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1 = 증례보고 = 망막동맥대혈관류파열로인한황반부출혈에대한유리체절제술후임상결과 대한안과학회지 2010 년제 51 권제 7 호 J Korean Ophthalmol Soc 2010;51(7): pissn: eissn: DOI : /jkos 김동현 1 유형곤 1,2 서울대학교의과대학안과학교실 1, 서울대학교의학연구원감각기관연구소 2 목적 : 망막동맥대혈관류파열로인한황반부출혈로유리체절제술을받은환자에서빛간섭단층촬영검사소견과시력의관계를알아보고자하였다. 대상과방법 : 망막동맥대혈관류에서발생한황반부출혈로유리체절제술을받은환자를대상으로후향적연구를시행하였다. 술후빛간섭단층촬영소견과시력의관계를분석하였다. 결과 : 대상환자는총 12 명이었다. 수술전 logmar 시력은 1.7±0.8 이었고수술후 0.6±0.5 로유의하게향상되었다 (p=0.004). 빛간섭단층촬영에서술전중심와두께는 437.5±161.5 μm 에서술후 3 개월째 252.8±84.9 μm 로유의하게감소하였다 (p=0.017). 술후유기화된출혈이많이제거되어중심와두께가얇을수록좋은최종시력을나타냈다 (p=0.048). 술후시력은빛간섭단층촬영에서중심와광수용체의파괴가관찰된경우에보존된경우보다불량하였다 (logmar: 1.4±0.4 vs 0.3±0.2, p=0.009). 결론 : 망막동맥대혈관류파열에합병된황반부출혈이있었던환자에서유리체절제술후빛간섭단층촬영에서의광수용체보존소견은좋은시력결과와연관이있었다. < 대한안과학회지 2010;51(7): > 망막동맥대혈관류는망막후극부의주요 4 분지동맥중에서발생하고, 원형또는방추상의모양을특징으로하는후천적인망막동맥의이상을보이는질환이다. 망막동맥대혈관류는우연히안저검사에서발견되는경우도있지만, 다수의경우급성파열로인한유리체출혈, 망막전출혈, 망막내출혈, 망막하출혈등이나만성적인삼출에의한황반부종, 장액망막박리로급격한시력저하를초래할수있다. 1,2 유리체절제술은망막동맥대혈관류의파열에의한황반부출혈 ( 유리체출혈, 망막전출혈, 망막내출혈, 망막하출혈 ) 에서도움이되는것으로알려져있고, 수술후에평균시력이향상되지만시력향상의정도는매우다양하다. 2-8 빛간섭단층촬영은황반부의정밀한해부학적영상을나타내며, 그소견은당뇨황반부종, 황반원공, 황반전막환자에서수술후시력예후와관련이있다고보고되고있다 그러나망막동맥대혈관류환자에서유리체절제술후빛간섭단층촬영의변화에대해서는아직잘알려져있 접수일 : 2009 년 11 월 9 일 심사통과일 : 2010 년 5 월 4 일 책임저자 : 유형곤서울시종로구연건동 28 서울대학교병원안과 Tel: , Fax: hgonyu@snu.ac.kr * 본논문의요지는 2009 년대한안과학회제 101 회학술대회에서구연으로발표되었음. 지않다. 본연구에서는망막동맥대혈관류의파열로인한황반부출혈로유리체절제술을시행받은환자를대상으로수술후빛간섭단층촬영의소견과시력예후의관계에대해알아보고자하였다. 대상과방법 2004년 1월부터 2009년 1월까지서울대학교병원안과에서망막동맥대혈관류로진단받고경과관찰중대혈관류의파열로인한황반부출혈이발생하여유리체절제술을받았거나, 원인미상의급성황반부출혈에대한유리체절제술중대혈관류를발견하였고, 적어도수술후 3개월이상추적관찰이가능했던 12명 12안에대해후향적연구를시행하였다. 첫내원시, 나안시력, 교정시력측정, 세극등현미경검사, 정밀안저검사, 형광안저촬영, 빛간섭단층촬영을시행하였다. 빛간섭단층활영은 STRATUS OCT (Carl Zeiss, Dublin, CA) 의 fast macular mode를이용하여검사하였다. 숙련된검사자의의해 fast macular mode의스캔사진으로단면구조를획득하였다. 수술전안저검사및형광안저검사를통해유리체출혈, 망막전출혈, 망막내출혈, 망막하출혈이있었던환자들을각각구분하였고, 대혈관류의위치및시신경으로부터의거리, 황반부출혈의크기를각각측정하였다. 수술은한명의 961

2 - 대한안과학회지 2010 년제 51 권제 7 호 - 동일술자에의해시행되었으며, 후유리체막박리및제거를포함한표준평면부유리체절제술을시행하였다. Lens Opacities Classification System III Grading에따라핵혼탁도가 3 이상인중등도백내장이있는경우에초음파수정유화술및후방인공수정체삽입술을유리체절제술과함께시행하였다. 망막내출혈의경우에는내경계막제거술후내경계막하출혈의제거를시행하였으며, 망막하출혈의경우에는황반부하이측주변부에망막절개술을시행한후, 평형염액 (Balanced salt solution) 이나 25 μg의 tissue plasminogen activator (t-pa) 를사용하여망막절개창을통해세척하는방법으로출혈을제거하고, 18% C 3F 8 가스를유리체강내주입후환자가 5~7일간복와위자세를유지하도록하였다. 수술후 3~6개월때, 빛간섭단층촬영을추가로시행하였다. 수술후의빛간섭단층촬영에서중심와두께및중심와광수용체의파괴정도를조사하였고, 중심와광수용체의파괴여부확인을위해광수용체외절과내절의경계부분의모양을확인하였다. 중심와두께는획득된빛간섭단층촬영스캔중황반두께지도 (macular thickness map) 에서중심 1 mm 이내의중심원의두께를사용하였다. 빛간섭단층촬영에서광수용체의내절과외절의경계는망막색소상피바로위의과반사되는층으로정의되는데, 이경계부위가주변황반및중심와에서일관되고연속적인 신호강도를보이면이상이없는것으로보았고, 이에이상이있을때에는광수용체의파괴가있는것으로정의하였다. 추적관찰중적어도 3개월이후에수술받은눈의교정시력을측정하였다. 결과 환자 12명중, 남자는 3명, 여자는 9명이었고, 평균연령은 69.3세 (49~79세) 였다. 동반된전신질환으로는고혈압이 9명에서있었고, 2명에서당뇨병이, 1명에서재생불량성빈혈이있었다. 망막동맥대혈관류의위치는 7안에서상이측에, 5안에서하이측에있었고, 시신경에서부터대혈관류까지의거리는평균 2.1 유두지름 (1.0~3.0 유두지름 ) 이었다. 1안에서상비측에동반된대혈관류가같이관찰되었다. 추적관찰기간은평균 21.2개월 (3~44 개월 ) 이었다. 수술전또는수술중소견에서망막하출혈, 망막내출혈이있었던경우는각각 9안과 11안이었다. 망막내또는망막하출혈중크기가가장컸던부위의출혈의범위는평균 5.5±2.5 시신경유두넓이였다. 출혈발생후부터수술까지소요된기간은평균 8.1주 (1~19주 ) 였다 (Table 1). 술전교정시력 (logmar) 은평균 1.7±0.8이었으며, 유리체절제술 1~2주후나안시력 (logmar) 은평균 1.3±0.7 Table 1. Patient characteristics Symptom Location Visual acuity OCT to surgery (distance Fundus erative No. Sex Age HTN Final F/U interval from optic finding 1-2 week photoreceptor BCVA BCVA (months) (weeks) disc) UCVA disruption 1 F ST (1DD), VH/PRH/ LS (-) 44 SN (2DD) IRH/ 2 F ST (1DD) VH/PRH/ 0.02 HM 0.02 (+) 27 IRH/ 3 F IT (2DD) PRH/IRH/ (-) 37 4 M 54-9 IT (2DD) PRH/IRH/ 0.04 FC 0.7 (-) 25 5 M 65-9 IT (2DD) VH/PRH/ LS (-) 28 IRH 6 F ST (2DD) PRH/IRH/ FC FC 0.1 (+) 29 7 F ST (2DD) PRH/IRH/ (-) 27 8 M 74-1 ST (2DD) VH/PRH/ HM (-) 7 IRH/ 9 F IT (2DD) IRH HM (-) 6 10 F ST (2DD) VH/PRH/ HM FC 0.04 (+) 18 IRH/ 11 F ST (2DD) PRH/IRH FC (-) 3 12 F IT (2DD) PRH/IRH/ (-)

3 - 김동현 유형곤 : 망막동맥대혈관류파열시유리체절제술 - RPE Figure 1. Optical coherence tomography (OCT) and fundus findings in patient in which postoperative photoreceptor is intact (Yellow arrows: photoreceptor IS-OS junction) (No. 7). Table 2. Comparison of preoperative and postoperative best corrected visual acuities (BCVA) and foveal thickness (n=12) P-value * BCVA (logmar) 1.7± ± Foveal thickness (μm) 437.5± ± * Wilcoxon test; Final BCVA; OCT in postoperative. Table 3. Comparison of final best corrected visual acuities (BCVA) between intact and disruptive photoreceptor group Intact photoreceptor (n=9) Disruptive photoreceptor (n=3) P-value Final BCVA (logmar) 0.3± ± * * Mann-Whitney U test. 으로시력향상은있었으나, 통계적으로유의하지는않았다 (p=0.131). 최종관찰시교정시력 (logmar) 은평균 0.6± 0.5로술전에비해통계적으로유의한시력향상이있었다 (p=0.004). 망막하출혈이있는군과없는군에서의평균최종시력 (logmar) 은각각 0.7±0.6, 0.3±0.3이었으며, 통계적으로유의한차이는보이지않았다 (p=0.600). 빛간섭단층촬영에서중심와두께는술전평균 437.5±161.5 μm 에서술후평균 252.8±85.0 μm로유의하게감소하였다 (Wilcoxon test, p=0.017) (Table 2). 수술전중심와두께와최종시력 (logmar) 과는큰상관관계가없었으나 (p=0.651, Spearman correlation analysis), 술후중심와두께와최종시력 (logmar) 간에는유의한양의상관관계를보였다 (p=0.048). 술후중심와두께가 250 μm 이상이었던환자들에서는망막내또는망막하에잔여유기화된출혈 (Remnant organized hemorrhage) 소견이관찰되었다. 술후빛간섭단층촬영에서중심와광수용체의파괴를 3안에서보였고, 이들모두에서 2줄이상의시력향상은없었다 (Figure 1). 반면, 중심와광수용체가보존된나머지 9안모두에서 2줄이상의시력향상을보였다 (Figure 2). 중심와광수용체가보존된군이파괴된군보다유의하게평균최종시력이좋았다 (logmar: 0.3±0.2, 1.4±0.4, p=0.009) (Table 3). 황반부출혈범위가 5 시신경유두지름보다작았던 6안에서평균최종시력은 0.9±0.8 (logmar) 이었고, 이는출혈이 6 시신경유두지름보다큰 6안에서의평균최종시력 0.4±0.6 (logmar) 에비해통계적인유의한차이는보이지않았다 (p=0.303) (Table 4). 술후최종 963

4 - 대한안과학회지 2010 년제 51 권제 7 호 - RPE Figure 2. OCT and fundus findings in patient in which postoperative photoreceptor is disruptive (Yellow arrows: photoreceptor IS-OS junction) (No. 10). Table 4. Comparison of final best corrected visual acuities (BCVA) between large and small macular hemorrhage group Macular Hemorrhage size Large ( 5 DD) (n=6) Small (<5 DD) (n=6) P value Final BCVA (logmar) 0.4± ± * * Mann-Whitney U test. 경과관찰까지황반원공이나유리체출혈, 망막박리등의합병증은보이지않았다. 고찰 망막동맥대혈관류는노령과동맥경화로인해혈관의내막콜라겐이증가하여, 내측근섬유가콜라겐으로대체됨으로써발생하는동맥벽의탄력성감소와동맥의내압증가에따른확장으로발생한다. 12,13 임상양상에따라출혈형과삼출형으로분류하나, 시력저하를보이는망막동맥대혈관류환자상당수에서급성파열에의한황반부출혈을보인다. Nakamura et al은망막동맥대혈관류환자들을대상으로한연구에서황반하출혈이있었던군보다황반하출혈이없고, 유리체출혈이나내경계막하출혈이있는군에서시력예후가좋다고보고하였다. 2 망막하출혈은피브린 (fibrin) 으로인한광수용체외절의손상, 철독성 (iron toxicity), 맥락막모세혈관으로부터의확산또는망막상피세포-광수용체간의대사반응에장애를초래하여, 감각신경망막에손상을 입힐수있다. 3 실제로망막하출혈후 2주안에망막변성이발생하므로, 많은연구에서망막하출혈을조기에제거하는것을추천하고있다. 3,4 그러나본연구에서는망막하출혈이있던군과없었던군과의비교에서최종교정시력에통계적으로유의한차이를보이지않았고, 빛간섭단층촬영을통해술후광수용체가잘보존된군에서광수용체가파괴가되었던군보다월등히우수한시력예후를보였다. 이를통해술전망막하출혈유무보다는술후광수용체의보존정도가최종시력예후에중요한인자임을알수있다. 물론망막하출혈이없었던군에서는수술후광수용체보존정도가모두양호하였지만, 망막하출혈이있었던군에서도수술후광수용체의보존이양호했던환자들의최종시력예후는좋은편이었다. 또한수술전망막내또는망막하출혈이잘제거되어, 수술후잔여유기화된출혈소견이없을수록, 더작은술후중심와두께를보였고, 좋은시력예후를보이는것으로볼때, 망막내또는망막하잔여출혈존재여부또한시력예후를판단할수있는요인임을확인하였다. 그러나극심한광수용체세포의소실을동반한경우에도중심와두 964

5 - 김동현 유형곤 : 망막동맥대혈관류파열시유리체절제술 - 께가얇아질수있으므로, 술후중심와두께가무조건작다고해서시력예후가좋을것으로판단해서는안될것이다. 여러연구에서망막동맥대혈관류의파열로인한황반부출혈에서망막하출혈이다수에서발생하는것으로알려져있고, 2,8,14 본연구에서도 12안중 9안에서망막하출혈이있었다. 망막하출혈은앞서언급되었던대로감각신경망막과광수용체에손상을입히기가쉬우므로, 망막동맥대혈관류파열에의한황반부출혈에서망막하출혈이동반된경우, 조기에유리체절제술을통해출혈을제거하는것이최종시력예후향상에도움을줄것으로보이며, 유리체출혈이나망막전출혈이심하여망막하출혈여부를확인할수없을때에도유리체절제술을통한치료가빠른시력회복에이르게할수있을것으로생각된다. 망막하출혈의제거는수술후 2주안에시도하는것이비교적좋은시력예후를나타낸다고하고, 시력저하발생 50일이후의수술에서최종시력이술전에비해향상되지않았다고보고되고있으나, 3,4 이번연구에서는망막하출혈을포함한황반부출혈발생 9 주뒤에수술을시행한환자에서 0.7 (No. 4), 12주뒤에시행한환자에서 0.5 (No. 3) 의우수한시력예후를보였다. 이로써망막동맥대혈관류파열로인한황반부출혈에서조기유리체절제술이최종시력예후향상에도움을주지만, 출혈발생후 2주이상지났다고하더라도일단수술을시도해보는것이좋을것으로보인다. 그리고수술후의빛간섭단층촬영검사를통한광수용체의보존상태는환자들의시력예후를짐작하는데주요도구로서, 중심와두께는보조도구로서활용될수있을것이다. 수술후빛간섭단층촬영을이용한광수용체의내절과외절의이음부에대한연구는이미당뇨황반부종, 황반원공, 특발성망막전막, 근시성중심와층간분리 (foveoschisis) 등에서진행되었고, 대부분의경우에광수용체의내절과외절의이음부의보존상태가좋을수록수술후의시력예후도좋다고보고되고있다. 9-11,15 망막동맥대혈관류의파열로인한황반부출혈에서빛간섭단층촬영을이용한연구는이제까지보고된바가없으며, 수술후광수용체보존상태를통해추후시력예후를판단하는데많은도움을받을수있다는사실을확인한측면을고려할때, 이번연구는적은대상군에도불구하고충분한의의가있다고할수있겠다. 현재활발히사용되고있는 spectral-domain OCT에서 Stratus OCT 보다좀더높은해상도의영상을얻을수있고광수용체의보존상태도월등하게잘확인할수있으므로, 앞으로수술후환자들의경과관찰시에는 Spectral domain OCT 의사용을추천한다. 망막동맥대혈관류의파열로인한황반부출혈환자들에있어서, 망막하출혈이동반되었다고하더라도유리체절제 술을통한출혈의제거를통해좀더좋은시력예후를기대해볼수있다. 본연구결과는망막동맥대혈관류의파열로인한황반부출혈환자에서빛간섭단층촬영이수술후시력예후를판단하는데도움을준다는것을제시한다. 또한이러한환자에서영구적인시력감소의주된원인은황반부출혈과연관된시세포층의손상에있다. 망막혈관대혈관류에대해향후보다많은증례를대상으로 Spectral domain OCT를사용한연구가필요할것으로보인다. 참고문헌 1) Asdourian GK, Goldberg MF, Jampol L, Rabb M. Retinal macroaneurysms. Arch Ophthalmol 1997;95: ) Nakamura H, Hayakawa K, Sawaguchi S, et al. Visual outcome after vitreous, sub-internal limiting membrane, and/or submacular hemorrhage removal associated with ruptured retinal arterial macroaneurysms. Graefes Arch Clin Exp Ophthalmol 2008;246: ) Ibanez HE, Williams DF, Thomas MA, et al. Surgical management of submacular hemorrhage. A series of 47 consecutive cases. Arch Ophthalmol 1995;113: ) Moriarty AP, McAllister IL, Constable IJ. Initial clinical experience with tissue plasminogen activator (tpa) assisted removal of submacular haemorrhage. Eye 1995;9: ) Lim JI, Drews-Botsch C, Sternberg P Jr, et al. Submacular hemorrhage removal. Ophthalmology 1995;102: ) Humayun M, Lewis H, Flynn HW Jr, et al. Management of submacular hemorrhage associated with retinal arterial macroaneurysms. Am J Ophthalmol 1998;126: ) Peyman GA, Nelson NC Jr, Alturki W, et al. Tissue plasminogen activating factor assisted removal of subretinal hemorrhage. Ophthalmic Surg 1991;22: ) Lee HJ, Chung MR, Kim HC. Treatment of retinal arterial macro- aneurysm. J Korean Ophthalmol Soc 2003;44: ) Sakamoto A, Nishijima K, Kita M, et al. Association between foveal photoreceptor status and visual acuity after resolution of diabetic macular edema by pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 2009;247: ) Chang LK, Koizumi H, Spaide RF. Disruption of the photoreceptor inner segment-outer segment junction in eyes with macular holes. Retina 2008;28: ) Suh MH, Seo JM, Park KH, Yu HG. Associations between macular findings by optical coherence tomography and visual outcomes after epiretinal membrane removal. Am J Ophthalmol 2009;147: ) Rabb MF, Gagliano DA, Teske MP. Retinal arterial macroaneurysms. Surv Ophthalmol 1988;33: ) Lavin MJ, Marsh RJ, Peart S, Rehman A. Retinal arterial macroaneurysms: a retrospective study of 40 patients. Br J Ophthalmol 1987;71: ) aszhao P, Hayashi H, Oshima K, et al. Vitrectomy for macular hemorrhage associated with retinal arterial macroaneurysm. Ophthalmology 2000;107: ) Sayanagi K, Ikuno Y, Soga K, Tano Y. Photoreceptor inner and outer segment defects in myopic foveoschisis. Am J Ophthalmol 2008;145:

6 - 대한안과학회지 2010 년제 51 권제 7 호 - =ABSTRACT= Clinical Results of Vitrectomy in Macular Hemorrhage From a Ruptured Retinal Artery Macroaneurysm Dong Hyun Kim, MD 1, Hyeong Gon Yu, MD 1,2 Department of Ophthalmology, Seoul National University College of Medicine 1, Seoul, Korea Sensory organ research institute, Medical Research Center, Seoul National University 2, Seoul, Korea Purpose: To evaluate the relationship between postoperative optical coherence tomography (OCT) findings and visual acuity in patients who underwent vitrectomy for macular hemorrhage related to the rupture of a retinal artery macroaneurysm. Methods: A retrospective case review was conducted for patients who underwent vitrectomy for macular hemorrhage caused by a retinal arterial macroaneurysm. The relationship between postoperative OCT findings and visual acuity was analyzed. Results: This study included 12 patients whose preoperative mean best corrected visual acuity (BCVA) (logmar) was 1.7±0.8 and whose mean final BCVA was 0.6±0.5. These values were statistically different (p=0.004). Mean foveal thickness by OCT was 437.5±161.5 μm at the preoperative period and 252.8±84.9 μm three months postoperative, and this difference was statistically significant (p=0.017). As the foveal thickness decreased after removal of the remnant organized retinal hemorrhage in the postoperative period, BCVA improved at the final follow-up (p=0.048). According to the postoperative OCT, the photoreceptor disruption group presented a lower BCVA than that of the photoreceptor preservation group at the final follow-up (logmar: 1.4±0.4 vs. 0.3±0.2, p=0.009). Conclusions: Photoreceptor preservation as observed by OCT was significantly associated with better visual outcome after vitrectomy in patients with macular hemorrhage caused by rupture of a retinal arterial macroaneurysm. J Korean Ophthalmol Soc 2010;51(7): Key Words: Retinal artery macroaneurysm, Macular hemorrhage, Vitrectomy, Optical coherence tomography, Prognosis of visual acuity Address reprint requests to Hyeong Gon Yu, MD Department of Ophthalmology, Seoul National University Hospital #28 Yeongeon-dong, Jongno-gu, Seoul , Korea Tel: , Fax: , hgonyu@snu.ac.kr 966

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