대한안신경의학회지 : 제 4 권제 1 호 ISSN: 2234-0971 REVIEW 빛간섭단층촬영 김응수 1,2 김안과병원 1, 건양대학교의과대학안과학교실 2 Optical Coherence Tomography Ungsoo Samuel Kim, MD 1,2 Kim s Eye Hospital, Seoul; 1,2 Department of Ophthalmology, Konyang University College of Medicine, Daejeon, Korea Optical coherence tomography (OCT) has developed in 1991, and has become an important part of ophthalmology examination because it is a non-invasive and non-contact technology. Currently, OCT is used to analyze the anterior and posterior segment of eye and it can be used to investigate the optic nerve head and retinal structures, especially, retinal nerve fiber layer. OCT is also used to investigate central nervous system disorders such as multiple sclerosis, neuromyelitis optica, Alzheimer s disease and Parkinson s disease through the examination of the retinal nerve fiber layer. Thus, OCT has many potential applications in neuro-ophthalmology. Keywords: Optical coherence tomography; Retinal nerve fiber layer; Optic nerve 서론빛간섭단층촬영 (Optical coherence tomography, OCT) 은비침습적인방법으로조직의단면을관찰할수있는방법으로 1991년도에개발되어임상적으로는 2002년 Carl Zeiss에서 Stratus OCT라는모델로처음사용되었다. 이후안과영역뿐아니라심혈관계, 치과, 피부과등에서도사용되고있으며가장널리사용되는안과영역에서는시신경유두, 망막및각막을포함한전안부의구조를파악하고정량적으로분석할수있어매우유용하게사용되고있다. 1 본론 직으로들어가반사되어나오는빛은그반사되는위치에따라시간차가발생하여돌아오게되어거울에서반사되어돌아오는빛과간섭현상을일으키게되고이간섭현상을측정하여분석하여영상을얻게된다 (Fig. 1). 초기의시간영역빛간섭단층촬영 (Time-domain optical coherence tomography, TD-OCT) 은기준거울이앞뒤로움직여두곳에서돌아오는빛의시간차를분석하므로분석에시간이소요되나 2006년푸리에 (Fourier) 분석을이용하여영상을해석하는스펙트럼영역빛간섭단층촬영 (Spectral domain OCT, SD-OCT, Fourier domain OCT) 이개발되어검사소요시간을줄이고해상도를향상시켜 3-5 µm 정도로해상력을향상시켰다. 2 1. OCT의원리 OCT는빛을만들어내는광원으로부터빛을둘로분리시켜한빛은조직으로보내고한빛은기준이되는거울로보내게된다. 조직과거울로부터반사되어오는두빛을융합시켜영상을분석하는데, 조 2. OCT의임상적용망막은속경계막 (internal limiting membrane) 부터시작되어망막색소상피층 (retinal pigment epithelium) 까지 10개의층으로구성되어있다. 이러한망막구조를관찰하기위해서는고식적인방법으로는병 Correspondence to: Ungsoo Samuel Kim, MD Department of Ophthalmology, Kim s Eye Hospital, 136 Yeongsin-ro, Youngdeungpo-gu, Seoul 150-034, Korea Tel: +82-1577-2639; Fax: +82-2-2677-9214; E-mail: ungsookim@kimeye.com Received: Apr. 16, 2014 / Accepted: Apr. 30, 2014 Copyright 2014 The Korean Society of Neuro-Ophthalmology http://neuro-ophthalmology.co.kr 17
Kim US Optical Coherence Tomography 리조직을얻어야하나이제는 OCT를통해생체내계측이가능해졌다 (Fig. 2). OCT의재현성 (reproducibility) 은우수하여병의진행경과를객관적으로관찰하는것이용이하여현재폭넓게사용되고있으며그영역이점점넓어지고있다. 3 1) 황반부분석망막의중심에해당하는부위를황반이라하는데이부위가시력에중요한역할을하고있으며 OCT에서는황반부의다양한분석이가능해졌다 (Fig. 3). OCT를이용하여황반부에구조적으로변화가일어날수있는다양한망막병증 ( 나이관련황반변성, 중심장액맥락망막병증, 망막전막, 잠복황반병증등 ) 을파악할수있고, 황반부의두께를정량적으로측정할수있어황반부종의변화를객관적으로측정할수있다. 또한시간영역OCT에서는구분이모호하던광수용체층의해부학적구조가스펙트럼영역 OCT에서는명확하게구분되어잠복황반병증과같은질환의진단에큰역할을하고있다. 4 2) 망막신경섬유층분석망막신경섬유층은망막신경절세포 (retinal ganglion cell) 에서나와가쪽무릎체 (lateral geniculate body) 로이어지는축삭의모임을말한다. OCT를이용한망막신경섬유층의측정은고식적인방법으로시신 경유두주위에서측정하였으나 (Fig. 4A) 최근황반부의망막신경절세포의형태학적분석도가능해져망막신경섬유층의손실을초기에진단할수있는장점이있어이에대한연구가진행되고있다 (Fig. 4B). 5 이러한분석을통해망막신경섬유층의결손이발생하는녹내장, 다양한시신경병증, 퇴행성대뇌질환등에서망막신경섬유층의감소를 OCT 를통해정량적으로분석이가능하게되었다. 3) 시신경유두의분석시신경유두는형태학적으로다양한소견을보일수있다. 이러한경우일부에서는병적인소견인지생리적소견인지모호한경우가있으며검사자간의해석이다를수있다. 하지만 OCT를이용하면정량적, 형태학적분석을객관적이고우수한재현성을통해분석이가능하므로시신경유두질환의감별에용이하다. 3. 신경안과영역에서의 OCT 1) 시신경병증과황반병증의감별스펙트럼영역 OCT의경우망막의미세한변화가잘관찰되어과거시신경병증으로오인되던잠복황반병증같은질환의감별이가능해졌다. 6 또한미세한시신경유두의창백이나독성시신경병증의초기에도시신경주변의망막신경섬유층의분석을통해유추할수있다. 7 Laser source Detector Splitter Fig. 1. Principle of optical coherence tomography. Tissue Reference mirror 2) 시신경유두부종의감별안저검사에서시신경유두의부종이관찰되는경우이부종이가성시신경유두부종인지진성시신경유두부종인지감별하는것이매우중요하다. 가성시신경유두부종의가장흔한원인인시신경유두드루젠 (optic disc drusen) 의경우망막내증밑으로드루젠에해당하는균일한종괴모양이관찰되어유두부종 (papilledema) 과의감별에큰도움을준다. 8 INL ONL ILM NFL CC IPL OPL MLM XLM RC IS OS Fig. 2. The correlation between anatomy and spectral domain optical coherence tomography. ILM, internal limiting membrane; NFL, nerve fiber layer; GC, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; MLM, middle limiting membrane; XLM, external limiting membrane; RC, photoreceptor cell; IS, inner segment; OS, outer segment 18 http://neuro-ophthalmology.co.kr
빛간섭단층촬영 김응수 3) 시신경병증의 감별 4) 대뇌질환과 관련된 망막신경섬유층 연구 우성유전시신경위축(autosomal dominant optic atrophy)의 경우 시 (1) 시신경염 신경창백이 진행되지 않은 경우 감별이 어려운 경우가 있는데 OCT를 Trip 등11은 2005년 연구에서 시신경염을 경험한 환자에서 대조군 이용한 경우 감별진단에 도움이 되며 망막신경섬유층의 두께가 시력 에 비해 시신경염을 앓은 눈에서는 33%, 건안에서는 11%의 망막신경 과 높은 연관성을 보이는 것으로 알려져 있다. 섬유층의 감소를 보고하였다. 이러한 망막신경섬유층의 감소의 90% 9,10 Fig. 3. Macular thickness map of Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, Calif). B A Fig. 4. (A) Peripapillary retinal nerve fiber layer analysis map. (B) Macular ganglion cell analysis map. Inferior peripapillary RNFL loss and inferior ganglion cell loss are noted in the left eye. http://neuro-ophthalmology.co.kr 19
Kim US Optical Coherence Tomography 정도는평균 2.38개월이내에이루어진다. 12 (2) 다발성경화증다발성경화증 (multiple sclerosis, MS) 은탈수초질환으로시신경염이발생하지않은경우에도망막신경섬유층의감소가보고되었다. Paisi 등 13 은시신경염을앓은눈에서는 46%, 건안에서는 26% 의망막신경섬유층의감소를보고하였다. 또한한연구에서는 75 μm의두께가시력예후를판별하는경계라주장하였고이보다감소했을때는시력예후가불량하다고보고하였다. 14 하지만일부연구에서는망막신경섬유층의감소와시력예후와상관관계가없다는연구도있다. 15 swept-source OCT의경우는맥락막의전층을확인할수있어맥락막과관련된질환에대한연구가용이해졌다. 24 최근에는기존의 2차원적인망막및시신경유두의분석뿐아니라소프트웨어의발달로 3차원적영상분석이가능해져 en-face 이미지를획득하여망막및시신경유두질환의생태병리기전을밝히는데이용되고있다. 25 또한도플러원리를이용한망막과맥락막의혈류를분석하는 OCT에대한연구가진행되고있어비침습적으로안구의혈류에대한연구가진행중이다. 26 결론 (3) 시신경척수염 (neuromyelitis optica, NMO) OCT를이용한망막신경섬유층연구는시신경척수염과다발성경화증의감별에이용될수있다. 16,17 NMO의망막신경섬유층감소는시신경염에비해훨씬심한데, Ratchford 등 18 의연구에서 26명의 NMO 와 378명의다발성경화증, 그리고 77명의건강한대조군을대상으로망막신경섬유층의두께를비교하였을때 NMO는 63 μm, MS는 88 μm, 그리고대조군은 102 μm으로세군간에유의한차이를보인다고하였다. 또한두눈의망막신경섬유층두께차이가 15 μm 이상일때 MS (24%) 보다는 NMO (75%) 로진단될확률이높다. (4) 퇴행성질환알츠하이머병 (Alzheimer s disease) 이나파킨슨병 (Parkinson s disease) 의경우에도망막신경섬유층의감소가보고되고있다. 19 알츠하이머병에서는 OCT를이용한망막신경섬유층분석에서상측망막신경섬유층의감소가특징적이며이부위는시피질의 cuneal gyrus로전달되는경로로알려져있다. 하지만이망막신경섬유층결손과병인과의인과관계에대해서는불분명한상황이다. 20 파킨슨병에서는시신경의하이측부위의감소가흔하다고보고되었으며이는알츠하이머병과는반대되는소견이다. 21 (5) 시각로질환가쪽무릎체이후의병변의경우에 trans-synaptic degeneration이발생하므로시야검사를통하지않고도병변의위치를유추해볼수있다. 22 4. 앞으로의 OCT 중심장액맥락망막병증, 고도근시, 나이관련황반변성등의병리기전에서맥락막이중요한위치를차지하고있으며스펙트럼영역 OCT 의경우맥락막의 70-75% 정도까지관찰이가능하다. 23 최근들어 OCT 는비침습적으로해부학적요소들을뛰어난해상력으로관 찰및분석이가능하여임상적으로매우유용하며최근다양한장비 와의연계가이루어져빠른발전을이루고있는광학기기이다. 따라서 OCT 를이용하여망막및시신경에대한다양한질환연구가가능하 며이러한연구들이향후신경안과영역에서다양하게적용될수있 을것으로생각된다. REFERENCES 1. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science 1991;254:1178-1181. 2. Leitgeb R, Hitzenberger C, Fercher A. Performance of fourier domain vs. time domain optical coherence tomography. Opt Express 2003;11:889-894. 3. Branchini L, Regatieri CV, Flores-Moreno I, Baumann B, Fujimoto JG, Duker JS. Reproducibility of choroidal thickness measurements across three spectral domain optical coherence tomography systems. Ophthalmology 2012;119:119-123. 4. Kim YG, Baek SH, Moon SW, Lee HK, Kim US. Analysis of spectral domain optical coherence tomography findings in occult macular dystrophy. Acta Ophthalmol 2011;89:e52-56. 5. Na JH, Lee K, Lee JR, Baek S, Yoo SJ, Kook MS. Detection of macular ganglion cell loss in preperimetric glaucoma patients with localized retinal nerve fibre defects by spectral-domain optical coherence tomography. Clin Experiment Ophthalmol 2013;41:870-880. 6. Ahn SJ, Ahn J, Park KH, Woo SJ. Multimodal imaging of occult macular dystrophy. JAMA Ophthalmol 2013;131:880-890. 7. Kim U, Hwang JM. Early stage ethambutol optic neuropathy: retinal nerve fiber layer and optical coherence tomography. Eur J Ophthalmol 2009;19:466-469. 8. Lee KM, Woo SJ, Hwang JM. Morphologic characteristics of optic nerve head drusen on spectral-domain optical coherence tomography. Am J Ophthalmol 2013;155:1139-1147 e1. 9. Ronnback C, Milea D, Larsen M. Imaging of the macula indicates early completion of structural deficit in autosomal-dominant optic atrophy. Ophthalmology 2013;120:2672-2677. 10. Russo A, Delcassi L, Marchina E, Semeraro F. Correlation between visual acuity and OCT-measured retinal nerve fiber layer thickness in a family 20 http://neuro-ophthalmology.co.kr
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