대한안과학회지 2008 년제 49 권제 10 호 J Korean Ophthalmol Soc 2008;49(10):1603-1610 DOI : 10.3341/jkos.2008.49.10.1603 나이관련황반변성에서광역학요법후발생한망막하출혈의임상분석 윤재문 김호숭 강재훈 윤희성 성모안과병원 목적 : 나이관련황반변성환자에서광역학요법후발생한망막하출혈의임상분석에대해보고하고자한다대상과방법 : 2005 년 1 월부터 2006 년 12 월까지나이관련황반변성으로진단받고광역학요법을시행하였던 243 명 267 안을후향적으로분석하였다. 치료후 1 주와 1 개월, 3 개월및그후매 3 개월마다경과관찰을하였다. 결과 : 광역학요법을시행받은 267 안중 36 안 (13.4%) 에서망막하출혈이발생하였다. 망막하출혈이발생한환자의나이는평균 69 세였고, 남자가 25 안여자가 11 안이었다. 평균시력은술전 logmar 0.80 술후 logmar 1.05 로평균 2.05 줄의시력저하를보였다. 형광안저혈관조영소견상우세전형적 2 안, 소수전형적 4 안, 숨은맥락막신생혈관 30 안이었다. 조사된 LASER spot size 는 3,000 µm 이하가 1 안, 3,000~5,000 µm 가 19 안, 5,000 µm 이상이 16 안이었다. 결론 : 나이관련황반변성환자에서광역학요법시망막하출혈은 13.4% 로발생하였고, 숨은맥락막신생혈관의경우와레이저조사반크기가큰경우망막하출혈의합병증의빈도가높으므로이런경우주의가필요할것으로생각된다. < 대한안과학회지 2008;49(10):1603-1610> 나이관련황반변성, 병적근시등에서동반되는맥락막신생혈관의치료에서광역학요법이사용되고있으며그효과가전향적무작위임상연구인 TAP (Treat ment of AMD with Photodynamic therapy) 연구와 VIP (Verteporfin in Photodynamic thera py) 연구에의해입증되었다. 1-4 이러한광역학요법에서여러가지부작용이발생할수있는데, 그중에서급격한시력저하는 0.7~4.4% 정도이다. 2,3 급격한시력저하의원인은망막하출혈의증가, 장액성망막박리의증가, 또는안저검사상특이소견을동반하지않는맥락막비관류등이며그중망막하출혈이가장흔한원인으로보고되었다. 5 특히나이관련황반변성환자에서광역학요법후발생한망막하출혈은, 출혈로인한추가적인광역학요법이불가능하게되고, 출혈에의한시력예후 < 접수일 : 2008 년 2 월 25 일, 심사통과일 : 2008 년 7 월 2 일 > 통신저자 : 윤희성부산시해운대구우 2 동 1078-7 성모안과병원 Tel: 051-743-0775, Fax: 051-743-0776 E-mail: heesyoon@dreamwiz.com * 본논문의요지는 2007 년대한안과학회제 97 회춘계학술대회에서구연으로발표되었음. 가나빠지며, 추가적인수술적조치가필요하게되는문제점을야기할수있다. 나이관련황반변성환자에서광역학요법후발생한망막하출혈의임상양상을분석하여광역학요법시발생할수있는망막하출혈의위험인자를알아보고자하였다. 대상과방법 2005 년 1 월부터 2006 년 12 월까지나이관련황반변성으로진단받고본원에서비쥬다인을이용한광역학요법을시행하였던 243 명 267 안을후향적으로분석하였다. 나이는 45 세부터 74 세까지로평균 63 세였고, 남자가 164 명, 여자가 79 명이었다. 경과관찰기간은 6 개월에서 26 개월까지평균 10.8 개월이었다. 치료후 1 주와 1 개월, 3 개월및그후매 3 개월마다경과관찰을하면서최대교정시력을측정하고, 안저검사및플루레신형광안저혈관조영술을시행하여그결과를분석하였다. 3 개월마다시행한플루레신형광안저혈관조영술소견상맥락막신생혈관에서의누출이있을때에는재치료를시행하였다. 광역학요법시플루레신형광안저혈관조영술에서병변부위중가장긴부분의길이 (Greatest Linear Dimension, GLD) 를컴퓨터소프트웨어 (Image 1603
윤재문외 : 광역학요법후망막하출혈 net) 를이용하여구하고, 카메라렌즈배율 (35 도인경우 2.5, 50 도인경우 1.8) 로나누어안저상에서의실제병변크기를구해서 1,000 µm 를더하여 spot size 를정하였다. 체표면적당 6 mg 의 verteporfin 을 3 ml/min 의속도로 10 분간정맥주입하였다. 레이저는 689 nm 파장의비온열다이오드레이저인 Opal Photoactivator 를사용하였다. 레이저를병변부위에 verteporfin 정맥주입시작후 15 분뒤에시작하여 83 초간 50 J/cm 2 이조사되도록했다. 통계학적분석은 SPSS 11.0 for windows 를이용하여 Pearson Chi-Square test 및 Fisher s Exact Test 를시행하였고유의수준은 0.05 로하였다. 결 Number of patients* 36 (13.4%) Age (years) 63.12±5.2 (45-74) Sex (M:F) 25:11 Preop BSCVA (logmar) 0.80 Postop BSCVA (logmar) 1.05 Change of VA (lines) 2.05 * Patients who had hemorrhage after photodynamic therapy; BSCVA=best spectacle-corrected visual acuity; Change of VA=difference between pre-operative BSCVA and postoperative BSCVA. Table 2. Onset of hemorrhage after photodynamic therapy Onset of hemorrhage after PDT* <1 week 1 week ~ < 1 month 1 month * PDT=photodynamic therapy. 과 광역학요법후 267 안중 36 안 (13.4%) 에서망막하출혈이발생하였다. 출혈소견을보인 36 명의평균연령은 63.1 세였으며, 성별은남자와여자가각각 25 명과 11 명이었다 (Table 1). 전신질환은고혈압을가진환자가 18 명이었고, 당뇨병환자 6 명, 허혈성심질환자 1 명이었으며항응고치료를받고있는환자는 1 명이었고나머지는특이사항이없었다. 치료전평균 logmar 시력 0.80, 치료후평균 logmar 시력 1.05 로평균 2.05 줄의시력감소를보였다. 형광안저혈관조영소견상우세전형적맥락막신생혈관 Table 1. Demographics of the patients who had a retinal hemorrhage after photodynamic therapy Eyes (percent) 9/36 (25.0%) 7/36 (19.4%) 20/36 (55.6%) 2 안 (5.6%), 소수전형적맥락막신생혈관 4 안 (11.1%), 숨은맥락막신생혈관 30 안 (83.3%) 이었다 (Fig. 2). 인도사이아닌그린형광안저혈관조영소견상맥락막신생혈관 18 안 (50.0%), 특발성결절성맥락막혈관병증 5 안 (13.9%), 망막색소상피박리를동반한맥락막신생혈관 11 안 (30.6%), 망막색소상피박리를동반한특발성결절성맥락막혈관병증 1 안 (2.8%) 그리고망막색소상피박리를동반한망막혈관종성증식 1 안 (2.8%) 이었다 (Fig. 3). 광역학요법시행후 1 주이내에출혈이발생한경우가 9 안 (25%) 이었으며 1 주에서 1 개월사이출혈이발생한경우가 7 안 (19.4%), 1 개월이후출혈이발생한경우 20 안 (55.6%) 이었다 (Table 2). 출혈의범위는 2 유두직경미만인경우가 18 안 (50%), 2 유두직경이상인경우가 9 안 (25%), 이측혈관궁범위를넘어가는경우가 3 안 (8.3%), 유리체출혈을동반하는경우가 6 안 (16.7%) 이었다 (Fig. 1)(Table 3). 조사된레이저반의크기는 3,000 µm 이하인경우가 1 안 (2.7%), 3,000~5,000 µm 인경우가 19 안 (52.8%), 5,000 µm 이상인경우가 16 안 (44.5%) 이었다. 전체망막하출혈이있었던경우의 97.2% 가레이저조사반이 3,000 µm 보다컸다 (Table 4). 조사대상 267 안중망막색소상피박리를동반한경우 68 안, 망막색소상피박리를동반하지않은경우가 199 안이었으며망막색소상피박리를동반한경우망막하출혈은 68 안중 13 안 (19.1%) 이었으며, 망막색소상피박리를동반하지않은경우망막하출혈은 199 안중 23 안 (11.6%) 으로망막색소상피박리를동반한경우망막하출혈의빈도가높았으나통계학적유의성은없었다 (Pearson Chi-Square test, P=0.12). 또한이 Table 3. Extent of hemorrhage after photodynamic therapy Extent of hemorrhage Eye (percent) < 2 disc diameter 18/36 (50.0%) 2 disc diameter 9/36 (25.0%) Massive hemorrhage* 3/36 (8.3%) Vitreous hemorrhage 6/36 (16.7%) * subretinal hemorrhage extends beyond the temporal vascular arcades; subretinal hemorrhage with vitreous hemorrhage. Table 4. Spot size of laser Spot size of laser (µm) < 3,000 3,000 ~ < 5,000 5,000 Eye (percent) 1/36 (2.7%) 19/36 (52.8%) 16/36 (44.5%) 1604
대 한 안 과 학 회 지 2008년 제 49 권 제 10 호 A B C D Figure 1. (A) Subretinal hemorrhage less than 2 disc diameter. (B) Subretinal hemorrhage more than 2 disc diameter. (C) Subretinal hemorrhage extends beyond the temporal vascular arcades. (D) Subretinal hemorrhage with vitreous hemorrhage. Figure 2. The fluorescein angiographic classification of age related macular degeneration which had subretinal hemorrhage after photodynamic therapy. 측 혈관궁 범위를 넘어가는 경우와 유리체 출혈을 동 반하는 경우를 광범위한 망막출혈(massive retinal hemorrhage)로 정의하였는데, 광범위한 망막출혈은 망막하출혈이 발생한 36안 중 9안으로 25%을 차지하 였다. 특히 광범위한 망막출혈은 망막색소상피박리를 동반한 경우(13안 중 5안: 38.5%)가 망막색소상피박 리를 동반하지 않은 경우(23안 중 4안: 17.4%)보다 Figure 3. The indocyanine green angiographic classification of age related macular degeneration which had subretinal hemorrhage after photodynamic therapy. (CNV=choroidal neovascularization; PCV=polypoidal choroidal vasculopathy; RAP=retinal angiomatous proliferation; PED=pigment epithelial detachment) 호발하였지만 통계학적 유의성은 없었다(Fisher s Exact Test, P=0.23). 망막색소상피박리를 동반한 망막하출혈 13안 중 망막색소상피박리의 크기가 2유두 직경이상인 경우가 3안, 2유두직경 미만인 경우가 10 안이었으며 광범위한 망막하출혈은 망막색소상피박리 1605
윤재문외 : 광역학요법후망막하출혈 의크기가 2 유두직경이상인 3 안중 2 안 (66.6%) 에서, 2 유두직경미만인 10 안중 3 안 (30.0%) 에서발생하여망막색소상피박리가큰경우광범위한망막출혈이높은빈도로발생하였지만통계학적유의성은없었다 (Fisher s Exact Test, P=0.51). 고 찰 나이관련황반변성은 50 세이상에서일어나는황반의변성질환으로연성드루젠과망막색소상피의과색소침착, 감각신경망막박리, 망막출혈, 망막색소상피의지도형위축, 맥락막신생혈관또는망막섬유성반흔등의소견을보인다. 6,7 맥락막신생혈관은신경망막또는망막색소상피아래에신생혈관이생기는질환으로맥락막신생혈관에서누출된삼출물, 혈액또는이들에의해이차적으로유발되는허혈, 섬유혈관조직에의한망막손상에의해시력저하가유발되며 8-10 발생원인으로는나이관련황반변성, 안히스토플라스마증, 병적근시, 특발성인경우등이알려져있다. 9,11 맥락막신생혈관의치료에는레이저광응고술, 약물요법, 방사선요법, 황반하수술, 황반변위술등이있으며중심와에발생한맥락막신생혈관치료에광역학요법이널리사용되고있다. 12 기존의암치료에서효과가인정된광역학요법은광감작물질을이용하여선택적으로맥락막신생혈관에작용하게한다. 광감작물질로널리쓰이는 Verteporfin 은정맥주입후신생혈관의내피세포내에축적되고, 비열성의빛을광감작된조직에조사하여광화학적반응이일어나직간접적으로신생혈관에혈전증이나혈관수축을일으켜결국신생혈관을폐쇄시키게된다. 13-15 광역학요법의부작용으로주입부위통증, 부종, 출혈, 염증, 요통, 알러지반응, 광과민반응, 시력저하, 유리체출혈등이알려져있다. 16,21 이러한부작용중광역학요법후발생한시력저하는망막하출혈의증가, 장액성망막박리의증가, 또는안저검사상특이소견을동반하지않는맥락막비관류등으로발생하게되며, 그중망막하출혈이가장흔한원인으로보고되고있다. 5 TAP 1 연구에서는나이관련황반변성환자를 3 개월간의경과관찰중망막내출혈과망막하출혈이관찰되었으며, 광역학요법으로치료한 402 안중망막출혈은 116 안 (29%) 으로치료하지않은 207 안의경우발생한망막출혈 95 안 (46%) 에비해낮은빈도로나타났으며, 치료군과대조군모두출혈의양상은치료에의한것이아닌나이관련황반변성의자연경과에의한것으로보았다. 16 Theodossiadis et al 17 는나이관련황반변성의광역학요법후 48 시간이내에생긴광범위한황반출혈 (extensive macular hemorrhage) 이 215 안중 4 안 (1.86%) 에서발생되었고, 출혈은광역학요법시직접적인레이저노출의결과로보았다. Do et al 18 은광역학요법 2~3 개월후 55 안중 5 안 (9%) 에서광범위한황반하출혈 (large submacular hemorr hage) 의발생을보고하였고, Gelisken et al 19 은광역학요법 2 주후 104 안중 23 안 (22%) 에서새로운중심와밑출혈 (new subfoveal hemorrhage) 이생겼다고하였으며, Diaz-de et al 20 은광역학요법후 504 안중 8 안 (1.58%) 의황반하출혈을보고하였다. JAT (Japanese Agerelated Macular Degene ration Trial) study group 에서는 64 안중광역학요법시행후 1 주일째에망막하출혈이발생하면서급격한시력저하를보인경우가 1 안 (1.56%) 에서발생하였고 12 개월째까지시력의회복을보이지않았다고하였다. 21 Kim et al 22 의연구에서도광역학요법후망막하출혈이치료전보다증가된경우가 21 안중 3 안 (19.0%) 에서발생하였고 21 안중 1 안 (4.8%) 에서유리체출혈을보고하였다 (Table 5). 본연구에서는광역학요법후 267 안중 36 안 (13.4%) 에서망막하출혈및유리체출혈이발생하였고출혈시기는광역학요법시행 1 개월후가 55.6% 로가장많았고출혈크기는 2 유두직경이하가 50% 로 Table 5. Comparison of published retinal hemorrhage rate after photodynamic therapy of age related macular degeneration Author Reference No. No. of treated eyes Follow-up Hemorrhage rate Hemorrhage type This study 267 6~26 mo* 36 (13.4%) subretinal, vitreous TAP study group 16 402 3 mo 116 (29%) subretinal, intraretinal Theodossiadis 17 215 48 hr 4 (1.86%) extensive macular Bressler 18 55 2~3 mo 5 (9%) large submacular Gelisken 19 104 2 wk 23 (22%) new subfoveal Diaz 20 504 34 mo 8 (1.58%) submacular JAT study group 21 64 12 mo 1 (1.56%) subretinal Kim 22 21 3~15 mo 4 (19.0%) subretinal, vitreous * mo=months; hr=hours; wk=weeks. 1606
대한안과학회지 2008 년제 49 권제 10 호 대부분을차지했다. Theodossiadis et al 17 에따르면나이관련황반변성의광역학요법후 48 시간이내에발생하고그범위가광범위한망막출혈은레이저노출의직접적인결과라고하였다. 본연구에서는망막하출혈이광역학요법일주일이내발생한경우가있었지만그범위가대부분 2 유두직경을넘지않았고, 광범위한망막하출혈이발생한경우도시기가대부분광역학요법후 1 개월이후로직접적인레이저노출에의한손상으로발생한출혈은없었던것으로보인다. 광역학요법후망막하출혈의발생원인에대해아직명확하게알려진바는없다. Michels and, Schmidt- Erfurth 23 은사람에서광역학요법시행후주변부신생혈관으로부터중심부로혈전생성이점차적으로진행하여 24 시간이내에대부분의환자에서신생혈관막의완전한폐쇄가발생한다고하였다. 이러한광혈전증에의한혈관폐쇄가맥락막신생혈관에서훨씬빠른시간내에선택적으로발생하지만, 신생혈관막주변의정상맥락막혈관에서도혈관내피가손상을입어, 부분적인혈관폐쇄가발생한다. 24 그리고인도사이아닌그린형광안저혈관조영상후기에분명한경계를갖는현저한저형광이광역학요법을시행한부위에국한되어나타나며, 이러한맥락막관류저하는광역학요법시행후약 1 주일째에가장심하게나타났다가 3 개월이되면정상에가깝게회복된다고하였다. 23,24 Ojima et al 25 은광역학요법후발생한광범위한망막출혈에대해레이저노출의직접적인결과가아니라, 광역학요법이비정상적인맥락막신생혈관과정상맥락막혈관을폐쇄시켜맥락막혈류의변화를가져오게되어그결과증가된맥락막혈류가취약한혈관부위에서광범위한망막출혈 을야기시킨것이라고하였다. 또다른가설로전체비정상맥락막혈관폐쇄가광역학요법레이저조사부위에일어나게되는데영양혈관 (feeder vessel) 폐쇄는일어나지않고유출혈관 (efferent vessel) 만이폐쇄된경우에광범위한망막출혈이일어나게될것이라고하였다. 26 Hirami et al 26 은레이저조사부위에모든비정상적인맥락막신생혈관의폐쇄가일어나더라도경과관찰중일부혈관의재관류가관찰될수있으며만약유입혈관 (afferent vessel) 이선택적으로재관류되면손상받은혈류가광범위한망막출혈을초래할것이라고하였다. Hirami et al 26 은조사된레이저반의크기가클수록광역학요법후유리체출혈의빈도가높아진다고보고하였고본연구에서도조사된레이저반의크기가클수록출혈의빈도가높은것으로나타났다. 이는광역학요법치료범위가클수록광혈전증에의한혈관폐쇄와손상의범위도커지게되어취약한혈관부위나불완전한영양혈관폐쇄, 선택적유입혈관의재관류의가능성도높아지게되어나타나는것으로보인다. 광역학요법이후발생한망막하출혈의시기와출혈의크기를살펴보면 1 주이내에발생한출혈의경우전체의 25% 였고크기는대부분 2 유두직경이내의작은출혈이었다 (77.8%). 반면 1 개월이후출혈이발생한경우는전체의 55.6% 를차지했으며유리체출혈을포함한광범위한망막출혈이발생한경우는모두광역학요법후 1 개월이후에발생하였다 (Table 6). 맥락막관류저하가광역학요법시행후약 1 주일째에가장심하게나타났다가 3 개월이되면정상에가깝게회복되는사실과 23,24 연관지어보면, 광역학요법에의해출혈을일으킬만한손상부위가존재하더라도맥락막재관류가 Table 6. The relation between onset of hemorrhage and extent of hemorrhage after photodynamic therapy Onset of hemorrhage Eyes (percent) Extent of hemorrhage <1 week 9/36 (25.0%) 7 eyes < 2DD 2 eyes 2DD 0 eye Massive hemorrhage* 0 eye Vitreous hemorrhage 1 week ~ < 1 month 7/36 (19.4%) 5 eyes < 2DD 2 eyes 2DD 0 eye Massive hemorrhage* 0 eye Vitreous hemorrhage 1 month 20/36 (55.6%) 6 eyes < 2DD 5 eyes 2DD 3 eyes Massive hemorrhage* 6 eyes Vitreous hemorrhage * subretinal hemorrhage extends beyond the temporal vascular arcades; subretinal hemorrhage with vitreous hemorrhage. 1607
윤재문외 : 광역학요법후망막하출혈 충분하지않은 1 주이내에는출혈이쉽게발생하지않으며출혈의양도많지않았던것으로보이며, 오히려재관류가완성되는 1 개월에서 3 개월사이에출혈이호발하고출혈양도많았던것으로보인다. 이러한사실로미루어광역학요법후발생하는망막하출혈은맥락막재관류와밀접한관련성이있을것으로사료되며, 본연구결과는출혈의기전으로서제시한선택적유입혈관의재관류가설에부합하는소견이다. 망막색소상피박리가동반된맥락막신생혈관에대한광역학요법은예후가좋지않으며 28,29 비교적높은빈도로망막하출혈이발생된다. 28,30 본연구에서도망막색소상피박리를동반한경우망막하출혈의빈도가높았고망막색소상피박리의크기가클수록발생한망막하출혈범위도넓었다. 이러한결과는비록분석통계학적유의성은없었으나본연구의결과로서기술적통계의의의는가진다. 망막색소상피박리가동반된맥락막신생혈관에대한광역학요법시망막하출혈이호발되었던요인으로광역학요법에의한망막색소상피파열을생각해볼수있다. 망막색소상피파열은망막색소상피박리의크기가클수록접선견인력 (tangential stress) 이커져서발생할가능성이높아지는것으로생각되고있는데, 망막색소상피박리의자연경과로서발생하는경우도있지만맥락막신생혈관에대한레이저광응고술후에발생하기도하고최근에는광역학요법후발생한예들이보고되고있다. 31,32 Han and Lee 29 은큰망막색소상피박리가동반된맥락막신생혈관에대한광역학요법을시행하였고 9 안중 3 안에서망막색소상피파열이발생하였는데모두망막색소상피박리면적이약 7 유두직경이상으로큰경우였다고한다. 따라서망막색소상피박리가동반된맥락막신생혈관에대한광역학요법시망막색소상피파열의발생과함께망막출혈의위험도높아질수있고, 특히망막색소상피박리의면적이큰경우에망막색소상피파열과망막출혈의위험성이더높아질수있을것으로생각된다. 항응고치료가나이관련황반변성에서망막하출혈의위험을증가시킨다고 27 보고되었으며본연구에서는망막출혈을보인 36 예중 1 예에서만항응고치료병력이있어항응고치료와광역학요법에의한망막하출혈위험의관련성을알수는없었다. 당뇨병, 고혈압등전신질환과의관련성도찾아볼수가없었다. 이는본연구의환자군의수가적고, 각환자군간의개체수의차이가큰것으로인한것으로보인다. 따라서이에대해서대규모의전향적인연구가추후필요할것으로사료된다. 나이관련황반변성의광역학요법치료후발생한망막하출혈은 13.4% 의빈도를차지하며, 숨은맥락막신 생혈관에서가장호발하였으며, 광역학요법의레이저조사반의크기가큰경우 ( 3,000 µm) 높은빈도로발생하였다. 따라서환자에게광역학요법이후망막하출혈의발생빈도와호발되는경우를충분히설명후시술을행해야할것으로생각된다. 참고문헌 1) Blinder KJ, Blumenkranz MS, Bressler NM, et al. Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial- VIP report No.3. Ophthalmology 2003;110:667-73. 2) Bressler NM. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photo dynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2. Arch Ophthalmol 2001;119:198-207. 3) Verteporfin In Photodynamic Therapy Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin In Photo dynamic Therapy report 2. Am J Ophthalmol 2001;131:541-60. 4) Verteporfin In Photodynamic Therapy Study Group. Photo dynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial-vip report no. 1. Ophthalmology 2001;108:841-52. 5) Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group and Verteporfin In Photodynamic Therapy (VIP) Study Group. Acute severe visual acuity decrease after photodynamic therapy with verteporfin: Case reports from randomized clinical trials- TAP and VIP Report No. 3. Am J Ophthalmol 2004;137:683-96. 6) Klein R, Klein BE, Linton KL. Prevalence of age related maculopathy. The Beaver Dam Eye Study. Ophthalmology 1992;99:933-43. 7) Klein R, Davis MD, Magli YL, et al. The Wisconsin age related maculopathy grading system. Ophthalmology 1991;98: 1128-34. 8) Bressler SB, Bressler NM, Fine SL, et al. Natural course of choroidal neovascular membranes within the foveal avascular zone in senile macular degeneration. Am J Ophthalmol 1982;93:157-63. 9) Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. Surv Ophthalmol 1988;32:375-413. 10) Guyer DR, Fine SL, Maguine MG, et al. Subfoveal choroidal neovascular membranes in age-related macular degeneration. Visual prognosis in eyes with relatively good visual acuity. Arch Ophthalmol 1986;104:702-5. 1608
대한안과학회지 2008 년제 49 권제 10 호 11) Klein BE, Klein R. Cataract and macular degeneration in older Americans. Arch Ophthalmol 1982;100:571-3. 12) Hart PM, Chakraverthy RF, Mackenzie G, et al. Therapy for subfoveal choroidal neovascularization of age-related macular degeneration: results of follow up in a non-randomized study. Br J Ophthalmol 1996;80:1046-1050. 13) Schmidt-Erfurth U, Hasan T, Gragoudas E, et al. Vascular targeting in photodynamic occlusion of subretinal vessels. Ophthalmology 1994;101:1953-61. 14) Miller JW, Walsh AW, Kramer M, et al. Photodynamic therapy of experimental chorioidal neovascularization using lipoprotein-derived benzoporphyrin. Arch Ophthalmol 1995;113: 801-8. 15) Kramer M, Miller JW, Michaud N, et al. Liposomal benzoporphyrin derivative verteporfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys. Ophthalmology 1996;103:427-38. 16) TAP Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age related macular degeneration with verteporfin. One year results of two randomized clinical trials-tap report 1. Arch Ophthalmol 1999;117:1329-45 17) Theodossiadis GP, Panagiotidis D, Georgalas IG, et al. Retinal hemorrhage after photodynamic therapy in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2003:241:13-8 18) Do DV, Bressler NM, Bressler SB. Large submacular hemorrhages after verteporfin therapy. Am J Ophthalmol 2004;137:558-60. 19) Gelisken F, Inhoffen W, Karim-Zoda K, et al. Subfoveal hemorrhage after verteporfin photodynamic therapy in treatment of choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 2005;243:198-203. 20) Diaz-De-Durana-Santa-Coloma E, Fernandez-Ares ML, Iturralde-Errea D, et al. Submacular hemorrhage following photodynamic therapy in the treatment of choroidal neovascularization. Ophthalmic Surg Lasers Imaging 2006;37: 278-83. 21) The Japanese Age-related Macular Degeneration Trial (JAT) Study Group. Japanese age-related macular degeneration trial: 1-year results of photodynamic therapy with verteporfin in Japanese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Am J Ophthalmol 2003;136:1049-61. 22) Kim JW, Kim HK, Kim HC. Photodynamic therapy for choroidal neovascularization caused by age-related macular degeneration. J Korean Ophthalmol Soc 2002;43:1435-43. 23) Michels S, Schmidt-Erfurth U. Sequence of early vascular events after photodynamic therapy. Invest Ophthalmol Vis Sci 2003;44:2147-54. 24) Schmidt-Erfurth U, Michels S, Barbazetto I, Laqua H. Photodynamic effects on choroidal neovascularizations and physiologic choroid. Invest Ophthalmol Vis Sci 2002;43: 830-41. 25) Ojima Y, Tsujikawa A, Otani A, et al. Recurrent bleeding after photodynamic therapy in polypoidal choroidal vasculopathy. Am J Ophthalmol 2006;141:958-60. 26) Hirami Y, Tsujikawa A, Otani A, et al. Hemorrhagic complications after photodynamic therapy for polypoidal choroidal vasculopathy. Retina 2007;27:335 41. 27) el Baba F, Jarrett WH II, Harbin TS Jr, et al. Massive hemorrhage complicating age-related macular degeneration. Clinicopathologic correlation and role of anticoagulants. Ophth almology 1986;93:1581-92. 28) Axer-Siegel R, Ehrlich R, Rosenblatt I, et al. Photodynamic therapy for occult choroidal neovascularization with pigment epithelium detachment in age-related macular degeneration. Arch Ophthalmol 2004;122:453-9. 29) Han JW, Lee WK. Photodynamic therapy of choroidal neovasculariation associated with large serous pigment epithelial detachment J Korean Ophthalmol Soc 2004:45:79-86 30) Pece A, Isola V, Vadalà M, Calori G. Photodynamic therapy with verteporfin for choroidal neovascularization associated with retinal pigment epithelial detachment in age-related macular degeneration. Retina 2007;27:342-8. 31) Moorfields Macular Study Group. Retinal pigment epithelial detachments in the elderly: a controlled trial of argon laser photocoagulation. Br J Ophthalmol 1982;66:1-16. 32) Pece A, Introini U, Bottoni F, Brancato R. Acute retinal pigment epithelial tear after photodynamic therapy. Retina 2001;21:661-5. 1609
윤재문외 : 광역학요법후망막하출혈 =ABSTRACT= Subretinal Hemorrhage After Photodynamic Therapy for Age-Related Macular Degeneration Jae Moon Yoon, M.D., Ho Soong Kim, M.D., Jae Hoon Kang, M.D., Hee Sung Yoon, M.D., Ph.D Sungmo Eye Hospital, Pusan, Korea Purpose: To evaluate the clinical features of subretinal hemorrhage after photodynamic therapy in eyes with exudative age-related macular degeneration. Methods: We retrospectively reviewed data for 267 eyes of 243 patients who had undergone PDT for the treatment of ARMD between January 2005 and December 2006. Best corrected visual acuity, fundus photography, fluorescein angiography, and ICG angiography were performed before and after treatment. We followed up the patients at 1 week, 1 month, and 3 months after treatment and at 3-month intervals thereafter. Results: Postoperative subretinal hemorrhage was seen in 36 (13.4%) of 267 eyes. The pretreatment and post-treatment mean visual acuities were logmar 0.80 and logmar 1.05 respectively, representing a decrease of 2.05 lines. On FAG, two eyes were predominantly classic, four eyes were minimally classic, and 30 eyes were occult. The laser irradiation spot size was under 3,000 µm in one case and from 3,000 µm to 5,000 µm in 19 cases and over 5,000 µm in 16 eyes. Conclusions: Subretinal hemorrhage after PDT for ARMD can be a common complication in patients who have been treated for larger irradiation spot sizes and for pigment epithelial detachment (PED), so doctors should be aware of the risk of serious hemorrhagic complications in such situations. J Korean Ophthalmol Soc 2008;49(10):1603-1610 Key Words: Age-Related Macular, Degeneration, Photodynamic Therapy, Subretinal hemorrhage, Address reprint requests to Hee Sung Yoon, M.D., Ph.D. Sungmo Eye Hospital #1078-7 Woo2-dong, Haeundae-gu, Pusan 612-022, Korea Tel: 82-51-743-0775, Fax: 82-51-743-0776, E-mail: heesyoon@dreamwiz.com 1610