대한안과학회지 2015 년제 56 권제 2 호 J Korean Ophthalmol Soc 2015;56(2):205-212 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) http://dx.doi.org/10.3341/jkos.2015.56.2.205 Original Article 만성중심장액맥락망막병증에서광역학치료와유리체강내라니비주맙주입술전후의맥락막과투과성변화에대한정량적비교 Comparison of Choroidal Hyperpermeability Change after Photodynamic Therapy and Ranibizumab for Chronic Central Serous Chorioretinopathy 김정아 1 신주영 1 배소현 2 안지윤 3 정흠 1 허장원 1 Jeong Ah Kim, MD 1, Joo Young Shin, MD 1, So Hyun Bae, MD 2, Jee Yun Ahn, MD 3, Hum Chung, MD 1, Jang Won Heo, MD, PhD 1 서울대학교의과대학서울대학교병원안과학교실 1, 한림대학교의과대학강동성심병원안과학교실 2, 서울특별시보라매병원안과 3 Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine 1, Seoul, Korea Department of Ophthalmology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine 2, Seoul, Korea Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center 3, Seoul, Korea Purpose: To compare changes in choroidal hyperpermeability after half-energy photodynamic therapy (PDT) and intravitreal ranibizumab in the treatment of chronic central serous chorioretinopathy (CSC). Methods: Post-hoc analysis was performed in a randomized, controlled trial comparing half-energy PDT versus intravitreal ranibizumab for chronic CSC; during the experiments, the other treatment was available for salvage treatment if the original was unsuccessful at 3 months. A commercially available image analysis program (Adobe Photoshop CS6 [Adobe Systems, Inc., San Jose, CA]) was used for quantification of change in choriodal hyperpermeability on indocyanine green angiography after half-energy PDT or three consecutive intravitreal injections of ranibizumab. Post-treatment images were subtracted from pre-treatment images after adjustments were made to create images depicting the change in choroidal hyperpermeability with treatment. Integrated gray scale values per area in this image were used for analysis of change in choroidal hyperpermeability. Results: The calculated change in choroidal hyperpermeability was significantly greater in the half-energy PDT group (17.36 ± 8.74) than in the ranibizumab group (6.78 ± 5.03) (p < 0.001). All eyes in the half-energy PDT group showed complete resolution of subretinal fluid, and no significant difference in change of choroidal hyperpermeability was found in eyes that received half-energy PDT as primary or salvage treatment. In the ranibizumab-treated group, subretinal fluid resolution was accomplished in 5 eyes, and these eyes showed a significantly larger decrease in choroidal hyperpermeability when compared with eyes showing poor response (10.31 ± 4.00 vs. 2.74 ± 2.16, p = 0.005). In the successfully treated eyes with ranibizumab, there was no significant difference in choroidal hypopermeability change when compared to half-energy PDT (p = 0.124). Conclusions: Using our novel method of analysis of change in choroidal hyperpermeability following treatment for chronic CSC, greater change was found in eyes with good response, and the superior outcome of half-energy PDT over ranibizumab may be attributed to greater influence on choroidal hyperpermeability. J Korean Ophthalmol Soc 2015;56(2):205-212 Key Words: Choroidal hyperpermeability, Chronic central serous chorioretinopathy, Half-energy photodynamic therapy, Intravitreal ranibizumab injection Received: 2014. 11. 1. Revised: 2014. 12. 15. Accepted: 2015. 1. 27. Address reprint requests to Jang Won Heo, MD, PhD Department of Ophthalmology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: 82-2-2072-2438, Fax: 82-2-741-3187 E-mail: hjw68@snu.ac.kr * This study was presented as a narration at the 109th Annual Meeting of the Korean Ophthalmological Society 2013. * This study was presented as a poster at the 2013 Annual Meeting of Association for Research in Vision and Ophthalmology. 중심성장액맥락망막병증 (central serous chorioretinopathy) 은망막색소상피층의병적변화와이에동반된장액성망막박리를특징으로하는질병으로대부분의경우자연호전되고, 좋은시력예후를보인다. 1,2 하지만, 양성경과를보이는환자들과달리, 만성, 재발성경과를보이는환자에서는광범위한망막색소상피위축, 낭포성황반변성, 망막하삼출, 맥락막신생혈관등의합병증이동반되고, 불량한시력예후를보이기때문에치료가필요하다. 3-5 c2015 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. 205
- 대한안과학회지 2015 년제 56 권제 2 호 - 중심장액맥락망막병증의병리기전은명확하게밝혀지지않았지만, 맥락막혈관의투과성증가와망막색소상피의펌프기능과방어벽기능저하로인해장액성망막박리및망막색소상피박리가유발되는것으로알려졌다. 6-11 이러한병리기전에착안하여, 만성중심장액맥락망막병증의치료로광역학치료 (Photodynamic therapy) 와유리체강내항혈관내피성장인자 (vascular endothelial growth factor, VEGF) 주입술이시도되었다. 8,9,12-14 TPA 연구 (Treatment of Age-related Macular degeneration with Photodynamic Therapy Study) 에서제시한프로토콜에따른 PDT는맥락막신생혈관의치료에효과적인 verteporfin (Visudyne; Novartis AG, Basel, Switzerland) 을이용하여, 맥락막모세혈관의일시적인저관류와장기적인맥락막혈관의리모델링으로맥락막의울혈, 과도한혈관투과성과혈관외누출의감소를유도함으로써우수한치료효과를보였다. 12,15 하지만망막색소상피층의위축, 맥락막모세혈관의허혈, 이차적인맥락막신생혈관등의합병증이보고되면서, 16-18 부작용이적고, 대등한효과를보이는절반에너지광역학치료가임상적으로많이사용되고있다. 13,19 또한구조적인손상을최소화하기위한시도로 anti-vegf agent의맥락막혈관의과투과성을억제하는기전을이용한유리체강내라니비주맙 (Lucentis; Novartis AG, Basel, Switzerland) 주입술이중심장액맥락망막병증의치료로제시되었다. 8-10,20,21 이에저자들은만성중심장액맥락망막병증에서절반에너지를이용한 PDT와유리체강내라니비주맙주입술간의치료효과를분석하고, 치료후맥락막과투과성의변화와치료효과의관련성을정량적으로분석하고자하였다. 대상과방법 본연구는만성중심장액맥락망막병증또는재발성중심장액맥락망막병증으로진단받은만 18세이상의환자를대상으로시행한무작위전향적연구이다. 모든환자들에게서치료전충분한설명에근거한서면동의를받았고, 서울대학교병원의학연구윤리심의위원회승인을받아전향적연구를시행하였다. 대상환자군연구대상기준은만성중심장액맥락망막병증또는재발성중심장액맥락망막병증으로진단받은만 18세이상의환자중에빛간섭단층촬영검사 (optical coherence tomography, OCT, Cirrus; Carl Zeiss Meditec, Inc., Dublin, California, USA) 에서 3개월이상지속된황반부의장액성망막박리가확인되고, 형광안저혈관조영술에서형광누출이관찰되며, 인도사이아닌그린형광조영술 (indocyanine green angiography, ICGA, Heidelberg Retina Angiography; Heidelberg Engineering, Heidelberg, Germany) 에서병변영역의맥락막과투과성및맥락막혈관의확장이관찰되는경우로정의하였다. 만성중심장액맥락망막병증은증상이최소 6개월이상지속되고, 안저검사와 OCT에서황반부의장액성망막박리혹은망막색소상피박리가관찰되며, 형광안저촬영상형광누출이관찰되는경우로정의하였고, 재발성중심장액맥락망막병증은중심장액맥락망막병증호전 6개월후에, 중심장액맥락망막병증이재발한경우로, 3개월이상중심장액맥락망막병증이지속된경우로정의하였다. 제외기준으로 1) 광역학치료, 국소레이저광응고술, 유리체강내스테로이드또는 anti-vegf agent 주입술을받은병력이있는경우, 2) 맥락막신생혈관또는결절맥락혈관병증이확인된경우, 3) 당뇨망막병증, 망막정맥폐쇄, 포도막염등의시력저하를야기하는안질환이동반된경우, 4) 심한매체혼탁으로검사의질이낮은경우, 5) 백내장수술을제외한안내수술을받은경우, 6) 12개월이내에전신적스테로이드나 anti-vegf agent 치료를받은경우, 7) 안압이조절되지않는녹내장을동반한경우로정의하였다. 모든환자는치료전과치료후 12개월까지매달경과관찰하도록하였고, 방문시마다최대교정시력, 세극등현미경검사, 안저검사, OCT를시행하였으며, 치료전과치료후 3개월마다형광안저조영술과 ICGA를시행하였다. 맥락막과투과성의변화를평가에필요한치료전후의 ICGA를시행하지못한환자는분석에서제외하였다. 치료방법만성중심장액맥락망막병증또는재발성중심장액맥락망막병증을진단받은환자들을절반에너지광역학치료군또는유리체강내라니비주맙주입술군으로무작위로배정하여치료하였다. 절반에너지를이용한 PDT는체표면적당 (m 2 ) 6 mg 의 verteporfin을 10분간정맥주사하고, 주사시작 15분후에 689 mm의다이오드레이저를상용하여, 300 mw의세기로 83초간병변부위에조사하였고 (25 J/cm 2, 300 mw/cm 2, for 83 seconds), 범위는맥락막과투과병변의장축을기준으로시행하였다. 라니비주맙주입술은 0.5 mg/0.05 ml의라니비주맙을 1달간격으로 3회연속으로유리체강내에주입하였다. 치료 3개월후에최대교정시력 (logmar) 과 OCT를이용하여, 치료효과를평가하였으며, 1) OCT에서망막하액이지속되고, 0.2 logmar 이상의시력저하가발생하거나, 2) 치료이전과비교하여, 망막하액의감소가없는경우, 또는 3) 재발된경우에서, 2달이상연속적으로망막하액의감소 206
- 김정아외 : 중심장액맥락망막병증에서맥락막과투과성 - 가없는경우에는구제치료를시행하였다. 구체치료는 1차치료로유리체강내라니비주맙주입술을시행받은경우, 1 회의절반에너지광역학치료를시행하였고, 1차치료로절반에너지광역학치료를받은경우, 유리체강내라니비주맙주입술을시행하였다. 치료효과및맥락막과투과성의변화의평가치료성공은 1차치료후, 12개월동안구제치료없이 OCT에서망막하액이관찰되지않고, 관해를유지한경우로정의하였고, 치료전과치료 3개월후의중심황반두께차이를비교하여, 치료효과를분석하였다. 중심황반두께는 OCT의중심와의안쪽망막표면과바깥쪽망막표면사이의거리로정의하였다. 맥락막투과성의변화를평가하기위해치료전과 3개월후의초기 ICGA영상에서관찰되는병변의맥락막투과성의차이를상용이미지분석소프트웨어 (Adobe Photoshop CS6 [Adobe Systems, Inc., San Jose, CA]) 를이용하여분석하였다. ICGA는색소농도, 사용기종및조명강도에따라조영양상이달라질수있기때문에, 한명의숙련된검사자가지정된검사실의동일한검사기기 (Heidelberg Retina Angiography; Heidelberg Engineering, Heidelberg, Germany) 를이용하여 ICGA를시행하였고, 모든검사에서같은농도의인도시아닌그린색소 (40 mg의인도시아닌그린색소를증류수 2 ml에희석 ) 를사용하였으며, 인도시아닌그린색소주입후, 1분경에촬영된치료전과치료후의 ICGA 영상을분석에사용하였다. 상용이미지분석소프트웨어의 차감기능 (subtraction) 을이용한영상분석은치과질환의치료효과의객관적인평가및분석을위해사용되는방법으로, 22-25 저자들은 Carvalho et al 22 과 Angerame et al 24 이소개한차이이미지분석방법 (digital subtraction radiography) 을이용하여치료전과치료 3개월후의 ICGA 영상간의차이이미지를얻었다. 22-23 상용이미지분석소프트웨어에서색상모드를 8비트회색음영 (grayscale) 으로설정한후에치료전과치료후의 ICGA 영상을불러온다 (0 gray scale 255, 0=black, 255=white). 특정해부학적기준위치 ( 시신경과주요혈관 ) 가일치하도록위치를조정한다. 두이미지간의동일한위치의정상영역을지정하여해당영역의평균그레이스케일의차이를구한다. 이미지 메뉴에서 연산 도구를선택한후, 도구상자에서 소스 1 과 소스 2 에각각 치료전 ICGA 영상 과 치료후 ICGA 영상 을선택하고, 회색채널 로설정한다. 혼합 에서 빼기 을선택하고, 두이미지간의전체밝기차이에의한그레이스케일값차이를보정하기위해 오프셋 에정상영역의평균그레이스케일의차이 (-255 offset 255) 를입력한후, 결과 에 새문서 를선택하면새로운 차이이미지 가생성된다. 차이이미지의정상영역은치료전과후의맥락막투과성의차이가없으므로, 차이이미지에서검은색으로나타나며, 그레이스케일은 0 으로나타난다 (0 gray scale 255, 0=black, 255=white). 상용이미지분석소프트웨어를이용하여, 차이이미지에서확인되는변화된영역의단위면적당그레이스케일값으로맥락막과투과성의변화를정량화하였다 ( 맥락막과투과성의변화 = 차이이미지에서관 A B C Pre-treatment ICGA image Post-treatment ICGA image Subtracted image Figure 1. The method of calculating choroidal hyperpermeability changes after treatment of chronic central serous chorioretinopathy. A 47-year-old female treated with half energy photodynamic therapy (HE-PDT) for chronic central serous chorioretinopathy (CSC). Hyperfluorescent dilated choroidal vessels seen before treatment (A) was disappeared after half-energy PDT (B). The dashed ovoid lines (A, B, and C) indicate the area with choroidal hypermeabity at pretreatment. We quantified the change in choroidal hyperpermeability after treatment for chronic central serous chorioretinopathy using commercially available image analysis software (Adobe Photoshop CS6 [Adobe Systems, Inc., San Jose, CA]). By this software, we calculated the mean gray scale in the reference area (circled area in A, B, and C) for correction the contrast difference between pre-treatment indocyanine green angiography (ICGA) image and post-treatment ICGA image. We subtracted post-treatment ICGA image from pre-treatment ICGA image to make the subtracted image representing the change in choroidal hyperpermeability after treatment for chronic CSC (C). We calculate integrated gray scale value per area in subtracted image for analysis of change in choroidal hyperpermeability. 207
- 대한안과학회지 2015 년제 56 권제 2 호 - Table 1. Demographic characteristics in each group Baseline characteristics Half-energy PDT Ranibizumab (n = 9) (n = 13) p-value Sex (M:F) 8:1 12:1 Age (years) 52.89 51.80 0.929 * BCVA 0.36 ± 0.19 0.35 ± 0.15 0.846 * CFT (μm) 303.2 ± 43.9 297.2 ± 61.4 0.421 * Choroidal hyperpermeability with dilated choroidal vasculature 9 (100) 13 (100) 0.999 on ICGA (n, %) Values are presented as mean ± SD unless otherwise indicated. PDT = photodynamic therapy; BCVA = best corrected visual acuity in logarithm of the minimum angle of resolution; CFT = central forveal thickness; ICGA = indocyanine green angiography. * Analyzed with Mann-Whitney U-test. Windows (SPSS Inc., Chicago, IL, USA) 를이용하여분석하였다. 치료방법에따른맥락막과투과성의변화를 Mann- Whitney U-test를이용하여비교분석하였고, linear regression analysis를이용하여, 치료전후의중심황반두께의변화와맥락막과투과성의변화의상관관계를분석하였다. p값이 0.05보다작은경우통계적으로유의한것으로정하였다. Figure 2. Flow chart of treatment progress. CSC = central serous chorioretinopathy; HE-PDT = half energy photodynamic therapy. Figure 3. The calculated changes in choroidal hyperpermeability after treatment for chronic central serous chorioretinopathy according to primary treatment methods (HE-PDT versus 3 consecutive intravitreal ranibizumab injections). HE-PDT = half energy photodynamic therapy. * Between-group comparison was evaluated by Mann-Whitney U-test. 찰되는병변의총 gray scale/ 병변의면적 ) (Fig. 1). 13,24 통계분석본연구에서는측정된결과를 PASW version 18.0 for 결과 총 22안이연구에포함되었다. 1차치료로 9안이절반에너지광역학치료를받았고, 13안이라니비주맙주입술을받았다 (Table 1). 절반에너지광역학치료군은남자가 8안, 여자가 1안이었고, 라니비주맙군은남자가 12안, 여자가 1 안이었다. 치료전의최대교정시력 (logmar) 은절반에너지광역학치료군이 0.36 ± 0.19, 라니비주맙치료군이 0.35 ± 0.15 였고, 중심황반두께는절반에너지광역학치료군이 303.2 ± 43.9 μm, 라니비주맙치료군이 297.2 ± 61.4 μm로두군간의차이는없었다 (p=0.846, p=0.421). 1차치료 3개월후, 절반에너지광역학치료를받은모든환자에서관해를보였으나, 라니비주맙주입술을받은군 13안중 5안 (38.46%) 만이관해를보여, 나머지 8안 (61.54%) 은구제치료로절반에너지를이용한 PDT를받았다 (Fig. 2). 상용이미지분석소프트웨어를이용하여얻은차이이미지에서맥락막과투과성의변화를확인할수있었다. 1차치료로절반에너지광역학치료를받은군은모두에서맥락막과투과성의감소를보였으나, 라니비주맙치료를받은군은맥락막과투과성의변화가없는경우도있었다. 두군간의 1차치료후맥락막과투과성의변화를비교하였을때, 절반에너지광역학치료군이라니비주맙치료군보다맥락막과투과성의감소가통계적으로유의하게컸다 (17.36 ± 8.74, 6.78 ± 5.03, p<0.001) (Fig. 3). 하지만, 1차치료로라니비주맙주입술을받고, 치료성공을보였던군과 1차치료로절반에너지광역학치료를받은군의맥락막과투과성 208
- 김정아외 : 중심장액맥락망막병증에서맥락막과투과성 - Figure 4. The comparison of change of choroidal hyperpermeability after treatment in the successfully treated eyes for chronic central serous chorioretinopathy (HE-PDT versus 3 consecutive intravitreal ranibizumab injections). HE-PDT = half energy photodynamic therapy. * Between-group comparison was evaluated by Mann-Whitney U-test. Figure 6. The association of the change in choroidal hyperpermeability with decrease in central forveal thickness. HE-PDT = half energy photodynamic therapy. 지광역학치료후의맥락막과투과성변화에는차이가없었다 (17.36 ± 8.74, 20.04 ± 6.01, p=0.427). 치료전후의맥락막과투과성의변화정도와 OCT에서중심황반두께의차이의상관분석을한결과, 맥락막과투과성의변화와 OCT에서의중심황반두께의감소가유의한상관관계가있었다 (r 2 =0.296, p=0.01) (Fig. 6). 고 찰 Figure 5. The comparison of change of choroidal hyperpermeability after treatment in the eyes treated with 3 consecutive intravitreal ranibizumab injections for chronic central serous chorioretinopathy. * Between-group comparison was evaluated by Mann-Whitney U-test. 의감소에는차이가없었다 (10.31 ± 4.00, 17.36 ± 8.74, p=0.124) (Fig. 4). 1차치료로라니비주맙주입술을받은환자들의치료성공여부에따른맥락막과투과성의변화를비교했을때, 치료에성공한군이치료에실패한군에비해맥락막과투과성이유의하게감소하였다 (10.31 ± 4.00, 2.74 ± 2.16, p=0.005) (Fig. 5). 1차치료로라니비주맙주입술후치료실패하여구제치료로절반에너지광역학치료를받은모든눈에서관해를보였으며, 1차치료로절반에너지광역학치료를받은군과구제치료로절반에너지광역학치료를받은군간의절반에너 저자들은본연구에서만성중심장액맥락망막병증의환자에서 1차치료결과, 만성중심장액맥락망막병증의환자에서절반에너지를이용한 PDT가유리체강내라니비주맙주입술에비해치료효과가우월함을알수있었다. 또한상용이미지분석소프트를이용한차이이미지분석방법으로맥락막과투과성의변화를확인할수있었고, 중심장액맥락망막병증의치료후, OCT에서의중심황반두께감소와 ICGA 영상에서의맥락막과투과성의감소간의유의한상관관계가있음을확인할수있었다. 중심장액맥락망막병증은감각신경망막층밑에장액이축적되는것을특징으로하는질환으로맥락막혈관의과투과성이병인으로알려져왔다 6,7,26-29 중심장액맥락망막병증환자에서 TPA 프로토콜에따른광역학치료가맥락막과투과성감소와국소적인망막색소상피누출을줄임으로써, 감각망막박리와시력을호전시키는효과가있어치료에많이사용되어왔다. 15,29-31 하지만, TPA 프로토콜에따른광역학치료후에발생하는망막색소상피의위축, 맥락막모세혈관의허혈변화, 이차성맥락막신생혈관형성등의합병증이보고되면서이를줄일수있는치료방법을모색하는치료들이시도되었다. 13,16-19 이러한시도중에하나인절반에너지광역학치료는 TPA 프로토콜에따른광역학치료에 209
- 대한안과학회지 2015 년제 56 권제 2 호 - 상응하는치료효과가있지만, 치료후의맥락막혈관의허혈의정도가유의하게낮아, 13,19 임상적으로많이사용되어왔고, 13,16,17,19 Anti-VEGF agent 역시맥락막혈관의과투과성을억제하는효과가있음이보고되면서중심장액맥락망막병증의새로운치료로시도되었다. 8-10,20,21 본연구에서만성중심장액맥락망막병증의 1차치료로라니비주맙주입술을받은군이절반에너지광역학치료를받은군과비교하여, 치료성공률은낮았지만, 일부에서효과를보였다. 라니비주맙주입술받은환자중에효과가있었던군은절반에너지를이용한절반에너지광역학치료를받은군과동등한맥락막투과성의감소가있어, 라니비주맙주입술의치료효과도맥락막투과성의감소와관련성이있음을확인할수있었다. 또한라니비주맙치료후호전되지않아절반에너지광역학치료로구제치료를받은경우에도, 1차치료로절반에너지광역학치료를한군과동일한치료효과가있었다. 따라서절반에너지광역학치료를받을수없는환자의경우, 라니비주맙주입술을 1차치료로시도해볼수있을것이라생각한다. 본연구는절반에너지광역학치료가라니비주맙주입술에비해서우월한치료효과가있음을확인하였고, 치료효과와맥락막과투과성의감소가유의한상관관계가있음을새로운분석방법을통해정량적으로확인할수있었다. 기존의연구에서중심장액맥락망막병증으로광역학치료를받은환자를대상으로광역학치료후에발생하는맥락막허혈의정도를평가하는방법을이용하여, 치료후의맥락막허혈의정도를분석한연구들이보고되었다. Reibaldi et al 19 은 Michels et al 18 의 grading system에따라만성중심장액맥락병증으로광역학치료를받은환자를대상으로치료후의맥락막허혈의정도를 5단계의 Grade system으로평가하여, 절반에너지를사용한광역학치료가 TPA 프로토콜에따른광역학치료에비해치료후의맥락막허혈의정도가낮음을확인하였다. 19 하지만 Michels et al 18 의 grading system은미세한변화를확인하는데제한이있고, 정량적분석이어렵다는한계가있다. 13 이에 Shin et al 13 은상용이미지분석소프트웨어를이용하여광역학치료의합병증인치료후에발생하는맥락막허혈의정도를객관적이고정량적으로분석하여, 절반에너지를이용한광역학치료가 TPA 프로토콜에따른광역학치료에비해치료후의맥락막허혈이유의하게낮음을정량적으로분석하였다. 이처럼기존의연구에서중심장액맥락망막병증에서광역학치료후에발생하는맥락막혈관의허혈정도를평가하는노력들이있어왔으나, 치료전후의맥락막과투과성의변화를평가하는연구는없었다. 13,19 이에저자들은 Shin et al 13 과 Carvalho et al 22 의분석방법을응용한새로운분석방법을통해맥락 막과투과성을보이는중심장액맥락망막병증환자에서절반에너지를이용한광역학치료또는 Anti-VEGF anget 치료후에맥락막과투과성의감소를분석하였다. 저자들의새로운분석방법으로맥락막과투과성의변화를시각화하여, 미세한변화도확인하였고, 중심장액맥락망막병증치료후치료후의맥락막과투과성의감소와중심황반두께감소간의유의한관련성이있음을정량적으로분석할수있었다. 본연구는촬영조건에따른 ICGA 영상간의밝기및명암대비의차이를줄이기위해모든 ICGA를동일한검사실에서, 한명의검사자가같은농도의색소를이용하나한개의기기로검사를시행하였지만, 정상영역의치료전후의 ICGA 영상간의밝기의차이가있어 ICGA 영상분석을위해이를보정할필요가있었다. Carvalho et al 22 은차이이미지분석방법에서방사선영상간의밝기와명암대비의차이에의한오차를보정하기위해한영상의전체영역의히스토그램에서나타나는평균 pixel intensity를보정하였으나, Angerame et al 24 은치료에의한병변의변화가전체영상의히스토그램에미치는영향을보정하기위해환자의방사선영상검사를할때, 함께촬영한 Benfica e Silva et al 32 의기준스케일 (reference scales) 의히스토그램이두영상간에일치하도록전체영상을보정한후, Carvalho et al 22 의방법으로차이이미지를획득함으로써, Carvalho et al 22 의방법을보완하였다. 저자들은중심장액맥락망막병증의치료후 ICGA 영상에서의병변의밝기변화가전체히스토그램에영향을미칠수있기때문에, Angerame et al 24 이제시한방법을응용하였으나, ICGA 촬영시에기준스케일을함께촬영할수없어, 정상영역을기준스케일로설정하여두영상간의밝기보정을하였기때문에분석에오차가발생할수있는제한점이있다. 24 저자들이사용한차이이미지분석방법은맥락막과투과성의변화를시각화하여, 미세한변화도시각적으로확인할수있고, 변화를정량적으로분석할수있다는장점이있으며, 맥락막과투과성의변화를정량적으로분석할수있는방법을제시함에본연구의의의가있다고생각한다. 하지만차이이미지분석방법에서촬영조건에따른두영상간의전체밝기차이에의한오차를보완할수있는추가연구가필요하다고생각한다. 저자들은 ICGA에서의맥락막과투과성의변화를정량적으로분석할수있는새로운방법을이용하여, 만성중심장액맥락망막병증에서치료효과와맥락막과투과성의감소간의유의한상관관계가있음을확인하였다. 절반에너지를이용한광역학치료가유리체강내라니비주맙주입술과비교하여맥락막과투과성을줄이는효과가더크기때문 210
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- 대한안과학회지 2015 년제 56 권제 2 호 - = 국문초록 = 만성중심장액맥락망막병증에서광역학치료와유리체강내라니비주맙주입술전후의맥락막과투과성변화에대한정량적비교 목적 : 만성중심장액맥락망막병증에서절반에너지광역학치료와유리체강내라니비주맙주입술치료후의맥락막과투과성의변화를정량적으로비교하고자하였다. 대상과방법 : 만성중심장액맥락망막병증에서절반에너지광역학치료와유리체강내라니비주맙주입술의무작위대조시험을시행하였다. 치료 3 개월후에효과를평가하여, 호전이없으면구제치료를시행하였다. 사후분석으로, 상용이미지분석소프트웨어를이용하여인도사이아닌그린혈관조영에서치료전후병변의맥락막과투과성변화를정량화하여비교하였다. 결과 : 절반에너지광역학치료를받은군은모두가망막하액이소실되었으나, 라니비주맙주입술을받은군은일부만이호전을보였다. 상용이미지분석소프트웨어를이용하여분석한결과광역학치료군이라니비주맙군에비하여, 치료후에맥락막과투과성의감소가통계적으로유의하게컸다 (p<0.001). 광역학치료를받은군에서일차치료와구제치료간의맥락막과투과성변화의차이는없었다 (p=0.427). 라니비주맙주입술을받은군내에서는호전된 5 안이치료효과가없었던 8 안에비해통계적으로유의하게맥락막과투과성이감소하였다 (p=0.005). 결론 : 인도사이아닌그린혈관조영에서맥락막과투과성의변화를정량화하는새로운방법을이용하여, 만성중심장액맥락망막병증에서치료효과와맥락막과투과성의감소의상관관계를확인하였다. 결론적으로절반에너지를이용한광역학치료가유리체강내라니비주맙주입술과비교하여맥락막과투과성을줄이는효과가더크기때문에만성중심장액맥락망막병증에서치료결과가더우수한것으로생각한다. < 대한안과학회지 2015;56(2):205-212> 212