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1 대한안과학회지 2017 년제 58 권제 4 호 J Korean Ophthalmol Soc 2017;58(4): ISSN (Print) ISSN (Online) Original Article 시신경유두좌우뒤바뀜이있는눈의망막신경섬유층및황반부신경절세포두께 Retinal Nerve Fiber Layer and Macular Ganglion Cell Thicknesses in Situs Inversus of Optic Discs 김민경 김재민 황영훈 Min Kyung Kim, MD, Jae Min Kim, MD, Young Hoon Hwang, MD 건양대학교의과대학김안과병원안과학교실명곡안연구소 Myung-Gok Eye Research Institute, Department of Ophthalmology, Kim s Eye Hospital, Konyang University College of Medicine, Seoul, Korea Purpose: To investigate circumpapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses as measured by optical coherence tomography in eyes with situs inversus of optic discs. Methods: RNFL and macular GCIPL thicknesses were measured in eyes with situs inversus of optic discs without other ocular abnormalities (situs inversus group) and in age- and refractive error-matched healthy eyes (control group). RNFL thickness (global area, superior, nasal, inferior, and temporal quadrants) and GCIPL thickness (global area, superior-temporal, superior, superior-nasal, inferior-nasal, inferior, and inferior-temporal sectors and minimum) were compared between the groups. Results: Nine eyes of 5 subjects with situs inversus of optic discs and 20 healthy eyes of 20 subjects (10 eyes for control groups A and B, respectively) were enrolled. No significant difference was found in superior or inferior quadrant RNFL thickness (p > 0.05); however, the situs inversus group showed a thicker RNFL in the nasal quadrant and a thinner RNFL in the temporal quadrant (p < 0.01). In macular GCIPL thickness, no significant difference was found in the superotemporal or inferiotemporal sector or for minimum thickness (p < 0.05); however, the situs inversus group showed thicker GCIPL in the global area, superior, superonasal, inferonasal, and inferior sectors than the control groups (p < 0.01). Conclusions: In eyes with situs inversus of optic discs, distribution of circumpapillary RNFL and macular GCIPL thickness were different from eyes without this condition. When assessing RNFL and macular GCIPL thicknesses in eyes with situs inversus of optic discs, caution is needed. J Korean Ophthalmol Soc 2017;58(4): Keywords: Optic nerve head, Retinal ganglion cell, Retinal nerve fiber layer, Situs inversus 시신경유두좌우뒤바뀜은안경 (optic stalk) 이안소포 (optic vesicle) 내에비정상적으로부착되면서생기는드문 Received: Revised: Accepted: Address reprint requests to Young Hoon Hwang, MD Department of Ophthalmology, Kim s Eye Hospital, #136 Yeongsin-ro, Yeongdeungpo-gu, Seoul 07301, Korea Tel: , Fax: brainh@hanmail.net 선천이상으로, 정상과비교했을때코쪽-귀쪽의모양이반전된시신경유두의형태를가지게된다. 1-3 즉, 정상안에서시신경유두주위혈관의주행방향이시신경유두중심으로부터귀쪽으로포물선을그리면서나타나는반면에, 좌우뒤바뀜이있는경우, 혈관이시신경유두중심으로부터코쪽으로주행하다가급격하게귀쪽으로꺾이는특징적인양상을보인다. 1-5 시신경유두주위의망막신경섬유층이망막혈관주행을따라분포하는것을고려해보았을때, 시신경유두좌우뒤바뀜환자에서망막신경섬유층의분포가정상 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. 437

2 - 대한안과학회지 2017 년제 58 권제 4 호 - 인과다를것을유추해볼수있다. 이에대해 Kang et al 4 은빛간섭단층촬영을통해서시신경유두좌우뒤바뀜이있는눈에서정상안에비해서시신경유두주변의코쪽망막신경섬유층이두껍고, 상이측, 이측, 하이측망막신경섬유층두께가얇다고보고한바있고, Han and Hwang 5 은시신경유두좌우뒤바뀜과녹내장이병합된증례를통해녹내장이진행하면서시신경유두주변의상비측과하비측망막신경섬유층손상이생기는양상을보고한바있다. 녹내장은시신경유두주변의망막신경섬유층두께의감소및그에대응하는시야결손이특징적인질병으로최근영상장비의발달로황반부의망막신경절세포두께의감소또한녹내장의평가에중요한역할을하는것으로알려져있다. 6-8 하지만시신경유두좌우뒤바뀜이있는눈에서의황반부망막신경절세포의두께에대한보고는아직없는상황이다. 따라서본연구에서는빛간섭단층촬영을이용하여시신경유두좌우뒤바뀜이있는눈의시신경유두주위망막신경섬유층및황반부신경절세포-내망상층의두께에대해서알아보고자한다. 안압이정상범위이면서 (<21 mmhg), (3) 녹내장성시신경변화 ( 시신경유두함몰비증가, 시신경유두출혈, 국소적이거나전반적인시신경테의얇음혹은패임, 등 ) 를보이지않고, (4) 시야검사에서이상이없는환자를대상으로하였다. 시야나시신경에영향을줄수있는녹내장을비롯한다른망막질환이있는경우는분석에서제외하였다. 빛간섭단층촬영의 Optic Disc Cube 스캔및 Macular Cube 스캔을이용해시신경유두주위망막신경섬유층및황반부의신경절세포-내망상층의두께를측정하였다. Optic Disc Cube 스캔은시신경유두중심을기준으로하여 6 6 mm 2 영역의망막신경섬유층두께및 3.46 mm의직경을가지는원부위에해당되는망막신경섬유층두께를제공하는데, 이를통해얻은평균및각사분면, 12시간영역의망막신경섬유층두께를분석에이용하였다. Macular Cube 스캔은황반부 A 대상과방법 본연구는본원임상시험심사위원회의승인을받은것으로 2014년 1월부터 2016년 1월까지본원외래를방문한환자들중, 시신경유두좌우뒤바뀜이있는눈 ( 뒤바뀜군 ) 과정상안 ( 대조군 ) 을대상으로빛간섭단층촬영을이용하여시신경유두주위망막신경섬유층및황반부신경절세포-내망상층의두께를측정하였다. 시신경유두좌우뒤바뀜은시신경유두의중심에서시작된위, 아래망막혈관이시신경의코쪽으로나와귀쪽으로급격히꺾여주행하는것으로정의하였다 (Fig. 1). 대조군은건강검진목적으로본원에내원한환자중뒤바뀜군과나이차이가 5세이내, 성별분포가같고, 구면렌즈대응치 (spherical equivalent) 의차이가 2 디옵터이내이면서, 시신경유두좌우뒤바뀜및다른이상이없는정상안으로선정하였다. 모든대상자에서병력조사, 시력측정, 굴절검사, 골드만압평안압계를이용한안압측정, 세극등현미경을이용한전안부검사, 90디옵터렌즈를이용한시신경유두및안저검사, 험프리시야검사계 (model 750; Carl Zeiss Meditec, Dublin, CA, USA) 의 24-2 Swedish Interactive Threshold Algorithm을이용한시야검사, 빛간섭단층촬영 (Cirrus highdefinition optical coherence tomography; Carl Zeiss Meditec, Dublin, CA, USA) 을이용한망막신경섬유층및황반부신경절세포-내망상층두께측정을시행하였다. 이상의검사에서 (1) 최대교정시력이 20/30 이상이고, (2) B C Figure 1. An example of optic disc in a healthy eye (left column) and an eye with situs inversus of optic disc (right column). Disc photograph (A), red-fee fundus photograph (B), and circumpapillary retinal nerve fiber layer thickness distribution as measured by Cirrus high definition optical coherence tomography(c). 438

3 - 김민경외 : 시신경유두좌우뒤바뀜 mm 2 에해당하는부위를 512 A-scan을구성하는 128 개의 horizontal B-scan으로측정하는방식이며, 이를통해얻어진데이터를 ganglion cell analysis (GCA) 알고리즘을통해분석하였다. GCA 알고리즘은내망상층의바깥쪽경계선과망막신경섬유층의바깥쪽경계선을인식하고이를통해신경절세포층과내망상층의두께를분석하는방식으로, 이를통해얻은황반부 mm 2 영역의평균, 최소값및 6개구역 ( 상측, 상이측, 하이측, 하측, 하비측, 상비측 ) 의두께를분석에활용하였다 (Fig. 2). 검사결과에서신호강도가 6 미만이거나중심이이탈되어있는경우, 그외에다른오류가있는경우는분석에서제외하였다. 뒤바뀜군과대조군의나이, 성별분포, 굴절값, 시야검사결과지표및빛간섭단층촬영을통해측정한시신경유두주위망막신경섬유층두께및황반부신경절세포- 내망상층의두께를비교하였다. 변수들의분포는정규분포를보이지않 A B Figure 2. An example of macular ganglion cell-inner plexiform layer thickness distribution. Presented by thickness map (A) and sector map (B) of Cirrus high definition optical coherence tomography in a healthy eye (left column) and an eye with situs inversus of optic disc (right column) presented in Figure 1. 았기때문에중위값 (median) 및사분위수범위 (interquartile range) 를이용하여기술하고, 두군사이의변수비교는 chi squared test 및 Mann-Whitney U-test를이용하였다. 통계분석은 SPSS Windows version 12.0 (SPSS Inc., Chicago, IL, USA) 를이용하였으며, p값이 0.05 미만인경우를통계적으로유의한것으로판정하였다. 결과 총 5명 9안 ( 여성 4안, 남성 5안 ) 이시신경유두좌우뒤바뀜군에포함되었고, 20명의 20안이대조군 ( 대조군 A 10안, 대조군 B 10안 ) 에포함되었다. 뒤바뀜군 5명중 1명의 1안은황반부에망막전막이동반되어있어서분석에서제외하였다. 대상안모두안과수술을받은과거력이없었다. 뒤바뀜군의나이는 48.0세 (40.0, 49.0세 ) ( 범위, 세 ) 였고, 굴절값은 -1.00디옵터 (-2.00, -0.50디옵터 ) ( 범위, -2.00~+0.50 디옵터 ) 였다. 뒤바뀜군과대조군 A, B 사이에나이, 성별, 굴절값, 시야검사결과에유의한차이를보이지않았다 (p>0.05, Table 1). 시신경유두주위망막신경섬유층두께의경우, 평균및위아래사분면의두께는유의한차이를보이지않았지만 (p>0.05) 뒤바뀜군이대조군에비해서코쪽사분면의망막신경섬유층이더두껍고, 귀쪽사분면이더얇은양상을보였다 (p<0.05, Table 2). 12시간영역의망막신경섬유층두께의경우, 1시방향에서 6시방향까지는뒤바뀜군에서대조군에비해두껍게측정되었고, 7시방향에서 11시방향의망막신경섬유층은대조군에비해얇게측정되었다 (p<0.05, Table 1). 신경절세포-내망상층의경우, 상이측, 하이측, 최소값은유의한차이를보이지않았지만 (p>0.05) 전체평균, 상측, 상비측, 하비측, 하측영역에서뒤바뀜군이대조군보다두꺼운양상을보였다 (p<0.05, Table 3). Table 1. Comparison of clinical data between control and situs inversus groups Control group A Control group B Situs inversus group (n = 9) p-value * p-value Age (years) 43.0 (39.0, 46.3) 44.5 (29.0, 52.0) 48.0 (33.0, 49.0) Sex (female:male) 5:5 5:5 4: Refractive error (diopter) (-1.00, -0.38) (-1.57, -0.69) (-2.00, -0.25) Visual field indices Mean deviation (db) (-1.89, 0.30) (-1.68, -0.08) (-1.28, 0.72) Pattern standard deviation (db) 1.55 (1.48, 1.94) 1.44 (1.14, 1.89) 1.67 (1.30, 2.21) Visual field index (%) 99.0 (99.0, 99.25) 99.5 (99.0, 100.0) (98.5, 100.0) Data are presented as median and interquartile range or number of eyes. * Mann-Whitney U-test: comparison between the control group A and situs inversus group; Mann-Whitney U-test: comparison between the control group B and situs inversus group. 439

4 - 대한안과학회지 2017 년제 58 권제 4 호 - Table 2. Comparison of circumpapillary retinal nerve fiber layer thickness (μm) between control and situs inversus groups Control group A Control group B Situs inversus group (n = 9) p-value * p-value Average 95.5 (87.5, 99.5) (95.8, 108.3) (94.5, 105.5) Superior quadrant (114.5, 143.3) (119.8, 134.5) (111.0, 143.0) Nasal quadrant 60.0 (51.5, 70.3) 64.5 (62.5, 76.3) 82.0 (71.5, 105.0) Inferior quadrant (110.0, 132.5) (125.5, 142.5) (123.0, 146.0) Temporal quadrant 70.5 (61.0, 77.0) 79.0 (73.0, 84.5) 56.0 (52.0, 60.5) <0.001 Clock-hour sectors (120.0, 155.0) (102.8, 137.8) (118.5, 156.5) (104.8, 122.0) (94.8, 114.0) (101.5, 188.0) (58.3, 82.3) 75.0 (68.5, 88.0) 99.0 (81.0, 132.5) (43.5, 61.0) 59.5 (55.0, 68.0) 76.0 (57.5, 88.0) (52.0, 66.8) 62.5 (57.3, 73.3) 92.0 (70.5, 103.0) (85.8, 109.5) 88.5 (84.8, 106.5) (115.0, 173.0) (108.0, 163.8) (123.8, 161.5) (156.5, 167.0) (130.8, 156.5) (149.5, 173.5) 90.0 (80.0, 101.5) <0.001 < (62.8, 80.8) 79.5 (72.0, 92.3) 54.0 (41.5, 58.0) < (51.0, 62.3) 57.5 (51.3, 70.0) 52.0 (47.0, 58.0) (68.8, 89.0) 93.0 (89.5, 103.5) 66.0 (60.5, 71.0) < (114.8, 133.0) (139.0, 168.0) 89.0 (77.5, 112.5) <0.001 Data are presented as median and interquartile range. * Mann-Whitney U-test: comparison between the control group A and situs inversus group; Mann-Whitney U-test: comparison between the control group B and situs inversus group. Table 3. Comparison of macular ganglion cell-inner plexiform layer thickness (μm) between control and situs inversus groups Control group A Control group B Situs inversus group (n = 9) p-value * p-value Average 82.0 (81.0, 87.0) 84.5 (81.8, 86.0) 90.0 (83.5, 91.5) Minimum 81.5 (79.8, 83.8) 82.0 (80.0, 85.0) 84.0 (80.5, 87.0) Superotemporal 82.5 (79.8, 85.3) 84.0 (79.8, 86.0) 83.0 (81.5, 88.0) Superior 82.5 (81.5, 85.8) 84.0 (82.3, 85.3) 89.0 (86.0, 93.0) Superonasal 85.0 (83.8, 88.5) 87.0 (84.75, 88.0) 94.0 (88.5, 95.5) Inferonasal 83.5 (81.8, 87.3) 85.5 (82.3, 86.0) 93.0 (85.0, 96.5) Inferior 80.0 (78.8, 85.3) 82.0 (79.5, 85.3) 89.0 (81.0, 91.5) Inferotemporal 81.5 (79.0, 86.5) 83.5 (81.5, 86.3) 86.0 (80.0, 88.5) Data are presented as median and interquartile range. * Mann-Whitney U-test: comparison between the control group A and situs inversus group; Mann-Whitney U-test: comparison between the control group B and situs inversus group. 고찰 본연구결과에의하면시신경유두주위망막신경섬유층두께의경우, 뒤바뀜군이대조군에비해서코쪽사분면의망막신경섬유층이더두껍고, 귀쪽사분면이더얇은양상을보였다. Kang et al 4 은시신경유두좌우뒤바뀜이있는 12안의망막신경섬유층분포를대조군과비교하여발표한바있는데, 본연구의결과와마찬가지로시신경유두좌우뒤바뀜이있는군에서코쪽망막신경섬유층이더두껍고, 귀쪽망막신경층이더얇은경향을보였으며, 위, 아래망막신경섬유층의가장두꺼운지점또한더코쪽으로이동한양상을보고한바있다. 이는혈관주행과마찬가지로, 시신경유두좌우뒤바뀜군에서망막신경섬유의주행또한 시신경유두의코쪽으로시작하여귀쪽으로주행이급격히바뀌기때문에시신경유두주변망막신경섬유층이코쪽에서상대적으로더밀집되어있고, 귀쪽이덜밀집되어서나타나는현상으로보인다. 황반부신경절세포-내망상층의경우, 상이측, 하이측, 최소값은유의한차이를보이지않았지만, 상측, 상비측, 하비측, 하측영역에서는뒤바뀜군이대조군보다두꺼운양상을보였다. 이는시신경유두좌우뒤바뀜이있는눈에서시신경유두주변의망막신경섬유층뿐만아니라황반부의신경절세포-내망상층의분포도정상안과다르다는점을시사한다. 즉망막신경섬유층에서와마찬가지로황반부의신경절세포-내망상층도정상안에비해서코쪽으로더밀집하게분포하고있을것으로예측할수있다. 반면, 상이측과하 440

5 - 김민경외 : 시신경유두좌우뒤바뀜 - 이측및최소신경절세포-내망상층두께는정상안과유의하게다르지않았다. 녹내장에서관찰되는황반부신경절세포-내망상층의변화가상이측과하이측에서먼저나타나는경우가많고, 최소신경절세포두께가높은녹내장진단력을가진다는점을고려한다면 6-8 시신경유두좌우뒤바뀜이있는눈에서초기녹내장진단시에는시신경유두주변의망막신경섬유층보다황반부신경절세포-내망상층두께분석이더유리할수있을것으로생각한다. 하지만상이측과하이측에서시작된신경절세포-내망상층의변화가상하측, 상비측, 하비측으로진행하는지를판단할때는시신경유두좌우뒤바뀜이있는눈의상대적으로두꺼운신경절세포-내망상층이진행의저평가를유발할수있기때문에주의가필요할것으로생각한다. 본연구결과에의하면시신경유두좌우뒤바뀜이있는눈에서코쪽황반부신경절두께가정상안보다두꺼웠지만이부위신경절세포의신경섬유에해당하는귀쪽망막신경섬유층두께는정상안보다얇았다. 이는시신경유두좌우뒤바뀜이있는눈에서귀쪽망막신경섬유가정상안보다더위아래로퍼져서분포하기때문일것으로유추해볼수있다. 이에대해서는더많은눈을대상으로하는추가연구가필요할것으로생각된다. 본연구는적은수의눈을대상으로했으며, 망막신경섬유층및황반부신경절세포의두께측정에영향을줄수있는안축장, 시신경유두크기, 망막기울기 9 등에대해서추가로분석하지못한한계점을가지고있다. 따라서결과해석시이러한한계점을고려해야할것이다. 요약하면, 시신경유두좌우뒤바뀜이있는눈에서는시신경유두주위망막신경섬유층과황반부신경절세포-내망상층의분포가정상안과달랐다. 특히코쪽망막신경섬유층이더두껍고, 귀쪽이더얇은분포를보였고, 황반부신경 절세포-내망상층의경우, 상이측과하이측, 최소값을제외한나머지부분이더두꺼운분포를보였다. 따라서시신경유두좌우뒤바뀜이있는눈의망막신경섬유층과황반부신경절세포-내망상층분석시에이러한분포차이를고려해야할것이다. REFERENCES 1) Brodsky MC. Congenital optic disk anomalies. Surv Ophthalmol 1994;39: ) Witmer MT, Margo CE, Drucker M. Tilted optic disks. Surv Ophthalmol 2010;55: ) Kothari M, Chatterjee DN. Unilateral situs inversus of optic disc associated with reduced binocularity and stereoacuity resembling monofixation syndrome. Indian J Ophthalmol 2010;58: ) Kang S, Jin S, Roh KH, Hwang YH. Peripapillary retinal nerve fiber layer and optic nerve head characteristics in eyes with situs inversus of the optic disc. J Glaucoma 2015;24: ) Han SY, Hwang YH. Glaucoma in an eye with situs inversus of the optic disc. Semin Ophthalmol 2014;29: ) Mwanza JC, Durbin MK, Budenz DL, et al. Glaucoma diagnostic accuracy of ganglion cell-inner plexiform layer thickness: comparison with nerve fiber layer and optic nerve head. Ophthalmology 2012;119: ) Jeoung JW, Choi YJ, Park KH, Kim DM. Macular ganglion cell imaging study: glaucoma diagnostic accuracy of spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci 2013; 54: ) Hwang YH, Jeong YC, Kim HK, Sohn YH. Macular ganglion cell analysis for early detection of glaucoma. Ophthalmology 2014; 121: ) Yamashita T, Sakamoto T, Yoshihara N, et al. Correlations between retinal nerve fiber layer thickness and axial length, peripapillary retinal tilt, optic disc size, and retinal artery position in healthy eyes. J Glaucoma 2017;26:

6 - 대한안과학회지 2017 년제 58 권제 4 호 - = 국문초록 = 시신경유두좌우뒤바뀜이있는눈의망막신경섬유층및황반부신경절세포두께 목적 : 시신경유두좌우뒤바뀜 (situs inversus) 이있는눈의시신경유두주위망막신경섬유층및황반부신경절세포 - 내망상층의두께에대해서알아보고자한다. 대상과방법 : 시신경유두좌우뒤바뀜이있으면서다른이상이없는눈 ( 뒤바뀜군 ) 과나이와굴절값이같은정상안 ( 대조군 ) 을대상으로빛간섭단층촬영을이용하여시신경유두주위망막신경섬유층및황반부신경절세포 - 내망상층의두께를측정하였다. 뒤바뀜군과대조군사이에망막신경섬유층 ( 전체평균및상측, 비측, 하측, 이측사분면 ) 및신경절세포 - 내망상층두께 ( 전체평균및상이측, 상측, 상비측, 하비측, 하측, 하이측, 최소값 ) 의차이를비교하였다. 결과 : 총 5 명의 9 안이뒤바뀜군에포함되었고, 20 명의 20 안이대조군 ( 대조군 A, B 각각 10 안 ) 에포함되었다. 망막신경섬유층두께의경우, 전체평균및위아래사분면의두께는유의한차이를보이지않았지만 (p>0.05) 뒤바뀜군이대조군에비해서코쪽사분면의망막신경섬유층이더두껍고, 귀쪽사분면이더얇은양상을보였다 (p<0.01). 신경절세포 - 내망상층의경우, 상이측, 하이측, 최소값은유의한차이를보이지않았지만 (p>0.05) 전체평균, 상측, 상비측, 하비측, 하측영역에서뒤바뀜군이대조군보다두꺼운양상을보였다 (p<0.01). 결론 : 시신경유두좌우뒤바뀜이있는눈의경우, 대조군과다른시신경유두주위망막신경섬유및황반부신경절세포 - 내망상층의분포를보였다. 따라서시신경유두좌우뒤바뀜이있는눈에서빛간섭단층촬영으로측정한망막신경섬유층및황반신경절세포 - 내망상층두께분석시주의가필요하다. < 대한안과학회지 2017;58(4): > 442

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