대한안과학회지 2008 년제 49 권제 10 호 J Korean Ophthalmol Soc 2008;49(10):1634-1640 DOI : 10.3341/jkos.2008.49.10.1634 녹내장및고안압증환자에서근시정도에따른망막신경섬유층두께차이 김정완 김용연 고려대학교의과대학안과학교실 목적 : 녹내장및고안압증안에서근시정도에따른망막신경섬유층 (Retinal Nerve Fiber Layer, RNFL) 두께의차이를알아보고자하였다. 대상과방법 : 녹내장과고안압증으로진단된환자 98 명 165 안을대상으로빛간섭단층촬영기 (optical coherence tomography, OCT), 가변각막보정주사레이저편광측정기 (scanning laser polarimetry using variable corneal compensation, GDx-VCC) 검사를시행하여굴절력차이에따른 RNFL 두께의상관관계를분석하였다. 나이, 좌우안, 안압및녹내장진행정도를나타내는시야검사상평균편차등의변수를통제하기위해편상관계수분석을이용하였다. 결과 : OCT 로측정한평균 RNFL 두께와코측, 상측및하측사분면의 RNFL 두께는근시가심해짐에따라통계적으로유의하게감소하였다 (p<0.05). GDx-VCC 로측정한결과는근시정도와유의한상관관계가없었다. 결론 : 녹내장및고안압증안에서근시가심해짐에따라 OCT 를이용하여측정한 RNFL 평균두께는얇아지는양상을보였다. < 대한안과학회지 2008;49(10):1634-1640> 녹내장은시신경병증으로정의되고있으며, 녹내장성시신경병증은시신경유두의함몰과망막신경섬유층의얇아짐이특징이다. 녹내장의진단을위하여는통상안압측정, 시신경검사및시야검사를시행하나, 녹내장의정의대로시신경및망막신경섬유층의변화가가장중요하다. 1-3 녹내장과굴절이상과의관계중특히근시에대하여는주의가필요한데, 근시가있는녹내장환자는근시로인한시신경모양의변화로인해녹내장진단및경과관찰이어렵기때문이다. 4 근시가진행할수록공막은점점얇아지며후극부의부분적팽창또한이루어진다. 맥락막의변성과위축이진행되면서 5 감각망막이얇아진다고한다. 6 이러한조직학적변화때문에근시환자의안저를판독할때에 < 접수일 : 2007 년 11 월 20 일, 심사통과일 : 2008 년 7 월 2 일 > 통신저자 : 김용연서울시구로구구로동길 97 고려대학교구로병원안과 Tel: 02-2626-1260, Fax: 02-857-8580 E-mail: yongykim@mail.korea.ac.kr * 본논문의요지는 2007 년대한안과학회제 98 회추계학술대회에서구연으로발표되었음. 주의를기울여야한다. 또한생리학적으로큰유두함몰, 시신경경사, 근시유두주위위축 (peripapillary atrophy) 때문에녹내장성변화를확인하고경과관찰하기가쉽지않다. 7-13 최근에는빛간섭단층촬영기 (optical coherence tomography, OCT) 가황반부와유두주위망막신경섬유층두께측정에활용되고있으며이는적외선계열 (840 nm) 의레이저간섭계를이용하여조직내에서반사되는빛의시간차이를통해고해상도의횡단영상을나타내는장비로서우수한해상력 (10 µm) 을가진다. 망막색소상피의앞쪽경계를기준으로망막신경섬유층의두께를정량적으로측정할수있고, 따라서망막질환뿐만아니라녹내장성변화의조기진단에도이용되고있다. 14-17 주사레이저편광측정기 (scanning laser polarimetry, GDx) 는편광변조기, 각막편광보정기및편광감지기가장착된공초점주사레이저편광계 (confocal scanning laser ophthalmoscope) 의일종이다. 일정한파장 (780 nm) 의다이오드레이저광선을편광시켜망막에조사하면복굴절매체인망막신경섬유층을통과하면서레이저광선의편광상태가변화하게되는데, 그뒤쳐짐 (retardation) 의정도를측정하여망막신경섬유층의 1634
대한안과학회지 2008 년제 49 권제 10 호 두께를간접적으로측정하게된다. 18-21 그러나각막의복굴절현상을충분히보정하지못하는단점이있어이를극복하기위해각안구마다변화된가변각막보정 (variable corneal compensation, VCC) 을사용하는기기가개발되었다. 22-24 근시와관련하여근시정도에따른망막신경섬유층두께의상관관계는많은연구가이미보고된바있다. 25,26 하지만근시진행정도에따른망막신경섬유층두께의변화를 OCT와 GDx-VCC 로동시에검사한후비교한연구는아직미미한편이다. 저자는본연구에서녹내장및고안압증환자에서근시정도에따른망막신경섬유층두께의차이를알아보고자하였다. 대상과방법 2005 년 11 월부터 2007 년 3 월까지고려대학교구로병원안과녹내장클리닉에녹내장검진을위해내원한환자중굴절검사와 GDx-VCC (Laser Diagnostic Technologies, Inc., San Diego, USA), Stratus OCT (Stratus OCT, model 3000; Zeiss Humphrey Systems, Dublin, USA), 망막신경섬유층촬영, 시신경유두입체촬영, 시야검사, 중심각막두께측정을모두시행한환자의의무기록을후향적으로조사하여이들중녹내장과고안압증으로최종진단된 98 명 165 안을대상으로연구를진행하였다. 안저검사상녹내장성시신경변화및망막신경섬유층촬영상신경섬유층결손이있거나시야검사상녹내장성시야결손이있는경우를녹내장으로진단하였고시신경이나시야의이상없이안압이 21 mmhg 이상인경우고안압증으로진단하였다. 녹내장성시신경변화는시신경유두함몰, 시신경망막띠얇아짐이나패임, 또는양안유두함몰비차이가 0.2 이상인경우로정의하였고녹내장성시야결손은 glaucoma hemifield test 상정상범위의 99% 밖의결과이거나정상범위의패턴표준편차 (pattern standard deviation) 의 95% 밖의결과로정의하였다. 모든환자에게기본적인문진을시행한후안과적검사와굴절검사, 안압측정, 시신경유두입체촬영, 안저검사를시행하였다. 경도의백내장, 경도의당뇨망막질환및이전에백내장및녹내장수술을받은과거력이있는환자들은제외하지않았으나각막혼탁이있거나시신경모양에변화를줄수있는전신적질병이있는경우, 그리고이차적인원인으로녹내장이생긴경우는제외하였다. 안압은 Goldmann 압평안압계로측정하였고굴절검사는 Canon Full Auto RK-F1 Autorefractor Keratometer (Canon Inc., Tokyo, Japan) 를이용하여측정하였다. 시야검사는 Humphrey automated field analyzer HFA II 750 (Humphrey Instruments, a division of Carl Zeiss, Inc., San Leandro, CA, USA) 를이용하여표준시야검사로시행하였다. 그리고시야검사상평균편차 (Mean Deviation) 값이 -10.00dB 이상인눈만을대상으로하였고, 평균편차값을녹내장의진행정도를판단하는기준으로정하였다. 단일검사자에의해측정된 OCT 검사로평균망막신경섬유층두께 (Avg. Thick.) 와각사분면즉, 상, 하, 귀, 코측의망막신경섬유층두께를구하였다. 검사결과시신경중심주사 (optic disc centration) 가잘된경우와 signal strength 가 6 ( 최대 10) 이상의자료만을채택하였다. GDx-VCC 도단일검사자에의해시행하였으며, 이경우녹내장가능성의지표가되는 NFI (Nerve Fiber Index, range 0-100) 와평균망막신경섬유층두께 (TSNIT Avg.) 를분석하였고상, 하측망막신경섬유층두께도비교하였다. GDx-VCC 의경우비정상복굴절뒤쳐짐 (artificial birefringence pattern) 을제외하기위해 TSS (typical scan score, range 1-100) 가 60 이상의자료만을채택하였다. 27 굴절률에따른망막신경섬유층두께변화의상관관계를비교분석하기위해이변량상관관계 (bivariate correlation) 는 Pearson 상관계수 (correlation coefficient) 를이용하여분석하였고 p value 0.05 미만을통계적으로유의한것으로판단하였다. 그리고굴절률과망막신경섬유층의두께변화에영향을미칠수있는인자들, 즉, 나이, 성별, 좌우안, 안압그리고시야검사상평균편차값을통제한후에순수한굴절률과망막신경섬유층의두께변화를알아보기위해이들의상관관계를다변량분석인편상관계수 (partial correlation coefficient) 를이용하여비교분석하였고역시 p value 0.05 미만을통계적으로유의한것으로판단하였다. 결 과 환자 98 명중남자는 63 명, 여자는 35 명이었으며평균나이는 44.92±13.43 세였다. 이들이병원에첫내원했을당시측정한평균안압은 17.76±4.72 mmhg 였으며, 시야검사상평균편차값은 -2.44±2.68dB 였다 (Table 1). 이변량상관관계분석시 OCT 를이용하여측정한평균망막신경섬유층의두께는근시가진행함에따라통 1635
김정완외 : 근시에따른망막신경섬유층두께차이 Table 1. Bivariate correlations associated with refraction Average (µm) r* P value Refraction (diopters) -2.38±2.65 1 Age (Years) 44.92±13.43 0.430 0.000 IOP (mmhg) 17.76±4.72-0.089 0.256 MD (db) -2.44±2.68 0.050 0.527 Stratus OCT Avg. Thick 94.98±16.65 0.323 0.000 Superior 114.85±22.62 0.245 0.001 Inferior 114.56±26.75 0.284 0.000 Temporal 74.32±16.54 0.124 0.114 Nasal 76.22±17.33 0.366 0.000 GDx-VCC NFI 31±18.12-0.091 0.243 TSNIT Avg 49.29±7.36-0.037 0.635 Superior 60.55±10.73-0.006 0.941 Inferior 58.18±10.69-0.073 0.352 TSNIT std. dev. 20.86±5.04-0.023 0.769 * Pearson correlation coefficient; Pearson test; IOP=Intraocular Pressure; MD=Mean Deviation; Stratus OCT=Stratus optical coherence tomography; GDx-VCC=Scanning Laser Polarimetry with Variable corneal compensation; Avg. Thick=Average retinal nerve fiber layer thickness obtained by optical coherence tomography; NFI=Nerve Fiber Index obtained by scanning laser polarimetry; TSNIT Avg=Average retinal nerve fiber layer thickness obtained by scanning laser polarimetry; TSNIT std. dev.=standard Deviation of the Average retinal nerve fiber layer thickness obtained by scanning laser polarimetry. Avg. Thick 140 120 100 80 60 40 20-14 -12 Refraction -10-8 Figure 1. Scattergram of the average retinal nerve fiber layer (RNFL) thickness obtained by optical coherence tomography (y) and the degree of myopia (x). As myopia increased, there was a significant decrease in the average RNFL Thickness obtained by the Stratus OCT (p=0.000, r=0.323). 계적으로유의하게점점얇아졌다 (r=0.323, p=0.000) (Fig. 1). 이를좀더자세하게각사분면별로즉, 상, 하, 귀, 코측의망막신경섬유층두께를확인한결과귀측을제외하고는근시가진행할수록통계적으로유의하게점점얇아지는경향을보였다 ( 상측 r=0.245, p=0.001, 하측 r=0.284, p=0.000, 귀측 r=0.124, -6-4 -2 0 2 p=0.114, 코측 r=0.366, p=0.000)(table 1). 안압, 시야검사상평균편차등은굴절률과유의한상관관계가없는반면 (p>0.05), 나이는증가할수록굴절률이감소하였다 (Table 1). GDx-VCC 를이용하여측정한 NFI 는근시의정도와유의한상관관계가없었고 (p=0.243) 평균망막신경섬유층의두께도근시의정도와유의한상관관계가없었다 (p=0.635). 그리고상, 하두구역으로나누어두께를확인한결과역시근시의정도와유의한상관관계가없었다 ( 상측 p=0.941, 하측 p=0.352)(table 1). 나이, 성별, 좌우안, 안압그리고시야검사상평균편차등이굴절력과망막신경섬유층두께변화에영향을미칠수있으므로, 이들을통제한후시행한편상관분석결과굴절력과망막신경섬유층두께간의상관관계또한변수를통제하기이전과동일한결과를보였다 (Table 2). 고 찰 녹내장환자들은병이진행함에따라가장먼저망막신경섬유층의두께가감소하는변화를보이고 1-3 이와별도로근시환자들은후극부의부분적팽창과같은조직학적변화로감각망막이얇아지게된다. 6 그결과근시가있는녹내장및고안압증환자에서병의악화가능성에대한의문점이제기되어왔다. 하지만근시로 1636
대한안과학회지 2008 년제 49 권제 10 호 Table 2. Correlations after adjusting age, sex, laterality, baseline IOP and mean deviation Average (µm) r* P value Stratus OCT Avg. Thick 94.98±16.65 0.287 0.000 Superior 114.85±22.62 0.265 0.001 Inferior 114.56±26.75 0.209 0.008 Temporal 74.32±16.54 0.073 0.363 Nasal 76.22±17.33 0.317 0.000 GDx-VCC NFI 31±18.12-0.114 0.156 TSNIT Avg 49.29±7.36-0.097 0.226 Superior 60.55±10.73 0.014 0.861 Inferior 58.18±10.69-0.104 0.195 TSNIT std. dev. 20.86±5.04 0.086 0.282 * Pearson correlation coefficient; Pearson test; Stratus OCT=Stratus optical coherence tomography; GDx-VCC=Scanning Laser Polarimetry with Variable corneal compensation; Avg. Thick=Average retinal nerve fiber layer thickness obtained by optical coherence tomography; NFI=Nerve Fiber Index obtained by scanning laser polarimetry; TSNIT Avg=Average retinal nerve fiber layer thickness obtained by scanning laser polarimetry; TSNIT std. dev.=standard Deviation of the Average retinal nerve fiber layer thickness obtained by scanning laser polarimetry. 인한시신경의형태학적변화로인해 7-13 시신경모양만보고녹내장여부를판단하기어려운부분이있으며 4 따라서근시로인한시신경의변화를감안하고시신경손상과망막신경섬유층의두께를측정하는여러가지장비들로서녹내장을조기에진단하고진행여부를판단하기위한노력이이루어지고있다. 녹내장환자에서근시가진행함에따라근시에의한조직학적변화와맥락막의변성및위축 5 으로망막신경섬유층의두께가얇아진다고한다. 6 따라서녹내장의진행으로인한망막신경섬유층두께의감소를고려하면근시가있는녹내장환자에서녹내장검사를시행할때에는근시로인한망막신경섬유층두께에대한변화를감안하여야할것이다. 실제로 Leung et al 28 은 115 명의근시환자를대상으로 OCT (version 3) 를이용하여망막신경섬유층의두께를측정한결과구면렌즈대응치가 -6.0D 이하인고도근시군이 -6.0D 이상인중증도근시군보다통계적으로유의하게 12, 1, 7 시방향에서얇아지는경향을확인하였다. 그리고안축장거리와굴절률이증가함에따라망막신경섬유층의두께가감소하였다 ( 안축장거리, r=-0.314, p=0.001, 굴절률, r=0.291, p=0.002). Ozdek et al 29 은 85 명의근시환자를대상으로 GDx (NFA-I) 을이용하여상, 하측망막신경섬유층두께를측정한결과근시가진행함에따라매디옵터마다각각 0.122 와 0.092 µm 만큼점차감소함을보고한바있고 Kremmer et al 30 도 75 명의건강한근시환자를대상으로 GDx (version 1.0.14, 2.0.10) 을이용하여평균망막신경섬유층두께와구면렌즈대응치사이의일차적관계를보고하였다. Salchow et al 31 은 17 세이하어린이 92 명을 대상으로 OCT-3 (version 4.0.1) 를이용하여망막신경섬유층의두께를측정한결과굴절률이증가할수록통계적으로유의하게얇아지는결과를보였다 (r= 1.671, p<0.001). 반면에 Bowd et al 32 은굴절이상범위가 -5D 에서 +5D 까지인 155 명의지원자에게 GDx (version 2.0.01) 와 OCT 2000 (version A5X1) 를이용하여망막신경섬유층두께를분석한결과굴절과망막신경섬유층수치와는관계가없다고보고한바있고 Hoh et al 33 또한 OCT-1 (version 4.1) 을이용한연구에서안축장거리, 구면렌즈대응치와평균망막신경섬유층두께와는관계가없다고보고하였다. 근시정도에따라망막신경섬유층두께가감소한다는결과와그렇지않다는상반된결과가모두보고되고있으며이는연구집단을선택하는과정혹은각기계의 software version 의차이때문으로생각할수있다. 본연구에서는비교적녹내장예측률이비슷하고정확한측정치를제공하는것으로알려진가장최신기종의두가지장비인 GDx-VCC 와 Stratus OCT 를동시에녹내장환자들에게시행하여이들의근시정도에따른망막신경섬유층두께의변화양상을파악하였다. 기존의 OCT 또는 GDx 만시행하여망막신경섬유층두께를측정했던연구와는다른시도라고할수있다. 그리고그결과녹내장환자에서근시가진행할수록 OCT 로측정한망막신경섬유층의두께는통계적으로유의하게감소하는것 (p=0.000) 으로확인되었고각사분면별로측정한망막신경섬유층도귀측을제외하고는같은결과를보여주었다. 이는 Leung et al 28 이 OCT 를이용하여근시환자에서망막신경섬유층두께 1637
김정완외 : 근시에따른망막신경섬유층두께차이 를측정한연구결과에서귀측을제외하고구면렌즈대응치와통계적으로유의한상관관계를보이고있다고보고한내용과일치하는결과이다. 이들은또한 115 명의건강한근시환자를대상으로망막신경섬유층의두께는구면렌즈대응치가음의값으로커질수록상관계수 0.291 로감소한다고보고하였는데, 본연구에서는이들의상관계수가 0.287 이었다. 즉본논문과 Leung et al 28 의연구를비교해보면근시가있으면서녹내장이있는환자에서는망막신경섬유층의두께감소가비슷한경향을보일것으로추측된다. 그러나본연구에서는정상인을조사하지않았기때문에이에대한명확한결론을내리는것은한계가있으며추후연구로보완되어야할것으로생각된다. 본연구에서 GDx-VCC 로측정한망막신경섬유층두께는굴절과상관관계를보이지않았다. 이는고도근시와연관된심한해부학적변화및유두주위위축의결과로공막반사율이증가함에따라, GDx-VCC 의비정상복굴절뒤쳐짐이증가해서 GDx-VCC 로측정한망막신경섬유층두께가더두껍게측정되었기때문으로생각된다. 34 본연구에서는복굴절뒤쳐짐효과를제외하기위하여 TSS 값이 60 이하인경우를제외하였으나그럼에도불구하고복굴점뒤쳐짐효과를완전히제거하지못하였을것으로추정된다. 본연구는후향적연구이며녹내장환자를대상으로하였기때문에망막신경섬유층두께에영향을미치는여러변수가복합적으로작용하여망막신경섬유층두께와근시정도의상관관계에영향을미칠수있는단점이있다. 그러나저자는녹내장환자를본연구에포함할경우경도의녹내장환자만을대상으로하였고 ( 시야검사상평균편차 -10dB 이상 ), 평균편차를녹내장의진행정도를나타내는지표로보았다. 저자의분석결과망막신경섬유층두께에영향을미칠수있는안압, 시야검사상평균편차등의변수와굴절력간의상관관계는이변량상관분석상통계적으로유의하지않았다. 나이도망막신경섬유층두께에영향을미칠수있다. 본연구결과나이는근시의정도와관계가있었으나나이가들어감에따라근시가감소하는경향을보여주었다. 일반적으로나이가들어감에따라망막신경섬유층두께가얇아지는것으로알려져있으므로, 고도근시일수록망막신경섬유층두께가얇아지는본연구결과에미친나이의영향은그관계가크지않을것으로판단된다. 또한저자는나이를포함한이들변수를통제한편상관관계분석에서도근시는망막신경섬유층두께에영향을미치는변수임을다시확인할수있었다. 일반적으로우안과좌안의성질은강한상관관계를가진다고한다. 따라서본연구와같은양안을포함한 분석은한눈곱하기 2 로중복분석될수있는위험성이있다. 이를통제하기위해본연구에서는편상관분석시우안과좌안이미치는영향을각각통제한후분석을시행하였으며그결과양안을동시에포함한것이본연구의상관관계에영향을미치지않았다. 일반인구를대상으로시행한연구를보면근시가진행할수록녹내장위험률이증가한다고한다. Blue Mountain Eye study 35 에서는근시와개방각녹내장과의연관성에대해서보고한바있으며, 스웨덴에서 32,000 명이상의인구를대상으로한연구 36 에서도근시가녹내장의중요한위험요소라고밝힌바있다. 근시와녹내장사이에발병기전은아직완벽하게밝혀지진않았지만근시성시신경이결체조직의구조와배열의변화로녹내장성손상에더취약할것으로판단되고망막신경섬유층의두께가녹내장과밀접한관계가있으므로근시가진행할수록망막신경섬유층의두께가감소하는본연구의결과는근시환자에서망막신경섬유층두께를측정하고판단할때주의가필요하다는것과근시에서망막신경섬유층두께가얇아진다면근시에서녹내장이많이발생하거나혹은많이진단될수있다는가능성을뒷받침해주고있다. 결론적으로본연구에서는녹내장및고안압증환자에서근시가진행할수록 OCT 를이용하여측정한망막신경섬유층두께도유의하게감소하는양상을보였다. 따라서녹내장을진단하고경과관찰할때에는굴절검사를통한환자의근시정도를파악하고그에따른망막신경섬유층두께변화를감안하는일이중요할것으로생각된다. 참고문헌 1) Quigley HA, Katz J, Derrick RJ, et al. An evaluation of optic disc and nerve fiber layer examinations in monitoring progression of early glaucoma damage. Ophthalmology 1992;99:19-28. 2) Sommer HA, Quigley HA, Robin AL, et al. Evaluation of nerve fiber layer assessment. Arch Ophthalmol 1984;102: 1766-71. 3) Quigley HA, Addicks EM, Green WR. Optic nerve damage in human glaucoma. Arch Ophthalmol 1982;100:135-46. 4) Hyung SM, Kim DM, Hong C, Youn DH. Optic Disc of the Myopic Eye: Relationship between Refractive Errors and Morphometric Characteristics. Korean J Ophthalmol 1992;6:32-5. 5) Curtin BJ, Karlin DB. Axial length measurements and fundus changes of the myopic eye. Am J Ophthalmol 1971;1:42-53. 6) Yanoff M, Fine BS. Ocular pathology: A text and atlas, 3rd ed. Philadelphia: JB Lippincott, 1989;408. 7) Tomlinson A, Philips CI. Ratio of optic cup to optic disc in 1638
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김정완외 : 근시에따른망막신경섬유층두께차이 =ABSTRACT= Changes in RNFL Thickness According to the Myopia in Patients with Glaucoma and Ocular Hypertension Jung Wan Kim, M.D., Yong Yeon Kim, M.D., Ph.D. Department of Ophthalmology, Korea University College of Medicine, Seoul, Korea Purpose: To evaluate the changes in retinal nerve fiber layer (RNFL) thickness according to the degree of myopia in patients with glaucoma and ocular hypertension. Methods: Ninety-eight patients (165 eyes) diagnosed with glaucoma or ocular hypertension underwent optical coherence tomography (OCT) and scanning laser polarimetry using variable corneal compensation (GDx-VCC) to analyze the correlation between the degree of myopia and the thickness of the RNFL. A partial correlation coefficient analysis was performed to adjust for various factors such as age, laterality, intraocular pressure, and the mean deviation from visual field test, which can influence the RNFL thickness. Results: The average, nasal, superior, and inferior sectorial RNFL thicknesses measured by OCT significantly decreased with increasing myopia (p<0.05). However, RNFL thickness measured by GDx-VCC was not significantly correlated with the degree of myopia. Conclusions: The RNFL thickness measured by OCT decreased with increasing myopia in eyes with glaucoma and ocular hypertension. J Korean Ophthalmol Soc 2008;49(10):1634-1640 Key Words: GDx-VCC, Myopia, OCT, RNFL thickness Address reprint requests to Yong Yeon Kim, M.D., Ph.D. Department of Ophthalmology, Guro Hospital, Korea University College of Medicine #80 Guro-dong, Guro-gu, Seoul 152-703, Korea Tel: 82-2-2626-1260, Fax: 82-2-857-8580, E-mail: yongykim@mail.korea.ac.kr 1640