Journal of Retina 2016;1(2): REVIEW ARTICLE ISSN Multimodal imaging 을통한다초점맥락막염과점상내측맥락막병증의비교,

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1 Journal of Retina 2016;1(2):59-67 REVIEW ARTICLE ISSN Multimodal imaging 을통한다초점맥락막염과점상내측맥락막병증의비교, 그리고그정의에대한고찰 Multifocal Choroiditis and Punctate Inner Choroidopathy through Multimodal Imaging: A Comment on the Present Nomenclature 강현승, 변석호 Hyunseung Kang, Suk Ho Byeon 연세대학교의과대학안과학교실시기능개발연구소 The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea Multifocal choroiditis (MFC) has been defined as a disease characterized by multifocal choroidal inflammatory lesions occurring predominantly in young myopic women, idiopathic in origin, and not associated with any systemic disorder. However, there are numerous diseases that share similar features and definitions, such as punctate inner choroidopathy (PIC), complicating the differential diagnosis. Many of the present authors regard MFC and PIC to be the same disorder and include them under the single diagnosis idiopathic MFC regardless of the presence of ocular inflammation. In addition, there are many diagnostic terms that overlap or duplicate idiopathic MFC, again complicating the differential diagnosis. Recent advancement in technology has allowed a technique called multimodal imaging, which has produced new findings about previously little-known diseases. These new findings have shown that many cases of what were diagnosed as idiopathic choroidal neovascularization (CNV) or myopic CNV were actually secondary to unrecognized MFC/PIC. In other words, the incidence of MFC/PIC was underestimated. Recent findings with multimodal imaging suggest a reappraisal of the pathophysiology of these diseases. Herein, we introduce recent reports of MFC/PIC based on multimodal imaging. Keywords: Enhanced depth imaging OCT; Multifocal choroiditis; Multifocal choroiditis and panuveitis; Multimodal imaging; Punctate inner choroidopathy 서론 1973년에 Nozik and Dorsch가 presumed ocular histoplasmosis (POHS) 와비슷한안저병변 (punched-out lesion) 을보이면서전방에염증을동반한환자들을보고하였고 [1], 1984년도에이르러서야현재많이사용하고있는 전체포도막염과동반된다초 점맥락막염 (multifocal choroiditis with panuveitis, MCP) 이라는용어가 Dreyer and Gass에의해소개되었다 [2]. 그들은이질환이맥락막의병변과더불어전방및유리체의염증이동반된다고기술하였고흔하게재발하는경향이있다고하였다. 같은해에 Watzke et al. [3] 이전방및유리체염증이없으면서흰노란점들이위축성반흔으로진행하는환자들을보고하였는데, Address reprint requests to Suk Ho Byeon, MD, PhD Department of Ophthalmology, Yonsei University College of Medicine, #50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: , Fax: shbyeon@yuhs.ac Received: Revised: Accepted: Copyright 2016 The korean retina 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.

2 JOURNAL OF RETINA 비염증성이란특징을강조하듯 " 점상내측맥락막병증 (punctate inner choroidopathy, PIC) 이라고명명하였다. 그들은이질환 이근시와연관이있다고보고이런병변이락커칠균열타입의 맥락망막흉터일것이라는가설을제안하였다. 하지만병변이지 속적으로활동성을띠며재발을반복하고급성대상잠재외망막 병증 (acute zonal occult outer retinopathy, AZOOR) 으로진행하 는증례들까지보고되면서 PIC 도결국염증성질환이라고여겨 지게되었다 [3,4]. Multifocal choroiditis (MFC)/PIC 는유전적감 수성을가진개인에게발생하는자가면역질환의눈증상중하 나라고설명되기도하나, 그원인병리론에대해서는아직밝혀 진바가없다. 최근에는 MFC/PIC 가동일한사이토카인다형성 을공유한다는연구결과가발표되면서이두질환이같은질병 이라는가설을뒷받침하였다 [5]. 이두질환은많은유사성을갖기때문에감별진단을위해 그동안앞포도막염및유리체염의유무, 형광안저혈관조영술 (fluorescein angiography, FA) 양상, 그리고안저검사상병변의 크기등을비교해왔다. 하지만시간이흐르면서맥락망막흉터 나위축병변이점차커지는경우크기만으로이둘을분간해 내기가불가능하고, 특히근시안의경우병변의크기변화에독 립적으로영향을미칠수있기때문에이러한차이점은감별에 큰도움이되지않는다. 또한, MFC 자체가비활동기에접어든 상태에서는앞포도막염및유리체염이관찰되지않기때문에 PIC 와의감별이더욱어려울수있다. 전통적으로 MFC/PIC 의진단검사법은안저검사와 FA 정도 에그쳤으나그동안컴퓨터시스템에기반한이미지분석기술 의눈부신발전에힘입어최근에는 multimodal imaging 을통해 모호한경계를갖는질환들을비교하고이해하는데도움이되 고있다 [6]. 본연구에서는 MFC/PIC 의임상양상에대해살펴 보고, 최근 multimodal imaging 을이용한연구결과들을통하 여새롭게정립되고있는질환에대한새로운개념과최신지견 에대해살펴보고자한다. 본론 임상양상 MFC/PIC 는근시를가진젊은건강한여성에게주로발병하며 대부분검사상양안을침범한양상을보이나증상은주로단 안의시력저하, 광시증, 비문증, 맹점확대로나타난다. 염증병 변이황반부에발생하거나맥락막혈관신생이동반될때중심시 력저하가발생하게된다. 병변은 50-1,000 μm 정도크기로안 저전체에퍼져있을수있으나주로후극부에서적도부까지위 치하며유리체에염증반응이관찰될수도있다. 여러개의황 색내지회색의병변들은망막색소상피나맥락막내층에위 치하며시간이지나염증이가라앉으면위축된과색소병변 (punched-out) 으로남는다. POHS 에서보이는시신경주위색 소변화 (peripapillary scarring) 도관찰되는것이특징이다. 풍토 지역은없으며 histoplasmin skin test 에대한양성률은매우낮 다. 낭포황반부종이 15-40% 까지보고되었으며, 약 25% 에서황 반부에망막하신생혈관이발생한다. 단순히맹점확대를보이 거나경미한시신경부종이관찰되기도하는데이것은아마도 시신경유두주변부의망막기능장애 (peripapillary retinal dysifunction) 때문이라고생각된다. 때때로안저소견과일치하지 않는커다란시야결손이나타나기도하는데이것은광수용체 의특정부분이급성손상을입은결과라고추정된다. 한구역 이거나여러개의작은구역일수있으며주로시신경유두주위 이거나망막주변부의큰영역을침범한다. 이러한큰영역의망 막수용체손상은결국망막혈관의가늘어짐과망막색소상피의 변질을일으키면서망막색소변성증과같은형상을띠기도한다. 이렇듯 MFC/PIC 의 휴지기 에는 AZOOR, Multiple evanescent white dot syndrome (MEWDS), acute idiopathic blind-spot enlargement (AIBSE) 와같은질환들과매우흡사하기에이모두 를통틀어 AZOOR complex disorder 라고분류하기도한다 [7,8]. 검사소견병력청취상감기유사증세가있을수있다. 이질환이바이러스 에의한것이라는가설이소개되었는데, Epstein-Barr virus 등 에대한 IgM, IgG 등이발견된다고하였고헤르페스바이러스 의가능성도제시되었으나아직조직생검상바이러스가발견된 적은없다 [9]. 이질환은원래일차적인원인질환이없는경우 진단내릴수있기때문에여러가지감염성질환, 예를들면결 핵, brucellosis, 사르코이도시스혹은기타진균감염에의해서 도비슷한양상을나타내는경우들이있어정밀검사가필요하 다. FA 상병변은초기에저형광으로시작해점차적으로채워지 다가후기에는누출이일어나고, punched-out lesion 은전형적 인창문비침을보이다가후기에는흐려진다 (fuzzy leakage). 인 도시아닌그린혈관조영 (indocyanine green angiography, ICGA) 에 서병변은지속적인저형광으로보이며종종안저검사나 FA 에 서보이는것보다더많은수의병변이관찰되는데, 이는시야 결손과관련이있다고알려져있다. 전기생리학적검사에서특 징적인소견은보이지않는다. 감별진단 MFC 와유사한망막소견을보이는질환으로는결핵, 사르코이 도시스, brucellosis, coccidiomycosis, 칸디다증, 그밖의다른 granulomatous disease (Blau syndrome) 등이있을수있다. 이러 한점에서 Spaide et al. [10] 은 POHS 를포함시킨이차성병변을 아우르는이름으로 MFC spectrum 이라는명칭을사용하기도 한다. POHS 에대해서는사실상임상양상이나표현형은 MFC/ PIC 와거의같다고보이지만, 그래도따로분류하는것이좋겠 60

Kang HS, et al. Multimodal Imaging: MFC and PIC 다. POHS는미국에서 histoplasma가풍토질환인특정한지역에서발현되고남성과여성이거의비슷한비율로다소늦은나이에발생하며근시와무관하게진행하고재발이드물다는점등이다른질환으로인정할만한특징들을갖고있다 (Fig. 1).

3 Kang HS, et al. Multimodal Imaging: MFC and PIC 다. POHS는미국에서 histoplasma가풍토질환인특정한지역에서발현되고남성과여성이거의비슷한비율로다소늦은나이에발생하며근시와무관하게진행하고재발이드물다는점등이다른질환으로인정할만한특징들을갖고있다 (Fig. 1). 율이높다하였는데, 기존에존재하던 일차성 국소맥락막함 몰부위에활동성염증이발생한후전형적인 MCP/PIC 의안저 변화를보였던증례를보고함으로써발생학적이상소견으로보 Multimodal Imaging 을통해제시된 MFC/PIC 에대한새로운개념들 2013 년 Spaide et al. [10] 은기존의정형화된진단기준에의거하 여진단된 MCP/PIC 환자 22 명 38 안을대상으로후향적관찰 연구를진행하였으며 multimodal imaging 컬러안저사진, FA, 자가형광안저촬영 (fundus autofluorescence, FAF), 스펙트럼영역 빛간섭단층촬영 (spectral domain optical coherence tomogra - phy, SD-OCT) 을통해관찰된각질환의맥락망막병변이거 의같은양상을보인다고보고하였다. 본연구에따르면급성의 병변은망막색소상피아래로결절성의저류로나타났다. 그리 고그러한고형의망막색소상피박리들은파열되면서외층망막 이나망막하공간으로염증성침윤이발생하는것으로보였으 며, 흔히염증성삼출물의범위밖으로광범위한망막외층구 조들의손실을보였다 (Fig. 2). 스테로이드를이용한치료로이 러한물질이빠른속도로줄어들고, 외층망막의구조는이보다 는느린속도로회복되는것이관찰되었다. 두질환모두맥락막 에서보이는일관된소견은보이지않았으나일부의급성병변 에서는다소의맥락막두께증가를보였으며, 스테로이드치료 후에는활동성병변아래맥락막의두께가국소적으로얇아지 는경우도있다고하였다. 두질환모두맥락막에서보이는일관 된소견은보이지않았으나일부의급성병변에서는다소의맥 락막두께증가를보였으며, 스테로이드치료후에는활동성병 변아래맥락막의두께가국소적으로얇아지는경우도있다고 하였다. 또다른최근보고에의하면발생학적이상소견으로여 겨지던국소맥락막함몰과관련하여중심장액성맥락막염과 같은다른맥락막질환보다 MCP/PIC 를동반하여관찰되는비 Idiopathic (Primary) Inflammation of Anterior segment and/or of Posterior segment No/minimal MFC Yes MFCPU MFC Spectrum Infectious Bacterial Fungal Viral Secondary Non-infectious Sarcoidosis Overlap: APMPPE Serpiginous Figure 1. Spectrum of MFC. MFC = multifocal choroiditis; MFCPU = multifocal choroiditis and panuveitis; APMPPE = acute posterior multifocal placoid pigment epitheliopathy. A D F I B G E Figure 2. This 40-year-old myopic woman complained of paracentral scotoma in the left eye. The first and second rows (A-E) were obtained at baseline. (A) Note the small white spots at superior and inferior macular areas. There were no cells in the anterior chamber or vitreous cavity. (B) Late in the fluorescein angiogram, there was staining of the lesion. Peripapillary scarring was better visualized than on the color fundus photo (white arrows). (C) Late indocyanine green angiography revealed the hypofluorescent lesions. (D) Spectral domain optical coherence tomography section indicated by the upper yellow arrow of the color fundus photo showed a sub-retinal pigment epithelium (RPE) hyperreflective material infiltrating the subretinal space. (E) In the inferior section, the sub-rpe infiltration seemed to sprout into the outer retina, however, no clear choroidal involvement was detected in either lesions. The best-corrected visual acuity was 20/40. Two years from baseline (F-J): (F) Under the suspicion of choroidal neovascularization being present, the patient was treated with intravitreal bevacizumab. After 4 injections of anti-vascular endothelial growth factor, color fundus photo demonstrates pigmentary changes. (G) On infrared imaging, the pigmented scars of multifocal choroiditis lesions were seen as hyperreflective lesions. (H) Fundus autofluorescence showed hyperautofluorescence surrounding hypoautofluorescent central lesions. (I) The hyperreflective infiltration appeared to be regressed, and yet the sub-rpe lesion remained. (J) Note the flattening of the RPE abnormality, however, the indiscrete hyperreflective nodule remained obliterating the photoreceptor layers. The visual acuity was 20/60. J C H 61

4 JOURNAL OF RETINA 이는국소맥락막함몰도실제로무증상 / 비임상형의국소맥락막염증에이차적으로발생한병변일수있다는가설을제시하였다 [11]. 흥미로운것은이들병변들에서주로침범되는부위가현재그들의명칭과부합하지않는망막색소상피하와망막외층이라고보고하였다. MCP와 PIC의활동성병변에서는근본적으로같은구조들이같은표현형으로나타나고같은방법으로치료하면되기때문에둘을구분하기위한노력이큰의미가없을수있다고하였다. Multimodal imaging을이용한결과를통해서이들질환에대한병리학적소견이나정의, 그리고명칭에대해서재평가가필요하다고결론내리고있다 년 Fung et al. [12] 은 41명 65안의연속증례를후향적으로관찰연구하였는데, 대상자로다발성맥락막염병변을보이면서앞포도막염이나유리체염증이최소한혹은동반되지않은 idiopathic MFC 환자들만포함이되었다. 그들의 multimodal imaging 컬러안저사진, 망막신경섬유층사진 (red free photo), FAF, FA, ICGA, SD-OCT 을분석하여임상적특징과진행양상을기술하고자하였다. 진단시평균연령은 38.4세 (range: 세 ) 였으며 70.7% 의환자가여성이었다. 평균굴절력은 diopters (range: +1.00~-20.00) 였으며, 평균시력은첫진단당시 20/46에서 92.6개월간의평균추적관찰기간후 20/42 로약간상승하였다. 60개월간시력이 20/50 이하로악화되지않은생존율이 100% 였다. 평균 92.6개월의추적관찰기간동안크기가증가하거나새롭게발생한맥락망막반점이약 1/2의환자에서관찰되었으며, 재발하거나새롭게발생한맥락막신생혈관 (choroidal neovascularization, CNV) 이 1/3에서관찰되었다. 60 개월간 CNV 없는생존율은 68.1% 였다. 첫진단시에약반수에서양안성을보였는데이는다른대부분의 MCP 증례들에서보고되는빈도보다는낮은것이다. 단안성으로나타난환자에서 1/4의경우에는 60개월이내에결국양안으로진행하였다. 과거에는전체포도막염이동반되지않은질환에대해서는다른질환군으로생각해야한다는주장들도있었지만실제로는전형적인 PIC의경우에도전체포도막염이동반된증례가보고된적이있었던것과같이, 사실 MFC와 PIC, 그리고전체포도막염의동반유무에관계없이같은질병의스펙트럼으로생각해야할것이다. 이러한점에서본논문에서는앞포도막염이나유리체염증이동반되지않은 MFC에대하여 multimodal imaging을통해임상적인양상과특징들을살펴보았는데, 처음엔단안성으로나타났던 PIC와비슷한양상의증례들이시간이지나면서결국엔양안성으로진행하거나새로운병변이나타나는등의경과를보임을확인하였다. 결국은이들이거의비슷한임상양상을보이는한질병의스펙트럼질환들임을의미하는것이라고생각한다. 2015년 Munk et al. [13] 은 idiopathic MFC 중특이한유형의환자들만을선정하여 multimodal imaging 컬러안저사진, 광각안저사진 (wide-field color fundus image), FA, ICGA, SD- OCT 를이용한 infrared (IR image) 와 red-free short-wave blue (488 nm) FAF, Optos 를이용한 green near-ir (787 nm) FAF, 그외에일부에서전체망막전위도 / 다국소망막전위도 을분석 하였는데, 이들은후극부에다발성맥락막염병변과동시에그 주위에한구역및다구역, 혹은전반적인외망막층 / 맥락망막 위축을보였다 [13]. 본연구는임상적으로관찰되는병변보다훨 씬광범위한영역의광수용체기능이상으로인해급격한시력 저하나중심암점이발생한 MFC/PIC 증례들을소개하였다. 그 리고이런변이형의환자들은치료없이도외망막층및시기능 의완전한회복부터영구적손실까지다양한임상결과를보였 다. 첫내원시환자들은안전수지및안전수동의극심한시력 저하를보이면서시야암점을호소하였는데, 이부위는 OCT 에 서광수용체층이희미해진부분과일치하였다 (Fig. 3). 이런변 화들은주로안저검사에서관찰가능한맥락망막병변에인접 해있었다. 또한, 이부위는 FAF 상과형광으로관찰되는데그 기전은정확히알려져있지않다. 가장가능성있는가설들로 활동성염증에의해망막색소상피내발광물질의축적이증가 해서이거나 [14], 광수용체층의파열이시색소물질의저하로연 결되어빛흡수능력이떨어지면서과형광을띠게되는것이다 [15]. ICGA 에서판 (plaque) 모양으로관찰되는저형광의원인은 아직도밝혀지지않았는데, 맥락막저관류, 맥락막허혈, 또는 형광차단효과등이가능한원인들로제시되었다. 활동성염증 이있을때, OCT 에서 ICGA 의저형광과상응하는부위의헨레 층에서고반사가관찰되고외망막층의손상이있는곳에맥락 막두께가두꺼워진것을고려해봤을때형광차단효과때문일 가능성이가장크다고생각되고있다 [16]. 그들이보고한이전 연구에서는이런 변이형 환자들일부에서광범위한영역의외 망막층 / 맥락망막위축병변이시간에따라점점더진행한다고 하였으며, 중심시력은질환의말기까지보존되는경우가많다 고하였다 [17]. 반면, 본연구에서는 multimodal imaging 을통해 MFC/PIC 환자들에서도지속적인시기능손실이가능하다는 것을보여주었다. 염증반응의정도에따라다양한결과를보일 수있는데, 광수용체층손상이저절로호전되거나면역조절제 에반응할수있으며, 최악의경우영구적일수도있다. 고찰 White dot syndrome 에포함되는질환군들중에는서로매우 유사한임상양상을공유하기도하고때로는한환자에서각각 의개별적인질환의특징적인임상양상이동시에혹은순차적 으로나타나는경우들이있다. 이들질환군들을비슷한병태 생리를가진다양한질환들로볼것이냐혹은한가지질환의 다양한임상양상으로볼것이냐에대한개념에대한논의가있 을수있다. 물론아직은이들질환에대한치료가, 특히각각의 질병별로, 개별적인치료에대한개념이확립되어있지않으므 로현실적으로큰의미를가지지못한다고생각할수있다. 하지 62

5 Kang HS, et al. Multimodal Imaging: MFC and PIC A B C D E F G H Figure 3. This 22-year-old man with myopia complained of central scotoma in the left eye right after suffering from upper respiratory infection. The best-corrected visual acuity was 20/60. (A) Color fundus photo revealed two large yellow chorioretinal lesions superior to the fovea. There were no cells in the anterior chamber or vitreous cavity ophthalmoscopically. (B) Fluorescein angiography demonstrated late staining of the chorioretinal lesions. (C, D) Indocyanine green angiography (ICGA) highlighted the hypofluorescent lesions but also had a plaque-like hypofluorescent area that corresponded to the hyperautofluorescent area seen with fundus autofluorescence, which outlined the ring-shaped hyperautofluorescence visible around the optic disc and the fovea. (E) Corresponding spectral domain optical coherence tomography (SD-OCT) showed attenuation of the external limiting membrane, inner segment/outer segment (IS/OS) and cone outer segment termination (COST) line adjacent to the chorioretinal lesions and where seemed to correspond to the hypofluorescent area on ICGA. The magnified inset showed the irregular photoreceptor layers in greater detail. There was no definite hyporeflectivity in the corresponding area on infrared imaging. There were inflammatory cells in the overlying vitreous (white arrows). (F) SD-OCT outlined the chorioretinal lesion visualized as a hyperreflective nodule, which broke through the retinal pigment epithelium disrupting the overlying retina. The adjacent outer retinal layers were not distinguishable. The magnified inset in the right showed the irregularity of the photoreceptor layers in greater detail. (G) The visual field (VF) defect corresponded to the area of hyperautofluorescence, where the IS/OS and COST lines were attenuated. (H) Ten days later, the VF defect was much improved, however, no further imaging study was performed to verify this finding. The visual acuity was 20/30. 63

6 JOURNAL OF RETINA 만, 우리가어떠한질환에대한명칭과개념을명확히하는것은서로간의단순한소통에있어서뿐아니라, 자연경과에대한관찰혹은향후새로운치료에대한연구를진행하는데있어서도매우중요하다고생각된다. 그동안 MFC/PIC의경우에있어서는그동안제한된진단방법과다양한임상양상으로인하여, 오히려개별연구자들이매번새로운명칭들을사용함으로써혼란이유발된상황으로생각된다. PIC의정의는현재의 idiopathic MFC와거의동일한데, 근 25년간 MFC보다병변의크기가더작고후극부에군집되어있는경우로그의미가좁혀졌었다 [18]. 하지만 2010년 Essex 등이병변의크기에따라임상양상에차이가없다고보고하면서다시기존의포괄적인정의를사용하기를권장하였다 [19]. Pseudo-POHS 라는용어는 Callanan and Gass [20] 에의해처음사용되었으며 Histoplasma의풍토지역과연관이없으면서 POHS와비슷한안저변화를보이는질환을일컫는데, 이는결국 MFC와같은것으로현재널리사용되고있지는않다. Multifocal inner choroiditis 는두가지의의미를갖는데, Krill 등은 POHS와흡사한안저병변과 CNV 가있으면서유리체염이없고 histoplasmin skin test에양성을보인군으로정의한반면 [21], Scheider는각각의특징들을단독으로갖고있는환자들을한집단으로그룹화하기위한용어로사용하였다 [22]. 각기다른뜻으로같은용어가중복되어현재는거의사용되고있지않다. Morgan과 Schatz는 PIC, MFC with panuveitis (MCP), MFC with progressive subretinal fibrosis를통틀어 Recurrent multifocal choroiditis 라고명명하기를제안하였는데모두현재 idiopathic MFC 안에속하는질환들로이용어는널리받아들여지지않았다 [23]. Multifocal choroidopathy 는 MFC/POHS-like 양상을띠는환자들을전부포함하기위한포괄적인용어로제안되었으나표현형이비슷하더라도엄연히다른질환들이기에같은진단으로분류하는것은바람직하지않다는지적을받았다 [24]. Disseminated inner choroiditis 는프랑스인에서 histoplasma에대한노출여부에상관없이 POHS-like 안저변화를보이는경우로정의하였다. 이환자들은근대의 idiopathic MFC에해당되며현재이용어는사용되고있지않다 [25]. Progressive subretinal fibrosis 는앞포도막염및유리체염이일정치않게동반되면서맥락막병변과망막하섬유증이관찰되는질환이다. Idiopathic MFC에서합병증으로 CNV가발생할수있는데 progressive subretinal fibrosis가이과정의공격적인형태라고보고있다 [26,27]. 유럽의젊은이들에게발견되었던 POHS-like 안저변화에동반된맥락막신생혈관막을 hemorrhagic maculopathy in young adults (macular choroidopathy) 라고지칭하였는데, 이는 CNV가합병된 idiopathic MFC로생각된다 [28,29]. 여기서강조할점은 hemorrhagic maculopathy in young adult, idiopathic CNV와같이 MFC/PIC 병변에동반된신생혈관과같 은합병증의경우에잘못진단되는경우가흔히있다는것이다. 2011년에 Freund는 multimodal imaging을통해 myopic CNV혹은 idiopathic CNV로진단받았던대다수의케이스들이실제로는 MFC였을것이란주장을내세웠다 [30]. 그보다더전인 2008 년에는 Machida et al. [31] 이 idiopathic CNV가염증성맥락막질환의초기증상일가능성을제시하였다. 실제로 MFC/PIC의병변부위에신생혈관이동반되는경우가흔하기때문에병변을명확히구분하는것은쉽지않지만, OCT상에서확인되는전형적인 MFC/PIC 병변인망막상피하침윤에대해서그동안신생혈관으로오해하는경우가드물지않았던것으로생각된다. 이러한병변의경우치료없이도혹은스테로이드등의항염증치료로병변이소실되고망막색소상피가회복되는경우들이있는데, 특히 anti-vascular endothelial growth factor (VEGF) 의투여후에이러한병변이소실된것을약제에의한신생혈관치료효과로오해하는일들이드물지않았던것으로보인다. 하지만, 만약섬유혈관조직인신생혈관의경우라면주사치료후 subretinal fibrosis/thickening 과같은흉터조직이남게되겠지만몇몇 idiopathic CNV 혹은 myopic CNV로생각되어 anti-vegf 치료를했던증례들중병변이완전히사라지고망막색소상피가회복되는경우들은진단자체에오류가있지않았는지확인해볼필요가있다고생각된다 (Fig. 4). 앞서소개한대로 Multimodal imaging 소견상병변이보이는특징을근거로 MFC/PIC는명칭의내용과는다르게맥락막침범은거의없으면서망막색소상피하침윤이주된병변이라는주장이제기되고있다 [10]. 또한, MEWDS를포함한몇몇 white dot syndrome에서도이러한 imaging, 특히 OCT와최근의 OCT angiography 에서관찰되는소견을근거로외측망막혹은망막색소상피하에국한된병변이라는주장이제기되고있다. 하지만, 아직은현재 imaging에서보이는맥락막의음성소견 ( 이상없음 ) 이과연신빙성이있는지에대한검증이필요할것이며, 또한스펙트럼으로나타나는질환들에서보이는맥락막변화를어떻게설명할수있을것이냐하는등의논란의여지가있다. 결론적으로, MFC와 PIC의경우최근 retinal imaging의발전으로두질병간의병변의양상이거의같음을확인할수있었고따라서같은질환으로분류하는것이타당하다고사료된다. 또한이러한병변의 imaging상의특징이그동안 idiopathic CNV 혹은 myopic CNV 등으로잘못진단되었던환자들에서발견되는경우들이드물지않다. 즉, 임상적으로실제 MFC/PIC 의빈도가상당히높음에도불구하고과소평가되었을가능성이있다. 이렇게 retinal imaging의발전은기존에비슷한임상양상으로인하여구분되지못하였던경우나, 혹은오히려같은질환군임에도다양한임상양상으로인하여다양한질환으로오인되었던경우에있어서질환의정확한진단과개념정립에기여하고있다. 64

Kang HS, et al. Multimodal Imaging: MFC and PIC A B C D E F Figure 4. This 45-year-old myopic woman complained of blurred vision in the left eye. The first three rows (A-E) were obtained at baseline.

7 Kang HS, et al. Multimodal Imaging: MFC and PIC A B C D E F Figure 4. This 45-year-old myopic woman complained of blurred vision in the left eye. The first three rows (A-E) were obtained at baseline. (A) Color fundus photo revealed one small yellow chorioretinal lesion temporal to the fovea in the left eye. Both fundi showed peripapillary scarring equally. There were no cells in the anterior chamber or vitreous cavity ophthalmoscopically. (B) Fundus autofluorescence highlighted the hypofluorescent lesion in the left eye. (C, D) Fluorescein angiography showed staining of the chorioretinal lesions throughout all phases and mild late leakage. (E) On the left, spectral domain optical coherence tomography section crossing the fovea showed a slight elevation of the external limiting membrane, inner segment/outer segment and cone outer segment termination lines. On the right, the chorioretinal lesion was presented as a hyperreflective sub-retinal pigment epithelium infiltration invading the overlying retina. The visual acuity was 20/50. (F) Five months after treating with subtenon injection of triamcinolone, the elevation of the photoreceptor layers was relieved at the fovea and the chorioretinal lesion was completely resolved with mild irregularity of the outer retinal layers left. The visual acuity was 20/30. Conflicts of Interest There are no conflicts of interest. References 1. Nozik RA, Dorsch W. A new chorioretinopathy associated with anterior uveitis. Am J Ophthalmol 1973;76: Dreyer RF, Gass DJ. Multifocal choroiditis and panuveitis. A syn- 65

8 JOURNAL OF RETINA drome that mimics ocular histoplasmosis. Arch Ophthalmol 1984;102: Watzke RC, Packer AJ, Folk JC, et al. Punctate inner choroidopathy. Am J Ophthalmol 1984;98: Taira K, Nakazawa M, Takano Y, Ota T. Acute zonal occult outer retinopathy in the fellow eye 5 years after presentation of punctate inner choroidopathy. Graefes Arch Clin Exp Ophthalmol 2006;244: Atan D, Fraser-Bell S, Plskova J, et al. Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci. Invest Ophthalmol Vis Sci 2011;52: Haen SP, Spaide RF. Fundus autofluorescence in multifocal choroiditis and panuveitis. Am J Ophthalmol 2008;145: Gass JD, Agarwal A, Scott IU. Acute zonal occult outer retinopathy: a long-term follow-up study. Am J Ophthalmol 2002;134: Holz FG, Kim RY, Schwartz SD, et al. Acute zonal occult outer retinopathy (AZOOR) associated with multifocal choroidopathy. Eye (Lond) 1994;8(Pt 1): Tiedeman JS. Epstein-Barr viral antibodies in multifocal choroiditis and panuveitis. Am J Ophthalmol 1987;103: Spaide RF, Goldberg N, Freund KB. Redefining multifocal choroiditis and panuveitis and punctate inner choroidopathy through multimodal imaging. Retina 2013;33: Kim H, Woo SJ, Kim YK, et al. Focal choroidal excavation in multifocal choroiditis and punctate inner choroidopathy. Ophthalmology 2015;122: Fung AT, Pal S, Yannuzzi NA, et al. Multifocal choroiditis without panuveitis: clinical characteristics and progression. Retina 2014;34: Munk MR, Jung JJ, Biggee K, et al. Idiopathic multifocal choroiditis/punctate inner choroidopathy with acute photoreceptor loss or dysfunction out of proportion to clinically visible lesions. Retina 2015;35: Schmitz-Valckenberg S, Holz FG, Bird AC, Spaide RF. Fundus autofluorescence imaging: review and perspectives. Retina 2008;28: Freund KB, Mrejen S, Jung J, et al. Increased fundus autofluorescence related to outer retinal disruption. JAMA Ophthalmol 2013;131: Chen SN, Hwang JF. Ocular coherence tomographic and clinical characteristics in patients of punctuate inner choroidopathy associated with zonal outer retinopathy. Ocul Immunol Inflamm 2014;22: Jung JJ, Khan S, Mrejen S, et al. Idiopathic multifocal choroiditis with outer retinal or chorioretinal atrophy. Retina 2014;34: Amer R, Lois N. Punctate inner choroidopathy. Surv Ophthalmol 2011;56: Essex RW, Wong J, Fraser-Bell S, et al. Punctate inner choroidopathy: clinical features and outcomes. Arch Ophthalmol 2010;128: Callanan D, Gass JD. Multifocal choroiditis and choroidal neovascularization associated with the multiple evanescent white dot and acute idiopathic blind spot enlargement syndrome. Ophthalmology 1992;99: Krill AE, Chishti MI, Klien BA, et al. Multifocal inner choroiditis. Trans Am Acad Ophthalmol Otolaryngol 1969;73: Scheider A. Multifocal inner choroiditis. Ger J Ophthalmol 1993;2: Morgan CM, Schatz H. Recurrent multifocal choroiditis. Ophthalmology 1986;93: Ongkosuwito JV, Kortbeek LM, Van der Lelij A, et al. Aetiological study of the presumed ocular histoplasmosis syndrome in the Netherlands. Br J Ophthalmol 1999;83: Saraux H, Pelosse B, Guigui A. Multifocal inner choroiditis: pseudohistoplasmosis. The European form of the presumed American histoplasmosis. J Fr Ophtalmol 1986;9: Cantrill HL, Folk JC. Multifocal choroiditis associated with progressive subretinal fibrosis. Am J Ophthalmol 1986;101: Palestine AG, Nussenblatt RB, Parver LM, Knox DL. Progressive subretinal fibrosis and uveitis. Br J Ophthalmol 1984;68: Flage T, Sand AB, Syrdalen P. Haemorrhagic maculopathy in young adults. Acta Ophthalmol (Copenh) 1977;55: Bottoni FG, Deutman AF. Idiopathic sub-retinal neovascular membranes in the macula (hemorrhagic macular choroidopathy of young adults). Clinical report and effectiveness of laser treatment. Doc Ophthalmol 1986;64: Vance SK, Khan S, Klancnik JM, Freund KB. Characteristic spectral-domain optical coherence tomography findings of multifocal choroiditis. Retina 2011;31: Machida S, Fujiwara T, Murai K, et al. Idiopathic choroidal neovascularization as an early manifestation of inflammatory chorioretinal diseases. Retina 2008;28:

9 Kang HS, et al. Multimodal Imaging: MFC and PIC 국문초록 Multimodal imaging 을통한다초점맥락막염과점상내측맥락막병증의비교, 그리고그정의에대한고찰 Multifocal choroiditis (MFC) 는주로근시를가진젊은여성에서다초점의맥락막염증병변이발생하는질환으로정의되어왔다. 이 용어는원래특발성으로발생하는경우를지칭하지만유사한망막소견을보이는 Punctate inner choroidopathy (PIC) 및여러가 지감염성질환들에서여러연구자들이사용한다양한병명들은 MFC 를이해하는데혼란을주고있다. 현재많은저자들이안구내염증 반응유무에관계없이 MFC 와 PIC 를같은스펙트럼질환이라고보고있으며, idiopathic MFC 라는포괄적인개념의진단명으로묶 어사용하고있다. 또한 imaging 상병변의특징이기존에 idiopathic choroidal neovascularization (CNV) 혹은 myopic CNV 등으로진단되었던환자들에서드물지않게발견되면서, 임상적으로실제 MFC/PIC 의빈도가과소평가되었을가능성도제시되었다. 이렇게 Retinal imaging 의발전은기존에비슷한임상양상으로인하여구분되지못하였던경우나, 혹은오히려같은질환군임에도다 양한임상양상으로인하여다양한질환으로오인되었던경우에있어서질환의정확한진단과개념정립에기여하고있다. 67

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<32332D31322D303228C0CCBAB4B7CE2DC0CCBBF3C7F E687770> 대한안과학회지 2014 년제 55 권제 7 호 J Korean Ophthalmol Soc 2014;55(7):1106-1110 pissn: 0378-6471 eissn: 2092-9374 http://dx.doi.org/10.3341/jkos.2014.55.7.1106 Case Report 칸디다맥락망막염에합병된맥락막신생혈관에서유리체강내베바시주맙주입술치료 Intravitreal