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

2017/2018 Daniela Filipa Silva Cerqueira Clinical profile of patients with Acanthamoeba keratitis – what are the por prognosis indicators? março, 2018 Daniela Filipa Silva Cerqueira Clinical profile of patients with Acanthamoeba keratitis – what are the poor prognosis indicators? Mestrado Integrado em Medicina Área: Oftalmologia Tipologia: Dissertação Trabalho efetuado sob a Orientação de: Doutor João Pinheiro-Costa E sob a Coorientação de: Dra. Carolina Madeira Trabalho organizado de acordo com as normas da revista: Cornea março, 2018 DEDICATÓRIA Terminada a realização desta Tese de Mestrado, não faria sentido deixar de agradecer ao meu Orientador, Doutor João Pinheiro-Costa, e à minha Co-orientadora, Doutora Carolina Madeira, por toda a disponibilidade e atenção prestada no decorrer da sua execução. Um agradecimento especial à Joana Ferraz Brandão, que procedeu à revisão linguística do texto. Por último, mas não menos importante, um enorme agradecimento à minha família 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 Carolina Madeira, MD*1 5 Daniela Cerqueira, 2 6 Luís Torrão, MD, 1 7 Raúl Moreira, MD, 1 8 Manuel Falcão, MD, PhD, 1,3 9 Fernando Falcão-Reis, MD, PhD, 1,3 10 João Pinheiro-Costa, MD, 1,4 11 12 *1Corresponding author: Department of Ophthalmology, Centro Hospitalar São João, 13 Porto, Portugal. Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. 14 [email protected]; +351917860495. 15 1. Department of Ophthalmology, Centro Hospitalar São João, Porto, Portugal 16 2. Faculty of Medicine, University of Porto, Portugal 17 3. Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 18 Portugal 19 4. Department of Biomedicine, Faculty of Medicine, University of Porto, Portugal 20 21 Conflict of interest: None declared. 22 Keywords: Acanthamoeba, keratitis, risk factors, prognosis factors, polymerase chain 23 reaction 24 25 Financial Disclosure: The authors declare that they received no funding to conduct 26 this work. 27 2 28 ABSTRACT 29 Purpose: To describe the risk factors, established treatment, visual outcome and to 30 establish poor prognosis predictors in patients with Acanthamoeba Keratitis (AK). 31 Methods: A retrospective analysis of 34 cases of AK diagnosed by polymerase chain 32 reaction (PCR) between march 2010 and august 2017 followed at Cornea Department 33 of Centro Hospitalar de São João. Clinical processes of these patients were reviewed, 34 and it has been collected data about demographics, visual acuity (VA), biomicroscopy, 35 therapeutics, visual outcome and complications of the disease. 36 Diagnosis was considered early if established before the first 15 days after the onset of 37 the symptoms and late if established afterwards. It was defined as poor visual outcome 38 a final best-corrected visual acuity (BCVA) ≥ 1 logarithm of minimal angle of resolution 39 (logMAR). 40 Results: A total of 34 eyes from 29 patients, all contact lens (CL) wearers, were 41 diagnosed with AK. Concerning the BCVA index, patients with poor visual outcome 42 were diagnosed later than those who had better results (28 [4-150] vs 14 [1-60] days; 43 p=0.01). The worst visual outcome was associated with an upper median age (37 [2344 66] vs 33 [19-43] years; p=0.04), poorer initial VA (1,3 [0.3-2.0] vs 0.5 [0.1-2.0] 45 logMAR; p=0.02) and stromal infiltrate (41.2 vs 7.1%; p=0.03) in biomicroscopy. About 46 35% patients underwent debridement and 29% keratoplasty. Those who underwent 47 cirurgical debridment had a better visual outcome (p=0.002). Complications rate was 48 higher in patients with worse visual outcome (82.4% vs 50.0%; p=0.06). 49 Conclusion: Patients with worse final VA had a later diagnosis with worse initial VA 50 and more advanced corneal disease in biomicroscopy at admission. 51 Diagnosis and treatment of patients with AK is still a challenge, it requires a high level 52 of surmise from eye care' providers to establish an early diagnosis which is crucial for a 53 good visual outcome. 54 55 3 56 INTRODUCTION 57 Acanthamoeba Keratitis (AK) is recognized as an increasing cause of infectious 58 keratitis1, 2, whose etiology includes several species of Acanthamoeba genus3, 4. These 59 free-living protozoa can be found in water, soil and water-air interface2, 5, 6, with two 60 existing forms: trophozoites, the infectious form, and cysts, responsible for the disease 61 resistance.2 62 With the use of contact lenses (CL) as the main risk factor5, 7, 8, AK may also be 63 associated with corneal trauma.5, 7 64 The initial symptomatology is often non-specific, and may include ocular pain 65 associated with photophobia, foreign body sensation and tearing.6, 8 In addition, more 66 characteristic signs, such as radial neuritis, aren’t always present.1, 7 In the early 67 stages, is frequent the formation of a dendritic pattern, resulting from the organization 68 of linear intraepithelial infiltrates, which is easily confused by signs of Herpes simplex 69 virus8, and in later stages, there are characteristic ring infiltrates, which are only 70 present in about 50% of patients.6 All these characteristics can make AK difficult to 71 diagnose, which leads to a delayed onset of the treatment and to a worse prognosis. 72 The diagnosis of AK implies the identification of the etiological agent in the corneal 73 scrapings and biopsy specimens8, by cultural exam, that remains the gold-standard 74 diagnostic examination.5 More recently, new diagnostic tools have emerged, such as 75 confocal microscopy, that can be perfomed in vivo5, however it is expensive and 76 requires an experienced operator.3 The polymerase chain reaction (PCR) testing is 77 also a good alternative diagnostic exam, since it has a high sensitivity and is faster 78 than the cultural exam to identify the agent’s DNA and it is operator independent.9 79 The AK treatment is challenging. An incomplete understanding of the pathophysiology 80 of the disease10 and, mainly, the treatment resistance caused by cysts6 are recognized 81 as treatment obstacles. Moreover, the use of steroids seems to degrade the prognosis 82 of the disease.6, 7 There is no specific treatment described for AK6, 11, however there 83 are some therapy regimens that can be used as the biguanides (they act at the 4 84 membrane and include polyhexamethylene biguanide and chlorhexidine) or the 85 diamines (inhibitors of DNA synthesis, include propamidine, hexamidine and 86 pentamidine).2, 11 Although there weren’t significant differences in the efficacy of both 87 drugs, biguanides had a higher effectiveness against cystic form using lower dosage, 88 so these are generally prefered. In more severe cases or when medical therapy is not 89 sufficient, debridement, penetrating keratoplasty or even amniotic membrane 90 transplantation may be used.2 91 Treatment is time consuming and complicated and a close follow-up is required to 92 assess the appearance of complications, ranging from ulcers or even corneal 93 perforation to blindness and enucleation.8 94 The present dissertation aims to describe the risk factors, established treatment, visual 95 outcome and to establish poor prognosis predictors in patients with positive PCR for 96 Acanthamoeba followed at the Cornea Department on Centro Hospitalar de São João. 97 98 METHODS 99 We performed a retrospective analysis of all suspected cases of AK that undergone 100 PCR screening for Acanthamoeba at Centro Hospitalar de São João, a tertiary 101 ophthalmologic centre in Porto, Portugal, between march 2010 and august 2017. 102 Of the 127 suspected cases analyzed, those that were positive and followed in our 103 Ophthalmology Cornea Department were described. 104 Clinical files of these patients were consulted and information about demographic data, 105 visual acuity (VA), clinical presentation symptoms, biomicroscopy findings, 106 therapeutics, visual outcome and complications of the disease were collected. VA was 107 recorded by the Snellen chart and converted logarithm of minimal angle of resolution 108 (logMAR) units for statistical analysis. 109 Diagnosis was considered early if established before the first 15 days after the onset of 110 the symptoms and late if established afterwards. It was defined as bad visual prognosis 111 a final best-corrected visual acuity (BCVA) ≥ 1 logMAR. 11 279 REFERENCES 280 1. Jiang C, Sun X, Wang Z, et al. Acanthamoeba keratitis: clinical characteristics 281 and management. Ocul Surf. 2015;13:164-168. 282 2. Anjos R, Vicente A, Vieira L, et al. Queratite por acantamoeba – Revisão de 6 283 casos clínicos. Centro Hospitalar Lisboa Central. Oftalmologia. 2013;37:283-290. 284 3. Lee MH, Abell RG, Mitra B, et al. Risk factors, demographics and clinical profile 285 of Acanthamoeba keratitis in Melbourne: an 18-year retrospective study. Br J 286 Ophthalmol. 2017. 287 4. Martin-Perez T, Criado-Fornelio A, Martinez J, et al. 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Ophthalmology. 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 Figure 1: Number of Acanthamoeba Keratitis (AK) cases per year from 2010 to 2017. 362 Table 1: Patients’ demographic and clinical characteristics (n=34). 363 Table 2: Comparison between cases with best-corrected visual acuity (BCVA) < 1 364 logarithm of minimal angle of resolution (logMAR) – good prognosis – and cases with 365 BCVA ≥ 1logMAR – poor visual outcome – in terms of demographic and clinical 366 characteristics; VA: Visual Acuity. 367 Table 3: Comparison between cases with BCVA < 1 logMAR – good prognosis – and 368 cases with BCVA ≥ 1logMAR – poor visual outcome – in terms of treatment and 369 complications; DALK: Deep Anterior Lamelar Keratoplasty. 370 Figure 2: AK-related observed complications. 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 Number of cases 8 7 6 5 4 3 2 1 0 12 10 8 6 4 2 0 Number of cases 16 Clinical features (n=14) (%) Female gender 18 (67,6) Age (years) 35,5 ± 13,4 Laterality - Right eye 34 (100) - Left eye 2 (6,0) - Bilateral 0 (0) Risk factors - Contact lens wear 34 (100) - Exposure to stagnant water 2 (6,0) - History of corneal traumatism 0 (0) Time from symptoms onset to diagnosis (days) 22 [1-150] Diagnosis - Early (≤15 days) - Late (>15 days) 13 (40,6) 19 (59,4) Initial diagnosis - Acute conjunctivitis 4 (12,5) - Herpetic keratitis/ulcer 14 (43,8) - Bacterial keratitis/ulcer 9 (28,1) - Fungal keratitis/ulcer 3 (9,4) - Acanthamoeba keratitis/ulcer 2 (6,3) Prediagnosis topic corticoid 22 (64,7) 407 408 409 410 411 17 BCVA <1 (n=14) (%) BCVA ≥1 (n=17) (%) p Male gender 3 (21,4) 6 (35,3) 0,39 Age (years) 33 [19-43] 37 [23-66] 0,04 Time from symptoms onset to diagnosis (days) 14 [1-60] 28 [4-150] 0,01 Diagnosis - Early - Late 10 (71,4) 4 (28,6) 3 (20) 12 (80) 0,005 Initial VA (logMAR) 0,5 [0,1-2,0] 1,3 [0,3-2,0] 0,02 Initial corticoid 10 (71,4) 10 (58,8%) 0,47 Biomicroscopy - Epithelial/subepithelial infiltrate 1 (7,1) 1 (5,9) 0,89 - Punctate keratopathy 6 (42,9) 4 (23,5) 0,25 - Perineuritis 1 (7,1) 0 (0) 0,26 - Epithelial defect 2 (14,3) 7 (41,2) 0,10 - Pseudodendritic defect 5 (35,7) 2 (11,8) 0,11 - Stromal infiltrate 1 (7,1) 7 (41,2) 0,03 - Ring infiltrate 1 (7,1) 6 (35,3) 0,06 - Ring ulcer 2 (14,3) 4 (23,5) 0,52 - Hypopyon 0 (0) 2 (11,8) 0,19 - Scleritis 0 (0) 1 (5,9) 0,36 412 413 414 415 416 417 18 BCVA <1 (n=14) (%) BCVA≥1 (n=17) (%) p Treatment - Chlorhexidine 1 (8,3) 0 (0) - Propamidine 1 (8,3) 5 (29,4) 0,22 - Chlorhexidine+Propamidine 10 (83,3) 12 (70,6) Epithelial debridement 9 (64,3) 2 (11,8) 0,002 Keratoplasty - Yes 3 (21,4) 7 (41,2) 0,24 - No 11 (78,6) 10 (58,8) Motive of keratoplasty - Terapeutic 2 (66,7) 5 (71,4) 0,88 - Optic 1 (33,3) 2 (28,2) Type of keratoplasty - Penetrating 3 (100) 6 (85,7) 0,49 - DALK 0 (0) 11 (14,3) Complications 7 (50) 14 (82,4) 0,06 - Cataract 3 (21,4) 11 (64,7) 0,016 - Ocular hypertension 3 (21,4) 11 (64,7) 0,016 - Leukoma 4 (28,6) 1 (5,9) 0,09 - Vitritis 0 (0) 4 (23,5) 0,05 - Phtisis 0 (0) 2 (11,8) 0,19 - Ocular perfuration 0 (0) 6 (35,3) 0,01 - Enucleation 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 Cataract Vitritis Phtisis Ocular hypertension Central/Paracentral leukoma Perfuration Enucleation 6,1% 12,1% 15,3% 18,2% 24,2% 42,4% 42,4% Cornea Online Submission and Review System SCOPE Cornea is a peer reviewed, scientific journal for the submission of original manuscripts describing clinical observations, clinical trials, basic investigation with clinical applicability, and unique and important case reports related to diseases of and medical and surgical treatment of the cornea and external eye. 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Publisher's contact E-mail corrected page proofs, reprint order form, and any other related materials to Aidan Derrico, E-mail: [email protected] Eye pain Photophobia Foreign body sensation Eye redness Blurred vision Tearing 12% 3% 15% 38% 68% 100% APPENDIX Figure 3: Initial symptoms of patients Figure 4: Initial signs in biomicroscopy Epithelial/subepithelial infiltrate Punctate keratopathy Perineuritis Epithelial defect Pseudodendritic defect Stromal infiltrate Ring infiltrate Ring ulcer Hypopyon Scleritis 3% 6% 3% 12% 21% 24% 24% 29% 29% 32%