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1 대한안과학회지 2013 년제 54 권제 8 호 J Korean Ophthalmol Soc 2013;54(8): pissn: eissn: = 증례보고 = 유리체강내베바시주맙주입술을이용한당뇨병유두병증의치료 1 예 신진희 최경식 순천향대학교의과대학안과학교실 목적 : 제 2 형당뇨병환자에서발생한당뇨병유두병증을유리체강내베바시주맙주입술을이용하여효과적으로치료하였기에이를보고하고자한다. 증례요약 : 47 세남자가당뇨망막병증검사를위하여내원하였다. 10 년전부터제 2 형당뇨병으로치료받고있었으며내원당시최대교정시력은우안 20/20, 좌안 20/30 이었고시력저하, 시야결손등의자각증상은없었다. 안저검사상좌안의시신경유두부종과신생혈관이있어범망막광응고술을시행하였다. 10 일후환자는좌안의무통성시력저하를호소하였고최대교정시력좌안 20/80, 안저검사상시신경유두부종과모세혈관의충혈이현저히증가한소견을보였다. 유리체강내베바시주맙주입술을 1 회시행하였고 2 달후최대교정시력은좌안 20/30 으로호전되었으며시신경유두부종과모세혈관충혈이감소하였다. 결론 : 당뇨병유두병증에서유리체강내베바시주맙주입술이시력회복에도움이될것으로생각한다. < 대한안과학회지 2013;54(8): > 당뇨병유두병증은당뇨병이있는환자에서비교적젊은연령에서단안이나양안에발생하는충혈성시신경유두부종으로무증상혹은경한시력저하를보이며좋은시력예후를나타내는것을특징으로한다. 1,2 시신경유두부종을보이는염증성병변이나감염증, 악성병변, 고혈압, 뇌압상승등의원인질환과감별이필요하며, 이러한질환들이모두배제되었을때진단할수있다. 3,4 이전연구에의하면당뇨망막병증으로인한망막허혈때문에당뇨병유두병증이발생하는것으로여겨지고있으나 1,5 아직명확한병태생리가알려져있지않고, 그치료또한정립되어있지않다. 최근신생혈관억제제일회요법을이용한당뇨병유두병증의장기적인치료효과가국외에서보고되고있다. 저자들은단안성으로발생한당뇨병유두병증에서유리체강내베바시주맙주입술을이용하여치료한 1예를경험하였으며이에대한국내증례가없어이를보고하고자한다. Received: Revised: ccepted: ddress reprint requests to Kyung Seek Choi, MD Department of Ophthalmology, Soonchunhyang University Seoul Hospital, #59 Daesagwan-ro, Yongsan-gu, Seoul , Korea Tel: , Fax: ckseek@schmc.ac.kr 증례보고 47세남자가당뇨망막병증검사를위하여내원하였다. 10년전부터제2형당뇨병으로치료받고있었으며최근혈중당농도 (ST; lood Sugar Test) 844 mg/dl, 당화혈색소 (Hb1c) 11.6% 로혈당조절이되지않아내과에입원중이었다. 안과초진당시시력은우안 20/20, 좌안 20/30 이었고안압은우안 17 mmhg, 좌안 15 mmhg였으며시력저하, 시야결손등의자각증상은없었다. 안저검사상양안의 4사분면에미세혈관류및점상출혈이있었으며좌안의시신경유두부종, 모세혈관확장과신생혈관이관찰되었다 (Fig. 1). 안구광학단층촬영 (SD-OCT; Heidelberg Engineering, Heidelberg, Germany) 에서좌안의황반부종소견을보였다 (Fig. 3). 형광안저혈관조영검사 (Heidelberg Engineering, Heidelberg, Germany) 에서양안에신생혈관으로인한누출소견이있었으며좌안시신경유두모세혈관의누출이저명하였다 (Fig. 1). 이에양안의증식성당뇨망막병증과좌안의당뇨병유두병증진단하에범망막광응고술을계획하고좌안부터시행하였다. 10일후환자는좌안의무통성시력저하를호소하였다. 내과에서는 ST 110 mg/dl 정도로급격하게혈당을조절한후유지하고있는상태였으며, 안과검사에서는좌안의최대교정시력이 20/80로저하되었고안압은 18 mmhg였 1298

- 신진희 최경식 : 베바시주맙의 당뇨병유두병증 치료 - Figure 1.

() Early phase fluorescein angiography shows the optic-disc leakage due to neovascularization. C D Figure 2.

in the left eye, with decreased visual acuity.

2 - 신진희 최경식 : 베바시주맙의 당뇨병유두병증 치료 - Figure 1. () Fundus photography showing the optic disc swelling in the left eye at patient s first visit. () Early phase fluorescein angiography shows the optic-disc leakage due to neovascularization. C D Figure 2. () t 10 days after initial presentation, fundus photography shows marked the optic disc swelling and hemorrhage in the left eye, with decreased visual acuity. () Fluorescein angiography shows hyperfluorescence on the optic disc early phase, (C) leakage from telangiectatic vessels, late phase. (D) fter intravitreal bevacizumab injection, there is significantly reduced swelling of the optic disc. CV improved from 20/400 to 20/

- 대한안과학회지 2013 년제 54 권제 8 호 - Figure 3. () SD-OCT showed hyporeflective subfoveal space and macular edema, which continued as the optic disc swelling in the left eye at patient s first visit.

3 - 대한안과학회지 2013 년제 54 권제 8 호 - Figure 3. () SD-OCT showed hyporeflective subfoveal space and macular edema, which continued as the optic disc swelling in the left eye at patient s first visit. () Two months after treatment, hyporeflective subfoveal space and macular edema were resolved in the left eye. 다. 안저검사상시신경유두부종과모세혈관의충혈이현저히증가한소견을보였으나 (Fig. 2), 양안의구심동공장애는없었고색각검사는정상이었다. 안구광학단층촬영에서황반부종과시신경유두부종의소견을확인할수있었으며 (Fig. 3) 형광안저혈관조영검사에서시신경유두모세혈관에서의초기과형광과후기누출소견이증가하였다 (Fig. 2, C). 형광충만시간의지연이나후모양체동맥의페색및시신경유두의저형광소견은없었으나비동맥성전부허혈성시신경증을완전히배제할수없어 methylprednisolone 1 gm씩 3일간정맥투여후경구복용으로바꾸어점차감량하였다. 치료 2주째좌안최대교정시력은 20/400로저하되었으며주시점침범과함께주변부시야결손이동반되었다. 시신경유두부종과모세혈관의충혈은지속되었지만구심동공운동장애는없었다. 치료에반응이없어베바시주맙 1.25 mg/0.05 cc를유리체내로주입하였고 methylprednisolone 은단계적으로감량하였다. 2달후좌안의최대교정시력은 20/30으로회복되었고시야결손증상도호전되었다. 안저검사에서시신경유두부종과모세혈관충혈이현저히감소하였고 (Fig. 2D), 안구광학단층촬영에서도좌안의황반부종과시신경유두부종의감소를확인할수있었다 (Fig. 3). 1년간의경과관찰동안당뇨병유두병증의증상재발은없었으며최대교정시력도 20/30 으로유지되었다. 고 찰 Lubow and Makley 1 에의해 1971 년당뇨병유두병증이 처음보고된이후, 구심동공장애와시력저하가없는젊은제1형당뇨병환자에서관찰된시신경유두부종이별다른치료없이호전되며좋은시력예후를나타낸다는여러증례가보고되었다. 2,6 그이후에 Regillo et al 3 과 ayraktar et al 4 은제2형당뇨병을가진고령의환자에서도당뇨병유두병증이발생한예를보고하여제1형당뇨병에더불어제2 형당뇨병역시당뇨병유두병증의발생인자임을보여주었다. 당뇨병유두병증의발생위험인자로당뇨병의긴유병기간이영향을미칠것으로여겨지고있다. 2,6 ayraktar et al 4 은제2형당뇨병에서당뇨병유두병증을나타낸 16명 24 안을대상으로한연구에서평균 10년이상의당뇨병유병기간을가진군에서당뇨병유두병증이발생했다고보고한바있다. 또다른위험인자로는최근의급격한혈당조절과작은시신경유두함몰비를생각해볼수있다. 7 Ostri et al 8 은당뇨병유두병증환자들에서발병전높은 Hb1c를유지하다급격히혈당을감량한공통점을발견하였으며, 이전 Hb1c 수치가높을수록양측성으로발생한다고하였다. 혈당조절을위하여급격한인슐린치료를시작하면첫 1 년동안은당뇨망막병증이진행하게되는데, 이는혈당저하로인하여망막혈관이갖는혈류저하조절기전에장애가오고혈관내피세포성장인자 (VEGF; vascular endotheilial growth factor) 의증가로인해혈관투과성이증가하게되는데서기인한다. 9 혈관투과성의증가는정맥울혈을일으키게되는데이는신경조직의부종을가져오게되며, 제한된공간안에서의신경부종은시신경유두에서구획증후군을유발하게되어시신경유두의허혈과부종을일으키게되는데, 10 이는작은시신경유두함몰비를가진경우에서더쉽게손상받을것으로생각되고있다. 7 이러한기전에따라 Hayreh 6,7 은당뇨병유두병증이시신경유두의허혈로인해발생하며비동맥성전부허혈성시신경병증의경한형태라고보고하였다. Heller and Tattersall 5 도당뇨병유두병증은허혈성시신경병증의한분류라고하였으며, Yang et al 11 은당뇨병유두병증에서전부허혈성시신경병증으로진행한증례를보고한바있다. 그러나비동맥성전부허혈성시신경병증에비해당뇨병유두병증은비교적젊은연령에서발생하며, 무증상으로서서히나타나고, 구심동공장애가동반되지않으며시신경위축과같은영구적변형이적다는점에서다르다고할수있다. 2,4 이전의당뇨병유두병증치료로 Whittaker et al 12 은범망막광응고술을시행하여한달후시력회복이회복되고시신경유두부종이소실된예를보고한바있고, Christiane et al 13 은유리체강내트리암시놀론을주입하는것이황반부종의감소와더불어유두부종도호전시킨다고보고하였다. 최 1300

4 - 신진희 최경식 : 베바시주맙의당뇨병유두병증치료 - 근에는 anti-vegf agent를이용한효과적인치료가국외에서보고되고있다. 2010년 Ornek and Ogurel 14 이처음으로당뇨병유두병증이발생한환자에서유리체강내베바시주맙 (vastin ; Roche, aserl, Switzerland) 일회주입술만으로도당뇨병유두병증에빠른효과를보였다고보고하였다. Hassan and rif 15 도이어당뇨병유두병증환자에서유리체강내베바시주맙주입술을시행하였으며치료 4주후시신경유두부종과모세혈관확장이감소하고시력이호전되었다고하였다. 2012년 Willerslev et al 16 은유리체강내라니비주맙 (Lucentis ; Novartis, asel, Switzerland) 주입술을시행하였으며 2주후부터현저한시력개선효과를보였고일회주입술만으로도 1년간의경과관찰기간동안재발하지않았다고보고하였다. nti-vegf agent의유리체강내주입이당뇨병유두병증에서치료효과를나타내는기전은아직명확하지는않다. 시신경유두가허혈상태에빠지면 VEGF의분비가증가되어빠르게혈관투과성을변화시키게되는데, 이는궁극적으로시신경유두부종을일으켜시신경유두허혈을지속시키는이차손상을일으키게된다. 17 이에대해 anti-vegf agent는 VEGF의발현과작용을억제시킴으로써시신경유두부종을완화시켜주고시신경유두허혈을개선시키는작용을하는것으로생각된다. 18 본증례에서저자들은좌안의증식성당뇨망막병증과당뇨병유두병증에대하여범망막광응고술을시행하였으나오히려당뇨병유두병증이진행하고시력이저하되었다. 범망막광응고술에의해발생할수있는합병증중하나인황반부종등으로인하여레이저치료가신경유두부종의진행을촉진하였을가능성도있겠다. 비동맥성전부허혈성시신경병증의경우 50-60대에많이발생하지만당뇨병이있는경우보다젊은나이에도발생할수있어진단에어려움이있었다. 그러나당뇨병유두병증은 1형당뇨에서빈도가높지만 2형당뇨에서도발생할수있으며, 3,4 증상발생전 ST 800 mg/dl 이상으로혈당이조절되지않는상태에서급격한인슐린치료를했다는점, 형광안저혈관조영검사에서형광충만시간의지연이나후모양체동맥의폐색소견이없고, 구심동공운동장애가없다는점을바탕으로당뇨병유두병증을우선생각해볼수있었다. 시신경병증을완전배제할수없어사용한고용량스테로이드요법에반응하지않았고, 이에유리체내베바시주맙주입술을시행하여 1회주입술만으로시신경유두부종과시력이호전되었으며 1년간의경과관찰기간동안재발하지않았다. 저자들은본증례를통하여시력저하가있는당뇨병유두병증에서유리체 강내베바시주맙주입술이효과적인치료법으로사용될수있을것으로판단되며당뇨망막병증으로인한황반부종의감소도더불어기대할수있을것으로생각한다. REFERENCES 1) Lubow M, Makley T Jr. Pseudopapilledema of juvenile diabetes mellitus. rch Ophthalmol 1971;85: ) ppen RE, Chandra SR, Klein R, Myers FL. Diabetic papillopathy. m J Ophthalmol 1980;90: ) Regillo CD, rown GC, Savino PJ, et al. Diabetic papillopathy. Patient characteristics and fundus findinga. rch Ophthalmol 1995;113: ) ayraktar Z, lacali N, ayraktar S. Diabetic papillopathy in type II diabetic patients. Retina 2002;22: ) Heller SR, Tattersall R. Optic disc swelling in young diabetic patients: a diagnostic dilemma. Diabetes Med 1987;4: ) Hayreh SS. nterior ischemic optic neuropathy. rch Neurol 1981;38: ) Hayreh SS, Zimmerman M. Nonarteritic anterior ischemic optic neuropathy: clinical characteristics in diabetic patients versus nondiabetic patients. Ophthalmology 2008;115: ) Ostri C, Lund-ndersen H, Sander, et al. ilateral diabetic papillopathy and metabolic control. Ophthalmology 2010;117: ) Grunwald JE, rucker J, raunstein SN, et al. Strict metabolic control and retinal blood flow in diabetes mellitus. r J Ophthalmol 1994;78: ) Larsen M. Unilateral macular oedema secondary to retinal venous congestion without occlusion in patients with diabetes mellitus. cta Ophthalmol Scand 2005;83: ) Yang DW, Lee SH, Kim IT, Yun SU. ilateral diabetic anterior ischemic optic neuropathy. J Korean Ophthalmol Soc 2004;45: ) Whittaker KW, Mehta JS, Tsaloumas MD. ilateral diabetic papillopathy associated with optic disc neovascularisation. Eye (Lond) 2000;14(Pt 6): ) l-haddad CE, Jurdi F, ashshur ZF. Intravitreal triamcinolonce acetonide for the management of diabetic papillopathy. m J Ophthalmol 2004;137: ) Ornek K, Oğurel T. Intravitreal bevacizumab for diabetic papillopathy. J Ocul Pharmacol Ther 2010;26: ) l-dhibi H, Khan O. Response of diabetic papillopathy to intravitreal bevacizumab. Middle East fr J Ophthalmol 2011;18: ) Willerslev, Munch IC, Larsen M. Resolution of diabetic papillopathy after a single intravitreal injection of ranibizumab. cta Ophthalmol 2012;90:e ) Van ruggen N, Thibodeaux H, Palmer JT, et al. VEGF antagonism reduces edema formation and tissue damage after ischemia/ reperfusion injury in the mouse brain. J Clin Invest 1999;104: ) Gunther J, ltaweel MM. evacizumab (vastin) for the treatment of ocular disease. Surv Ophthalmol 2009;54:

5 - 대한안과학회지 2013 년제 54 권제 8 호 - =STRCT= Intravitreal evacizumab Injection in Diabetic Papillopathy Jin Hee Shin, MD, Kyung Seek Choi, MD Department of Ophthalmology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea Purpose: To report a case where intravitreal bevacizumab injection was an effective treatment for diabetic papillopathy in a type 2 diabetic patient. Case summary: 47-year-old male with a 10-year history of diabetes mellitus type 2 presented to our clinic for evaluation of diabetic retinopathy. There were no subjective symptoms including blurred vision or visual defect, and best corrected visual acuity (CV) was 20/20 in the right eye and 20/30 in the left eye. Fundus examination showed hyperemic optic disc swelling with telangiectatic new vessels, and fluorescein angiography leakage from the optic disc with neovascularization. The patient underwent fractionated panretinal photocoagulation. Ten days later, he complained of painless blurred vision with significant optic nerve head swelling and CV was 20/80 in the left eye. Intravitreal bevacizumab injection was administered, optic disc swelling was significantly decreased and CV improved to 20/30 after two months. Conclusions: Diabetic papillopathy with severe decreased visual acuity can be treated with intravitreal bevacizumab injection. J Korean Ophthalmol Soc 2013;54(8): Key Words: evacizumab injection, Diabetic papillopathy ddress reprint requests to Kyung Seek Choi, MD Department of Ophthalmology, Soonchunhyang University Seoul Hospital #59 Daesagwan-ro, Yongsan-gu, Seoul , Korea Tel: , Fax: , ckseek@schmc.ac.kr 1302

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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