대한안과학회지 2016 년제 57 권제 7 호 J Korean Ophthalmol Soc 2016;57(7):1093-1101 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2016.57.7.1093 Original Article 세가지유형의삼출성나이관련황반변성에서빛간섭단층촬영의특징비교 Comparison of Optical Coherence Tomography Characteristics among Three Subtypes of Exudative Age-related Macular Degeneration 안소은 안동섭 양헌 윤희성 Soh-Eun Ahn, MD, Dong Seob Ahn, MD, Heon Yang, MD, Hee Seong Yoon, MD, PhD 성모안과병원 Sungmo Eye Hospital, Busan, Korea Purpose: To compare the characteristics of optical coherence tomography in eyes with treatment-naïve typical neovascular age-related macular degeneration (typical namd), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). Methods: One hundred fifty-three eyes newly diagnosed with exudative AMD were retrospectively collected. All study eyes were classified into three subtypes: typical namd, PCV, and RAP. Subfoveal choroidal thickness (SFCT) was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Central macular thickness (CMT) and other OCT features including intraretinal cystoid fluid and subretinal fluid were also evaluated in all eyes. SFCT, CMT and other OCT features were compared among the three subtypes of exudative AMD. Results: Seventy-four eyes with typical namd, 55 eyes with PCV, and 24 eyes with RAP were included. SFCT was significantly thickest in PCV and thinnest in RAP (p < 0.001). RAP showed the thickest CMT and the highest frequency of intraretinal cystoid fluid (p = 0.004, p < 0.001, respectively). Conclusions: In patients with exudative AMD, different characteristics of OCT were observed according to the three subtypes. Identification of OCT characteristics could help differentiate the subtypes of exudative AMD. J Korean Ophthalmol Soc 2016;57(7):1093-1101 Keywords: Age-related macular degeneration, Optical coherence tomography, Polypoidal choroidal vasculopathy, Retinal angiomatous proliferation 나이관련황반변성은고령층에서심각한시력손실및실명을야기하는주된원인질환으로알려져있다. 1 혈관내피세포성장인자 (vascular endothelial growth factor, VEGF) 를 Received: 2016. 3. 24. Revised: 2016. 4. 14. Accepted: 2016. 5. 17. Address reprint requests to Hee Seong Yoon, MD, PhD Sungmo Eye Hospital, #409 Haeun-daero, Haeundae-gu, Busan 48064, Korea Tel: 82-51-743-0775, Fax: 82-51-743-0776 E-mail: heesyoon@dreamwiz.com 포함한혈관신생인자들이분비되어맥락막신생혈관이발생한경우를삼출성나이관련황반변성이라하며맥락막신생혈관으로부터부종과출혈이발생함으로써급격하고심각한시력저하가야기된다. 2 결절맥락막혈관병증 (polypoidal choroidal vasculopathy, PCV) 은삼출성나이관련황반변성의하위유형으로인도시아닌그린혈관조영상에서맥락막혈관의결절성확장과분지혈관망의존재를특징으로한다. 3,4 또다른하위유형인망막혈관종성증식 (retinal angiomatous proliferation, RAP) 은망막에서유래한것으로생각되는신생혈관을특징으로한다. 5,6 PCV와 RAP는전형적인 c2016 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 1093
- 대한안과학회지 2016년 제 57 권 제 7 호 - 삼출성 나이관련황반변성(typical neovascular age-related 가 맥락막 및 맥락막모세혈관의 순환상태를 반영하는 하나 macular degeneration, typical namd)과 비교하여 서로 다 의 지표로 사용되고 있다.12,13 또한 해상도가 높아지면서 황 른 임상경과와 치료반응을 나타낸다고 알려져 있으며,7-9 진 반부 미세구조의 관찰이 더욱 용이해졌고 삼출성 나이관련 단 당시 유형을 구분하는 것이 연구 목적뿐만 아니라 임상 황반변성의 병태생리를 이해하는 데 있어서 큰 역할을 하 에서의 치료 방향 설정이나 환자 설명에 있어서도 중요하게 고 있다.14 나이관련황반변성과 관련하여 맥락막두께를 비롯한 빛 되었다. 현재까지 형광안저혈관조영술(fluorescein angiography)과 간섭단층촬영의 특징적 소견을 연구한 논문은 다양하게 존 인도시아닌그린혈관조영술(indocyanine green angiography) 재하지만,15-19 typical namd, PCV, RAP와 같이 유형별로 이 삼출성 나이관련황반변성을 확진하는 데 있어서 핵심적 분류하고 각각의 특징을 비교 분석한 논문은 찾아볼 수 없 인 역할을 수행하고 있으며, 빛간섭단층촬영(optical coher- 었다. 빛간섭단층촬영을 통한 삼출성 나이관련황반변성 유 ence tomography, OCT) 역시 진단 및 치료 반응을 평가함 형별 비교는 각각의 병태생리를 이해하고 감별진단하는 데 에 있어서 중요하게 자리매김하고 있다. 비침습적인 진단 있어서 큰 도움이 될 것이라 생각된다. 이에 저자들은 삼출 장비라는 측면에서 혈관조영술에 비해 OCT의 활용도는 매 성 나이관련황반변성 환자에서 typical namd, PCV, 그리 우 높으며, 기술적인 발전이 더해지면서 망막의 미세구조 고 RAP의 세 가지 유형에 따른 빛간섭단층촬영의 특징을 를 더욱 자세하게 관찰할 수 있게 되어 삼출성 나이관련황 비교하고자 하였다. 반변성의 진단 및 치료에 있어 차지하는 역할이 점차 커지 고 있다.10,11 대상과 방법 OCT의 발전으로 깊이증강모드(enhanced depth imaging [EDI] mode)가 개발되면서 맥락막층을 더욱 정교하게 평 가할 수 있게 되었고, 이를 통해 측정된 중심하 맥락막두께 대상 선정 및 자료 획득 2013년 1월부터 2015년 8월까지 본원을 내원한 삼출성 A B C Figure 1. Representative images of three subtypes of exudative age-related macular degeneration (AM D). Fundus photograph, indocyanine green angiography and optical coherence tomography images of typical neovascular AM D (A), polypoidal choroidal vasculopathy (B), and retinal angiomatous proliferation (C). 1094
- 안소은외 : 삼출성나이관련황반변성의유형별비교 - 나이관련황반변성환자중에서치료기왕력이없는 153명 153안을대상으로하였다. 모든환자는내원당시최대교정시력, 안압측정, 굴절검사, 안저검사, 형광안저혈관조영, 인도시아닌그린혈관조영및빛간섭단층촬영을시행하였다. 최대교정시력은 Snellen 시력표를사용하여측정한뒤 log- MAR로변환하였다. 삼출성나이관련황반변성은황반부의맥락막신생혈관, 망막하액, 망막색소상피박리, 망막하삼출물과출혈을시사하는과형광및후기누출을보이는경우로정의하였으며, 20 안저소견, 형광안저혈관조영소견, 인도시아닌그린혈관조영결과를종합적으로판단하여 3개의군으로나누었다. 분지하는혈관망과그말단부의결절병변을보이는특징적소견이있는경우결절맥락막혈관병증 (polypoidal choroidal vasculopathy, PCV) 으로진단하였고특징적인망막-망막혹은망막-맥락막문합이발견되는경우망막혈관종성증식 (RAP) 으로진단하였으며이를제외한경우를전형적삼출성황반변성 (typical neovascular AMD, typical namd) 으로분류하였다 (Fig. 1). Lens Opacities Classification System III 분류에서 NO3, C3, P3 이상의백내장을동반한경우와고도근시 (6디옵터이상 ) 환자, 시력에영향을줄수있는다른질환이나병태를동반한경우본연구에서제외하였다. 이전에유리체망막수술을시행받았거나, 나이관련황반변성으로진단받고안구내주사또는레이저치료를시행받은경우역시연구에서제외하였다. 빛간섭단층촬영은 spectral-domain optical coherence tomography (SD-OCT; Cirrus TM HD-OCT 4000, Carl Zeiss Meditec, Dublin, CA, USA) 를사용하였고, 황반부큐브스캔 (macular cube scan mode) 및고해상도라스터스캔 (high-definition raster scan mode) 방법으로촬영하였으며, 7 이상의신호강도 (signal strength) 를보이는영상만을분석하였다. 중심하맥락막두께의측정중심하맥락막두께는 EDI 기법으로촬영된고해상도라스터스캔영상에서 Cirrus 소프트웨어에서제공하는직선측정도구 (linear measurement tool) 를이용하여, 망막색소상피 (retinal pigment epithelium, RPE) 의외측경계에서부터공막의내측경계까지수직선을그어측정하였다 (Fig. 2). 12,16,21 두명의저자 (ASE, ADS) 가독립적으로측정하여도출한 Figure 2. Measurement of subfoveal choroidal thickness. The image was obtained using enhanced-depth imaging optical coherence tomography (OCT). Choroidal thickness (double-head arrow) was defined as the vertical distance drawn from the outer border of the retinal pigment epithelium to the inner border of the sclera using Cirrus High-Definition-OCT software. A B Figure 3. Central macular thickness modification using a built-in segmentation-modifying tool of optical coherence tomography. Segmentation lines for retinal pigment epithelium (red dotted line) are determined automatically for each of the volume scans, and the central macular thickness is provided (A). Using the modifying tool, the cursor line on retinal pigment epithelium is moved to the level of Bruch s membrane. With this movement, the modified central macular thickness is determined (B). 1095
- 대한안과학회지 2016 년제 57 권제 7 호 - A B C Figure 4. Morphologic features of optical coherence tomography related to age-related macular degeneration. Intraretinal cystoid fluid is defined as round, hyporeflective cystic spaces within the neurosensory retina (A, arrow). Subretinal fluid is identified as nonreflective space between the posterior boundary of the neurosensory retina and the retinal pigment epithelium (B, arrow). Subretinal hyperreflective material appears as poorly defined, medium- to hyperreflective mass between neurosensory retina and retinal pigment epithelium (C, arrow). Pigment epithelial detachment is defined as a focal elevation of the reflective RPE band over an optically clear or moderately reflective space (B, C; arrowhead). 맥락막두께의평균값을분석에사용하였다. 중심하맥락막두께의측정자간일치도를분석한결과, 급내상관계수 (intra-class correlation coefficient) 0.984 (95% confidence interval [CI]: 0.978-0.988, p<0.001) 로높은신뢰도를보였다. 수정된중심망막두께중심망막두께는 cube scan data로부터계산된 Early Treatment Diabetic Retinopathy Study 영역중에서중심 1 mm 영역의평균망막두께로정의하였다. 중심망막두께의경우삼출성황반변성질병의특성상 SD-OCT 촬영에서흔하게발생하는망막내경계및망막외경계설정오류를 built-in segmentation-modifying tool을이용하여보정한후새롭게도출된중심 1 mm 영역의평균망막두께를사용하였다 (Fig. 3). 기타빛간섭단층촬영의특징적소견 OCT에서보이는특징적소견을망막내낭포액 (intraretinal cystoid fluid, IRCF), 망막하액 (subretinal fluid), 망막하고반사물질 (subretinal hyperreflective material), 망막색소상피박리 (pigment epithelial detachment, PED) 로분류하고존재유무를확인하였다 (Fig. 4). 22 통계분석 Typical namd, PCV, RAP 세가지유형에따른중심하맥락막두께, 중심망막두께및기타빛간섭단층촬영의특징적소견들의발생빈도를비교분석하였다. 통계분석은 SPSS version 18.0 (SPSS Inc., Chicago, IL, USA) 을사용하였다. 세가지유형간의비교분석은연속형변수의경우 one way analysis of variance (ANOVA) test, 범주형변수의경우카이제곱검정을이용하였으며, p-value가 0.05보다작은경우를통계적으로유의한것으로간주하였다. 유의한차이가있는경우각각의집단을본페로니검정 Table 1. Demographic data of the patients Characteristics Data Number of eyes (n) 153 Age (years) 71.9 ± 8.6 Sex (M:F) 96:57 Mean BCVA (log MAR) 0.662 ± 0.458 Mean SFCT (μm) 218.71 ± 64.47 Mean central macular thickness (μm) 465.09 ± 161.17 OCT characteristics (eyes, n [%] ) Intraretinal cytroid fluid 64 (41.8) Subretinal fluid 120 (78.4) Subretinal hyperreflective material 62 (40.5) Pigment epithelial detachment 142 (92.8) Values are presented as mean ± SD or n (%) BCVA = best corrected visual acuity; log MAR=logarithm of the minimum angle of resolution; SFCT = subfoveal choroidal thickness; OCT = optical coherence tomography. (bonferroni test) 을통해확인하였다. 결 과 전체대상군은총 153 명, 153 안으로남자 96 안, 여자 57 안이었으며평균나이는 71.9 ± 8.6세였다 (Table 1). 이중에서전형적삼출성나이관련황반변성 (typical namd군 ) 74 안 (48.4%), 결절맥락막혈관병증 (PCV군) 55안 (35.9%), 망막혈관종성증식 (RAP군) 24안 (15.7%) 이었다. 유형별연령, 성별, 진단당시굴절력및최대교정시력은 Table 2에제시하였으며통계학적유의한차이는보이지않았다. 진단당시중심하맥락막두께는 typical namd군이 207.26 ± 57.163 μm, PCV군이 253.76 ± 65.38 μm, RAP군이 173.71 ± 39.83 μm로통계적으로유의한차이를보였다 (p<0.001). PCV군이가장두꺼운맥락막두께를보였고, typical namd군이뒤를이었으며 RAP군이가장얇은맥락막두께를보였다 (Table 2, 3). 각각의그룹에서중심하맥 1096
- 안소은외 : 삼출성나이관련황반변성의유형별비교 - Table 2. Comparison of baseline characteristics among three subtypes of exudative age-related macular degeneration Typical namd PCV RAP p-value Number of eyes (n, %) 74 (48.4%) 55 (35.9%) 24 (15.7%) Age (years) 72.9 ± 8.5 69.8 ± 8.8 73.4 ± 7.9 0.086 Sex (M:F) 48:26 37:18 11:13 0.169 Mean SE (diopters) 0.18 ± 1.03 0.31 ± 0.82 0.40 ± 1.34 0.824 Mean BCVA (log MAR) 0.665 ± 0.490 0.657 ± 0.471 0.666 ± 0.323 0.993 Mean SFCT (μm) 207.26 ± 57.16 253.76 ± 65.38 173.71 ± 39.83 <0.001 * Mean CMT (μm) 442.39 ± 168.96 452.27 ± 135.87 564.46 ± 159.27 0.004 * Values are presented as mean ± SD unless otherwise indicated. One way ANOVA for continuous variables; χ 2 test for categorical variables. namd = neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy; RAP = retinal angiomatous proliferation; SE = spherical equivalent; BCVA = best corrected visual acuity; log MAR = logarithm of the minimum angle of resolution; SFCT = subfoveal choroidal thickness; CMT = central macular thickness. * p-value<0.05 was set as statistical significance. Table 3. Post-hoc analysis p-value among three subtypes Typical namd vs. PCV p-value PCV vs. RAP p-value RAP vs. typical namd p-value Subfoveal choroidal thickness <0.001 * <0.001 * 0.010 * Central macular thickness 1.000 0.012 * 0.003 * Bonferroni s method for post-hoc analysis. namd = neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy; RAP = retinal angiomatous proliferation. * p-value<0.05 was set as statistical significance. 락막두께와환자연령사이에의미있는연관관계를보이지는않았다 (Pearson s correlation coefficient, r=0.043, -0.017 and 0.103, p=0.823, 0.900 and 0.631, respectively). 맥락막두께와굴절력또한유의한상관관계를보이지않았다 (Pearson s correlation coefficient, r=0.174, 0.257 and 0.231, p=0.318, 0.158 and 0.277, respectively). 수정된중심망막두께는 RAP군이 564.46 ± 159.27 μm로 typical namd군 442.39 ± 168.96 μm, PCV군 452.27 ± 135.87 μm에비해유의하게두꺼운중심망막두께를보였다 (one way ANOVA test with Bonferroni s correction, p=0.003, 0.012, respectively) (Table 2, 3). 기타 OCT에서보이는특징적소견은유형별로서로다른빈도를보였다. 망막내낭포액의경우 RAP군에서 typical namd군과 PCV군에비해빈번하게관찰되었으며 (typical namd vs. PCV, p-value=0.469; PCV vs. RAP, p-value<0.001; RAP vs. typical namd, p-value<0.001), 망막하액은상대적으로 RAP군에서낮은빈도로관찰되었다 (typical namd vs. PCV, p-value=0.110; PCV vs. RAP, p-value=0.001; RAP vs. typical namd, p-value=0.021). 망막색소상피박리는 typical namd군에서 PCV군에비해낮은빈도로관찰되었고 (typical namd vs. PCV, p-value=0.005; PCV vs. RAP, p-value=0.304; RAP vs. typical namd, p-value=0.285), 망막하고반사물질은세군에서비슷한빈도로관찰되었다 (typical namd vs. PCV, p-value=0.763; PCV vs. RAP, p-value =0.990; RAP vs. typical namd, p-value=0.829) (Fig. 5). Figure 5. Comparative incidence of morphological features on optical coherence tomography in each subtypes of exudative age-related macular degeneration. Accounting for a Bonferroni correction, p-values less than 0.017 were considered to indicate statistical significance. namd = neovascular age-related macular degeneration; PCV = polypoidal choroidal vasculopathy; RAP = retinal angiomatous proliferation; IRCF = intraretinal cytroid fluid; SRF = subretinal fluid; HRM = subretinal hyperreflective material; PED = pigment epithelial detachment. * The frequency of morphological characteristics which have p-values less than 0.017 when compared with other subtype using Chi-square test. 고 찰 본연구는삼출성나이관련황반변성을전통적인방법인형광안저혈관조영술, 인도시아닌그린혈관조영술결과에따 1097
- 대한안과학회지 2016 년제 57 권제 7 호 - 라 typical namd, PCV, RAP 세가지유형으로나누고, 빛간섭단층촬영을통해측정한중심하맥락막두께, 중심망막두께및기타특징적소견들을유형별로비교분석해본결과, 유의한차이를보인다는것을확인하였다. Verteporfin을이용한광역학요법 (photodynamic therapy) 이나이관련황반변성의표준치료법이었던시기에는형광안저혈관조영술을통해맥락막신생혈관의유형을잠복형 (occult) 과전형적 (classic) 형태로구분하는것이치료반응을예측하는측면에서중요하게여겨졌다. 그렇지만현재는항혈관내피성장인자 (VEGF) 의유리체강내주사가표준치료방법으로서널리이용되고있으며, 맥락막신생혈관의형태에관계없이전반적으로좋은치료효과를나타냄이알려져있다. 23-25 이로인해실제임상에서삼출성나이관련황반변성환자를진단하고치료할때맥락막신생혈관의형태에따른전통적인분류는그유용성이낮아지고있으며, 그보다는예후나치료경과에있어서차이를보이는 PCV와 RAP를 typical namd와구분하는것이임상적으로더욱의미있을것으로생각된다. 결절맥락막혈관병증 (PCV) 는일반적으로전형적인맥락막신생혈관에비해양호한자연경과를보이지만, 반복적인출혈이나삼출변화로만성, 재발성경과를거치게되어결국시력저하를보이게되는경우도많다. 7,8 PCV의병인은아직완전히밝혀져있지않으나, 망막-맥락막기능부전및이로인한혈관이상으로시력저하를일으키는황반부질환이라는점과유전학적으로보체인자와관련된유사한발생배경을지닌다는점에서 AMD의한유형으로보여진다. 26 망막혈관종성증식 (RAP) 은다른종류의삼출성나이관련황반변성에비해예후가나쁘며양안성으로발생하는경우가많은것으로알려졌다. 9 전형적인삼출황반변성과비교하였을때, 망막혈관종성증식으로진단된환자는비교적나이가많고맥락막이더얇으며, 드루젠이나거짓드루젠과같은망막의연령관련변성소견이더높은빈도로나타나는것으로알려져있다. 27,28 본연구에서는안저소견, 형광안저혈관조영술및인도시아닌그린혈관조영술의결과를토대로 typical namd, PCV, RAP의세가지유형으로삼출성나이관련황반변성을분류하였다. typical namd, PCV, RAP 순으로 48.4%, 35.9%, 15.7% 의분포율을보였으며국내환자를대상으로한이제까지의연구결과와비교하였을때, 29 PCV의경우비슷한빈도를보였으나 RAP의경우본연구에서다소높은빈도를나타냈다. 이제까지여러연구를통해맥락막의순환과나이관련황반변성과의연관성이언급되어왔고, 맥락막의순환부전이삼출성나이관련황반변성의병태생리에있어서중요한 원인중의하나로보고되었다. 30,31 본연구에서는 PCV와 RAP 환자에서 typical namd와비교하여맥락막두께에있어서유의한차이를보였다. PCV군이가장두꺼운맥락막두께를보였고 typical namd, RAP 순으로얇은맥락막두께를보였다. Kim et al 27 은 RAP와 typical namd를비교한연구에서 RAP가 139.0 ± 65.5 μm로 184.9 ± 68.5 μm의 typical namd에비해더얇은맥락막두께를보인다고보고하였으며, 본연구에서도유사한결과를보였다. Kim et al 27 은 RAP에서얇은맥락막두께와더불어더넓은범위의드루젠분포를보이며이는 RAP 발생기전에있어서맥락막순환부전이더크게작용함을시사한다고하였다. PCV 의경우, Chung et al 16 의연구에서정상안및 AMD군에비해 PCV가 438.3 ± 87.8 μm로보다두꺼운맥락막두께를가짐이보고되었고, Kim et al 17 의연구에서도 PCV가 319.9 ± 68.7 μm로 AMD군에비해두꺼운맥락막두께를보였다. Rishi el al 32 또한 PCV가 285.9 μm로정상안과 wet AMD 안에비해두꺼운맥락막두께를가진다고보고하였다. 본연구에서도 PCV군이 253.76 ± 65.38 μm로통계적으로유의하게 typical namd와 RAP에비해두꺼운맥락막두께를보였다. 이는 PCV의발생기전에있어서맥락막혈관의위축보다는확장, 그리고이로인한혈류순환의장애가관여할것임을시사한다. 세가지유형의 AMD 모두맥락막순환부전이발생한다는점에서같은맥락의질환으로볼수있으나, 그원인에있어서 typical namd나 RAP의경우얇아진맥락막두께로미루어짐작하건대맥락막의전반적인위축으로인한혈류량의저하가신생혈관의발생과연관되어있을것으로보인다. 반면 PCV의경우두꺼운맥락막두께로판단하건대혈관벽의확장및얇아짐으로인해혈류속도의저하가초래되고이로인해맥락막순환부전을일으키는것으로생각된다. 정상안을대상으로한연구에서는연령이증가함에따라맥락막두께가감소함이알려져있으나, 33 본연구에서는세가지유형의삼출성나이관련황반변성모두연령과의상관성은보이지않았으며굴절력과도유의한상관관계가도출되지않았다. 정상안과는달리삼출성나이관련황반변성의경우연령이나굴절력에비해질병의활성도 (activity) 또는단계 (stage) 와같은변수들이맥락막두께에더큰영향을미쳤을것으로판단된다. 또한본연구에포함된대상들의연령및굴절률의범위가상대적으로좁기때문에연관성이 masking되었을가능성도배제할수없다. 본연구에서는 typical namd, PCV군에비해 RAP군에서유의하게두꺼운중심망막두께를보였다. RAP군에서다른군에비해망막하액은낮은빈도로관찰되고망막내낭포액이높은빈도로관찰된것으로미루어보아 RAP군에 1098
- 안소은외 : 삼출성나이관련황반변성의유형별비교 - 서중심망막두께가두꺼운것은망막하액보다는망막내낭포액에의한것으로보인다. 망막내낭포액은빛간섭단층촬영에서관찰되는저반사도의낭포성공간으로정의하며망막내층에축적된누출액으로인한부종과연관된다. 22 기존의연구결과를살펴보면, IRCF는삼출성나이관련황반변성에서초기시력과치료후최대교정시력의예측인자로보고되고있으며, classic choroidal neovascularization (CNV), RAP 또는후기단계 occult CNV 병변에서특징적으로관찰됨이알려져있다. 34 다시말해 IRCF는 RPE-choroid complex를넘어감각신경망막층의구조적변화를일으킨형태에서관찰되는소견임을알수있으며, 본연구에서도 RAP군에서다른두군에비해높은빈도로 IRCF가관찰되었고, 이는망막에서유래한것으로보이는신생혈관을특징으로하는 RAP의병태생리와연관된것으로생각된다. 망막하액은삼출성나이관련황반변성에서 70-85% 의빈도로나타나며, anti-vegf 치료에따라높은시력회복을기대할수있는예측인자로보고된다. 34 망막하액을동반한병변일수록적극적인치료후에도 RPE 위축의빈도가낮은것으로알려졌다. 35 본연구에서는 RAP군에서다른두군에비해망막하액의빈도가상대적으로낮게나타났으며, 이는 anti-vegf injection을반복함에따라지도형위축발생의빈도가높은 RAP의특성과어느정도연관성이있을것으로생각된다. 36 망막하액의빈도가낮은것과시력및치료반응과의연관성에관련하여서는추가연구가필요할것으로보인다. 망막색소상피박리는 PCV에서 typical namd에비해유의하게높은빈도로나타났다. 이는출혈성또는삼출성망막색소상피박리를잘일으키고, 폴립에서주변부돔모양의전형적인 PED로연결되는형태가흔한 PCV의임상적특징과일맥상통하며, typical namd는신생혈관이망막색소상피를뚫고나와망막하공간에서증식하는 type 2 CNV 의경우 PED를동반하지않기때문에낮은빈도를보인것으로생각된다. 망막색소상피박리는형태에따라 serous PED, fibrovascular PED, hemorrhagic PED 등으로세부분류하기도하며, 22 PED 형태별로발생빈도를비교해보는것또한임상적의미를가질것으로보여추후관련연구를진행해보고자한다. 망막하고반사물질은보통은 anti-vegf injection을시행함에따라 CNV가활성을잃어가면서섬유성조직으로변할때 OCT에서관찰되는소견이나, 활성화된삼출성나이관련황반변성의경우망막하출혈과지질성삼출물이망막하고반사물질로나타나며맥락막신생혈관의활성및누출정도와관련성있음이보고되었다. 37 Liakopoulos et al 38 은 type I CNV에비해 type II, III CNV 병변에서망막하고반사물질이흔하게발견된다고하였으나, 본연구에서와같이 typical namd, PCV, RAP로분류하여비교하였을때에는유형에따른빈도차이가보이지않았다. 본연구는후향적인단면연구법에의한분석이었다는점에서제한점이있다. 또한맥락막두께측정의경우중심하맥락막두께가전체적인맥락막의두께와형태를반영할수있는가하는의문점이따른다. Margolis and Spaide 21 의 enhanced depth imaging optical coherence tomography (EDI-OCT) 를이용한정상안에서의맥락막두께연구에따르면중심와아래에서가장두꺼운맥랙막두께를보이며, 주변부로갈수록얇아지는동일한패턴을보인다고하였다. 또한전형적삼출성나이관련황반변성과결절맥락막혈관병증의맥락막두께를비교한기존연구결과 16 에서상측, 하측, 비측, 이측으로 1,500 μm 떨어진지점에서측정한맥락막두께의차이가중심하맥락막두께에서보인차이와비슷한양상을보였다는점에서중심하맥락막두께의측정이전반적인맥락막의두께를어느정도반영할수있을것으로판단된다. 마지막으로두께를측정하는객관적인소프트웨어의부재로주관적인측정법에의해연구가진행되었다는한계점을갖는다. 두명의측정자간신뢰도가높았다는점에서주관성으로인한한계를어느정도보완하였다고판단되며, 추후새로운소프트웨어와장비가개발됨에따라보다정확한연구결과를얻을수있을것으로보인다. 본연구는아직까지국내에발표된바없는삼출성나이관련황반변성의세가지하위분류별빛간섭단층촬영의특징적소견을비교분석한연구이며, 비교적많은환자를대상으로했다는점에서의의가있다고하겠다. 추후진단장비가점차발전되어구조적으로망막과맥락막을더욱자세하고세밀하게가시화하는것이가능해지고영상의객관적인분석방법이고안된다면이와관련된보다의미있는연구결과를도출할수있을것으로기대한다. REFERENCES 1) Wong TY, Chakravarthy U, Klein R, et al. The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology 2008;115:116-26. 2) Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med 2008;358:2606-17. 3) Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina 1990;10:1-8. 4) Ciardella AP, Donsoff IM, Huang SJ, et al. Polypoidal choroidal vasculopathy. Surv Ophthalmol 2004;49:25-37. 5) Yannuzzi LA, Negrão S, Iida T, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina 2001;21:416-34. 1099
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- 안소은외 : 삼출성나이관련황반변성의유형별비교 - = 국문초록 = 세가지유형의삼출성나이관련황반변성에서빛간섭단층촬영의특징비교 목적 : 한번도치료받지않은삼출성나이관련황반변성환자에서전형적삼출성나이관련황반변성 (typical neovascular age-related macular degeneration [namd]), 결절맥락막혈관병증 (polypoidal choroidal vasculopathy, PCV), 망막혈관종성증식 (retinal angiomatous proliferation, RAP) 세가지하위분류에따른빛간섭단층촬영의특징을비교하고자하였다. 대상과방법 : 치료기왕력이없는삼출성나이관련황반변성환자 153 명 153 안을대상으로하였다. 깊이증강모드빛간섭단층촬영을이용하여진단시점에서의중심하맥락막두께와중심망막두께를측정하고망막내낭포액, 망막하액을비롯한구조적특징들을확인하였다. 전체환자군을전형적 namd, PCV, RAP 세그룹으로나누고특징들을비교하였다. 결과 : 총 153 안중에서 typical namd 가 74 안, PCV 가 55 안, RAP 가 24 안이었다. 연령과최대교정시력은그룹별유의한차이를보이지않았다. 중심하맥락막두께는 PCV 가가장두껍고, typical namd, RAP 순서로얇은두께를보였으며통계적으로유의한차이를보였다 (p<0.001). RAP 에서다른두군에비해유의하게두꺼운중심망막두께 (p=0.004) 와높은빈도의망막내낭포액의존재 (p<0.001) 를보였다. 결론 : 삼출성나이관련황반변성은세가지유형에따라서로다른빛간섭단층촬영의특징을보였다. PCV 는가장두꺼운맥락막두께를보였고, RAP 는가장얇은맥락막두께와두꺼운중심망막두께, 그리고높은빈도의망막내낭포액을보였다. 삼출성나이관련황반변성을유형별로감별진단하는데빛간섭단층촬영의특징분석이도움이될것으로보인다. < 대한안과학회지 2016;57(7):1093-1101> 1101