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1 대한안과학회지 2021 년제 62 권제 1 호 J Korean Ophthalmol Soc 2021;62(1):12-20 ISSN (Print) ISSN (Online) Original Article 각막이식실패를초래하는고위험군에대한조사 Patients at High Risk for Failure of Penetrating Keratoplasty 권혜지 1 정호석 1 이용민 2 김영준 3 고병이 2 김현승 4 정태영 3 현준영 5 차흥원 1 Hye Ji Kwon, MD 1, Ho Seok Chung, MD 1, Yong Min Lee, MD 2, Young Jun Kim, MD 3, Byung-Yi Ko, MD, PhD 2, Hyun Seung Kim, MD, PhD 4, Tae-Young Chung, MD, PhD 3, Joon Young Hyon, MD 5, Hungwon Tchah, MD, PhD 1 울산대학교의과대학서울아산병원안과학교실 1, 건양대학교의과대학안과학교실 2, 성균관대학교의과대학삼성서울병원안과학교실 3, 가톨릭대학교의과대학서울성모병원안과학교실 4, 서울대학교의과대학분당서울대학교병원안과학교실 5 Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine 1, Seoul, Korea Department of Ophthalmology, Konyang University College of Medicine 2, Daejeon, Korea Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine 3, Seoul, Korea Department of Ophthalmology, Seoul St. Mary s Hospital, College of Medicine, The Catholic University of Korea 4, Seoul, Korea Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine 5, Seongnam, Korea Purpose: We report the clinical characteristics and the primary underlying diseases of patients at high risk for failure of penetrating keratoplasty (PKP) in Korea. Methods: Patients at high risk of PKP failure among those who visited the ophthalmological clinics of tertiary care hospitals in Korea from April 2019 to April 2020 and who were indicated for PKP were retrospectively enrolled. We epidemiologically investigated 119 eyes of 104 patients via medical chart review. Results: Herpes simplex virus (HSV) keratitis was the most common primary underlying disease (26.1%). The most common primary cause of poor bilateral visual acuity was Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (41.7%) followed by chemical burns (19.4%). Of the 119 eyes, 40.3% had a history of previous PKP and 20.2% had undergone three or more PKP. The average number of prior PKPs was 1.02 ± Corneal neovascularization and corneal opacity were reported in 82.4 and 92.4% of cases, respectively. As the severity of these conditions increased, the eye distributions became larger. Of all patients, 47.9 and 31.9%, respectively, received the highest corneal neovascularization and corneal opacity scores. Conclusions: Our study of patients at high risk of PKP failure improves our understanding of the relevant clinical characteristics and primary underlying diseases. Such patients require careful observation and aggressive treatment. Possible alternatives to PKP should be considered if PKP consistently fails. This study will aid clinicians in deciding whether to proceed to surgery if a poor postoperative prognosis is predictable. J Korean Ophthalmol Soc 2021;62(1):12-20 Keywords: Corneal graft failure, Corneal transplantation, High risk, Penetrating keratoplasty Received: Revised: Accepted: Address reprint requests to Hungwon Tchah, MD, PhD Department of Ophthalmology, Asan Medical Center, #88 Olympic ro 43 gil, Songpa gu, Seoul 05505, Korea Tel: , Fax: , hwtchah@amc.seoul.kr * Financial support: This research was supported by TE BioS grant as well as Research and Business Development Program through the Korea Institute for Advancement of Technology (KIAT) funded by the Ministry of Trade, Industry and Energy (MOTIE) (grant number: P ). * This study was presented as a narration at the 124th Annual Meeting of the Korean Ophthalmological Society * Conflicts of Interest: The authors have no conflicts to disclose. c2021 The Korean Ophthalmological 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. 12

2 - 권혜지외 : 각막이식실패의고위험군에대한조사 - 각막이식은시행한지 110년이상된수술로, 다양한원인으로발생한영구적인각막혼탁의유일한치료방법으로써전세계적으로널리사용되고있다. 각막이식은동종이식중다른장기에비해수술성공률이높으며, 전체층각막이식외에심부앞층판각막이식, 데스메막박리내피각막이식, 데스메막내피각막이식등다양한층판각막이식수술방법이여러단계를거치면서도입되었다. 각막이식의성공과관계된요인으로나이, 각막혈관신생, 술전염증성안질환, 주변홍채앞유착, 녹내장, 앞선각막이식편거부반응및이식편실패등이있으며, 스티븐스-존슨증후군, 단순포진각막염, 화학화상등의질환이술후불량한예후인자로알려져있다. 1-4 이러한위험요인을갖고있는고위험군에서는각막이식의성공률이높지않고, 이전수술이실패한경우반복하여각막이식을시행함에따라재이식안의비율이높아지며, 각막이식을여러번반복한경우수술의성공률은낮아진다. 1,5,6 각막이식실패를초래하는고위험군에대한관리및치료를위해스테로이드, 칼시뉴린억제제인타크롤리무스 (tacrolimus) 와사이클로스포린 (cyclosporin A), 항대사약제인마이코페놀레이트 (mycophenolate mofetil) 와아자티오프린 (azathioprine), 그외항혈관내피세포성장인자 (anti-vascular endothelial growth factor) 나생물학적제제 (biological agent) 등면역억제제를이용한다양한시도가이루어졌으나각막이식편생존율을높이기위해명확히정립된치료는마땅하지않은실정이다. 2,7 각막이식의성공률이저조할것으로예상되는고위험군에서수술적치료의성공률을높이기위한대안으로인공각막이도입되었다. 8,9 다양한소재와디자인의인공각막중보스톤인공각막을이용한이식은여러연구를통해실패율위험이높은고위험군에서의각막이식혹은반복된각막이식의대안으로서가능성을보였으나, 인공각막후막, 조직괴사, 녹내장등의합병증이발생할경우경우에따라인공각막제거를요하며, 망막박리나안내염등의심각한술후합병증의비율이높게보고되고있다. 10,11 이러한단점을극복하기위한다양한종류의인공각막및유도만능줄기세포유래각막세포이식이연구중에있으나, 12 인공각막이식의잠재적대상자인각막이식실패를초래하는고위험군에대한국내분석및역학조사는드문실정이다. 2006년 Choi et al 13 이국내전체각막이식대기자의특성과각막이식수술의결과에대한역학조사를보고하였으며 2009년 Lee and Chung 14 은국내에서각막이식후 20년이상장기간투명각막을유지한환자의특성을분석하여낮은성공률및이식실패의관련요인에대해보고하였다. 2011년 Jang et al 15 은국내 3회이상전체층각막이식을시행한환자를대상으로한연구에서이식수술사이의기간이짧거 나각막혈관신생이있는경우를이식실패의위험인자로보고하였으며이식횟수가증가할수록이식편생존기간이감소한다고밝혔다. 그러나, 아직까지국내에서각막이식실패를초래하는고위험군에대한조사는보고된바없다. 이에본연구에서는각막이식실패를초래하는고위험군에대한현황조사를시행하고자하였다. 대상과방법 본연구는 2019년 4월부터 2020년 4월까지국내 5개병원 ( 가톨릭대학교서울성모병원, 건양대학교병원, 분당서울대학교병원, 서울삼성서울병원, 서울아산병원 ) 외래에내원한환자들중각막이식실패를초래하는고위험군으로분류된 104명 119안을대상으로의무기록을바탕으로한후향적연구를시행하였으며, 임상시험심사위원회 (Institutional Review Board, IRB) 의심사및승인을받았다 ( 승인번호 : ). 고위험군의대상은선천성각막질환 ( 무홍채증, 피터스이상, 선천성유전성각막내피이상증등 ), 안표면질환 ( 스티븐스-존슨증후군, 독성표피괴사용해, 반흔유사천포창, 단순포진각막염, 화학화상, 외상등 ), 이전에동종각막이식실패력이있고반복각막이식이필요한경우및임상의판단하고위험군으로생각되는경우 ( 예, 각막혈관신생정도가 1점이상인경우 ) 였다. 약물및수술적치료에도안압조절이되지않는녹내장, 약물에의해조절되지않는진행성안염증, 시력저하의주된원인이망막혹은시신경의질환인경우조사대상에서제외하였다. 대상환자에대해서나안시력, 최대교정시력, 반대안시력, 안압, 이전각막이식시행횟수, 녹내장이환여부, 평균이식편생존기간, 각막혈관신생의유무및정도, 각막혼탁의유무및정도에대해조사하였다. 각막이식이필요하게된원인질환을조사하였으며, 각원인질환별로나누어각막혈관신생정도와각막혼탁정도를조사하였다. 양안시력이불량한경우는양안시력이모두안전수지이하로측정된경우로정의하였다. 이식편의생존기간은수술후부터이식편의실패전마지막각막투명도를유지한추적관찰시기또는추적관찰이종료될때까지의기간으로하였으며, 이식편의실패는수술후최소 2주간투명한상태를유지하였던이식각막에서부종과혈관화된반흔이비가역적으로발생하는상태로, 16 사진상혹은의무기록상이러한각막상태에대한기술이있을때안과전문의가이식편의실패로평가하였다. 각막혈관신생정도는신생혈관이없는경우 0점, 주변부에국한되면서한사분면이상의표층신생혈관이있거나두사분면이하의심층신생혈관이있는경우 1점, 중심부를침범하거나세사분면이상의심층신생혈관이있는경우 2점 13

3 - 대한안과학회지 2021 년제 62 권제 1 호 - 으로구분하였다. 17 각막혼탁의정도는각막혼탁이없는경우 0점, 세극등현미경검사상에서만보이는경도의각막부종의경우 1점, 경도의각막혼탁이있으나홍채의세부적관찰이명확히가능한경우 2점, 중등도의각막혼탁으로명확한홍채관찰이어려운경우 3점, 중증의각막혼탁으로전방내구조관찰이어려운경우 4점으로구분하였다. 18 통계적분석은 SPSS version 21.0 (IBM Corp., Armonk, NY, USA) 를이용하였으며, 연속형자료는기술통계를통해평균 ± 표준편차및중앙값, 사분범위로표기하였으며, 범주형자료는빈도분석을통해서빈도로표기하였다. 결 과 대상환자는총 104명 119안으로남자 85안, 여자 34안이었고, 평균나이 ± 16.09세였다. 평균최대교정시 Table 1. Demographics and clinical characteristics of high risk group for the failure of penetrating keratoplasty High risk for the failure of Demographics and characteristic penetrating keratoplasty (n = 119) Age (years) ± ( ) Sex (male/female) 85/34 BVCA (logmar) 1.83 ± ( ) BCVA (contralateral eye, logmar) 1.00 ± ( ) Intraocular pressure (mmhg) ± ( ) Number of previous penetrating 1.02 ± 1.46 keratoplasty (n) 0.00 ( ) Glaucoma 38 (31.93) Poor bilateral visual acuity 36 (30.25) Numerical values presented as mean ± standard deviation as well as median (interquartile range) or number (%). BCVA = best corrected visual acuity; logmar = logarithm of minimal angle of resolution. Table 2. Primary underlying disease of eyes at high risk for the failure of penetrating keratoplasty Primary disease Value HSV keratitis 31 (26.1) SJS/TEN 22 (18.5) Trauma 16 (13.4) Chemical burn 14 (11.8) Pseudophakic bullous keratopathy 5 (4.2) Values are presented as number (%). HSV = Herpes simplex virus; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis. 력은 logmar 1.83 ± 0.74, 평균반대안시력은 logmar 1.00 ± 1.15, 안압은평균 ± 7.10 mmhg였으며, 녹내장이환율은 31.93% 였다 (Table 1). 진단된질환으로는단순포진각막염 31안 (26.1%), 스티븐스-존슨증후군 / 독성표피괴사용해 22안 (18.5%), 외상 16안 (13.4%), 화학화상 14안 (11.8%), 무수정체수포각막병증 5안 (4.2%) 순으로나타났다 (Table 2). 양안이모두고위험군으로포함된경우는 15명 30안이었으며, 이중양안모두안전수지이하의시력인경우는 9명 18안 (60%) 이었다. 양안시력이모두불량한경우는 27명 36안 (30.25%) 이었으며 (Table 1), 양안불량한시력저하의원인질환으로는스티븐스-존슨증후군 / 독성표피괴사용해가 8명 15안 (41.7%) 로가장많았으며화학화상이 5명 7안 (19.4%), 무수정체수포각막병증이 3명 3안 (8.33%) 순으로높은비율을차지했다. 각막이식의과거력이있는경우가 48안 (40.3%) 이었으며, 71안 (59.7%) 은각막이식을시행받지않았다. 이전에각막이식을시행받은횟수는평균 1.02 ± 1.46회였으며전체평균이식편생존기간은 ± 29.21개월이었다. 각막이식횟수에따른대상안의분포및이식편생존기간을분석하여 Table 3에기술하였다. 전체중 3회이상각막이식을시행받은경우가 24안 (20.2%) 이었으며, 3회이상각막이식후평균이식편생존기간은 ± 16.79개월이었다. 각막이식횟수별평균이식편의생존기간은 3회의경우 21.81개월, 4회의경우 11.26개월, 5회의경우 18.85개월이었다. 각원인질환별로각막이식을시행받은과거력이있는경우는단순포진각막염 6안 (19.4%), 스티븐스-존슨증후군 / 독성표피괴사용해 4안 (18.2%), 외상 5안 (31.3%), 화학화상 3안 (21.4%) 이었으며, 평균이식편생존기간을비교한결과단순포진각막염의경우 14.08개월, 스티븐스-존슨증후군 / 독성표피괴사용해의경우 2.25개월, 화학화상의경우 12.80개월로전체평균보다짧게나타났다 (Table 4, 5). 각막혈관신생의정도및각막혼탁의정도에따른분포 Table 3. Mean survival period of previous penetrating keratoplasty Number of previous Graft survival period Value penetrating keratoplasty (months) 0 71 (59.7) (10.1) ± ( ) 2 12 (10.1) ± ( ) 3 24 (20.2) ± ( ) Graft survival period presented as mean ± standard deviation as well as median (interquartile range) or number (%). 14

4 - 권혜지외 : 각막이식실패의고위험군에대한조사 - Table 4. Subgroup analysis of graft survival period of previous penetrating keratoplasty according to the primary disease Primary disease Graft survival period of previous penetrating keratoplasty (months) HSV keratitis (n = 6) ± ( ) SJS/TEN (n = 4) 2.25 ± ( ) Trauma (n = 5) ± ( ) Values are presented as mean ± standard deviation as well as median (interquartile range). HSV = Herpes simplex virus; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis. Chemical burn (n = 3) ± ( ) Table 5. Number of previous penetrating keratoplasty according to the primary disease Primary disease HSV keratitis (n = 31) SJS/TEN (n = 22) Trauma (n = 16) Chemical burn (n = 14) Number of previous penetrating keratoplasty 0 25 (80.6) 18 (81.8) 11 (68.8) 11 (78.6) 1 3 (9.7) 3 (13.6) 3 (18.8) 1 (7.1) (6.3) (9.7) 1 (4.6) 1 (6.3) 2 (14.3) Values are presented as number (%). HSV = Herpes simplex virus; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis. Table 6. Distribution of eyes and mean survival period of previous grafts according to the grade of corneal neovascularization and corneal opacity Grade Value Graft survival period (months) Corneal neovascularization 0 21 (17.6) ± ( ) 1 41 (34.5) ± ( ) 2 57 (47.9) ± ( ) Corneal opacity 0 9 (7.6) ± ( ) 1 14 (11.8) ± ( ) 2 22 (18.5) ± ( ) 3 36 (30.3) ± ( ) 4 38 (31.9) ± ( ) Graft survival period presented as mean ± standard deviation as well as median (interquartile range) or number (%) ± 26.96개월이었다. 전체중각막혼탁정도 4점인경우가 38안 (31.9%) 으로가장많았으며 3점 36안 (30.3%), 2점 22안 (18.5%), 1점 14안 (11.8%), 0점 9안 (7.6%) 순이었다. 각막혼탁정도 4점인경우평균이식편생존기간은 ± 9.59개월로가장짧았으며, 3점 ± 10.47개월, 2점 ± 7.58개월, 1점 ± 28.89개월, 0점 ± 35.29개월이었다. 각질환별각막혈관신생정도와각막혼탁정도의비율을질환의빈도순으로 Table 7에기술하였으며각질환에서각막혈관신생및각막혼탁을잘보여주는대표적인증례사진을 Fig. 1에나타내었다. 단순포진각막염, 스티븐스-존슨증후군 / 독성표피괴사용해, 화학화상에서각막혈관신생정도 2점인경우가각각가장많은비율을보였으며 ( 각각 54.8%, 68.2%, 85.7%), 각막혼탁정도는스티븐스-존슨증후군 / 독성표피괴사용해와화학화상에서 4점인경우가가장많았고 ( 각각 40.9%, 64.3%) 단순포진각막염에서는 3점이가장많은비율을차지했다 (51.6%). 그에비해안외상의경우다른질환에비해각막혈관신생정도가 0점인경우가 56.25% 를차지했으며, 각막혈관신생정도와각막혼탁정도의중증도가비교적심하지않은것으로나타났다. 비율및이식편생존기간을 Table 6에기술하였다. 전체중각막혈관신생정도 2점인경우가 57안 (47.9%) 로가장많았고 1점 41안 (34.5%), 0점 21안 (17.6%) 순이었다. 각막혈관신생정도 2점인경우평균이식편생존기간은 ± 6.25개월로가장짧았으며, 1점 ± 38.48개월, 0점 고찰 본연구에서는각막이식의실패를초래하는고위험군을대상으로임상양상, 진단질환, 이전각막이식시행횟수및이식편생존기간에대해서알아보았으며, 나아가각막혈 15

5 - 대한안과학회지 2021 년제 62 권제 1 호 - 관신생및각막혼탁의정도의분포비율및이에따른대상질환의분포및이식편생존기간에대해서조사하였다. 이는각막이식실패를초래하는고위험군의현황에대한조사로서국내에서의첫보고이다. 본연구의결과에따르면진단질환은단순포진각막염이가장많았으며, 그다음으로는스티븐스-존슨증후군 / 독성표피괴사용해, 외상, 화학화상, 무수정체수포각막병증순으로뒤를이었다. 2006년에보고된한국인각막이식대기자의임상진단의비율은감염성각막염이 22.0% 로가장높았고, 외상이 21.0%, 인공수정체또는무수정체수포각막병증이 13.8%, 원추각막이 12.5%, 기질이상증이 5.1%, 화학물 질에의한손상이 4.5% 였다 년국내에서각막이식후 20년이상장기간투명각막을유지한환자의특성을분석한결과이식실패의원인질환으로외상이 23.7% 로가장많았으며, 단순포진각막염이 17.5% 로뒤를이었다. 14 본연구에서고위험군대상에서는기존에각막이식대기자에서높은비율로보고된단순포진각막염, 외상외에도스티븐스-존슨증후군 / 독성표피괴사용해와화학화상의비율이높게나타났으며 ( 각각스티븐스-존슨증후군 / 독성표피괴사용해 18.5%, 화학화상 11.8%), 이두질환은양안모두시력이불량한경우의원인으로 61.1% 를차지했다 ( 각각스티븐스- 존슨증후군 / 독성표피괴사용해 41.7%, 화학화상 19.4%). Table 7. Subgroup analysis of corneal neovascularization and corneal opacity according to the primary disease Primary disease HSV keratitis (n = 31) SJS/TEN (n = 22) Trauma (n = 16) Chemical burn (n = 14) Grade of corneal neovascularization 0 4 (12.9) 2 (9.1) 10 (62.5) (32.3) 5 (22.7) 4 (25.0) 2 (14.3) 2 17 (54.8) 15 (68.2) 2 (12.5) 12 (85.7) Grade of corneal opacity 0 1 (3.2) 2 (9.1) 4 (25.0) (9.7) 3 (13.6) 2 (12.5) (22.6) 2 (9.1) 4 (25.0) 2 (14.3) 3 16 (51.6) 6 (27.3) 2 (12.5) 3 (21.4) 4 4 (12.9) 9 (40.9) 4 (25.0) 9 (64.3) Values are presented as number (%). HSV = Herpes simplex virus; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis. A B C D Figure 1. Slit-lamp photography showing representative cases of (A) Herpes simplex virus keratitis, (B) Stevens-Johnson syndrome/toxic epidermal necrolysis, (C) trauma, and (D) chemical burn. 16

6 - 권혜지외 : 각막이식실패의고위험군에대한조사 - 원추각막과기질이상증은앞선여러연구에서각막이식의결과가양호한것으로알려져있어본연구의대상질환으로포함하지않았다. 본조사에서각막혈관신생및각막혼탁의정도에따른대상안의분포를분석한결과각각의정도가심할수록그비율이높았다. 각막이식후이식편생존기간은 3회이상각막이식후평균 19.12개월로전체평균 20.33개월보다짧았으며, 각막혈관신생정도및각막혼탁정도가심할수록이식편생존기간이짧은경향을보였다. 기존의많은연구에서반복된각막이식을술후이식편생존의불량한예후인자로분석하였으며, 재이식안에서과거이식횟수가높을수록술후성공률은 50-60% 로낮게보고되었다. 1,6,19 각막혈관신생역시기존연구와대규모메타분석을통해이식편실패의위험인자로알려져있다. 20,21 국내 3회이상전체층각막이식을시행한환자를대상으로시행한분석에서이식수술사이의기간이짧거나각막혈관신생이있는경우를이식실패의위험인자로보고하였으며, 이식횟수가증가할수록이식편생존기간이감소한다고밝혔다. 15 각막이식실패를초래하는고위험군을대상으로한본연구에서보인각막혈관신생정도및각막혼탁정도가심한경우의높은분포비율및짧은이식편생존기간은앞선보고와상응하는결과를보였다. 각질환별각막혈관신생정도와각막혼탁정도를분석한결과각막혈관신생의경우가장높은 2점의비율이단순포진각막염에서 54.8%, 스티븐스- 존슨증후군 / 독성표피괴사용해에서 68.2%, 화학화상에서 85.7% 였다. 이러한결과는특정원인질환과각막혈관신생사이의강한상호관계에기인한것으로생각된다. 단순포진각막염의경우단순포진바이러스감염으로호중구가각막실질로이동하면서혈관내피세포및혈관주위세포의손상으로혈관내피성장인자발현이증가되며혈관내피성장인자와그수용체의불균형이야기된부분에백혈구축적, 각막내피세포기저막파괴및세포외기질손상, 혈관내피세포증식과이동이순차적으로일어나새로운혈관내강이생성되며뻗어나가는과정으로각막혈관신생이촉진된다 또한, 단순포진각막염은각막혈관신생형성정도가심하고질환의재발이높으며면역학적기전에의한각막이식편거부반응을촉진하는특성으로인해이식편실패의위험이높다고알려져있다 본조사에서도단순포진각막염으로진단받은경우각막혈관신생정도가 2점인경우의비율이가장높게나타나앞서알려진바와일치하는결과를보였다. 본연구에포함된진단질환중스티븐스-존슨증후군 / 독성표피괴사용해및화학화상으로진단받은경우각막혈관신생정도및각막혼탁정도모두심할수록해당되는안의 분포비율이높게나타났으며, 이두질환은앞서밝힌바와같이본연구에서양안불량한시력의주된원인질환으로보였다. 스티븐스-존슨증후군 / 독성표피괴사용해의중요한임상적특징인각막혈관신생은만성적인염증, 반복적인깜박임에의해의한미세반흔형성, 눈꺼풀판반흔형성및술잔세포기능부전에의한눈물막불안정성등에의해발생되는것으로알려져있다 이러한각막혈관신생은장기적시력저하와관련있는인자로밝혀졌으며스티븐스 -존슨증후군/ 독성표피괴사용해에서술후감염, 지속각막상피결손, 각막천공및면역학적거부반응의위험도가높아각막이식성공률이불량하다. 30,31 화학화상은본조사에서모든원인질환중각막혈관신생및각막혼탁의정도가가장심한질환으로나타났다. 화학화상으로인한손상은각막에만성염증을일으키며다양한염증매개물질및사이토카인의축적으로인해각막혈관신생이비교적심하게발생하는특징을보이며, 각막부종및반흔조직형성과윤부줄기세포결핍으로인해각막이식후이식편실패의불량한예후인자로알려져있다. 3,32-34 스티븐스-존슨증후군 / 독성표피괴사용해와화학화상은질환의정도가심할경우윤부줄기세포결핍을동반할가능성이높으며, 본조사결과두원인질환에서윤부줄기세포결핍을동반한안은전체의 5.9% 로적지않은비율을차지하고있었다. 윤부줄기세포결핍을동반한경우각막표면을유지하는기능이저하되어있고표면신생혈관형성및결막화의특징을보이며, 윤부줄기세포이식이포함된안구표면이식술시행이후각막이식을시행한경우에도각막이식거부반응의위험이높아서다른원인질환에서의각막이식과다른특성을이해하고치료에접근해야한다. 35,36 안압조절및염증억제를위한적극적인치료를먼저시행하고, 동종각막윤부이식등의안구표면이식술로표면을안정화한다음신중하게각막이식을고려할수있지만그럼에도수술예후는좋지않다. 37 이렇듯각막이식의불량한예후의원인이면서불량한양안시력의상당한부분을차지하는스티븐스-존슨증후군 / 독성표피괴사용해와화학화상은추후진행할국내인공각막이식연구의대상으로신중히고려해볼수있겠다. 최근보고에따르면원인질환의진단과이전각막이식의실패가각막이식후이식편실패를예측하는가장중요한인자로생각되며, 질환중화학화상의예후가가장불량하였고이전각막이식시행횟수가증가할수록성공률이낮다고보고하였다. 3 본조사에서원인질환의상당부분을차지하는단순포진각막염의경우항바이러스제와스테로이드를이용한초기적극적인치료를행함으로써질환의상태조절이필요하다. 단순포진각막염뿐만아니라스티븐스-존슨증후군과화학화상등대부분의원인질환에서공 17

7 - 대한안과학회지 2021 년제 62 권제 1 호 - 통적으로면억억제제, 항혈관내피세포성장인자및최근연구되는다양한혈관신생억제제등의적극적인치료로초기에활동성염증을조절하여각막혈관신생을억제하여야한다. 23 이미각막혈관신생및각막혼탁이진행하여시력이불량한경우에는각막이식전후실패요인을줄이려는노력이필요하며, 그럼에도불량한예후가예측되는경우궁극적으로각막이식의대안으로가능한치료를고려해야겠다. 본현황조사의결과에서보인각막이식실패를초래하는고위험군및불량한예후를초래하는해당원인질환에대한이해를통하여각원인질환에서악화인자에대한적극적인치료및수술전후환경개선노력에도움을줄수있으며수술여부결정과수술후예후예측에도움이될것이다. 본연구의한계점은 5개병원을대상으로한연구로환자수가제한적이라는점으로, 향후국내의주요병원들을대상으로대규모역학조사가필요하겠다. 본연구에포함된총 119안중이전각막이식수술의과거력이있는 48안 (40.3%) 에서과거각막이식수술의집도의및수술전후환경이기관마다상이한점이존재하며, 이는다기관연구인본연구의제한점이다. 본조사결과전체고위험군의약 60% 에서각막이식수술력이없었으며실제임상에서도고위험원인질환으로인한경우에는이식수술후불량한예후로인해각막이식을시행하지않고지켜보는경우가많다. 또한, 국내에서기증되는각막의수급부족으로인하여고위험군에서의수술결정이더욱어렵다. 이러한실정에서각막이식실패를초래하는고위험군에대한주의깊은관찰및실패요인교정을위한적극적인치료가필요하겠으며나아가고위험군의각막이식대기를줄이려는방법을모색하여야하겠다. 각막이식실패위험이높은상태이거나과거각막이식수술력이있는경우기존의각막이식을시행할경우향후연속적인각막이식실패를초래할수있으므로한계가있으며, 이경우유도만능줄기세포유래각막세포이식이나인공각막이식등을기존각막이식의대안으로고려해볼수있다. 본연구는국내에서처음으로시행된각막이식실패를초래하는고위험군을대상으로한조사로서, 본연구결과를바탕으로각막이식을대체할가능성이있는방법으로인공각막이식혹은유도만능줄기세포유래각막세포이식등에대한추가적인연구진행이가능할것으로생각된다. REFERENCES 1) Fasolo A, Capuzzo C, Fornea M, et al. Risk factors for graft failure after penetrating keratoplasty: 5-year follow-up from the corneal transplant epidemiological study. Cornea 2011;30: ) Jabbehdari S, Rafii AB, Yazdanpanah G, et al. Update on the management of high-risk penetrating keratoplasty. Curr Ophthalmol Rep 2017;5: ) Barraquer RI, Pareja-Aricò L, Gómez-Benlloch A, Michael R. Risk factors for graft failure after penetrating keratoplasty. Medicine (Baltimore) 2019;98:e ) Inoue K, Amano S, Oshika T, Tsuru T. Risk factors for corneal graft failure and rejection in penetrating keratoplasty. Acta Ophthalmol Scand 2001;79: ) Claesson M, Armitage WJ. Clinical outcome of repeat penetrating keratoplasty. Cornea 2013;32: ) Al-Mezaine H, Wagoner MD. King Khaled Eye Specialist Hospital Cornea Transplant Study Group. Repeat penetrating keratoplasty: indications, graft survival, and visual outcome. Br J Ophthalmol 2006;90: ) Yamazoe K, Yamazoe K, Yamaguchi T, et al. Efficacy and safety of systemic tacrolimus in high-risk penetrating keratoplasty after graft failure with systemic cyclosporine. Cornea 2014;33: ) Park CY, Lee JK, Gore PK, et al. Keratoplasty in the United States: A 10-year review from 2005 through Ophthalmology 2015; 122: ) Lee WB, Shtein RM, Kaufman SC, et al. Boston keratoprosthesis: outcomes and complications: a report by the American Academy of Ophthalmology. Ophthalmology 2015;122: ) Srikumaran D, Munoz B, Aldave AJ, et al. Long-term outcomes of boston type 1 keratoprosthesis implantation: a retrospective multicenter cohort. Ophthalmology 2014;121: ) Ahmad S, Mathews PM, Lindsley K, et al. Boston Type 1 keratoprosthesis versus repeat donor keratoplasty for corneal graft failure: a systematic review and meta-analysis. Ophthalmology 2016; 123: ) Hayashi R, Ishikawa Y, Sasamoto Y, et al. Co-ordinated ocular development from human ips cells and recovery of corneal function. Nature 2016;531: ) Choi SH, Lee YW, Kim HM, et al. Epidemiologic studies of keratoplasty in Korea. J Korean Ophthalmol Soc 2006;47: ) Lee KM, Chung SK. Studies of patients maintaining clear cornea over 20 years following penetrating keratoplasty. J Korean Ophthalmol Soc 2009;50: ) Jang JY, Woo JM, Yoon KC. Long-term results after three or more penetrating keratoplasties and risk factors for graft failure. J Korean Ophthalmol Soc 2011;52: ) Weisbrod DJ, Sit M, Naor J, Slomovic AR. Outcomes of repeat penetrating keratoplasty and risk factors for graft failure. Cornea 2003;22: ) Halberstadt M, Machens M, Gahlenbek KA, et al. The outcome of corneal grafting in patients with stromal keratitis of herpetic and non-herpetic origin. Br J Ophthalmol 2002;86: ) Abbas A, Khan B, Feroze AH, Hyman GF. Thalidomide prevents donor corneal graft neovascularization in an alkali burn model of corneal angiogenesis. J Pak Med Assoc 2002;52: ) Yalniz-Akkaya Z, Burcu Nurozler A, Yildiz E, et al. Repeat penetrating keratoplasty: indications and prognosis, Eur J Ophthalmol 2009;19: ) Bachmann B, Taylor RS, Cursiefen C. Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: an evidence-based meta-analysis. Ophthalmology 2010;117: e7. 21) Thompson RW Jr, Price MO, Bowers PJ, Price FW Jr. Long-term 18

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9 - 대한안과학회지 2021 년제 62 권제 1 호 - = 국문초록 = 각막이식실패를초래하는고위험군에대한조사 목적 : 각막이식실패를초래하는고위험군에서임상양상및원인질환에대해알아보고자하였다. 대상과방법 : 2019 년 4 월부터 2020 년 4 월까지국내 5 개병원에내원한각막이식실패를초래하는고위험군 104 명 119 안을대상으로원인질환및임상적특성에대해후향적의무기록분석을시행하였다. 결과 : 환자의 71.4% 가남자였으며, 원인질환으로단순포진각막염이 26.1% 로가장많았다. 양안시력이불량한경우 ( 양안시력모두안전수지이하 ) 의원인으로스티븐스 - 존슨증후군 / 독성표피괴사용해와화학화상이각각 41.7% 와 19.4% 를차지했다. 각막이식의과거력이 3 회이상인경우는 20.2% 였으며이전각막이식과거력의평균횟수는 1.02 ± 1.46 회였다. 각막혈관신생과각막혼탁이존재한경우는각각 82.4% 와 92.4% 였다. 각막신생혈관정도및각막혼탁정도가심할수록대상안의분포비율이높았으며각막신생혈관의경우가장높은 2 점이 47.9%, 각막혼탁의경우가장높은 4 점이 31.9% 를차지했다. 결론 : 각막이식실패를초래하는고위험군에대한특성을분석함으로써각막이식의예후가불량한원인질환에대한이해가가능하다. 해당질환에대한보다주의깊은관찰과적극적인치료로각막이식성공률을높이기위한노력이필요하며, 연속적인각막이식실패방지를위해각막이식의대안으로가능한새로운치료법에대한추후연구가필요할것으로생각된다. 본연구의분석결과는각막이식여부결정과술후예후예측에도움이되겠으며추후연구에참고자료로활용할수있다. < 대한안과학회지 2021;62(1):12-20> 권혜지 / Hye Ji Kwon 울산대학교의과대학서울아산병원안과학교실 Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine 20

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R