Acanthamoeba Keratitis: What is the Best Time for Keratoplasty in Patients with Resistance to Conservative Therapy?

Abstract

Acanthamoebic keratitis (AK) is a sight-threatening infectious keratitis caused by Acanthamoeba. Timely and appropriate conservative treatment of AK can lead to a cure of the keratitis with good visual acuity, without the need for keratoplasty in the further course of the disease. In treatment-resistant cases, keratoplasty after intensive anti-amoebic therapy (AAT), so-called “low-load keratoplasty”, appears to offer a better overall prognosis and earlier visual and psychological rehabilitation than actively delayed keratoplasty (optical/therapeutic). Further studies directly comparing early and delayed keratoplasty are needed to even better determine the optimal timing of corneal transplantation in AK.

Keywords

Acanthamoeba keratitis - low-load keratoplasty - conservative therapy - optic keratoplasty - therapeutic keratoplasty

Publikationsverlauf

Eingereicht: 05. Dezember 2024

Angenommen: 11. März 2025

Artikel online veröffentlicht:
16. Juni 2025

• References/Literatur

• 1 Lorenzo-Morales J, Khan NA, Walochnik J. An update on Acanthamoeba keratitis: Diagnosis, pathogenesis and treatment. Parasite 2015; 22: 10
• 2 Nagington J, Watson PG, Playfair TJ. et al. Amoebic infection of the eye. Lancet 1974; 2: 1537-1540
• 3 Ting DSJ, Ho CS, Deshmukh R. et al. Infectious keratitis: An update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance. Eye (Lond) 2021; 35: 1084-1101
• 4 Nielsen SE, Ivarsen A, Hjortdal J. Increasing incidence of Acanthamoeba keratitis in a large tertiary ophthalmology department from year 1994 to 2018. Acta Ophthalmol 2020; 98: 445-448
• 5 Seal DV, Beattie TK, Tomlinson A. et al. Acanthamoeba keratitis. Br J Ophthalmol 2003; 87: 516
• 6 Roth M, Balasiu A, Daas L. et al. Impact of implementation of polymerase chain reaction on diagnosis, treatment, and clinical course of Acanthamoeba keratitis. Graefes Arch Clin Exp Ophthalmol 2023; 261: 1951-1959
• 7 Claerhout I, Goegebuer A, Van Den Broecke C. et al. Delay in diagnosis and outcome of Acanthamoeba keratitis. Graefes Arch Clin Exp Ophthalmol 2004; 242: 648-653
• 8 List W, Glatz W, Riedl R. et al. Evaluation of Acanthamoeba keratitis cases in a tertiary medical care centre over 21 years. Sci Rep 2021; 11: 1036
• 9 Sarink MJ, Koelewijn R, Stelma F. et al. An international external quality assessment scheme to assess the diagnostic performance of polymerase chain reaction detection of Acanthamoeba keratitis. Cornea 2023; 42: 1027-1033
• 10 Vilares-Morgado R, Ferreira AM, Marques-Couto P. et al. Clinical outcomes and prognostic factors in Acanthamoeba keratitis. Cont Lens Anterior Eye 2024; 47: 102119
• 11 Shimmura-Tomita M, Takano H, Kinoshita N. et al. Risk factors and clinical signs of severe Acanthamoeba keratitis. Clin Ophthalmol 2018; 12: 2567-2573
• 12 Carnt N, Robaei D, Minassian DC. et al. Acanthamoeba keratitis in 194 patients: risk factors for bad outcomes and severe inflammatory complications. Br J Ophthalmol 2018; 102: 1431-1435
• 13 Alkharashi M, Lindsley K, Law HA. et al. Medical interventions for acanthamoeba keratitis. Cochrane Database Syst Rev 2015; (2015) CD010792
• 14 Szentmáry N, Daas L, Shi L. et al. Acanthamoeba keratitis – Clinical signs, differential diagnosis and treatment. J Curr Ophthalmol 2019; 31: 16-23
• 15 Kuennen RA, Smith RH, Mauger TF. et al. Enucleation following treatment with intravenous pentamidine for Acanthamoeba sclerokeratitis. Clin Ophthalmol 2010; 4: 1145
• 16 Shi L, Hager T, Fries FN. et al. Reactive uveitis, retinal vasculitis and scleritis as ocular end-stage of Acanthamoeba keratitis: a histological study. Int J Ophthalmol 2019; 12: 1966-1971
• 17 Awwad ST, Heilman M, Hogan RN. et al. Severe reactive ischemic posterior segment inflammation in Acanthamoeba keratitis: a new potentially blinding syndrome. Ophthalmology 2007; 114: 313-320
• 18 Daas L, Szentmáry N, Eppig T. et al. The German Acanthamoeba keratitis register: Initial results of a multicenter study. Ophthalmologe 2015; 112: 752-763
• 19 Wright P, Warhurst D, Jones BR. Acanthamoeba keratitis successfully treated medically. Br J Ophthalmol 1985; 69: 778-782
• 20 Awwad ST, Petroll WM, McCulley JP. et al. Updates in Acanthamoeba keratitis. Eye Contact Lens 2007; 33: 1-8
• 21 Kaufman AR, Tu EY. Advances in the management of Acanthamoeba keratitis: A review of the literature and synthesized algorithmic approach. Ocul Surf 2022; 25: 26-36
• 22 Dart JKG, Papa V, Rama P. et al. The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08 % (polihexanide) and placebo versus PHMB 0.02 % and propamidine 0.1. Ophthalmology 2024; 131: 277-287
• 23 Fanselow N, Sirajuddin N, Yin XT. et al. Acanthamoeba keratitis, pathology, diagnosis and treatment. Pathogens 2021; 10: 1-11
• 24 Shing B, Balen M, McKerrow JH. et al. Acanthamoeba keratitis: An update on amebicidal and cysticidal drug screening methodologies and potential treatment with azole drugs. Expert Rev Anti Infect Ther 2021; 19: 1427-1441
• 25 Abu Dail Y, Flockerzi E, Munteanu C. et al. Rethinking keratoplasty for patients with Acanthamoeba keratitis: Early “low load keratoplasty” in contrast to late optical and therapeutic keratoplasty. Microorganisms 2024; 12: 1801
• 26 Heaselgrave W, Hamad A, Coles S. et al. In vitro evaluation of the inhibitory effect of topical ophthalmic agents on Acanthamoeba viability. Transl Vis Sci Technol 2019; 8: 17
• 27 Bagga B, Sharma S, Gour RPS. et al. A randomized masked pilot clinical trial to compare the efficacy of topical 1 % voriconazole ophthalmic solution as monotherapy with combination therapy of topical 0.02 % polyhexamethylene biguanide and 0.02 % chlorhexidine in the treatment of Acanthamoeba keratitis. Eye (Lond) 2021; 35: 1326-1333
• 28 Abu Dail Y, Daas L, Flockerzi FA. et al. [Bilateral chronic contact lens-associated keratitis]. Ophthalmologie 2024; 121: 410-414
• 29 Robaei D, Carnt N, Minassian DC. et al. The impact of topical corticosteroid use before diagnosis on the outcome of Acanthamoeba keratitis. Ophthalmology 2014; 121: 1383-1388
• 30 Scruggs BA, Quist TS, Zimmerman MB. et al. Risk factors, management, and outcomes of Acanthamoeba keratitis: A retrospective analysis of 110 cases. Am J Ophthalmol Case Rep 2022; 25: 101372
• 31 Robaei D, Carnt N, Minassian DC. et al. Therapeutic and optical keratoplasty in the management of Acanthamoeba keratitis: Risk factors, outcomes, and summary of the literature. Ophthalmology 2015; 122: 17-24
• 32 Lim N, Goh D, Bunce C. et al. Comparison of polyhexamethylene biguanide and chlorhexidine as monotherapy agents in the treatment of Acanthamoeba keratitis. Am J Ophthalmol 2008; 145: 130-135
• 33 Tu EY, Joslin CE, Sugar J. et al. Prognostic factors affecting visual outcome in Acanthamoeba keratitis. Ophthalmology 2008; 115: 1998-2003
• 34 Pérez-Samonja JJ, Kilvington S, Hughes R. et al. Persistently culture positive acanthamoeba keratitis: In vivo resistance and in vitro sensitivity. Ophthalmology 2003; 110: 1593-1600
• 35 Shi L, Muthukumar V, Stachon T. et al. The effect of anti-amoebic agents and Ce6-PDT on Acanthamoeba castellanii trophozoites and cysts, in vitro. Transl Vis Sci Technol 2020; 9: 29
• 36 Vontobel S, Abad-Villar EM, Kaufmann C. et al. Corneal penetration of polyhexamethylene biguanide and chlorhexidine digluconate. J Clin Exp Ophthalmol 2015; 6: 1000430
• 37 Hamburg A, De Jonckheere JF. Amoebic keratitis. Ophthalmologica 1980; 181: 74-80
• 38 Hirst LW, Green WR, Merz W. et al. Management of Acanthamoeba keratitis: a case report and review of the literature. Ophthalmology 1984; 91: 1105-1111
• 39 Awwad ST, Parmar DN, Heilman M. et al. Results of penetrating keratoplasty for visual rehabilitation after Acanthamoeba keratitis. Am J Ophthalmol 2005; 140: 1080-1084
• 40 Bacon AS, Frazer DG, Dart JKG. et al. A review of 72 consecutive cases of Acanthamoeba keratitis, 1984–1992. Eye (Lond) 1993; 7: 719-725
• 41 Kitzmann AS, Goins KM, Sutphin JE. et al. Keratoplasty for treatment of Acanthamoeba keratitis. Ophthalmology 2009; 116: 864-869
• 42 Alfaro Rangel R, Szentmáry N, Lepper S. et al. Large-diameter penetrating keratoplasties are mostly due to very severe infectious keratitis and cannot always prevent secondary enucleation. Klin Monbl Augenheilkd 2022; 239: 1361-1368
• 43 Seitz B, Langenbucher A, Naumann GOH. [The penetrating keratoplasty. A 100-year success story]. Ophthalmologe 2005; 102: 1128-1139
• 44 Papa V, van der Meulen I, Rottey S. et al. Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers. Br J Ophthalmol 2022; 106: 190-196
• 45 Zhang T, Xie L, Dong Y. et al. Therapeutic keratoplasty for severe Acanthamoeba keratitis: Risk factors, clinical features, and outcomes of postoperative recurrence. Graefes Arch Clin Exp Ophthalmol 2023; 261: 1299-1309
• 46 Kashiwabuchi RT, De Freitas D, Alvarenga LS. et al. Corneal graft survival after therapeutic keratoplasty for Acanthamoeba keratitis. Acta Ophthalmol 2008; 86: 666-669