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1 대한안과학회지 2009 년제 50 권제 11 호 J Korean Ophthalmol Soc 2009;50(11): DOI : /jkos = 증례보고 = 접수번호 : 망막신경섬유층사진과주파수배가시야검사계의녹내장조기진단능력의비교 이준성 1 허환 1 박상우 1 양건진 2 전남대학교의과대학안과학교실 1, 베스트안과의원 2 목적 : 망막신경섬유층사진과비교하여주파수배가시야검사계의녹내장조기진단의유용성을알아보고자하였다. 대상과방법 : 전체 98 명의환자에서 98 안을대상으로 3 개월이내에주파수배가시야검사계, 망막신경섬유층사진촬영및빛간섭단층촬영을시행하였다. 망막신경섬유층사진과주파수배가시야검사계의결과를기준으로환자를 4 개의군으로분류하였으며, 각군에서빛간섭단층촬영기를이용하여측정한망막신경섬유층의두께를비교하였다. 결과 : 망막신경섬유층사진은정상소견을보이나주파수배가시야검사계에서이상소견을보인환자군에서빛간섭단층촬영기를이용하여측정한망막신경섬유층의두께치는두가지검사모두에서정상소견을보인환자군에비해 6 시, 7 시, 10 시에서통계적으로유의하게낮은것으로나타났다 (p<0.050). 결론 : 망막신경섬유층사진은정상이나주파수배가시야검사계에서이상소견을보인환자군에서빛간섭단층촬영기로측정한망막신경섬유층의두께는제한된영역에한하여유의한감소를보였다. 이는녹내장의조기진단에있어망막신경섬유층사진에비하여주파수배가시야검사계가더민감할수있음을제시하는소견일수있다. < 대한안과학회지 2009:50(11): > 녹내장은비가역적진행성질환으로시신경유두및망막신경섬유층 (retinal nerve fiber layer, RNFL) 에특징적인손상을일으킨다. 1 일반적인녹내장의진단은세극등현미경을이용한시신경유두및망막신경섬유층의검사, 안압측정 및전방각검사, 시야검사등으로이루어진다. 일반적으로녹내장에의한망막신경섬유층의손상은시신경유두의변화나시야결손에선행하는것으로알려져있다. 2,3 하지만최근 RNFL의 구조적손상이시야결손에반드시선행하지않을수있다는 보고또한있었다. 4 망막신경섬유층의구조적손상은일반적인안저검사로는진단하기가어려워망막신경섬유층사진 (RNFL photography) 이도입되었는데이는적색차단필터 (red-free filter) 를이용하여상대적으로붉은망막색소상피층과맥락막의색을줄이고하얀색의망막신경섬유층이잘모이도록대조도를높여주는원리를이용한것으로망막신경섬유층손상의조기진단및영구적이고객관적인평가를가능하게하였다. 5 Sommer et al 2 은시야검사에서이상이나타나 접수일 : 2008 년 11 월 3 일 심사통과일 : 2009 년 4 월 7 일 통신저자 : 박상우광주시동구학동 8 번지전남대학교병원안과 Tel: , Fax: exo70@jnu.ac.kr * 본논문의요지는 2008 년대한안과학회제 100 회추계학술대회에서구연으로발표되었음. 기약 6년전에 60% 의환자에서망막신경섬유층사진에서비정상소견이발견되었다고보고하였다. 기능적검사방법으로주파수배가시야검사계 (Frequency doubling technology perimeter FDT) 는망막의 M-y신경세포절 (Y subset of Magnocellular ganglion cell; M-y) 의기능을빈도배가환영 (Frequency doubling illusion) 을이용하여선택적으로분석하는것으로, M-y 신경세포절을이용하는이유는전체망막신경절세포의 3~5% 를차지하여중복이적은 M-y세포가손상을입을경우초기에녹내장을진단할수있으며, 조직학적으로큰축삭을가진 M-y세포가녹내장성손상을받기쉽고, 또한 M-y 세포는가쪽무릎핵 (lateral geniculate body) 의 M-y층으로투사하는데녹내장환자에서가쪽무릎핵의 M-y 층의세포밀도가감소되어있다는연구결과에기인한다. 6 실제로 FDT가표준자동시야측정계 (Standard automated perimetry; SAP) 보다먼저녹내장성시야손상을인지할수있다는보고들이있다. 7,8 이에저자들은시야검사에서나타나는시야결손에선행하여비정상소견을인지할수있다고알려진위두가지검사에대하여녹내장조기진단에있어유용성을비교해보고자하였다. 대상과방법 2007 년 8 월부터 2008 년 7 월까지녹내장클리닉에내원

2 - 이준성외 : FDT 와망막신경섬유층사진의비교 - 한환자에대하여우안을선택하여세극등현미경검사, 골드만압평안압계로안압측정, 전방각경검사, Humphrey시야검사 (Zeiss Humphrey, San Leandro, CA, USA), 산동후안저검사, 시신경유두사진및 RNFL photography, 각막두께측정 (ultrasonic pachymeter, UP1000, Nidek, Japan) 경면현미경검사 (specular microscope, Noncon ROBO CA, Konan, Japan), FDT, 빛간섭단층촬영 (Optical coherence tomography; OCT) 등을시행하였으며검사에영향을줄수있는기타안과적 ( 매체혼탁포함 ), 전신적인질환이있거나, 단순백내장제거술및인공수정체삽입술을제외한안과적수술력및시술기왕력, 현성굴절검사에의한구면렌즈대응치 (Spherical equivalent) ±5D 이상, 최대교정시력 (BCVA) 0.5 이하인자는대상에서제외하였다. RNFL photography, FDT, OCT는 3개월이내에이세가지검사를모두시행한환자를대상으로하였다. RNFL photography는디지털카메라 (Nikon D200, JAPAN) 가장착된안저카메라 (TOPCON TRC NW6, JAPAN) 및안저카메라에내장된 red-free 필터를이용하여촬영하였으며촬영된사진은환자의정보를모르는두명의녹내장전문의가 17인치액정모니터를통하여평가하였다. 평가시스템은 Quigley 의망막신경섬유층평가방법 (grading system) 을이용하였으며두검사자모두에서의판정이 grade D1 이상일때를비정상으로분류하였다. 9 FDT (Zeiss-Humphrey Systems, New york, USA) 는방안의조명이꺼진상태에서시력교정을한후 threshold C-20 알고리즘을사용하여평가하였으며 pattern deviation plot에서 3점 (p<5%) 이상모여있고, 그중한점이 p<1% 일경우비정상으로간주하였다. 최소 2회이상의검사를시행하여공통된부위에시야결손이있는자를대상에포함하였고위음성 (false negative) 및위양성 (false positive) 30% 이상, 주시상실 (fixation loss) 20% 이상인 경우대상에서제외하였다. 이상의기준을만족하는환자를대상으로 RNFL photography와 FDT의결과에따라각각정상- 정상, 정상-비정상, 비정상-정상, 비정상-비정상으로분류하였으며각군에서의망막신경섬유층의두께를 OCT를이용하여분석하였다. OCT (software 3.0: Carl zeiss meditec. Dublin, CA USA) 는 fast RNFL scan을이용하여측정하였고각군에서전체평균두께, 상측, 비측, 하측, 외측사분역, 12개시분역에서의망막신경섬유층의두께 (RNFL thickness) 를비교하였다. 2회이상측정을하였고동심원이시신경유두의중심에위치하고 6 이상의신호강도를보이는경우만대상에포함하였으며비정상- 비정상인군에서시야결손부위와망막신경섬유층사진의결손부위의대응위치가일치하지않는경우는제외하였다. 각그룹간에서 RNFL thickness를비교하는과정에서연령이유의한영향을미치는것으로나타나연령을보정한후공분산분석 (ANOVA) 을이용하였고, 각그룹간의차이는사후검정 (Scheffe, Duncan, Dunnett) 을이용하였다. 또한그룹 1과그룹 2에서 95% 신뢰구간미만인환자의비율을카이제곱검정 (chi-square test) 을통하여비교하였다. 모든통계분석은 SPSS 14.0 통계프로그램을이용하였고유의수준은 p<0.050으로정의하였다. 결과 이상의기준을만족한 98명 98안을대상으로 RNFL photograph와 FDT의결과에따라분류한결과각각정상-정상 (33안), 정상- 비정상 (23안 ), 비정상- 정상 (6안), 비정상 -비정상(36안) 이었다. 비정상-정상군은통계적으로유의한결과를나타내기에는수가부족하여조사에서제외하였으며정상-정상군을그룹 1, 정상-비정상군을그룹 2, 비 Table 1. Patient demographics and clinical characteristics of each group Group 1 Group 2 Group 3 p Number Gender (Male/Female) 21/12 14/9 14/ Age 57.6± ± ± Spherical equivalent (D) -0.76± ± ± BCVA П (LogMar) 0.07± ± ± Intraocular pressure (mmhg) 12.67± ± ± Central corneal thickness (μm) ± ± ± SAP # MD * (db) -1.03± ± ± SAP # PSD (db) 1.76± ± ± FDT ** MD * (db) -2.43± ± ± FDT ** PSD (db) 1.94± ± ± * MD=mean deviation; PSD=pattern standard deviation; Chi-square test; Analysis of variance (ANOVA); П BCVA=best corrected visual acuity; # SAP=standard automated perimetry; ** FDT=frequency doubling technology

3 - 대한안과학회지 2009 년제 50 권제 7 호 - 정상-비정상군을그룹 3으로명명하였다. 각그룹에서연령은각각 57.6±10.4, 60.1±9.2, 66.1±8.3으로유의한차이가있었으며 (p=0.010) 기타성별, 구면렌즈대응치, 교정시력등은통계적으로유의한차이를보이지않았다. 각그룹간의 FDT의 mean deviation은각각 -2.43±1.75dB, -3.42±1.27dB, -7.04±4.06dB (p=0.010), pattern standard deviation 은각각 1.94±1.27dB, 3.74±0.99dB, 6.65± 2.98dB (p=0.010) 으로그룹 3에서그룹 1,2에비하여더좋지않은결과를보였다 (Table 1). 세그룹간의 RNFL thickness의비교에서외측사분역및 4시분역을제외하고모든영역에서통계적으로유의한차이가있음을보였다. 사후검정비교에서전체평균, 상사분역, 하사분역, 비측사분역, 1시분역, 3시분역에서는그룹 3이그룹 1과 2보다유의하게평균두께치가낮은것으로나타났고, 6시분역, 7시분역, 10시분역에서그룹 1과그룹 2, 3간에각각유의한차이가있음이나타났다. 5시분역, 8 시분역, 9시분역, 11시분역에서는그룹 1과그룹 3 사이에서만차이가있었다 (Table 2). 그룹 1과그룹 2간의카이제곱검정 (chi-square test) 를이용한 95% 신뢰구간미만인환자비율의비교에서는하사분역과 6시분역 (p<0.050) 을제외한모든영역에서통계적으로유의한차이를나타내지않았다 (Table 3). 고찰 녹내장은초기에자각증상이없으므로조기진단이무엇 Table 2. Mean retinal nerve fiber layer thickness measured by optical coherence tomography Group 1 Group 2 Group 3 p Post Hoc Average (μm) 93.5± ± ±22.7 < , 2 vs 3 Nasal quadrant (μm) 74.9± ± ±16.0 < , 2 vs 3 Inferior quadrant (μm) 125.0± ± ±38.2 < , 2 vs 3 Temporal quadrant (μm) 65.8± ± ± Superior quadrant (μm) 116.3± ± ±27.7 < , 2 vs 3 1-o clock (μm) 101.8± ± ± , 2 vs 3 2-o clock (μm) 74.0± ± ± vs 3 3-o clock (μm) 64.2± ± ± , 2 vs 3 4-o clock (μm) 60.6± ± ± o clock (μm) 107.9± ± ± vs 3 6-o clock (μm) 129.3± ± ± vs 2, 3 7-o clock (μm) 125.2± ± ±41.4 < vs 2, 3 8-o clock (μm) 80.5± ± ± vs 3 9-o clock (μm) 63.5± ± ± vs 3 10-o clock (μm) 94.5± ± ±25.9 < vs 2, 3 11-o clock (μm) 124.5± ± ±32.8 < vs 3 12-o clock (μm) 122.0± ± ±30.7 < , 2 vs 3 Table 3. Proportion of eyes with RNFL thickness confidence interval <5% in group 1 and group 2 Group 1 Group 2 p Average 3 (9%) 5 (22%) Nasal quadrant 5 (15%) 7 (30%) Inferior quadrant 3 (9%) 7 (30%) Temporal quadrant 3 (9%) 4 (17%) Superior quadrant 5 (15%) 8 (35%) o clock 4 (12%) 7 (30%) o clock 4 (12%) 5 (22%) o clock 3 (9%) 5 (22%) o clock 4 (12%) 6 (26%) o clock 3 (9%) 5 (22%) o clock 3 (9%) 7 (30%) o clock 4 (12%) 7 (30%) o clock 4 (12%) 7 (30%) o clock 5 (15%) 8 (35%) o clock 5 (15%) 7 (30%) o clock 2 (6%) 4 (17%) o clock 4 (12%) 6 (26%)

4 - 이준성외 : FDT 와망막신경섬유층사진의비교 - 보다중요하며이를위한검사들로는크게시신경유두및망막신경섬유층의형태를관찰하는것과이들의기능을평가하는것이있다. 형태를관찰하는방법중의하나로써 RNFL photography 는일반적인검안경검사에비해상대적으로검사자간의다양성을줄일수있고, 영구적이며여러가지평가방법 (grading system) 에의해반정량화가가능하다. 10 Park et al 11 은 RNFL photography가녹내장의조기진단율을 50% 향상시켰다고보고하였다. FDT는축삭돌기의크기가크고수는적은 M-y세포를선택적으로검사하여녹내장의조기진단에도움을준다. FDT가표준자동시야측정계 (Standard automated perimetry SAP) 보다조기에시야결손을발견할수있다는보고는이미많이발표되었는데, Medeiros et al 7 은 SAP에서정상소견을보였던환자에서 FDT를이용하여추후 SAP 에서의시야결손을예측할수있다고하였으며, Kim et al 12 은 SAP은정상이나 FDT는비정상인환자에서두가지검사모두에서정상인환자보다제한된영역에서 RNFL thickness가더낮다고하였다. 이두가지검사의조기진단의도구로서의효용성을비교하기위하여저자들은앞서설명한바와같이 RNFL photography와 FDT의결과에따라환자군을분류하였고전영역, 각사분역, 각시분역의 RNFL thickness를비교하였다. 그룹 3과그룹 2와의비교에서전체평균두께및비측사분역, 하사분역, 상사분역, 1, 3, 12시분역에서그룹 3은그룹 2에비해낮은 RNFL thickness를보였으며, 이는두가지검사에서모두비정상인그룹과 RNFL photography는정상이나 FDT만비정상인그룹사이에진단적으로의미있는차이가있음을나타낸다. 한편그룹 1과그룹 2의비교에서는대부분의영역에서그룹 2는그룹 1에비해더낮은 RNFL thickness치를가졌으나, 6, 7, 10시분역을제외하고는통계적으로유의한차이를보이지는않았으며, 두그룹간의 95% 이하의신뢰구간을갖는환자의비율의비교에서는하사분역및 6시분역에서만의미있는차이를보였다. 하지만녹내장초기에손상을받는것으로알려진시신경유두의아래쪽영역에서유의한차이가있다는것은두가지검사모두에서정상인군에비해 RNFL phtography는정상이나 FDT는비정상인군에서 OCT로측정가능한망막신경섬유층의구조적변화가해당영역에존재했음을의미하고이는 FDT의조기진단도구로서의유용성을뒷받침해준다고볼수있으며, 대상환자의수가늘어나면유의한차이를갖는영역은늘어날것으로생각된다. Quigley et al 9 은망막신경섬유층의밝기, 질감 (texture), 혈관이보이는정도를척도로망막신경섬유층의결손을평가하는반정량적이며재현성이높다고밝혀진 grading system 을제안하였는데, 이는망막신경섬유층의결손을정량화할수있다는장점이있으나여전히검사자의주관적인측면을완전히배제할수없으며국소망막신경섬유층의결손또한 grading system에포함되기는하나주로미만성의결손의평가에더적합한 system임을고려할때국소적손상보다발견하기어렵다고알려진미만성손상이일부누락될가능성도있어녹내장의집단검사등에는부적절하다는보고도있었다. 5,13,15 본연구에서 RNFL photography는비정상이나 FDT에서는정상을보인환자군이 6안으로그수가다른군에비해적은것은 RNFL photography 평가에있어위에서언급한 Quigley grading system을이용한이유도있겠으나, 이를감안하더라도그룹 2(RNFL photography: 정상, FDT: 비정상 ) 에비교할때현저한환자의수적차이는 FDT가조기진단에조금더유용하다는단서일수있겠다. 본연구의제한점으로는앞서언급한적은대상환자의수, 서로상관지표가없는형태적인검사방법인 RNFL photography와기능적인평가방법인 FDT의직접적인비교분석이부족하다는점, 두검사의비교하는데있어 OCT 를사용하였으나, OCT 또한형태적인검사방법이라는점, RNFL photography를평가하는데한가지 grading system 만을사용한점, FDT는정상이나 RNFL photography는비정상인환자군이적은수로인해비교에서제외된점등을들수있겠으며앞으로이에대한연구및보완이필요하다. 결론적으로녹내장의진단은형태학적인이상소견과기능적인이상소견을모두고려하여도출하여야하지만각각의검사마다민감도의차이가있을수있다. 녹내장의조기진단에있어 RNFL phtography와 FDT를살펴본본연구에서 RNFL phtography는정상이나 FDT는비정상인환자군은 OCT를이용하여측정한 RNFL thcikness에서두검사모두에서정상인환자군에비해제한된영역에서유의한차이를보였으며이는 FDT의녹내장에대한조기진단도구로서의유용성을뒷받침한다. 또한망막신경섬유층사진은정상이나 FDT는비정상인군의환자수에비해망막신경섬유층사진은비정상이나 FDT는정상인환자군의숫자가현저히적은것은직접적인비교가힘든두검사에있어 FDT가 RNFL photography에비해조기진단에더민감할수있다는단서일수있으며이에대해추가적인연구가요구된다. 참고문헌 1) Sommer A, Miller NR, Pollack I, et al. The nerve fiber layer in the

5 - 대한안과학회지 2009 년제 50 권제 7 호 - diagnosis of glaucoma. Arch Ophthalmol 1977;95: ) Sommer A, Katz J, Quigley HA, et al. Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol 1991;109: ) Tuulonen A, Lehtola J, Airaksinen PJ. Nerve fiber layer defects with normal visual fields. Do normal optic disc and normal visual field indicate absence of glaucomatous abnormality? Ophthalmology 1993;100: ) Hood DC, Kardon RH. A framework for comparing structural and functional measures of glaucomatous damage. Prog Retin Eye Res 2007;26: ) Han ES, Park KH, Kim TW, Kim DM. The detection of retinal nerve fiber layer defect by modification of non-mydriatic digital fundus photograph. J Korean Ophthalmol Soc 2006;47: ) Clement CI, Goldberg I, Graham S, Healey PR. Humphrey matrix frequency doubling perimetry for detection of visual field defects in open-angle glaucoma. Br J Ophthalmol 2009;93: ) Medeiros FA, Sample PA, Weinreb RN. Frequency doubling technology perimetry abnormalities as predictors of glaucomatous visual field loss. Am J Ophthalmol 2004;137: ) Bayer AU, Erb C. Short wavelength automated perimetry, frequency doubling technology perimetry and pattern electroretinography for prediction of progressive glaucomatous standard visual field defect. Ophthalmology 2002;109: ) Quigley HA, Reacher M, Strahlman E, et al. Quantitative grading of nerve fiber layer photographs. Ophthalmology 1993;100: ) Sim JO, Park CK. Optic nerve head analysis obtained by optical coherence tomography for the diagnosis of glaucoma in Koreans. J Korean Ophthalmol Soc 2004;45: ) Park SJ, Park KH, Yu YS, et al. Early detection of glaucoma with retinal nerve fiber layer photograph. J Korean Ophthalmol Soc 1998;39: ) Kim TW, Zangwill LM, Bowd C, et al. Retinal nerve fiber layer damage as assessed by optical coherence tomography in eyes with a visual field defect detected by frequency doubling technology perimetry but not by standard automated perimetry. Ophthalmology 2007;114: ) Weinreb RN, Shakiba S, Sample P, et al. Association between quantitative nerve fiber layer measurement and visual field loss in glaucoma. Am J Ophthalmol 1995;120: ) Weinreb RN, Zangwill L. Retinal nerve fiber layer evaluation in glaucoma. J Glaucoma 2001;10:S

6 - 이준성외 : FDT 와망막신경섬유층사진의비교 - =ABSTRACT= Comparison of Frequency Doubling Technology Perimeter and RNFL Photography for Early Diagnosis of Glaucoma Jun Sung Lee, MD 1, Hwan Heo, MD 1, Sang Woo Park, MD 1, Kun-Jin Yang, MD 2 Department of Ophthalmology, Chonnam National University Medical School and Hospital 1, Gwangju, Korea Best Eye Clinic 2, Gwangju, Korea Purpose: To compare the frequency doubling technology perimeter (FDT) with retinal nerve fiber layer (RNFL) photography as a tool for the early detection of glaucoma. Methods: Ninety-eight eyes of 98 patients were evaluated over a period of 3 months. According to the results of RNFL photography and FDT, Patients were divided into four groups based on the results of RNFL photography and optical coherence tomography (OCT). A comparison of the RNFL thickness of each group was performed using the OCT results. Results: RNFL thickness in the group with abnormal FDT and normal RNFL were significantly decreased from those in the group with normal FDT and RNFL photography at the 6, 7 and, 10 o clock area (p<0.05). Conclusions: There were statistically significant differences in the RNFL thickness between the group with abnormal FDT and normal RNFL photography, and the group with normal FDT and RNFL photography within the limited areas. These results imply that FDT is more useful for the early detection of glaucoma than RNFL photography. J Korean Ophthalmol Soc 2009;50(11): Key Words: FDT, Glaucoma, RNFL photography, Stratus OCT Address reprint requests to Sang Woo Park, MD Department of Ophthalmology, Chonnam National University Medical School and Hospital #8 Hak-dong, Dong-gu, Gwangju , Korea Tel: , Fax: , exo70@jnu.ac.kr

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