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1 대한안과학회지제 49 권제 3 호 2008 J Korean Ophthalmol Soc 49(3): , 2008 DOI : /jkos 비강내누낭비강문합술시시행한양막충전술의단기임상결과 최영재 황상준 이태수 고려대학교의과대학안과학교실 목적 : 비강내누낭비강문합술시양막으로감싼 Merocel R 을골공에위치시킨후단기임상결과를알아보고자하였다. 대상과방법 : 2005년 10월부터 2006년 4월까지비루관폐쇄의치료로비강내누낭비강문합술을시행받은환자 60명을대상으로전향적인연구를시행하였다. 30명의환자들에게는술후양막으로감싼 Merocel R 을골공에 10일에서 14일간위치시키고 (1군), 나머지 30명의환자들에게는일반적인 Merocel R 만을충전하였다 (2군). 추적관찰기간동안두군간의수술창상치유과정및육아종의발생, 골공의유지정도등을비교, 분석하였다. 결과 : 수술 6개월후의성공률은 1군에서 93.3%, 2군에서는 86.7% 로 1군에서다소높았으나통계학적으로유의하지는않았다 (p=0.67). 수술후평균창상치유기간은 1군에서 4.8±1.5주 (3~10주), group 2에서 7.3±1.5주 (5~12주) 로 1군에서더짧았다 (p<0.001). 수술후 2개월까지육아종이발생한환자는 1군과 2군에서각각 4명 (13%) 과 11명 (33%) 으로 1군에서더적었다 (p=0.04). 그러나수술후 6개월에는각각 11명 (33%) 과 14명 (46%) 에서육아종이발생하여두군에서차이가없었다. 결론 : 비강내누낭비강문합술시양막으로감싼 Merocel R 충전술후단기임상결과상창상의염증이줄어들고창상치유속도가빨라졌으며초기육아종발생을줄일수있었다. < 한안지 49(3): , 2008> 양막은태반을둘러싸는태아쪽으로향한가장안쪽막으로 1910 년 Davis 1 가피부이식을위해양막을사용한이래로여러분야에서사용되고있다. 안과영역에서는 1940 년 de Rotth 2 가결막의검구유착과결손의치료에처음사용하였고 1995 년 Kim and Tseng 3 이각막상피제거및각막윤부층판절제술을시행한토끼모델에서양막을사용하여성공적인안구표면의재형성을보고하고양막의처치와보관방법을발전시킨이후최근까지널리사용되고있다. 각막화상, 4 스티븐스 - 존슨증후군 (Stevens-Johnson syndrome), 5 재발된익상편 6 등다양한안구표면질환의치료에성 < 접수일 : 2007 년 3 월 16 일, 심사통과일 : 2007 년 8 월 21 일 > 통신저자 : 이태수서울시구로구구로동길 97 고려대학교구로병원안과 Tel: , Fax: * 본논문의요지는 2006 년대한안과학회제 96 회추계학술대회에서구연으로발표되었음. 공적으로이용되고있으며치유되지않는각막궤양및지속성상피세포결손, 7-10 괴사성공막염, 11,12 각막천공 13 등의난치성질병에도사용되고있다. 또한녹내장환자에서섬유주절제술후여과포유지에도움이된다는보고도있고 14 엑시머레이저를이용한수술후섬유아세포증식을억제하고각막혼탁발생을줄이는것으로보고되었다 한편비강내누낭비강문합술후비강내창상치유기간은경피적누낭비강문합술에비해긴것으로알려져있고수술초기에실패의흔한요인으로창상치유기간동안에발생하는육아종, 염증, 반흔조직의과다형성등이알려져있다 이에저자들은비강내누낭비강문합술후양막으로감싼 Merocel R 을골공부위에충전함으로써단기임상결과상비강내점막의창상치유속도가빠르고육아종이적게발생하는등의결과를얻었기에이를국내에서처음으로보고하는바이다. 대상과방법 2005 년 10 월부터 2006 년 4 월까지비루관폐쇄증으로진단되어고려대학교구로병원안과에서비강내누 384

2 대한안과학회지제 49 권제 3 호 2008 년 낭비강문합술을시행받은 60 명의환자 60 안을대상으로이들중 30 안에대해서는수술후양막으로감싼 Merocel R 을비강내골공에충전하였고 (1 군 ), 나머지 30 안에대해서는일반적인 Merocel R 을충전하여 (2 군 ) 그결과를전향적으로비교분석하였다. 양막의채취는 B 형, C 형간염, HIV, 매독등의혈청검사상음성인산모의정규제왕절개시시행하였고수술전산모및보호자에게이에대한인지동의서를받았다. 양막의처리및보관은 Kim and Tseng 3 이보고한방법에따라시행하였다. 제왕절개직후태반으로부터양막을분리하고 phosphate buffered saline (penicillin 50 µg/mg, gentamicin 8 µg/mg, amphotericin B 2.5 µg/mg 함유 ) 을이용하여씻고이후양막의상피쪽이반대로향하도록 Nitrocellulose paper 위에얇게펼친후 Dulbecco s modified Eagle Medium (Life Technologies Inc, N.Y., USA) 과 100% glycerin 을 1:1 로섞은 media 에넣어영하 70 냉장고에보관하였다. 모든환자는수술전내시경검사를시행하여비강의크기, 비강내다른병변의유무와비중격만곡등의비강상태를확인하였고심한비중격만곡이있는경우는이비인후과에서비중격교정술을수술전에시행받도록하였으며비강의크기및비강의상태에따라전신마취또는국소마취로수술을시행하였다. 수술과정중점막의제거는단극성소작기나 radiosurgical unit (Ellman ntl. Inc., NY, USA) 을사용하였고드릴과 Kerrison 펀치를사용하여직경 5~8 mm 의골공을만들었다. 그후 Nd:YAG 레이저 (Laserscope R, San Jose, CA, USA) 소식자 (Laser optics, 0.6 mm in diameter) 를누소관을통하여누낭에집어넣고내시경으로비강을통하여누낭의내측벽을관찰하면서내측벽을제거하였다 (Contact mode, laser power: 15 watt, continuous mode). 이후두개의실리콘관 (Guibor canalicular intubation sets R, Xomed-Treace, Jacksonville, FL, USA) 을삽입하여금속클립으로결찰하고실리콘여분이 5 mm 정도되도록절단하여비강내에안착시켰다. 그후출혈을방지하기위하여 Merocel sponge 를비강내에 packing 하였다. 이때 1 군에서는 Merocel R 을양막으로감싸고 6-0 silk 를이용하여고정시킨후 (Fig. 1) 비강내에 packing 하였고 2 군에서는일반적인 Merocel R 을 packing 하였다. 수술후점안항생제와 0.1% fluorometholone 안약을첫날부터하루 4 회점안하고생리식염수비강세척기를이용하여한달간하루 3 회정도비강세척을하도록교육하였다. 경과관찰은술후첫한달간은매주마다, 그다음한달간은 2 주마다, 그이후로는한달마다시행하였다. 매내원시마다유루증의유무를확인하고내시경을통해창상의치유과정, 비강내누공의상태와합병증유무를관찰하였고이를디지털사진으로기록하여이를토대로결과를분석하였다. 충전된 Merocel R 은 1 군의경우에는술후 10~14 일째되는날제거하였고감염을우려해중간에내원시항생제세척을시행하였다. 항생제세척시에는먼저흡입기를이용하여분비물을깨끗하게제거한후 23 G 바늘을이용하여이미팽창되어있는 Merocel R 내로항생제를주사하였다. 2 군에서는수술후 1 주일째에 Merocel R 을제거하였다. 두군에서양막으로둘러싼 Merocel R packing 이외의위와같은수술과정및수술후처지, 추적관찰등은모두동일하게시행하였다. 수술의성공은환자의유루증상이소실되고내측누공이개통되어있고형광색소검사상 +1 이하인경우로정의하였다. 또한재상피화시기는내시경으로관찰하여창상의상피화가완전히이루어진가장빠른내원일로하였다. Figure 1. Merocel R was wrapped with amniotic membrane (A) and fixed with 6-0 silk (B). 385

3 최영재외 : 비강내누낭비강문합술시양막충전술 결 과 환자들의평균나이는 1 군에서 52.0±17.5 세 (29~ 75 세 ) 2 군에서는 53.9±13.8 세 (33~84 세 ) 였으며그밖에성별, 추적관찰기간등은두군에서차이가없었다 (Table 1). 수술 6 개월후의일차성공률은 1 군에서 93.3% (28/30 안 ), 2 군에서 86.6% (26/30 안 ) 으로 1 군에서다소높았으나통계적으로유의하지는않았다 (p= 0.67). 수술후창상치유기간은 1 군에서평균 4.8±1.5 주 (3~10 주 ), 2 군에서 7.3±1.5 주 (5~12 주 ) 로 1 군에서더짧았다 (p<0.001). Figure 2 는 1 군환자들중 평균적인창상치유과정을보여주는사진으로수술후 4 주째창상치유가대부분완료된것을볼수있다. 수술후합병증은육아종형성, 염증, 비강내반흔형성등이있었는데이중육아종형성이가장많았다 (Table 2). 술후 2 개월째에육아종발생은 1 군에서 30 안중 4 안 (13.3%), 2 군에서는 30 안중 11 안 (36.6%) 로 1 군에서유의하게적었으나 (p=0.037), 술후 6 개월째에는 1 군과 2 군에서각각 30 안중 11 안 (36.6%), 14 안 (46.7%) 에서육아종이발생하여두군에서차이가없었다. 육아종의발생시기는 1 군에서평균 11.6±2.9 주 (8~18 주 ), 2 군에서는평균 8.9 ± 2.4 주 (6~16 주 ) 로 1 군에서육아종이발생하는시기가더늦었다. Table 1. Characteristics of patients Group 1 Group 2 p-value Number of eyes Age (yrs) 52.0± ± * Sex (M/F) 7/23 6/ Right/Left 13/17 11/ F/U duration (months) 8.5± ± * * Student s t-test; Pearson s chi-square test. POD 2 weeks POD 6 weeks POD 4 weeks POD 8 weeks Figure 2. Serial photographs of postoperative wound healing process in group 1. Wound healing was nearly completed at 4 weeks after surgery. 386

4 대한안과학회지제 49 권제 3 호 2008 년 Table 2. Postoperative complications Group 1 (No. of patients) Group 2 (No. of patients) p value* At 2 months Granuloma 13.3% (4/30) 36.6% (11/30) Rhinitis 6.6% (2/30) 10% (3/30) Synechia 0 3.3% (1/30) At 6 months Granuloma 36.6% (11/30) 46.7% (14/30) Rhinitis 10% (3/30) 13.3% (4/30) Synechia 3.3% (1/30) 3.3% (1/30) * Pearson s chi-square test. 고 찰 비강내누낭비강문합술의실패원인으로비강측누공의육아종, 반흔조직등에의한폐쇄가가장흔한것으로알려져있고특히육아종발생이수술실패의가장흔한원인으로여러연구를통해알려져있다 또한육아종은창상치유과정에서주로생기기때문에창상치유기간이길수록육아종이생길가능성이좀더높으며실제로 Lee et al 21 은재상피화가늦게되면육아종과염증이더많이발생하지만창상이깨끗하게치유된경우에는성공률이높다고보고한바있다. 따라서창상치유기간을줄이고좀더창상을깨끗하게유지하는것이수술의실패를줄일수있을것이다. 저자들은안구표면질환에서양막이상처치유에도움이된다는여러연구를바탕으로누낭비강문합술후에양막을골공에충전한다면비강내점막의창상치유에도움이되어창상치유기간을줄이고창상을깨끗하게유지할수있을것이라는가정하에본연구를진행하였다. 본연구에서비강내누낭비강문합술후창상치유기간은대조군의경우평균 7.3±1.5 주로서이는저자들이이전에보고한 860 명의성인의평균창상치유기간인 7.1 주와유사하였다. 22 반면양막을이용하여 Merocel R packing 을시행한군에서는평균 4.8±1.5 주로창상치유기간이현저히줄어든것을알수있었다. 이는다음과같은양막의효과에서기인하는것으로생각된다. 첫째양막이상피세포의이동을용이케하고 23,24 기저상피세포 (basal epithelial cell) 의유착을강화시키며, 25 상피분화를증진시키는역할을하여 26,27 창상의상피화를증진시키는것으로알려져있다. 실제로 Meller et al 23 과 Meller and Tseng 24 의연구에서윤부상피세포나결막상피세포의이동및분화를양막이촉진시키며이를임상에적용하여좋은결과를얻었다는보고가있다. 둘째양막은 IL-1ra, IL-10 등의항염증단백을함유하고있고 28 IL-1, IL-8, PMN cell, elastase, neutrophile activation peptide-78 등의케모카인 (chemokine) 을 down regulation 시켜항염증작용을나타내는것으로알려져있다. 29,30 이러한작용으로창상의염증이줄어들고따라서창상치유기간도줄어들었으리라생각된다. 또한양막은항균효과를가져 31,32 수술후창상의감염을최소화시킬수있으며신생혈관형성을억제하는기능이있어 28 창상치유에도움이되는것으로알려져있다. 그밖에도 TGF-β 신호전달체계 (signaling system) 에관여하여섬유아세포의활동과근섬유세포로의분화를억제시키므로반흔형성을줄일수있다고보고되고있다. 33,34 한편육아종은창상치유가대부분완료되는수술후 2 개월까지는양막을이용한 Merocel R 충전술을시행한군에서대조군보다적게발생하는것으로나타났으나수술 2 개월이후로는많이발생하여수술후 6 개월에는두군에서유의한차이가없었다. 이는비강내점막의창상은안구표면질환들과달리비교적치유기간이길어초기에는양막의효과로인해육아종발생이어느정도줄어들었다가후기에는양막에서나오는인자들의효과가없어지면서일어나는염증반응에의한것으로생각된다. 특히육아종발생의큰원인들중하나로실리콘튜브의지속적인기계적자극이주위조직에만성적인염증반응을일으키기때문인것으로알려져있다. 35 본연구에서양막충전술군에서수술 2 개월이후에육아종발생이증가한것은이러한실리콘튜브의작용이큰것으로사료된다. 한편 Merocel R 을제거하는시기가 1 군에서약 3 일에서 7 일정도더길었는데이는양막의효과가충분히나타날수있도록하기위함이었으며두군간에제거시기가차이나는기간이짧고감염을최대한방지하기위해항생제세척을충분히했으므로 Merocel R 을제거시기를다르게한것이결과에미치는영향은거의없을것이라고생각된다. 결론적으로수술후양막으로감싼 Merocel packing 을시행하는것은수술초기의염증반응을최소화하고비강내점막의재상피화를촉진시켜창상치유기간을단축시킬수있었고수술후초기에육아종의발생 387

5 최영재외 : 비강내누낭비강문합술시양막충전술 률을줄일수있어수술의성공률이다소높았다. 그러나양막의효과가떨어지는수술후 2 개월이후로는육아종의발생이다시증가하는경향을보여앞으로양막충전술을시행한환자에대해서는조기에실리콘튜브를제거하는것과좀더많은환자들을대상으로장기추적관찰을하는연구가필요할것으로생각된다. 참고문헌 1) Davis JW. Skin transplantation with a review of 550 cases at the Johns Hopkins Hospital. Johns Hopkins Med J 1910;15: ) De Rotth A. Plastic repair of conjunctival defects with fetal membrane. Arch Ophthalmol 1940;23: ) Kim JC, Tseng SC. Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas. Cornea 1995;14: ) Meller D, Pires RT, Mack RJ, et al. Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology 2000;107: ) Tsubota K, Satake Y, Ohyama M, et al. Surgical reconstruction of the ocular surface in advanced ocular cicatrical pemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol 1996;122: ) Shimazaki J, Shinozaki N, Tsubota K. Transplantation of amniotic membrane and limbal autograft for patients with recurrent pterygium associated symblephron. Br J Ophthalmol 1998;82: ) Letko E, Stechschulte SU, Kenyon KR, et al. Amniotic membrane inlay and overlay grafting for corneal epithelial defects and stromal ulcers. Arch Ophthalmol 2001;119: ) Lee SH, Tseng SC. Amniotic membrane transplantation for persistent epithelial defects with ulceration. Am J Ophthalmol 1997;123: ) Hanada K, Shimazaki J, Shimmura S, Tsubota K. Multilayered amniotic membrane transplantation for severe ulceration of the cornea and sclera. Am J Ophthalmol 2001;131: ) Chen HJ, Pires RT, Tseng SC. Amniotic membrane transplantation for severe neurotrophic corneal ulcers. Br J Ophthalmol 2000;84: ) Alsagoff Z, Tan DT, Chee SP. Necrotising scleritis after bare sclera excision of pterygium. Br J Ophthalmol 2000;84; ) Han YK, Wee WR. Use of immunosuppressant in the treatment of surgically induced necrotizing scleritis (SINS) after pterygium excision. J Korean Ophthalmol Soc 2003;44: ) Kim JH, Cheong TB, Kim JC. Amniotic membrane transplantation in perforation or impending perforation of cornea. J Korean Ophthalmol Soc 1999;40: ) Fujishima H, Shimazaki J, Shinozaki N, Tsubota K. Trabeculectomy with the use of amniotic membrane for uncontrollable glaucoma. Ophthalmic Surg Lasers 1998;29: ) Woo HM, Kim MS, Kweon OK. The effect of amniotic membrane graft on the inhibition of corneal haze in rabbit. J Korean Ophthalmol Soc 1999;40: ) Wang MX, Gray TB, Park WC, et al. Reduction in corneal haze and apoptosis by amniotic membrane matrix in excimer laser photoablation in rabbits. J Cataract Refract Surg 2001;27: ) Yeom HY, Park SB, Lee HK, Kim EK. Effects of amniotic membrane after LASEK on epithelial healing, clinical and refractive outcomes. J Korean Ophthalmol Soc 2004;45: ) Kong YT, Kim TI, Kong BW. A report of 131 cases of endoscopic laser lacrimal surgery. Ophthalmology 1994;101: ) Lee HC, Chung WS. Success rate of endonasal dacryocystorhinostomy. J Korean Ophthalmol Soc 1996:37: ) Kim JH, Shin JC. Clinical evaluation of endoscopic transnasal dacryocystorhinostomy. J Korean Ophthalmol Soc 1997:38: ) Lee TS, Kim SW, Park BW. The relationship between rate of wound healing and success rate after endonasal laser-drill assisted dacryocystorhinostomy. J Korean Ophthalmol Soc 1999:40: ) Shin HY, Lee TS, Beak SH. The comparision of surgical results of endonasal dacryocystorhinostomy in childen and adults. J Korean Ophthalmol Soc 2006:47; ) Meller D, Pires RT, Tseng SC. Ex vivo preservation and expansion of human limbal epithelial stem cells on amniotic membrane cultures. Br J Ophthalmol 2002;86: ) Meller D, Tseng SC. Conjunctival epithelial cell differentiation on amniotic membrane. Invest Ophthalmol Vis Sci 1999;40: ) Khodadoust AA, Silverstein AM, Kenyon DR, Dowling JE. Adhesion of regenerating corneal epithelium. The role of basement membrane. Am J Ophthalmol 1968;65: ) Guo M, Grinnell F. Basement membrane and human epidermal differentiation in vitro. J Invest Dermatol 1989;93:372?8. 27) Kurpakus MA, Stock EL, Jones JC: The role of the basement membrane in differential expression of keratin proteins in epithelial cells. Dev Biol 1992;150: ) Hao Y, Ma DH, Hwang DG. Identification of antiangiogenic and antiinflammatory proteins in human amniotic membrane. Cornea 2000;19: ) Bultmann S, You L, Spandau U, et al. Amniotic membrane down-regulate chemokine expression in human keratocyte. Invest Ophthalmol Vis Sci 1999;40:S ) Solomon A, Rosdnblatt M, Monroy D, et al. Suppression of interleukin 1α and interleukin 1β in human limbal epithelial cells cultured on the amniotic membrane stromal matrix. Br J Ophthalmol 2001;85:444?9. 31) Kjaergaard N, Helmig RB, Schonheyder HC. Chorioamniotic membranes constitute a competent barrier to group B streptococcus in vitro. Eur J Obstet Gynecol Reprod Biol 1999;83:

6 대한안과학회지제 49 권제 3 호 2008 년 32) Kjaergaard N, Hein M, Hyttel L. Antibacterial properties of human amnion and chorion in vitro. Eur J Obstet Gynecol Reprod Biol 2001;94: ) Li DQ, Lee SB, Tseng SC. Differential expression and regulation of TGF-beta1, TGF-beta2, TGF-beta3, TGF-beta RI, TGFbeta RII and TGF-beta RIII in cultured human corneal, limbal,and conjunctival fibroblasts. Curr Eye Res 1999;19: ) Tseng SCG, Li, D-Q, Ma, X. Downregulation of TGF- β1,β2, β3, and TGF-β receptor II expression in human corneal fibroblasts by amniotic membrane. Invest Ophthalmol Vis Sci 1998;39:S ) Dresner SC, Codere F, Brownstein S, Jouve P. Lacrimal drainage system inflammatory masses from retained silicone tubing. Am J ophthalmol 1984:98; =ABSTRACT= Short-Term Clinical Results of Amniotic Membrane Application to Endonasal Dacryocystorhinostomy Young Jae Choi, M.D., Sang Jun Hwang, M.D., Tae Soo Lee, M.D. Department of Ophthalmology, Korea University College of Medicine, Seoul, Korea Purpose: To evaluate the short-term surgical results of Merocel R nasal packing wrapped with human amniotic membrane on the internal ostium during endonasal dacryocystorhinostomy (DCR). Methods: Sixty patients who underwent endonasal DCR to treat nasolacrimal duct obstruction from October 2005 to April 2006 were enrolled in this prospective study. The patients were divided into two groups: 30 patients treated with Merocel R packing wrapped with amniotic membrane were assigned to group 1, and the remaining 30 patients were assigned to group 2. During the follow-up period, the authors evaluated surgical wound healing, the incidence of granuloma, and the patency of the internal ostium. Results: Success rates at 6 months after surgery were higher in group 1 than in group 2, but these rates showed no statistically significant difference between the two groups (group 1: 93.3%, group 2: 86.7%, p=0.67). The time for mean wound healing in group 1 was significantly shorter than that in group 2 (group 1: 4.8±1.5 weeks, group 2: 7.3±1.5 weeks, p<0.001). The incidence of granuloma in group 1 was lower than that in group 2 at 2 months after surgery (group 1: 13% (4/30), group 2:33% (14/30), p=0.04). However, there was no difference of granuloma formation between the two groups at 6 months postoperatively (group 1: 33% (11/30), group 2: 46% (14/30)). Conclusions: The authors believe that the use of Merocel R packing wrapped with amniotic membrane after endonasal DCR might decrease postoperative inflammation, accelerate wound healing, and decrease granuloma formation in the early postoperative period. J Korean Ophthalmol Soc 49(3): , 2008 Key Words: Amniotic membrane, Endonasal dacryocystorhinostomy, Merocel Address reprint requests to Tae Soo Lee, M.D., Ph.D. Department of Ophthalmology, Guro Hospital, Korea University College of Medicine #97 Guro-donggil, Guro-gu, Seoul , Korea Tel: , Fax: , 389

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