대한안과학회지 2019 년제 60 권제 1 호 J Korean Ophthalmol Soc 2019;60(1):75-79 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2019.60.1.75 Case Report 데스메막내피각막이식술후발병한단순포진바이러스각막염 1 예 A Case of Herpes Simplex Keratitis after Descemet Membrane Endothelial Keratoplasty 황유숙 조양경 Yousook Hwang, MD, Yang Kyung Cho, MD, PhD 가톨릭대학교의과대학안과및시과학교실 Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea Purpose: We report a case of herpes simplex keratitis after Descemet membrane endothelial keratoplasty (DMEK). Case summary: A 67-year-old male underwent DMEK in his left eye due to pseudophakic bullous keratopathy. One week after DMEK, re-bubbling was performed due to partial detachment of Descemet s membrane at the corneal periphery. After re-bubbling, the cornea remained clear and the patient s visual acuity gradually improved. Two months after DMEK, the patient presented with mild discomfort and decreased visual acuity. The cornea showed an irregular, narrow dendrite with an epithelial defect and surrounding opacity. After confirming that Descemet s membrane was attached, the patient was started on oral valacyclovir for suspected herpes keratitis. Herpes simplex virus type 1 was eventually identified by polymerase chain reaction. The corneal lesion resolved after three weeks of antiviral treatment. Conclusions: Similar to penetrating keratoplasty, DMEK can trigger outbreaks of herpes simplex keratitis. Herpes simplex keratitis should remain on the clinician s differential diagnosis for patients who present with a corneal epithelial irregularity and decreased visual acuity following DMEK. J Korean Ophthalmol Soc 2019;60(1):75-79 Keywords: Descemet membrane endothelial keratoplasty, Herpes, Valacyclovir 데스메막내피각막이식 (descemet membrane endothelial keratoplasty, DMEK) 은오직한층의 20 μm 두께의데스메막을이식하는각막이식의최신술기이다. 데스메막내피각막이식은전체층각막이식뿐만아니라데스메막박리내피각막이식 (descemet stripping endothelial keratoplasty, DSEK) Received: 2018. 5. 31. Revised: 2018. 7. 26. Accepted: 2018. 12. 28. Address reprint requests to Yang Kyung Cho, MD, PhD Department of Ophthalmology and Visual Science, The Catholic University of Korea St. Vincent s Hospital, #93 Jungbu-daero, Paldal-gu, Suwon 16247, Korea Tel: 82-31-249-7340, Fax: 82-31-251-6225 E-mail: yangkyeung@hanmail.net * Conflicts of Interest: The authors have no conflicts to disclose. 보다각막후면의불규칙성을줄일수있고빠른시력회복과드문면역거부반응을장점으로한다. 또한전체층각막이식이 1개의공여각막으로한차례의이식만가능한반면, 내피층각막이식에서는공여각막에서내피층이성공적으로분리되면이를내피층각막이식술에사용하고나머지조직은각막의실질혼탁이나형태의변형등으로시력이저하된환자에게추가적으로사용할수있다는장점이있다. 따라서최근에이술기는각막내피질환의치료를위한기대되는치료로행해지고있다. 1-3 하지만이러한데스메막각막이식에는여러가지합병증이보고되고있는데, 데스메막절편을만드는도중에찢어져완벽한절편을얻지못하는경우도있고, 수술도중절편의위아래가뒤집혀서각막내피가기능을못하는경우도있다. 가장많은수술후합병증은데스메막이식편이 c2019 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 75
- 대한안과학회지 2019 년제 60 권제 1 호 - 각막간질의후면부에완벽하게유착되지않아서각막후면으로부터분리되는경우이다. 여러보고에의하면데스메막의재부착을위해전방내공기주입을해야하는빈도가다른각막이식에비해많다. 4-6 단순포진바이러스각막염은백내장수술, 굴절교정수술, 각막이식수술등각막에외과적인수상을가하는다양한수술에서발생이보고되어왔다. 7-9 각막이식중공여자각막의전체층을이식하는전체층각막이식에서는각막층에분포해있는삼차신경의절단이 360 에서행해지므로이로인한자극이헤르페스각막염을유발시키는빈도가다른부분층판각막이식보다높은것으로되어있다. 10 또한수술후사용하는스테로이드와같은면역억제제의사용이헤르페스각막염의빈도에도영향을줄수있다. 11 전체층각막이식후발생한단순포진바이러스에관한많은보고가있으나, 현재까지국내에데스메막내피각막이식후발생한단순포진바이러스각막염은보고된바가없다. 저자들은한국인에서데스메막내피각막이식후발생한단순포진바이러스각막염을경험하였기에이를보고하고자한다. 증례보고 67세남자환자가 15년전양안백내장수술을받고, 약 2년전부터지속된좌안의각막부종및시력감소로의뢰되었다. 의뢰서기록상과거력에관한특이소견은없었으며, 백내장수술후좌안의최대교정시력은 0.4로기록되어있었다. 과거력청취에서이때까지단순포진바이러스각막염을의심할만한증상이나과거력은없었으며본원에서규칙적인경과관찰을하던중에도단순포진바이러스에의한각막염의소견을보인적은없었다. 각막이식수술을계획하고공여각막을기다리는도중에한안과적검사에서는좌안의최대교정시력은 0.02였고, 안압은 8.0 mmhg였다. 안저는명확히보이지않았으나 B-scan 초음파 (Compact II TM ; Quantel Medical, Cournon d'auvergne, France) 에서특이소견은없었다. 수술전세극등현미경검사에서미세수포를동반한각막부종및혼탁을보였고상부에홍채절제술이시행되어있었다 (Fig. 1). 경면현미경검사에서정확한내피세포는찍히지않았고각막두께는 Pentacam (Oculus, Wetzler, Germany) 샤임플러그이미지에서수동으로측정시약 700 μm였다. 좌안의인공수정체수포각막병증으로진단하고, 데스메막내피각막이식을준비하였다. 수술은전신마취하에진행되었다. 먼저각막상피를벗겨내어수술시야를좋게한후환자의하부홍채에미세가위와겸자를이용한홍채절제를시행하였고, 상부각막에하나의주된절개창과두군데의 전방천자를미리해두었다. 환자의경우상부에이미홍채절제술이되어있었다. 하지만데스메막내피각막이식수술후전방에공기가가득차있는상태에서상부의홍채절제술을통한방수의흐름이가능하게하려면장시간동안환자의머리위치가턱을들고이마를수평보다낮추는자세가유지되어야함을고려하여, 전방에삽입한공기에의한동공폐쇄를막기위해서아래쪽에또하나의홍채절제술을시행하였다. 공여각막에서데스메막을분리하기위해먼저쉬발베선부터분리한데스메막을 8.25 mm trephine으로원형천공한후 0.06% trypan blue (VisionBlue, Dutch Ophthalmic Research Center, Exeter, NH, USA) 로염색하여잘보이게한후데스메막절편을 2개의겸자로중심부까지분리한후미세공막원형천공기로 2 mm, 1 mm의방향을표시했다. 즉공여각막의내피쪽에서시계방향으로상부에 2 mm, 1 mm 의순서로반원모양의절개를하고, 아래쪽에시계방향으로반원모양으로 2 mm, 1 mm의순서로반원모양의절개를하면완성된 DMEK 절편을수여자눈에삽입한후각막상피쪽에서봤을때반원모양의절개는시계방향으로 1 mm, 2 mm의순서로각막의상부와하부에위치하게되므로절편이뒤집혀삽입되지않음을확인할수있다. 데스메막절편을 intraocular lens injector (Viscoject TM -BIO; Medicel, Widnau, Switzerland) 를이용하여조심스럽게전방으로데스메막내피절편을주입하였다. 평형염액 (Balanced salt solution [BSS] ; Alcon, Fort Worth, TX, USA) 과공기를이용해서각막부분을두드려가며데스메막절편의방향을잘잡은후마지막으로공기를주입하여후부각막간질에부착을시도하였다. 수술약 1주일후까지약 6시부터 8시까지의 2 3 mm 정 Figure 1. Preoperative cornea at slit lamp examination. Edematous cornea by slit lamp microscopic examination. Diffuse linear descemet's membrane's folding and corneal thickening was observed. 76
- 황유숙 조양경 : 데스메막내피각막이식후단순포진각막염 - 도의데스메막편의유착이불완전하여국소마취하에전방내공기재주입을시도하였다 (Fig. 2). 이후각막부종은감소하였고투명성은점차회복되어경면현미경검사가가능했으며, 각막의경면현미경검사에서각막두께는 587 μm로측정되었다 (Fig. 2C). 환자는데스메막내피각막이식수술당일은안약점안을하지않고 1일후부터 0.5% moxifloxacin (Vigamox, Alcon) 하루 4회와 1% prednisolone (Predforte, Allergan, Irvine, CA, USA) 을하루 4회점안하였다. 데스메막내피각막이식수술 1달후점차 Vigamox 와 Predforte 의점안횟수를 3회로줄이고, 데스메막내피각막이식수술 7주이후두약제를 2회로더줄여서시용하였다. 자가혈청점안액도추가하여수술후 2달까지부터하루 4회점안하였다. 데스메막내피각막이식수술후약 2달이내의네차례의경과관찰기간동안특이소견없이최대교정시력 0.3으 로유지되었다. 수술약 2달후경과관찰때환자는약 1주전부터시작된약간의불편감과시력감소를호소하였다. 환자의최대교정시력은 0.1로감소하였고, 각막상피는아주얇은수지상상피결손및불규칙한선모양의혼탁이중심부쪽에뻗어있었고플루오레신염색이되었다 (Fig. 3). 수지상각막병변을보였고, 동반된각막의부종부위의데스메막내피절편이잘유착되어있는것을확인하여절편분리에의한부종이아님을확인한후, Herpes simplex virus-1 (HSV-1) polymerase chain reaction (PCR) 검사를약 100 μl의 normal saline 으로병변부위를세척한후모아서나갔다. 임상적진단하에경구항바이러스제 Valacyclovir (Valtrex ; GlaxoSmithKline Inc., Ontario, Canada) 로치료를하고최종적으로 PCR에서 HSV-1을확인했다. 이때부터는 Vigamox 와 Predforte 를 A B C Figure 2. Cornea after rebubbling. (A) Cornea in slit lamp examination one day after re-bubbling. (B) Pentacam scheimpflug image after re-bubbling. (C) Specular microscope image after re-bubbling. APEX = polymorphism; AVE = average cell area; NUM = cell number analyzed; CD = cell density; CV = coefficient of cell deviation; AREA = polymegathism. A B Figure 3. Cornea at slit lamp examination. (A) slight edematous cornea. (B) faint irregularity in slit lamp examination with fluorescent stain. 77
- 대한안과학회지 2019 년제 60 권제 1 호 - Figure 4. Cornea after antiviral treatment. Disappearance of dendritic lesion after antiviral treatment. Improvement in corneal transparency. 모두하루에 1회점안하였다. 약 3주간의 Valtrex 2,000 mg 복용후수지상각막염은회복되었다 (Fig. 4). 이후약 3달동안예방목적으로 Valtrex 500 mg을경구투여하였다. 상피독성을염려하여국소항바이러스연고는사용하지않았다. 헤르페스각막염이치료된후 Vigamox 하루 2회, Predforte 를 0.5% Loteprednol (Lotemax ; Bausch & Lomb Inc., Rochester, NY, USA) 로바꾸어하루 2회점안하다가수술후 6개월까지 Vigamox 와 Lotemax 를하루 1회점안하였다. 고 찰 안과적수술중, 수술후단순포진바이러스의감염에의한각막염을나타내는경우는백내장수술, 레이저굴절교정술, 각막이식술등이있으며초자체망막수술후에도발생한다. 7,8,12 각막이식후단순포진바이러스각막염의발생의기전을살펴보면, 먼저예전에단순포진바이러스각막염을앓은과거력이없던경우에는실제로첫번째감염일수도있고혹은삼차신경절에잠복상태에만있던헤르페스바이러스의재활성화에의한각막염일수도있으며, 드물게는공여각막에있는단순포진바이러스에의한감염도생각해볼수있다. 예전에단순포진바이러스각막염을앓은적이있던환자의경우에는그바이러스의재발로볼수있다. 8,10 본증례의환자는 67세환자로과거력청취에서이때까지단순포진각막염을의심할만한증상이나과거력이없었으며, 본원에서규칙적이경과관찰을하던중에도단순포진바이러스에의한각막염의소견을보인적이없었다. 따라서이경우는잠복했던단순포진바이러스가각막수술 이하나의견인자역할을해서재활성화된것으로의심해볼수있다. 하지만전체층각막이식과달리 360 전체의각막의천공에의한삼차신경의자극도없으며천공성각막절개는 3군데만했기때문에다른원인, 즉사용하고있는스테로이드제점안약제가바이러스의활성화에기여했을가능성도배제할수없다. 11 지금까지데스메막내피각막이식수술후단순포진바이러스각막염에대한보고는해외에서 Zarei-Ghanavati et al 13 에의한단순포진바이러스각막내피염이있었다. 이보고에서는헤르페스각막내피염에의한각막부종및이식절편의각막후면에부분적인분리가보고되었다. 본증례에서는헤르페스에의한상피각막염이있으나전방염증이나내피염은동반되어있지않았기때문에데스메막이식절편은잘유착되어있었고, 항바이러스치료에잘반응하였다. 각막내피이식후발생한단순포진바이러스각막염에대한국내보고로는 Jeong et al 14 의데스메막박리자동내피각막이식후발생한각막염사례가있었다. 이보고에서는지속상피결손으로치유에약 6개월정도의시간이걸린것으로보고되었다. 본증례의경우에도이전에헤르페스각막염의과거력이없었으므로공여각막의바이러스를하나의원인으로의심할수는있으나본증례처럼각막전층을이식하는것이아닌, 1개의층인데스메막만이식하는데스메막내피각막이식에서공여각막의데스메막에서기인한단순포진각막염을의심하기어려운이유는일단각막간질이아닌데스메막에있을수있는바이러스의영향은미미할것으로보여서다. 15 데스메막내피각막이식처럼각막에분포한삼차신경절단이많지않은수술에서도단순포진각막염의재활성화가있을수있으므로이식면역거부반응이상대적으로다른각막이식에비해드문데스메막내피각막이식수술후에는수술후점안하는스테로이드제제와같이면역억제가가능한약제들은반드시필요한기간동안만사용하도록하는것이중요할수있다. 데스메막내피각막이식수술후에도단순포진바이러스각막염의재발이관찰되었으므로, 각막내피이식특히데스메막내피각막이식수술후초기경과관찰에서이전에보이지않던각막의상피병변이나각막부종을보일때는먼저데스메막절편의유착여부를확인하고, 유착이되어있음에도상피병변이나부종을보인다면헤르페스각막염도감별진단의하나로포함시켜야할것으로보인다. REFERENCES 1) Tourtas T, Laaser K, Bachmann BO, et al. Descemet membrane en- 78
- 황유숙 조양경 : 데스메막내피각막이식후단순포진각막염 - dothelial keratoplasty versus descemet stripping automated endothelial keratoplasty. Am J Ophthalmol 2012;153:1082-90.e2. 2) Ham L, Dapena I, van Luijk C, et al. Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy: review of the first 50 consecutive cases. Eye (Lond) 2009;23:1990-8. 3) Kim HW, Hwang HS, Lim SA, Kim MS. Four cases of split cornea transplantation from a single cornea. J Korean Ophthalmol Soc 2016;57:988-93. 4) Gorovoy MS. DMEK Complications. Cornea 2014;33:101-4. 5) Melles GR, Ong TS, Ververs B, van der Wees J. Preliminary clinical results of descemet membrane endothelial keratoplasty. Am J Ophthalmol 2008;145:222-7. 6) Hlinomazová Z, Horácková M, Pirnerová L. DMEK (Descemet membrane endothelial keratoplasty)--early and late postoperative complications. Cesk Slov Oftalmol 2011;67:75-9. 7) Rezende RA, Uchoa UB, Raber IM, et al. New onset of herpes simplex virus epithelial keratitis after penetrating keratoplasty. Am J Ophthalmol 2004;137:415-9. 8) Jhanji V, Ferdinands M, Sheorey H, et al. Unusual clinical presentations of new-onset herpetic eye disease after ocular surgery. Acta Ophthalmol 2012;90:514-8. 9) Jain V, Pineda R. Reactivated herpetic keratitis following laser in situ keratomileusis. J Cataract Refract Surg 2009;35:946-8. 10) Beyer CF, Hill JM, Reidy JJ, Beuerman RW. Corneal nerve disruption reactivates virus in rabbits latently infected with HSV-1. Invest Ophthalmol Vis Sci 1990;31:925-32. 11) Haruta Y, Rootman DS, Xie LX, et al. Recurrent HSV-1 corneal lesions in rabbits induced by cyclophosphamide and dexamethasone. Invest Ophthalmol Vis Sci 1989;30:371-6. 12) Chen HF, Yeung L, Yang KJ, Sun CC. Persistent corneal epithelial defect after pars plana vitrectomy. Retina 2016;36:148-55. 13) Zarei-Ghanavati S, Alizadeh R, Yoo SH. Herpes simplex virus endotheliitis following descemet's membrane endothelial keratoplasty. J Ophthalmic Vis Res 2015;10:184-6. 14) Jeong SH, Cho JK, Yoon KC. A case of herpes simplex keratitis after descemet stripping automated endothelial keratoplasty. J Korean Ophthalmol Soc 2012;53:473-7. 15) Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res 2010;90:478-92. = 국문초록 = 데스메막내피각막이식술후발병한단순포진바이러스각막염 1 예 목적 : 데스메막내피각막이식술시행후발병한각막염 1 예를보고하고자한다. 증례요약 : 67 세남자환자가좌안의인공수정체수포각막병증으로데스메막내피각막이식술을시행받았다. 주변부데스메막의부분적인분리로수술 1 주후전방내공기주입을한이후각막혼탁없이상피치유잘되었으며, 수술전에비해시력이향상되어유지되었다. 데스메막내피각막이식 2 개월후환자는약간의불편감과시력감소를주소로내원하였다. 환자각막상피는아주얇은수지상상피결손및얇고불규칙한가느다란선모양의혼탁이중심부쪽에뻗어있었고플루오레신염색이되었다. 환자의데스메막이분리되지않고잘유착되어있음을확인하고, 단순포진각막염의심하에경구항바이러스제 Valacyclovir (Valtrex, GlaxoSmithKline Inc., Ontario, Canada) 로치료를시작하였으며, polymerase chain reaction 에서 herpes simplex virus type 1 을확인했다. 약 3 주간의항바이러스치료후각막의수지상병변은회복되었다. 결론 : 전체층각막이식이아닌데스메막내피각막이식후에도단순포진각막염의재활성화를유발할수있으며, 갑작스러운각막표면의불규칙성이나환자의시력감소등이동반될때세극등현미경검사에서데스메막절편의분리가없다면단순포진각막염의발병을의심해야한다. < 대한안과학회지 2019;60(1):75-79> 황유숙 / Yousook Hwang 가톨릭대학교의과대학안과및시과학교실 Departments of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea 79