검안및콘택트렌즈학회지 2018 년제 17 권제 2 호 Ann Optom Contact Lens 2018;17(2):39-43 ISSN 2384-0919 (Print) ISSN 2384-0927 (Online) Case Report 헤르페스각막염치료중발생한홍채후면칸디다진균구 Fungal Abscess in Posterior Iris during Herpes Keratitis Treatment 방슬기 1 강민석 1 김태기 2 진경현 1 Seul Ki Bang, MD 1, Min Seok Kang, MD 1, Tae Gi Kim, MD 2, Kyung Hyun Jin, MD, PhD 1 경희대학교의과대학경희대학교병원안과학교실 1, 경희대학교의과대학강동경희대학교병원안과학교실 2 Department of Ophthalmology, KyungHee University Hospital, KyungHee University College of Medicine 1, Seoul, Korea Department of Ophthalmology, KyungHee University Hospital at Gangdong, KyungHee University College of Medicine 2, Seoul, Korea Purpose: To report a case of fungal infection in posterior iris during medical and surgical management of herpetic keratitis. Case summary: A 44-year-old women diagnosed with a dilated cardiomyopathy was presented with decreased visual acuity in the left eye. Best corrected visual acuity was 0.05 in the left eye and slit-lamp examination revealed peripheral ulcerative dendritic keratitis with stromal infiltration. The anti-viral agents and steroid eye drops were initiated under impression of herpetic keratitis and corneal endothelitis. The inflammatory reactions in anterior chamber were increased and the thinning of ulcerative lesion was aggravated at 6 months after treatment. The amniotic membrane transplantation (AMT) was done in the left eye. Despite the continuous medical management, ulcerative thinning readily progressed and the hypopyon in anterior chamber with anterior protrusion of iris in inferonasal portion was observed at 3 months after AMT. The corneal perforation occurred during secondary AMT and iris exposure was observed as perforated region enlarged. The primary closure with conjunctival flap was performed and the penetrating keratoplasty (PKP) was done at 3 days later. The whitish abscess pocket with 1 to 2 mm diameter was found in the posterior portion of protruded iris and the fungal keratitis was confirmed following biopsy. The intravitreal amphotericin B injection was done and fortified voriconazole eye drops were maintained for 4 months after PKP. Both anterior and posterior segment showed no inflammatory reaction and recurrence for 20 months follow-up period after PKP. Conclusions: Infective keratitis that do not respond to treatment after long-term use of anti-viral agents and steroids in immune-suppressed patients may also be accompanied by fungal infection and abscess in posterior iris. Ann Optom Contact Lens 2018;17(2):39-43 Key Words: Fungal abscess; Herpetic keratitis; Posterior iris; Fungal infection 전안부를침범한칸디다감염은세균성각막궤양이나헤르페스각막염과유사한초기병변을보이기때문에병변이상당히진행된이후에치료가시작되는경우가많다. 칸디다를포함한진균에의한감염은세균성감염과는달리 Received: 2018. 2. 6. Revised: 2018. 3. 20. Accepted: 2018. 4. 3. Address reprint requests to Kyung Hyun Jin, MD, PhD Department of Ophthalmology, KyungHee University Hospital, KyungHee University College of Medicine, #23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea Tel: 82-2-958-8452, Fax: 82-2-966-7340 E-mail: khjinmd@khmc.or.kr 각막기질까지침습하여전방, 홍채, 수정체까지도달하는경우가많고이경우치료가어려워진다고보고되었다. 특히홍채를침범하는후방칸디다감염은매우드물고홍채의고름주머니형성이나홍채결절등의형태로나타나는것으로알려져있다. 2002년 Myers et al 1 에의해감염성포도막염환자에서홍채결절의형태로나타난칸디다감염 1예가보고되었고 2011년 Braich et al 2 에의해내인성안내염환자에서홍채와수정체전면을침범한칸디다감염 1예가보고된바있다. 전안부의감염을일으키는진균은크게효모와사상진균과이상성사상균으로구분되고, 칸디다종 (Candida species) 은가장흔한효모균으로알려져있다. 칸 Copyright 2018, The Korean Optometry Society The Korean Contact Lens Study Society Annals of Optometry and Contact Lens is an Open Access Journal. All articles are 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. 39
- 검안및콘택트렌즈학회지 2018 년제 17 권제 2 호 - 디다감염은각막의상피세포결손부를통해각막기질로침투하는경로를통해발생하게된다. 따라서칸디다감염의위험인자는각막자체의방어기전이저하되어각막상피세포의결손을초래하는경우로알려져있다. 반면, 후안부칸디다감염은특징적인망막및맥락막소견을보이며, 진단에안구초음파가매우유용하다. 따라서전안부의감염과는달리진단이늦어지는경우는적은것으로알려져있다. 저자들은헤르페스각막염으로진단된면역저하환자에서장기간동안스테로이드점안제및항바이러스제를사용하면서각막궤양이점진적으로악화됨을경험하였고, 칸디다각막염으로진행된뒤치료에반응하지않는홍채후면에발생한칸디다진균구감염을확인하였기에전안부의전후방모두를침범한칸디다감염에대해보고하고자한다. 증례 44세여자환자가 3주전부터시작된좌안의시력저하와통증을주소로내원하였다. 내원당시최대교정시력은우안 0.8, 좌안 0.05였으며비접촉안압계로측정한안압은우안 19 mmhg, 좌안 30 mmhg였다. 세극등현미경검사에서결막충혈을동반한각막주변부로수지상궤양 (dendritic ulcer) 이관찰되었고하부의부분적인상피결손과광범위한각막점상미란이확인되었다 (Fig. 1A). 환자과거력상확장성심근병증으로경피적관동맥형성술후장기간와파린을복용중이었으며, 혈액검사상젖산탈수소효소, 크레아틴인산화효소및간세포효소수치의상승이관찰되었다. 양안모두경도의핵경화성백내장소견을보였으나추가적인이상소견은관찰되지않았다. 우선헤르페스각막염및각막내피염진단하에항바이러스연고 (Acyclovir 3% 30 mg/g, q 3 hrs [Herpesid eye oint, Samil, Seoul, Korea]) 및안압하강제 (Dorzolamide hydrochloride 22 mg/ml, q 12 hrs [Merck and Company, Inc, Whitehouse, NJ, USA]) 를사용하였다. 1주뒤추적관찰에서좌안전방염증세포관찰되어스테로이드점안제 (Prednisolone acetate 10 mg/ml, q 8 hrs [Pred forte, Allergan, Irvine VA, USA]) 를추가하였고항바이러스제 (Acyclovir, [Zovirax tab 400 mg, Dong-A ST, Seoul, Korea] 800 mg) 를복용하기시작했다. 6주후전안부증상호전및안압이안정적으로유지되어스테로이드점안제를기존사용하던 prednisolone acetate에서 fluorometholone 0.2 mg/ml 로바꿔유지하였으며, 안압하강제와항바이러스연고사용을중단하였다. 5개월까지전방염증소견및안압은안정화되었고부분적인각막혼탁은관찰되었으나나안시력은 0.4까지회복되어점안항생제와인공누액및 fluorometholone Figure 1. Anterior segment photograph of left eye. (A) Peripheral dendritic ulcer with multiple punctate epithelial erosion. (B) Five months later from first visit. Focal opacity was detected. (C) Peripheral corneal ulceration with peripheral corneal thinning. (D) Eight days after AMT. Focal stromal infiltrate with corneal thinning was covered with a double layer of amniotic membrane graft. AMT = amniotic membrane transplantation. 40
- 방슬기외 : 각막염치료중발생한칸디다진균구 1 예 - 을유지하여외래경과관찰을진행하였다 (Fig. 1B). 호전후 1달뒤, 전방염증세포가증가하고나안시력은 0.15, 안압 24 mmhg 까지상승하였으며궤양부위가얇아진소견이보여양막이식술을시행하였다 (Fig. 1C, 1D). 양막이식후에도항바이러스제복용은유지하였고치료용콘택트렌즈와항생제및스테로이드점안제를사용하였다. 하지만양막이식 3개월후각막침윤이증가하고나안시력 0.01까지저하되며안압 27 mmhg로재차상승하면서이식부위가다 시얇아진것이확인되었다. 또한세극등현미경검사에서하비측홍채의전방돌출과전방축농이동반되었으며각결막배양결과 Candida albicans가동정되었다 (Fig. 2A). 이에칸디다각막염진단하에 2시간간격으로보리코나졸을점안하였고스테로이드점안제는중단하였으며 2차양막이식술을시행하였다. 하지만너무얇아진이식부위로인해수술중각막천공이발생하였고수술후천공부위넓어져홍채의노출이발생하였다 (Fig. 2B). 이에추가로결막판봉합술 Figure 2. Anterior segment photograph of left eye after AMT. (A) One month after AMT. Hypopyon appeared in anterior chamber. Central thinning and impending perforation was detected at central cornea. (B) One day after second AMT. Peripheral temporal corneal perforation with iris prolapse and iris was in contact with amniotic membrane. (C) Five days after second AMT. Conjunctival flap was done. (D) Two days after conjunctival flap. Flap was loosened and pus like material leakage was found underneath the flap. AMT = amniotic membrane transplantation. Figure 3. Surgical microscopic finding of left eye during PKP. (A) Perforated recipient cornea (blue arrow) and protruded iris due to underlying pus like material (white arrow). (B) Pus like material was forming pocket 1 to 2mm in diameter and extended to ciliary body. PKP = penetrating keratoplasty. 41
- 검안및콘택트렌즈학회지 2018 년제 17 권제 2 호 - Figure 4. Histopathologic finding of perforated corneal ulcer site. (A) Fungal hyphae (arrow) in the corneal stroma was seen (Gomori-methenamine silver stain, 50). (B) Corneal infiltrate was composed of neutrophil and histiocyte (arrow) (H&E stain, 50). 을실시하여천공부위를봉합하였으나결막판아래로흰색의고름누출과함께봉합부위가벌어지는양상보여, 3일뒤좌안전층각막이식술을시행하였다 (Fig. 2C, 2D). 수술소견으로각막과접촉해있던홍채뒷면으로지름 1-2 mm 의흰색고름주머니가관찰되었고각막천공부위와고름주머니의조직검사결과진균각막염으로진단되었다 (Fig. 3, 4). 전방내출혈이지속되어 1일뒤전방세척과유리체내암포테리신 B 주사를함께시행하였다. 퇴원후치료용콘택트렌즈를지속적으로착용하고전층각막이식술후 9개월까지보리코나졸을점안하면서경과를관찰하였으며전안부및후안부에염증재발없이유지되고있다. 고찰 헤르페스각막염은흔한각막염의형태로각막의치유및방어기능의저하를유발하여각막상피를불안정하게만든다. 이경우바이러스에의한각막상피의신경지배약화에의하여신경영양각막염을유발할수있고수지상각막염에의하여각막상피의결손이지속적으로발생하였을때이차적인감염도일으킬수있는것으로알려져있다. 3 특히칸디다와같은진균에의한이차감염이발생하는경우항바이러스제에의한치료가효과적이지않기때문에치료양상과임상양상의변화를파악하여신속한추가도말검사및배양검사가이루어져야한다. 4 칸디다각막염은다른감염각막염과혼동되는경우가많아신속한진단이어려운것으로알려져있다. 전형적인칸디다각막염의특징은그람양성세균각막염과유사하여분명한가장자리경계와분리된각막기질의화농을동반한난원형궤양을주로보인다. 칸디다각막염의위험인자로는고령, 과거안질환의기왕력, 각막수술의기왕력, 노촐성각막염, 만성각막염, 만성적스테로이드사용, 면역결핍질 환등이보고되어있다. 5 특히점안스테로이드의장기간사용은진균각막염의발생을증가시키고경과를악화시킬수있다. 또한전신스테로이드의복용은전신면역억제를통한진균각막염의호발에영향을줄수있다고알려져있다. 6,7 이와같이칸디다각막염은방어기전이저하된각막에서발생하는기회감염이기에임상양상은선행질환에따라다양하게나타날수있고다른세균성복합각막염의형태도가능하다. 칸디다각막염은천천히진행되고초기증상이심하지않아늦게발견되는경우가많으며, 앞서언급한바와같이세균성각막염과감별이어렵고상품화된진균약이거의없어적절한치료를선행하기힘들다. 항진균제의발달에따라암포테리신, 보리코나졸, 나타마이신등의점안약을통해일차적인각막염의호전소견을기대할수있으나, 8-10 항진균제에대한반응이없는경우항진균제의결막하주사, 11 전방또는유리체강내항진균제투여, 12,13 적절한시기를놓치지않고괴사조직제거또는결막피판, 각막이식술등의수술적치료로전환하는것이보다효과적이다. 특히약물치료에도불구하고각막궤양이진행되거나농양을형성하는경우, 염증이조절되지않고각막이얇아지거나천공되는경우에는각막이식까지고려해야한다. 본증례에서와같이홍채내고름주머니형성이나홍채결절등의형태로홍채를침범하는후방칸디다감염은매우드문것으로알려져있다. 14 2002년 Myers et al 1 은감염성포도막염환자에서전방염증소견및홍채결절소견을보이는칸디다감염 1예를보고하였으며, 2003년 Monshizadeh et al 15 은면역결핍환자에서홍채와수정체내진균구를갖는전신칸디다증환자증례를보고하였다. 또한 2011년 Braich et al 2 에의해내인성안내염환자에서홍채와수정체전면을침범한칸디다감염 1예가보고된바있으나아직국내에는이와유사한사례가보고된바가없다. 후방칸디 42
- 방슬기외 : 각막염치료중발생한칸디다진균구 1 예 - 다감염은그진행이매우느리고, 병변의위치에따른다소상이한임상증상을갖는특징을보인다. 진단에는안구초음파를통한수정체나홍채주변부의병변을확인하는것이유용하며, 진균에의한내인성안내염이의심될경우추가적으로유리체내도말및배양검사를통해이를확진할수있다. 4 본저자들은헤르페스각막내피염환자에서장기간항바이러스제및스테로이드를통한지속적인치료중에각막궤양이점진적으로악화되면서칸디다각막염과함께홍채후면에동반된칸디다진균구감염을확인하였고, 이에감염각막염에동반된홍채후면칸디다감염을보고하고자한다. 이러한이유로난치성의감염각막염에서반드시홍채후방의감염을동시에고려해야한다는점이본증례의의의가되겠다. REFERENCES 1) Myers TD, Smith JR, Lauer AK, Rosenbaum JT. Iris nodules associated with infectious uveitis. Br J Ophthalmol 2002;86:969-74. 2) Braich PS, Chang JS, Albini TA, Schefler AC. Irido-lenticular abscess as the initial sign of Candida albicans endogenous endophthalmitis. https://www.healio.com/ophthalmology/journals/osli/2011-11-42-6/%7bd66e51e7-56fa-4eed-8ce1-3809b4914f39%7d/irido-lentic ular-abscess-as-the-initial-sign-of-candida-albicans-endogenousendophthalmitis. Accessed Dec 8, 2011. 3) Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness : a global perspective. Bull World Health Organ 2001;79:214-21. 4) Chang HY, Chodosh J. Diagnostic and therapeutic considerations in fungal keratitis. Int Ophthalmol Clin 2011;51:33-42. 5) Keay LJ, Gower EW, Iovieno A, et al. Clinical and microbiological characteristics of fungal keratitis in the United States, 2001-2007: a multicenter study. Ophthalmology 2011;118:920-6. 6) Srinivasan M. Fungal keratitis. Curr Opin Ophthalmol 2004;15:321-7. 7) Bharathi MJ, Ramakrishnan R, Vasu S, et al. Epidemiological characteristics and laboratory diagnosis of fungal keratitis. A three-year study. Indian J Ophthalmol 2003;51:315-21. 8) Hariprasad SM, Mieler WF, Lin TK, et al. Voriconazole in the treatment of fungal eye infections: a review of current literature. Br J Ophthalmol 2008;92:871-8. 9) Sonego-Krone S, Sanchez-Di Martino D, Ayala-Lugo R, et al. Clinical results of topical fluconazole for the treatment of filamentous fungal keratitis. Graefes Arch Clin Exp Ophthalmol 2006;244:782-7. 10) Lee SJ, Lee JJ, Kim SD. Topical and oral voriconazole in the treatment of fungal keratitis. Korean J Ophthalmol 2009;23:46-8. 11) Carrasco MA, Genesoni G. Treatment of severe fungal keratitis with subconjunctival amphotericin B. Cornea 2011;30:608-11. 12) Seo JH, Wee WR, Lee JH, Kim MK. Risk factors affecting efficacy of intracameral amphotericin injection in deep keratomycosis. J Korean Ophthalmol Soc 2007;48:1202-11. 13) Jeong SH, Lee HS, Cho JK, Yoon KC. Clinical effects of intracameral voriconazole injection in patients with fungal keratitis refractory to conventional treatment. J Korean Ophthalmol Soc 2013;54:696-703. 14) Clare G, Mitchell S. Iris root abscess and necrotizing sclerokeratitis caused by Mycobacterium abscessus and presenting as hemorrhagic anterior uveitis. Cornea 2008;27:255-7. 15) Monshizadeh R, Sands RE, Lara WC, Driebe W. Isolated anterior uveitis as the initial sign of systemic candidemia. Arch Ophthalmol 2003;121:137-8. 43