대한안과학회지 2019 년제 60 권제 8 호 J Korean Ophthalmol Soc 2019;60(8):792-796 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2019.60.8.792 Case Report 방사상각막신경염의임상양상을보인에로모나스각막염 Radial Keratoneuritis in Aeromonas Keratitis 김예슬 1 신희봉 2 이시형 1 Yeseul Kim, MD 1, Hee Bong Shin, MD, PhD 2, Si Hyung Lee, MD 1 순천향대학교의과대학부천병원안과학교실 1, 순천향대학교의과대학부천병원진단검사유전학교실 2 Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine 1, Bucheon, Korea Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine 2, Bucheon, Korea Purpose: We report a case of Aeromonas keratitis presenting as radial keratoneuritis. Case summary: A 33-year-old woman with a history of cleaning her contact lenses with tap water presented with decreased visual acuity for 1 day in the left eye. The patient showed diffuse corneal edema, stromal infiltration, and radial keratoneuritis, which were thought to be pathognomonic for Acanthamoeba keratitis. Based on the patient s clinical findings and past history, a diagnosis of Acanthamoeba keratitis was made and she was prescribed topical fortified cefazolin (50 mg/ml, 5%), tobramycin (3 mg/ml), and 0.02% chlorhexidine per hour. Culture results from the contact lens and contact lens solution confirmed infection by Aeromonas hydrophilia. Polymerase chain reaction results for Acanthamoeba were negative. After 8 days of treatment, the uncorrected visual acuity was 0.7/0.3 with improvement in her corneal findings. Conclusions: Radial keratoneuritis is not always pathognomic for Acanthamoeba keratitis and can be present in Aeromonas keratitis. Therefore, ophthalmologists should be cautious when interpreting this clinical sign. J Korean Ophthalmol Soc 2019;60(8):792-796 Keywords: Aeromonas, Cornea, Radial keratoneuritis 가시아메바각막염은 1974 년에처음으로보고되었으며, 1 안통, 광시증등의증상을동반하며각막에심각한염증을일으키며, 각막실질침윤, 각막상피결손, 각막혼탁을남기고, 시력소실의위험이있다. 2 가시아메바각막염은오염된물에노출된경우와연관이있으며, 1980년대미국에서 Received: 2019. 1. 3. Revised: 2019. 1. 15. Accepted: 2019. 7. 18. Address reprint requests to Si Hyung Lee, MD Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, #170 Jomaru-ro, Bucheon 14584, Korea Tel: 82-32-621-5053, Fax: 82-32-621-6460 E-mail: sieh12@schmc.ac.kr * This work was supported by the Soonchunhyang University Research Fund. 콘택트렌즈착용환자들에서가시아메바각막염의발생률이증가한것으로보아콘택트렌즈사용과도관련이있다. 3 Moore는방사상각막신경염이가시아메바각막염의특징적인징후라고보고하였고, 3 조기에진단을하고적절한치료를시작할경우성공적인치유가가능하며, 내과적치료에효과가없는경우각막이식등의수술을고려해볼수있고, 최근에는콜라겐교차결합술, 굴절교정각막절제술등도시도되고있다. 2 그러나매우드문질환으로대부분진단이늦어지며, 가시아메바각막염이외의각막염에서도방사상각막신경염이관찰된문헌의보고가있었다. 4,5 그리하여저자들은콘택트렌즈를착용하는환자에서방사상각막신경염의임상양상을보인에로모나스각막염을경험및치료한 1예를보고하고자한다. * Conflicts of Interest: The authors have no conflicts to disclose. 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. 792
- 김예슬외 : 방사각막신경염양상의에로모나스각막염 - 증례보고 33세여자환자가내원 1일전부터시작된좌안의시력저하및안구통을주소로본원으로내원하였다. 환자는외상에대한과거력은없었고, 수주동안소프트콘택트렌즈를착용해왔으며, 규칙적으로수돗물로콘택트렌즈를세척하였다. 본원내원당시좌안시력은 0.03으로측정되었다. 세극등현미경전안부검사상좌안결막의충혈이관찰되었으며, 각막의상피부종과 7시방향에방사상각막신경염, 각막실질의침윤이관찰되었다 (Fig. 1). 전방내의염증세포및전방축농은관찰되지않았으며, 그외의안과학검사상특이소견은관찰되지않았다. 환자의병력과임상양상을토대로가시아메바각막염이강력히의심되었다. 병변부위의각막을찰과및콘택트렌즈와렌즈보존액에대해균배양검사를시행하였으며원인세균과가시아메바영양형또는포낭형을검출하기위해 Giemsa 염색과 Gram 염색을시행하였다. 배양결과가나오기전까지는경험적항생제로 0.02% chlorhexidine, fortified cefazoline (50 mg/ml, 5%), 그리고 fortified tobramycin (3 mg/ml) 을매시간마다유지시키고, 조절마비제를하루 4번점안하였다. 콘택트렌즈및렌즈보존액에서시행한균배양검사와현미경검사에서다수의그람음성막대균이동정되었으며가시아메바영양형또는포낭형은동정되지않았다. 생화학동정시스템 (Vitek -2; biomérieux, Marcy-l Étoile, France) 을통해 Aeromonas 종으로확인되었으며 rpob 유전자분석을통해 Aeromonas 종들간의식별을시행하였다. 6 MEGA 5.0 software를사용하여, 분리된임상검체의뉴클레오티드서열과연관된표준균주에대해 Unweighted Pair Group Method with Arithmetic Mean (UPGMA) 분석을통해계통수를만들었다 (Fig. 2). 7 Fig. 2에서볼수있듯이 Aeromonas 종이다른균종들과의연관성이있는것을확인할수있으며, 특히방사상각막신경염양상이나타날수있는 Pseudomonas aeruginosa와의유사성도확인할수있었다. 가시아메바감염을진단하기위해, 콘택트렌즈와렌즈보존액에대하여다중중합효소연쇄반응을실시하였으며, 8 결과는음성이었다. 치료 8일째, 시력은 0.3으로측정되었고각막병변은매우호전되었으나작은각막실질침윤이남아있었고, 환자는더이상내원하지않아추적관찰을할수없었다 (Fig. 3). 고찰 방사상각막신경염은가시아메바각막염의특징적인징후로알려져있다. 2 그러나 1990년도초기에 Feist et al 4 은 Pseudomonas 각막염에서방사상각막신경염이나타났다고보고하였으며, 각막실질형태의헤르페스각막염에서도방사상각막신경염이보고되었다. 5 또한국내에서도세라티아마르세센스각막염에서방사상각막신경염이관찰되었다고보고되었으며, 세라티아각막염의경우임상적특징이다른그람음성균과비슷하나다중약물내성균으로 levofloxacin과 tobramycin에저항성을보이는것으로보아배양검사를통해방사상각막신경염을보이는각막염의원인균을동정하는것이치료에필수적일것으로생각한다. 9 최근인체감염에서 A. hydrophilia의역할이연구되었으나, 10 인체각막에감염을일으켰다는보고는거의없었다. Feaster et al 11 은 A. hydrophilia 각막궤양을보고하였으며, Pinna et al 12 은콘택트렌즈를착용하는환자에서 A. caviae 각막염을진단및치료하였다고보고하였다. Aeromonas 각막염의임상적특징으로는각막실질침윤, 각막상피미란및결손, 전방염증, 전방축농이있다. 대부분의 Aeromonas A B Figure 1. Anterior segment photographs of the left eye at presentation. Small dense stromal infiltrates at the center (A, arrows) and radial keratoneuritis (B, arrow) were revealed at inferonasal area. 793
- 대한안과학회지 2019 년제 60 권제 8 호 - Figure 2. UPGMA phylogenetic trees based on the rpob sequence. The relationships with the strains of genus Aeromonas and other closely related bacterial strains were shown. Nucleotide sequence of clinical isolate from the patient was revealed as Aeromonas hydrophilia in this tree (highlighted with box). Aeromonas species and Pseudomonas species were closely related in the tree. UPGMA = Unweighted Pair Group Method with Arithmetic Mean. A B Figure 3. Anterior segment photographs of the left eye on day 8. The patient showed dramatic improvement with small dense stromal infiltrations at the center (A, B; arrows) and radial keratoneuritis was resolved. 종은 chloramphenicol, tetracycline, fluoroquinolone, 3세대 cephalosporin, 그리고 aminoglycoside에감수성을보이므로이를통해 Aeromonas 각막염의효과적인치료가가능하며, 대부분은심하지않은경과를보이나다른그람음성균과비슷하게약물에저항성을보일수있으므로항생제감수성검사가필수적이다. 12,13 Aeromonas 속은 30개이상의종으로이루어져있으며, A. hydrophila 복합체, A. caviae, 그리고 A. veronii 복합체만 이사람병원체로보고되었다. 현재상용되고있는생화학동정시스템으로는서로다른종을정확히구별하지못하기때문에, Aeromonas 종을동정하는것은어렵다. 14 그리하여본논문에서는 rpob 유전자분석을통해 A. hydrophilia를동정하였으며 UPGMA 분석을사용하여만든계통수를통해 Aeromonas 종과 Pseudomonas 종의유연관계가높은것을알수있었다. 따라서 Pseudomonas 각막염에서방사상각막신경염이나타났다는이전문헌들로미루어 794
- 김예슬외 : 방사각막신경염양상의에로모나스각막염 - 보아본연구의 Aeromonas 각막염에서또한방사상각막신경염양상이나타날수있는것은유전적으로높은유사도를보인다는점에서기인할것으로생각한다. 그러나이러한유전적유사도로인해방사상각막신경염이생기는원리에대해서는추가적인연구가필요할것으로사료된다. 본증례는국내에서최초로가시아메바각막염의임상적특징을보인 A. hydrophilia 감염을콘택트렌즈와렌즈보존액에대한미생물학적검사로진단하였음을보고했음에의의가있다. 본증례에서가시아메바각막염진단에부합하지않는요소로는증상이빠르게나타난점과미만의표층각막염이없었다는점이다. 각막신경염은가시아메바각막염에서가시아메바영양형이각막신경주변으로결집하여나타나는것으로알려져있으나, non-acanthamoeba 각막염에서나타나는각막신경염의병리생리학에대해서는잘알려져있지않고, 일부의사들은균의내독소와연관된어떠한과정이연관이있을것이라고제시하고있다. 15 방사상각막신경염은본증례에서보고한바와같이항상가시아메바각막염에서만나타나는특징적인징후가아님을고려해야한다. 저자들은본증례가매우드물기는하지만, 콘택트렌즈와연관된각막궤양과세균감염에서항상가시아메바가원인이되는것이아니며, 방사상각막신경염임상양상을보이는 non-acanthamoeba 각막염이존재하므로, 임상결과를해석할때주의를요할것을강조하는바이다. REFERENCES 1) Naginton J, Watson PG, Playfair TJ, et al. Amoebic infection of the eye. Lancet 1974;2:1537-40. 2) Lorenzo-Morales J, Khan NA, Walochnik J. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite 2015;22:10. 3) Moore MB, McCulley JP, Kaufman HE, Robin JB. Radial keratoneuritis as a presenting sign in Acanthamoeba keratitis. Ophthalmology 1986;93:1310-5. 4) Feist RM, Sugar J, Tessler H. Radial keratoneuritis in Pseudomonas keratitis. Arch Ophthalmol 1991;109:774-5. 5) Mutoh T, Matsumoto Y, Chikuda M. A case of radial keratoneuritis in non-acanthamoeba keratitis. Clin Ophthalmol 2012;6:1535-8. 6) Shin HB, Yoon J, Lee Y, et al. Comparison of MALDI-TOF MS, housekeeping gene sequencing, and 16S rrna gene sequencing for identification of Aeromonas clinical isolates. Yonsei Med J 2015;56:550-5. 7) Tamura K, Peterson D, Peterson N, et al. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011;28:2731-9. 8) Lehmann OJ, Green SM, Morlet N, et al. Polymerase chain reaction analysis of corneal epithelial and tear samples in the diagnosis of Acanthamoeba keratitis. Invest Ophthalmol Vis Sci 1998; 39:1261-5. 9) Kim YJ, Kim BS, Yoo WS, et al. A case of serratia marcescens keratitis presenting as radial keratoneuritis. J Korean Ophthalmol Soc 2014;55:1380-3. 10) Shilkin KB, Annear DI, Rowett LR, Laurence BH. Infection due to Aeromonas hydrophila. Med J Aust 1968;1: 351-3. 11) Feaster FT, Nisbet RM, Barber JC. Aeromonas hydrophila corneal ulcer. Am J Ophthalmol 1978;85:114-7. 12) Pinna A, Sechi LA, Zanetti S, et al. Aeromonas caviae keratitis associated with contact lens wear. Ophthalmology 2004;111:348-51. 13) Motukupally SR, Singh A, Garg P, Sharma S. Microbial keratitis due to aeromonas species at a tertiary eye care center in Southern India. Asia Pac J Ophthalmol (Phila) 2014;3:294-8. 14) Persson S, Al-Shuweli S, Yapici S, et al. Identification of clinical aeromonas species by rpob and gyrb sequencing and development of a multiplex PCR method for detection of Aeromonas hydrophila, A. caviae, A. veronii, and A. media. J Clin Microbiol 2015; 53:653-6. 15) Roels D, De Craene S, Kestelyn P. Keratoneuritis is not pathognomonic of Acanthamoeba keratitis: a case report of Pseudomonas keratitis. Int Ophthalmol 2017;37:257-8. 795
- 대한안과학회지 2019 년제 60 권제 8 호 - = 국문초록 = 방사상각막신경염의임상양상을보인에로모나스각막염 목적 : 방사상각막신경염의임상양상을보인에로모나스각막염 1 예를보고하고자한다. 증례요약 : 33 세여자환자가내원 1 일전부터시작된좌안의시력저하를주소로내원하였다. 환자는콘택트렌즈를수돗물로세척하여사용하고있었다. 전안부검사상미만성각막부종, 기질침윤및아메바성각막염의특징적인징후인방사상각막신경염소견이관찰되었다. 환자의임상양상과과거력을바탕으로가시아메바각막염의심하에 5% fortified cefazoline (50 mg/ml), tobramycin (3 mg/ml) 과 0.02% chlorhexidine 을 1 시간간격으로점안하였다. 콘택트렌즈와콘택트렌즈세척액의배양검사상 Aeromonas hydrophilia 가동정되었다. 중합효소연쇄반응 (polymerase chain reaction) 검사상 Acanthamoeba 는동정되지않았다. 치료 8 일후시력은 0.7/0.3 이었으며각막염은호전되었다. 결론 : 방사상각막신경염이항상아메바성각막염에서만관찰되는특징적인임상양상은아니며, 에로모나스각막염에서도나타날수있다. 그러므로임상결과를해석할때주의가필요하다. < 대한안과학회지 2019;60(8):792-796> 김예슬 / Yeseul Kim 순천향대학교의과대학부천병원안과학교실 Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine 796