두껫값과통계적으로유의한양의상관관계가있음을확인하였다. 기존의연구에서도큰 tbut값을가지는경우눈물지질층두께가얇아져있지않음을시사하여, tbut값측정과눈물지질층 두께가연관이있는것으로알려졌으며 Isreb et al 21 의연구는눈물지질층두께의정량화방법에있어서본연구와차이가있으나눈물지질층두껫값과 Schirmer test, tbut 간의유의한양의상관관계를보고한바있다. 이는눈물지질층이눈물층의안정성유지에관여하여양의상관성을보인것으로해석해볼수있으며기존여러연구에서도눈물지질층의양적, 질적인상태가건성안및마이봄샘의기능과연관성이있음이밝혀져있다. 5,21-24 쉬르머검사는기존에 5분을시행하였을때눈물생산량을주로반영하는검사로알려져있으나 Tomlinson et al 8 에의해짧은시간동안검사를진행하는경우안구표면의눈물의양을반영할수있는수치로제시된바있다. 또한 Nichols et al 22,25 은쉬르머검사와안구표면안정성및 tbut 검사간에유의한상관관계를보고한바있다. 그러나본연구에서는쉬르머검사는평균및최대눈물지질층두께와일정한양의상관관계를보였으나통계적으로유의하지 792

6 - 김래영외 : 눈물지질층두께와안구표면임상인자 - A B C D Figure 2. Pearson correlation scatter plot of tear break-up time (tbut) and maximum lipid layer thickness (LLT) using implanted data set 1 (A), 2 (B), 3 (C), and 4 (D). (A) r = 0.390, p-value = (B) r = 0.178, p-value = (C) r = 0.331, p-value = (D) r = 0.279, p-value = p-values were calculated by Pearson correlation test. 않아이를확인할수없었다. 이는결측값등의영향을고려하여향후많은수의환자를대상으로한분석을통한확인이필요하다. 눈물지질층은극성, 비극성인지질의특징에따라층의형태를띠고있으며 23 눈깜박임발생시상안검이하측으로내려가면서아코디언형태 (concertina-wise) 로접혔다가상안검이올라갈때다시펴지는모양을띠게된다고알려져있다. 26 이를고려하면눈물지질층의최댓값이나최솟값의경우눈물지질층의펴짐 (unfolding) 이덜완전하게일어난상태에서측정될가능성이있으므로순간적인최대치보다는전체의평균값이눈물막의안정성과관련이있는지표를잘반영할수있을것으로생각해볼수있다. 그러나본연구에서는최대및평균눈물지질층두께에서모두건성안의지표인눈물막파괴시간과유의한연관성을보였으며, 이는 LipiView II 간섭계의측정방식이빛의간섭현상을이용하기때문에눈물지질층의최댓값이눈깜박임에의한상안검의움직임이어느정도끝난다음 측정되기때문에평균값과유사하게눈물막파괴시간과상관관계를보였을것으로생각된다. Blackie et al 11 은 137명을대상으로초기형태의안구표면간섭계를통한눈물지질층두께와표준건성안환자평가 (Standard Patient Evaluation of Eye Dryness, SPEED) 로측정한증상간에유의한상관관계를보고하였으며 Finis et al 12 은마이봄샘의형태와눈물지질층두께의유의한상관성을보고하였으나본연구에서는임상적으로측정한마이봄샘기능부전정도및 OSDI 점수에서최대, 최소, 평균눈물지질층두께모두와유의한상관관계를보이지않았다. 또한이를확인하기위해본연구의대상환자중 OSDI 설문조사를시행한환자만을대상으로눈물지질층두께에따라 2개군으로나누어 (LLT <60 nm, LLT 60 nm) 각각의군에서증상중증도에따른분포의차이를분석한결과에서도유의한차이를보이지않았다. 이는, 위의두연구는본연구와같이건성안환자를대상으로연구를시행하였으나본연구보다많은환자를대 793

7 - 대한안과학회지 2017 년제 58 권제 7 호 - A B C D Figure 3. The percentage of patients with shorten (<10 sec) or normal ( 10 sec) tear break-up time (tbut) in each relatively thin lipid layer thickness (LLT) (<60 nm) or relatively thick LLT ( 60 nm) (A: average LLT, B: maximum LLT). The percentage of patients with shorten (<5 mm) or normal ( 5 mm) Schirmer test in each relatively thin LLT (<60 nm) or relatively thick LLT ( 60 nm) (C: average LLT, D: maximum LLT). p-values were calculated by Chi-square test. 상으로분석을시행하였기때문에다른결과를보였을수있다. 또한, 중등도의측면에서도위의두연구는대상환자를설정하지않았으나본연구에서는 DEWS 분류중중증도 2, 3, 4 건성안을진단받은환자군만을대상으로하여대상환자의구성면에서도차이가있을수있다. 또한 Finis et al 12 의연구의경우 110명 199안을대상으로하여일부환자에서양안의분석결과를포함하였으나본연구에서는단안의결과만을대상으로분석을시행하였기때문에다른결과를보였을것으로생각해볼수있다. 또한본연구에서평균눈물지질층두께가눈물막증발건성안의지표인눈물막파괴시간과유의한양의상관성이 있는결과를보였으나, 이는건성안을직접반영하는수치는아니며환자의증상에관여하는다양한요인이작용하였기때문에 OSDI와는유의한상관성을보이지않은것으로생각된다. 본연구는 49명총 49안을대상으로시행한연구였으나모든환자에서안구표면에대한검사가이루어지지않음으로써발생한결측값의영향을받을수있다는점, 건성안환자만을연구대상으로포함하였다는점에서정상인의눈물지질층값을통계적으로반영할수없었다는점및여러차례반복검사를통한개인의눈물지질층두께및안구표면상태의변화를반영할수없었다는점에서한계가있 794

8 - 김래영외 : 눈물지질층두께와안구표면임상인자 - 다. 이에대해서는추후좀더넓은범위의증상및임상적 소견을가진환자군및정상인을대상으로충분한경과관찰 및측정과정을통해비교연구가필요할것으로생각된다. 본연구를통하여건성안환자에서 LipiView II 를이용 한최대및평균눈물지질층두께가 tbut 값과유의한상 관관계를보인다는점에서 LipiView II 간섭계를이용한 눈물지질층두께측정이건성안진단및경과관찰에도움 을줄수있음을확인하였고추후정상안및마이봄샘기능 부전환자군에대해서는비교연구가더필요하겠다. REFERENCES 1) Shine WE, McCulley JP. The role of cholesterol in chronic blepharitis. Invest Ophthalmol Vis Sci 1991;32: ) Shine WE, McCulley JP. Role of wax ester fatty alcohols in chronic blepharitis. Invest Ophthalmol Vis Sci 1993;34: ) Shine WE, McCulley JP. Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality. Arch Ophthalmol 1998;116: ) Shine WE, McCulley JP. Polar lipids in human meibomian gland secretions. Curr Eye Res 2003;26: ) Bron AJ, Tiffany JM. The contribution of meibomian disease to dry eye. Ocul Surf 2004;2: ) Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 2003;1: ) Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2011;52: ) Tomlinson A, Bron AJ, Korb DR, et al. The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci 2011;52: ) Greiner JV, Glonek T, Korb DR, et al. Volume of the human and rabbit meibomian gland system. Adv Exp Med Biol 1998;438: ) Chew CK, Jansweijer C, Tiffany JM, et al. An instrument for quantifying meibomian lipid on the lid margin: the Meibometer. Curr Eye Res 1993;12: ) Blackie CA, Solomon JD, Scaffidi RC, et al. The relationship between dry eye symptoms and lipid layer thickness. Cornea 2009; 28: ) Finis D, Pischel N, Schrader S, Geerling G. Evaluation of lipid layer thickness measurement of the tear film as a diagnostic tool for Meibomian gland dysfunction. Cornea 2013;32: ) 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: ) Jeon SJ, Baek JW, Doh SH, Chung SK. Tear meniscus evaluation using optical coherence tomography in meibomein gland dysfunction patients. J Korean Ophthalmol Soc 2015;56: ) Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology 2008;115: ) Mathers WD. Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology 1993;100: ) Mathers WD, Lane JA. Meibomian gland lipids, evaporation, and tear film stability. Adv Exp Med Biol 1998;438: ) Craig JP, Tomlinson A. Importance of the lipid layer in human tear film stability and evaporation. Optom Vis Sci 1997;74: ) Eom Y, Lee JS, Kang SY, et al. Correlation between quantitative measurements of tear film lipid layer thickness and meibomian gland loss in patients with obstructive meibomian gland dysfunction and normal controls. Am J Ophthalmol 2013;155: e2. 20) Goto E, Dogru M, Fukagawa K, et al. Successful tear lipid layer treatment for refractory dry eye in office workers by low-dose lipid application on the full-length eyelid margin. Am J Ophthalmol 2006;142: ) Isreb MA, Greiner JV, Korb DR, et al. Correlation of lipid layer thickness measurements with fluorescein tear film break-up time and Schirmer's test. Eye (Lond) 2003;17: ) Nichols JJ, Nichols KK, Puent B, et al. Evaluation of tear film interference patterns and measures of tear break-up time. Optom Vis Sci 2002;79: ) Korb DR, Blackie CA. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Cornea 2008;27: ) Mishima S, Maurice DM. The oily layer of the tear film and evaporation from the corneal surface. Exp Eye Res 1961;1: ) Nichols KK, Nichols JJ, Lynn Mitchell G. The relation between tear film tests in patients with dry eye disease. Ophthalmic Physiol Opt 2003;23: ) Bron AJ, Tiffany JM, Gouveia SM, et al. Functional aspects of the tear film lipid layer. Exp Eye Res 2004;78:

9 - 대한안과학회지 2017 년제 58 권제 7 호 - = 국문초록 = 눈물지질층두께와안구표면임상인자간의상관관계분석 목적 : LipiView II R 간섭계 (LipiView R Ocular Surface Interferometer, TearScience R, Morrisville, NC, USA) 를이용하여측정한눈물지질층두께 (tear film lipid layer thickness, tear film LLT) 를임상적으로이용되는안구표면질환의지표들과비교하여상관관계를분석하고자한다. 대상과방법 : 건성안을진단받은환자 49 명을대상으로전향적연구를시행하였다. 환자들은안구표면질환지표 (ocular surface disease index, OSDI) 설문조사를받았다. 세극등현미경검사, 눈물막파괴시간 (tear film break-up time, tbut) 측정, 쉬르머검사 (Schirmer test), 각막및결막형광염색, 마이봄샘기능부전에대한평가를시행하였다. LipiView II R 간섭계를통한눈물지질층두께, 동적투과조명마이봄샘촬영및눈깜박임횟수를측정하였다. 결측값을보정하기위해다중대체방법을사용하여 4 개의결측값대체모델을만들어 Pearson 상관분석을시행하였다. 눈물지질층두께에따라환자들을두군으로구분 (LLT <60 nm, LLT 60 nm) 하여카이제곱교차분석을시행하였다. 결과 : 안구표면질환의지표중눈물막파괴시간이눈물지질층두께의평균, 최댓값과유의한상관관계를보였으며 (average LLT; p=0.008, 0.035, 0.006, 0.049, maximum LLT; p=0.006, 0.042, 0.020, 0.049, Pearson correlation analysis with multiple imputation) 최솟값과는유의한관계가없었다 (minimum LLT; p=0.048, 0.090, 0.079, 0.039). 평균및최대눈물지질층두께가상대적으로얇게측정된환자군 (LLT <60 nm) 에서는각각 80% 와 88% 의환자에서 tbut 가 10 초미만인값을보였고이와대조적으로상대적으로눈물지질층두께가두껍게측정된환자군 (LLT 60 nm) 에서는각각 39%, 47% 의환자에서 tbut 가 10 초미만으로나타났다. 결론 : 건성안환자에서눈물지질층두께의평균및최댓값은눈물막파괴시간과유의한상관관계를보였고평균, 최대눈물지질층두께가상대적으로얇은환자에서눈물막파괴시간이단축된경향을보였다. 이는눈물막증발건성안환자에서 LipiView II R 간섭계를이용한평균눈물지질층두께를측정하는것이진단및경과관찰에도움을줄수있음을보여준다. < 대한안과학회지 2017;58(7): > 796

03-JKOS hwp

03-JKOS hwp 대한안과학회지 2019 년제 60 권제 6 호 J Korean Ophthalmol Soc 2019;60(6):519-527 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2019.60.6.519 Original Article 백내장수술후마이봄샘기능부전과눈물지질층분석 Meibomian