Clinical profile of patients with Acanthamoeba keratitis - what are the poor prognosis indicators?

2017/2018 Daniela Filipa Sil a Ce quei a Clinical p o ile o pa ien s wi h Acan hamoeba ke a i is – wha a e he po p ognosis indica o s? ma ço, 2018 Daniela Filipa Sil a Ce quei a Clinical p o ile o pa ien s wi h Acan hamoeba ke a i is – wha a e he poo p ognosis indica o s? Mes ado In eg ado em Medicina Á ea: O almologia Tipologia: Disse ação T abalho e e uado sob a O ien ação de: Dou o João Pinhei o-Cos a E sob a Coo ien ação de: D a. Ca olina Madei a T abalho o ganizado de aco do com as no mas da e is a: Co nea ma ço, 2018 DEDICATÓRIA Te minada a ealização des a Tese de Mes ado, não a ia sen ido deixa de ag adece ao meu O ien ado , Dou o João Pinhei o-Cos a, e à minha Co-o ien ado a, Dou o a Ca olina Madei a, po oda a disponibilidade e a enção p es ada no deco e da sua execução. Um ag adecimen o especial à Joana Fe az B andão, que p ocedeu à e isão linguís ica do ex o. Po úl imo, mas não menos impo an e, um eno me ag adecimen o à minha amília e amigos, pelo apoio e pela paciência. 1 1 CLINICAL PROFILE OF PATIENTS WITH ACANTHAMOEBA KERATITIS - WHAT 2 ARE THE POOR PROGNOSIS INDICATORS? 3 4 Ca olina Madei a, MD*1 5 Daniela Ce quei a, 2 6 Luís To ão, MD, 1 7 Raúl Mo ei a, MD, 1 8 Manuel Falcão, MD, PhD, 1,3 9 Fe nando Falcão-Reis, MD, PhD, 1,3 10 João Pinhei o-Cos a, MD, 1,4 11 12 *1Co esponding au ho : Depa men o Oph halmology, Cen o Hospi ala São João, 13 Po o, Po ugal. Alameda P o . He nâni Mon ei o, 4200-319 Po o, Po ugal. 14 ania.ca olina.madei [email protected]; +351917860495. 15 1. Depa men o Oph halmology, Cen o Hospi ala São João, Po o, Po ugal 16 2. Facul y o Medicine, Uni e si y o Po o, Po ugal 17 3. Depa men o Su ge y and Physiology, Facul y o Medicine, Uni e si y o Po o, 18 Po ugal 19 4. Depa men o Biomedicine, Facul y o Medicine, Uni e si y o Po o, Po ugal 20 21 Con lic o in e es : None decla ed. 22 Keywo ds: Acan hamoeba, ke a i is, isk ac o s, p ognosis ac o s, polyme ase chain 23 eac ion 24 25 Financial Disclosu e: The au ho s decla e ha hey ecei ed no unding o conduc 26 his wo k. 27 2 28 ABSTRACT 29 Pu pose: To desc ibe he isk ac o s, es ablished ea men , isual ou come and o 30 es ablish poo p ognosis p edic o s in pa ien s wi h Acan hamoeba Ke a i is (AK). 31 Me hods: A e ospec i e analysis o 34 cases o AK diagnosed by polyme ase chain 32 eac ion (PCR) be ween ma ch 2010 and augus 2017 ollowed a Co nea Depa men 33 o Cen o Hospi ala de São João. Clinical p ocesses o hese pa ien s we e e iewed, 34 and i has been collec ed da a abou demog aphics, isual acui y (VA), biomic oscopy, 35 he apeu ics, isual ou come and complica ions o he disease. 36 Diagnosis was conside ed ea ly i es ablished be o e he i s 15 days a e he onse o 37 he symp oms and la e i es ablished a e wa ds. I was de ined as poo isual ou come 38 a inal bes -co ec ed isual acui y (BCVA) ≥ 1 loga i hm o minimal angle o esolu ion 39 (logMAR). 40 Resul s: A o al o 34 eyes om 29 pa ien s, all con ac lens (CL) wea e s, we e 41 diagnosed wi h AK. Conce ning he BCVA index, pa ien s wi h poo isual ou come 42 we e diagnosed la e han hose who had be e esul s (28 [4-150] s 14 [1-60] days; 43 p=0.01). The wo s isual ou come was associa ed wi h an uppe median age (37 [23- 44 66] s 33 [19-43] yea s; p=0.04), poo e ini ial VA (1,3 [0.3-2.0] s 0.5 [0.1-2.0] 45 logMAR; p=0.02) and s omal in il a e (41.2 s 7.1%; p=0.03) in biomic oscopy. Abou 46 35% pa ien s unde wen deb idemen and 29% ke a oplas y. Those who unde wen 47 ci u gical deb idmen had a be e isual ou come (p=0.002). Complica ions a e was 48 highe in pa ien s wi h wo se isual ou come (82.4% s 50.0%; p=0.06). 49 Conclusion: Pa ien s wi h wo se inal VA had a la e diagnosis wi h wo se ini ial VA 50 and mo e ad anced co neal disease in biomic oscopy a admission. 51 Diagnosis and ea men o pa ien s wi h AK is s ill a challenge, i equi es a high le el 52 o su mise om eye ca e' p o ide s o es ablish an ea ly diagnosis which is c ucial o a 53 good isual ou come. 54 55 3 56 INTRODUCTION 57 Acan hamoeba Ke a i is (AK) is ecognized as an inc easing cause o in ec ious 58 ke a i is1, 2, whose e iology includes se e al species o Acan hamoeba genus3, 4. These 59 ee-li ing p o ozoa can be ound in wa e , soil and wa e -ai in e ace2, 5, 6, wi h wo 60 exis ing o ms: ophozoi es, he in ec ious o m, and cys s, esponsible o he disease 61 esis ance.2 62 Wi h he use o con ac lenses (CL) as he main isk ac o 5, 7, 8, AK may also be 63 associa ed wi h co neal auma.5, 7 64 The ini ial symp oma ology is o en non-speci ic, and may include ocula pain 65 associa ed wi h pho ophobia, o eign body sensa ion and ea ing.6, 8 In addi ion, mo e 66 cha ac e is ic signs, such as adial neu i is, a en’ always p esen .1, 7 In he ea ly 67 s ages, is equen he o ma ion o a dend i ic pa e n, esul ing om he o ganiza ion 68 o linea in aepi helial in il a es, which is easily con used by signs o He pes simplex 69 i us8, and in la e s ages, he e a e cha ac e is ic ing in il a es, which a e only 70 p esen in abou 50% o pa ien s.6 All hese cha ac e is ics can make AK di icul o 71 diagnose, which leads o a delayed onse o he ea men and o a wo se p ognosis. 72 The diagnosis o AK implies he iden i ica ion o he e iological agen in he co neal 73 sc apings and biopsy specimens8, by cul u al exam, ha emains he gold-s anda d 74 diagnos ic examina ion.5 Mo e ecen ly, new diagnos ic ools ha e eme ged, such as 75 con ocal mic oscopy, ha can be pe omed in i o5, howe e i is expensi e and 76 equi es an expe ienced ope a o .3 The polyme ase chain eac ion (PCR) es ing is 77 also a good al e na i e diagnos ic exam, since i has a high sensi i i y and is as e 78 han he cul u al exam o iden i y he agen ’s DNA and i is ope a o independen .9 79 The AK ea men is challenging. An incomple e unde s anding o he pa hophysiology 80 o he disease10 and, mainly, he ea men esis ance caused by cys s6 a e ecognized 81 as ea men obs acles. Mo eo e , he use o s e oids seems o deg ade he p ognosis 82 o he disease.6, 7 The e is no speci ic ea men desc ibed o AK6, 11, howe e he e 83 a e some he apy egimens ha can be used as he biguanides ( hey ac a he 4 84 memb ane and include polyhexame hylene biguanide and chlo hexidine) o he 85 diamines (inhibi o s o DNA syn hesis, include p opamidine, hexamidine and 86 pen amidine).2, 11 Al hough he e we en’ signi ican di e ences in he e icacy o bo h 87 d ugs, biguanides had a highe e ec i eness agains cys ic o m using lowe dosage, 88 so hese a e gene ally p e e ed. In mo e se e e cases o when medical he apy is no 89 su icien , deb idemen , pene a ing ke a oplas y o e en amnio ic memb ane 90 ansplan a ion may be used.2 91 T ea men is ime consuming and complica ed and a close ollow-up is equi ed o 92 assess he appea ance o complica ions, anging om ulce s o e en co neal 93 pe o a ion o blindness and enuclea ion.8 94 The p esen disse a ion aims o desc ibe he isk ac o s, es ablished ea men , isual 95 ou come and o es ablish poo p ognosis p edic o s in pa ien s wi h posi i e PCR o 96 Acan hamoeba ollowed a he Co nea Depa men on Cen o Hospi ala de São João. 97 98 METHODS 99 We pe o med a e ospec i e analysis o all suspec ed cases o AK ha unde gone 100 PCR sc eening o Acan hamoeba a Cen o Hospi ala de São João, a e ia y 101 oph halmologic cen e in Po o, Po ugal, be ween ma ch 2010 and augus 2017. 102 O he 127 suspec ed cases analyzed, hose ha we e posi i e and ollowed in ou 103 Oph halmology Co nea Depa men we e desc ibed. 104 Clinical iles o hese pa ien s we e consul ed and in o ma ion abou demog aphic da a, 105 isual acui y (VA), clinical p esen a ion symp oms, biomic oscopy indings, 106 he apeu ics, isual ou come and complica ions o he disease we e collec ed. VA was 107 eco ded by he Snellen cha and con e ed loga i hm o minimal angle o esolu ion 108 (logMAR) uni s o s a is ical analysis. 109 Diagnosis was conside ed ea ly i es ablished be o e he i s 15 days a e he onse o 110 he symp oms and la e i es ablished a e wa ds. I was de ined as bad isual p ognosis 111 a inal bes -co ec ed isual acui y (BCVA) ≥ 1 logMAR. 11 279 REFERENCES 280 1. Jiang C, Sun X, Wang Z, e al. Acan hamoeba ke a i is: clinical cha ac e is ics 281 and managemen . Ocul Su . 2015;13:164-168. 282 2. Anjos R, Vicen e A, Viei a L, e al. Que a i e po acan amoeba – Re isão de 6 283 casos clínicos. Cen o Hospi ala Lisboa Cen al. O almologia. 2013;37:283-290. 284 3. Lee MH, Abell RG, Mi a B, e al. Risk ac o s, demog aphics and clinical p o ile 285 o Acan hamoeba ke a i is in Melbou ne: an 18-yea e ospec i e s udy. B J 286 Oph halmol. 2017. 287 4. Ma in-Pe ez T, C iado-Fo nelio A, Ma inez J, e al. 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Oph halmology. 339 2014;121:1383-1388. 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 14 359 FIGURE LEGENDS 360 361 Figu e 1: Numbe o Acan hamoeba Ke a i is (AK) cases pe yea om 2010 o 2017. 362 Table 1: Pa ien s’ demog aphic and clinical cha ac e is ics (n=34). 363 Table 2: Compa ison be ween cases wi h bes -co ec ed isual acui y (BCVA) < 1 364 loga i hm o minimal angle o esolu ion (logMAR) – good p ognosis – and cases wi h 365 BCVA ≥ 1logMAR – poo isual ou come – in e ms o demog aphic and clinical 366 cha ac e is ics; VA: Visual Acui y. 367 Table 3: Compa ison be ween cases wi h BCVA < 1 logMAR – good p ognosis – and 368 cases wi h BCVA ≥ 1logMAR – poo isual ou come – in e ms o ea men and 369 complica ions; DALK: Deep An e io Lamela Ke a oplas y. 370 Figu e 2: AK- ela ed obse ed complica ions. 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 15 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 Numbe o cases 8 7 6 5 4 3 2 1 0 12 10 8 6 4 2 0 Numbe o cases 16 Clinical ea u es (n=14) (%) Female gende 18 (67,6) Age (yea s) 35,5 ± 13,4 La e ali y - Righ eye 34 (100) - Le eye 2 (6,0) - Bila e al 0 (0) Risk ac o s - Con ac lens wea 34 (100) - Exposu e o s agnan wa e 2 (6,0) - His o y o co neal auma ism 0 (0) Time om symp oms onse o diagnosis (days) 22 [1-150] Diagnosis - Ea ly (≤15 days) - La e (>15 days) 13 (40,6) 19 (59,4) Ini ial diagnosis - Acu e conjunc i i is 4 (12,5) - He pe ic ke a i is/ulce 14 (43,8) - Bac e ial ke a i is/ulce 9 (28,1) - Fungal ke a i is/ulce 3 (9,4) - Acan hamoeba ke a i is/ulce 2 (6,3) P ediagnosis opic co icoid 22 (64,7) 407 408 409 410 411 17 BCVA <1 (n=14) (%) BCVA ≥1 (n=17) (%) p Male gende 3 (21,4) 6 (35,3) 0,39 Age (yea s) 33 [19-43] 37 [23-66] 0,04 Time om symp oms onse o diagnosis (days) 14 [1-60] 28 [4-150] 0,01 Diagnosis - Ea ly - La e 10 (71,4) 4 (28,6) 3 (20) 12 (80) 0,005 Ini ial VA (logMAR) 0,5 [0,1-2,0] 1,3 [0,3-2,0] 0,02 Ini ial co icoid 10 (71,4) 10 (58,8%) 0,47 Biomic oscopy - Epi helial/subepi helial in il a e 1 (7,1) 1 (5,9) 0,89 - Punc a e ke a opa hy 6 (42,9) 4 (23,5) 0,25 - Pe ineu i is 1 (7,1) 0 (0) 0,26 - Epi helial de ec 2 (14,3) 7 (41,2) 0,10 - Pseudodend i ic de ec 5 (35,7) 2 (11,8) 0,11 - S omal in il a e 1 (7,1) 7 (41,2) 0,03 - Ring in il a e 1 (7,1) 6 (35,3) 0,06 - Ring ulce 2 (14,3) 4 (23,5) 0,52 - Hypopyon 0 (0) 2 (11,8) 0,19 - Scle i is 0 (0) 1 (5,9) 0,36 412 413 414 415 416 417 18 BCVA <1 (n=14) (%) BCVA≥1 (n=17) (%) p T ea men - Chlo hexidine 1 (8,3) 0 (0) - P opamidine 1 (8,3) 5 (29,4) 0,22 - Chlo hexidine+P opamidine 10 (83,3) 12 (70,6) Epi helial deb idemen 9 (64,3) 2 (11,8) 0,002 Ke a oplas y - Yes 3 (21,4) 7 (41,2) 0,24 - No 11 (78,6) 10 (58,8) Mo i e o ke a oplas y - Te apeu ic 2 (66,7) 5 (71,4) 0,88 - Op ic 1 (33,3) 2 (28,2) Type o ke a oplas y - Pene a ing 3 (100) 6 (85,7) 0,49 - DALK 0 (0) 11 (14,3) Complica ions 7 (50) 14 (82,4) 0,06 - Ca a ac 3 (21,4) 11 (64,7) 0,016 - Ocula hype ension 3 (21,4) 11 (64,7) 0,016 - Leukoma 4 (28,6) 1 (5,9) 0,09 - Vi i is 0 (0) 4 (23,5) 0,05 - Ph isis 0 (0) 2 (11,8) 0,19 - Ocula pe u a ion 0 (0) 6 (35,3) 0,01 - Enuclea ion 0 (0) 8 (47,1) 0,003 418 419 420 421 422 19 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 Ca a ac Vi i is Ph isis Ocula hype ension Cen al/Pa acen al leukoma Pe u a ion Enuclea ion 6,1% 12,1% 15,3% 18,2% 24,2% 42,4% 42,4% Co nea Online Submission and Re iew Sys em SCOPE Co nea is a pee e iewed, scien i ic jou nal o he submission o o iginal manusc ip s desc ibing clinical obse a ions, clinical ials, basic in es iga ion wi h clinical applicabili y, and unique and impo an case epo s ela ed o diseases o and medical and su gical ea men o he co nea and ex e nal eye. 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Rep in s a e no mally shipped 6 o 8 weeks a e publica ion o he issue in which he i em appea s. Con ac he Rep in Depa men , Lippinco Williams & Wilkins, 351 W. Camden S ee , Bal imo e, MD 21201; Fax: (410) 528-4434; E-mail: ep in s@wol e skluwe .com wi h any ques ions. Publishe 's con ac E-mail co ec ed page p oo s, ep in o de o m, and any o he ela ed ma e ials o Aidan De ico, E-mail: Aidan.De ico@wol e skluwe .com Eye pain Pho ophobia Fo eign body sensa ion Eye edness Blu ed ision Tea ing 12% 3% 15% 38% 68% 100% APPENDIX Figu e 3: Ini ial symp oms o pa ien s Figu e 4: Ini ial signs in biomic oscopy Epi helial/subepi helial in il a e Punc a e ke a opa hy Pe ineu i is Epi helial de ec Pseudodend i ic de ec S omal in il a e Ring in il a e Ring ulce Hypopyon Scle i is 3% 6% 3% 12% 21% 24% 24% 29% 29% 32%