Navigating the Challenges of Acanthamoeba Keratitis: Current Trends and Future Directions
Abstract
:1. Introduction
2. Diagnosis of Acanthamoeba
2.1. Classification
2.2. Pathogenesis
2.3. Clinical Symptoms and Signs
2.4. Current Techniques
3. Management
3.1. Medical Treatment
3.2. Use of Corticosteroids and NSAIDs
3.3. Surgical Options
4. Future Directions
4.1. Use of Artificial Intelligence in AK Diagnosis
4.2. Standardized Treatment Protocols
4.3. Cross-Linking
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Castellani, A. An amoeba found in culture of yeast: Preliminary note. J. Trop. Med. Hyg. 1930, 33, 160. [Google Scholar]
- Visvesvara, G.S.; Stehr-Green, J.K. Epidemiology of free-living ameba infections. J. Protozool. 1990, 37, 25S–33S. [Google Scholar] [CrossRef] [PubMed]
- Sinclair, J.L.; McClellan, J.F.; Coleman, D.C. Nitrogen Mineralization by Acanthamoeba polyphaga in Grazed Pseudomonas paucimobilis Populations. Appl. Environ. Microbiol. 1981, 4, 667–671. [Google Scholar] [CrossRef]
- Kilvington, S.; Gray, T.; Dart, J.; Morlet, N.; Beeching, J.R.; Frazer, D.G.; Matheson, M. Acanthamoeba keratitis: The role of domestic tap water contamination in the United Kingdom. Investig. Ophthalmol. Vis. Sci. 2004, 45, 165–169. [Google Scholar] [CrossRef]
- Rayamajhee, B.; Willcox, M.D.P.; Henriquez, F.L.; Petsoglou, C.; Subedi, D.; Carnt, N. Acanthamoeba, an environmental phagocyte enhancing survival and transmission of human pathogens. Trends Parasitol. 2022, 38, 975–990. [Google Scholar] [CrossRef] [PubMed]
- Radford, C.F.; Minassian, D.C.; Dart, J.K. Acanthamoeba keratitis in England and Wales: Incidence, outcome, and risk factors. Br. J. Ophthalmol. 2002, 86, 536–542. [Google Scholar] [CrossRef]
- Aiello, F.; Gallo Afflitto, G.; Ceccarelli, F.; Turco, M.V.; Han, Y.; Amescua, G.; Dart, J.K.; Nucci, C. Perspectives on the Incidence of Acanthamoeba keratitis: A Systematic Review and Meta-Analysis. Ophthalmology 2025, 132, 206–218. [Google Scholar] [CrossRef] [PubMed]
- Pussard, M.; Pons, R. Morphology of the cyst wall and taxonomy of the genus Acanthamoeba. Protozoa Amoebida 1977, 8, 557–598. [Google Scholar]
- Derda, M.; Wojtkowiak-Giera, A.; Kolasa-Wołosiuk, A.; Kosik-Bogacka, D.; Hadaś, E.; Jagodziński, P.P.; Wandurska-Nowak, E. Acanthamoeba infection in lungs of mice expressed by toll-like receptors (TLR2 and TLR4). Exp. Parasitol. 2016, 165, 30–34. [Google Scholar] [CrossRef]
- Fuerst, P.A.; Booton, G.C.; Crary, M. Phylogenetic analysis and the evolution of the 18S rRNA gene typing system of Acanthamoeba. J. Eukaryot. Microbiol. 2015, 62, 69–84. [Google Scholar] [CrossRef]
- Lorenzo-Morales, J.; Khan, N.A.; Walochnik, J. An update on Acanthamoeba keratitis: Diagnosis, pathogenesis and treatment. Parasite. 2015, 22, 10. [Google Scholar] [CrossRef] [PubMed]
- Adl, S.M.; Simpson, A.G.; Farmer, M.A.; Andersen, R.A.; Anderson, O.R.; Barta, J.R.; Bowser, S.S.; Brugerolle, G.; Fensome, R.A.; Fredericq, S.; et al. The new higher level classification of eukaryotes with emphasis on the taxonomy of protists. J. Eukaryot. Microbiol. 2005, 52, 399–451. [Google Scholar] [CrossRef] [PubMed]
- Khan, N.A. Acanthamoeba: Biology and increasing importance in human health. FEMS Microbiol. Rev. 2006, 30, 564–595. [Google Scholar] [CrossRef]
- Schroeder, J.M.; Booton, G.C.; Hay, J.; Niszl, I.A.; Seal, D.V.; Markus, M.B.; Fuerst, P.A.; Byers, T.J. Use of subgenic 18S ribosomal DNA PCR and sequencing for genus and genotype identification of acanthamoebae from humans with keratitis and from sewage sludge. J. Clin. Microbiol. 2001, 39, 1903–1911. [Google Scholar] [CrossRef]
- Stothard, D.R.; Schroeder-Diedrich, J.M.; Awwad, M.H.; Gast, R.J.; Ledee, D.R.; Rodriguez-Zaragoza, S.; Dean, C.L.; Fuerst, P.A.; Byers, T.J. The evolutionary history of the genus Acanthamoeba and the identification of eight new 18S rRNA gene sequence types. J. Eukaryot. Microbiol. 1998, 45, 45–54. [Google Scholar] [CrossRef]
- Panjwani, N. Pathogenesis of Acanthamoeba keratitis. Ocul. Surf. 2010, 8, 70–79. [Google Scholar] [CrossRef] [PubMed]
- Niederkorn, J.Y. The biology of Acanthamoeba keratitis. Exp. Eye Res. 2021, 202, 108365. [Google Scholar] [CrossRef]
- Iovieno, A.; Ledee, D.R.; Miller, D.; Alfonso, E.C. Detection of bacterial endosymbionts in clinical acanthamoeba isolates. Ophthalmology 2010, 117, 445–452. [Google Scholar] [CrossRef]
- Greub, G.; Raoult, D. Microorganisms resistant to free-living amoebae. Clin. Microbiol. Rev. 2004, 17, 413–433. [Google Scholar] [CrossRef]
- Nunes, T.E.; Brazil, N.T.; Fuentefria, A.M.; Rott, M.B. Acanthamoeba and Fusarium interactions: A possible problem in keratitis. Acta Trop. 2016, 157, 102–107. [Google Scholar] [CrossRef]
- Steenbergen, J.N.; Nosanchuk, J.D.; Malliaris, S.D.; Casadevall, A. Interaction of Blastomyces dermatitidis, Sporothrix schenckii, and Histoplasma capsulatum with Acanthamoeba castellanii. Infect. Immun. 2004, 72, 3478–3488. [Google Scholar] [CrossRef] [PubMed]
- Toney, D.M.; Marciano-Cabral, F. Resistance of Acanthamoeba species to complement lysis. J. Parasitol. 1998, 84, 338–344. [Google Scholar] [CrossRef]
- Alizadeh, H.; Apte, S.; El-Agha, M.S.; Li, L.; Hurt, M.; Howard, K.; Cavanagh, H.D.; McCulley, J.P.; Niederkorn, J.Y. Tear IgA and serum IgG antibodies against Acanthamoeba in patients with Acanthamoeba keratitis. Cornea 2001, 20, 622–627. [Google Scholar] [CrossRef] [PubMed]
- Heffler, K.F.; Eckhardt, T.J.; Reboli, A.C.; Stieritz, D. Acanthamoeba endophthalmitis in acquired immunodeficiency syndrome. Am. J. Ophthalmol. 1996, 122, 584–586. [Google Scholar] [CrossRef]
- Jones, D.B.; Visvesvara, G.S.; Robinson, N.M. Acanthamoeba polyphaga keratitis and Acenthamoeba uveitis associated with fatal meningoencephalitis. Trans. Ophthalmol. Soc. U K 1975, 95, 221–232. [Google Scholar]
- Moshari, A.; McLean, I.W.; Dodds, M.T.; Damiano, R.E.; McEvoy, P.L. Chorioretinitis after keratitis caused by Acanthamoeba: Case report and review of the literature. Ophthalmology 2001, 108, 2232–2236. [Google Scholar] [CrossRef] [PubMed]
- Daas, L.; Szentmáry, N.; Eppig, T.; Langenbucher, A.; Hasenfus, A.; Roth, M.; Saeger, M.; Nölle, B.; Lippmann, B.; Böhringer, D.; et al. Das Deutsche Akanthamöbenkeratitis-Register: Erste Ergebnisse einer multizentrischen Erhebung [The German Acanthamoeba keratitis register: Initial results of a multicenter study]. Ophthalmologe 2015, 112, 752–763. [Google Scholar] [CrossRef]
- Illingworth, C.D.; Cook, S.D.; Karabatsas, C.H.; Easty, D.L. Acanthamoeba keratitis: Risk factors and outcome. Br. J. Ophthalmol. 1995, 79, 1078–1082. [Google Scholar] [CrossRef]
- Tabin, G.; Taylor, H.; Snibson, G.; Murchison, A.; Gushchin, A.; Rogers, S. Atypical presentation of Acanthamoeba keratitis. Cornea 2001, 7, 757–759. [Google Scholar] [CrossRef]
- Dart, J.K.; Saw, V.P.; Kilvington, S. Acanthamoeba keratitis: Diagnosis and treatment update 2009. Am. J. Ophthalmol. 2009, 148, 487–499. [Google Scholar] [CrossRef]
- Alkharashi, M.; Lindsley, K.; Law, H.A.; Sikder, S. Medical interventions for Acanthamoeba keratitis. Cochrane Database Syst. Rev. 2015, 2015, CD010792. [Google Scholar] [CrossRef] [PubMed]
- Wilhelmus, K.R.; Jones, D.B.; Matoba, A.Y.; Hamill, M.B.; Pflugfelder, S.C.; Weikert, M.P. Bilateral Acanthamoeba keratitis. Am. J. Ophthalmol. 2008, 145, 193–197. [Google Scholar] [CrossRef] [PubMed]
- Claerhout, I.; Goegebuer, A.; Van Den Broecke, C.; Kestelyn, P. Delay in diagnosis and outcome of Acanthamoeba keratitis. Graefes Arch. Clin. Exp. Ophthalmol. 2004, 242, 648–653. [Google Scholar] [CrossRef]
- Awwad, S.T.; Petroll, W.M.; McCulley, J.P.; Cavanagh, H.D. Updates in Acanthamoeba keratitis. Eye Contact Lens. 2007, 33, 1–8. [Google Scholar] [CrossRef]
- Goodall, K.; Brahma, A.; Ridgway, A. Acanthamoeba keratitis: Masquerading as adenoviral keratitis. Eye 1996, 10, 643–644. [Google Scholar] [CrossRef] [PubMed]
- Lorenzo-Morales, J.; Martín-Navarro, C.M.; López-Arencibia, A.; Arnalich-Montiel, F.; Piñero, J.E.; Valladares, B. Acanthamoeba keratitis: An emerging disease gathering importance worldwide? Trends Parasitol. 2013, 29, 181–187. [Google Scholar] [CrossRef]
- Tu, E.Y.; Joslin, C.E.; Sugar, J.; Shoff, M.E.; Booton, G.C. Prognostic factors affecting visual outcome in Acanthamoeba keratitis. Ophthalmology 2008, 115, 1998–2003. [Google Scholar] [CrossRef]
- Papathanassiou, M.; Gartry, D. Sterile corneal ulcer with ring infiltrate and hypopyon after recurrent erosions. Eye 2007, 21, 124–126. [Google Scholar] [CrossRef]
- Thomas, K.E.; Purcell, T.; Tanzer, D.J.; Schanzlin, D.J. Delayed diagnosis of microsporidial stromal keratitis: Unusual Wessely ring presentation and partial treatment with medications against Acanthamoeba. BMJ Case Rep. 2011, 201, bcr0820103233. [Google Scholar] [CrossRef]
- Kelley, P.S.; Dossey, A.P.; Patel, D.; Whitson, J.T.; Hogan, R.N.; Cavanagh, H.D. Secondary glaucoma associated with advanced Acanthamoeba keratitis. Eye Contact Lens. 2006, 32, 178–182. [Google Scholar] [CrossRef]
- Awwad, S.T.; Heilman, M.; Hogan, R.N.; Parmar, D.N.; Petroll, W.M.; McCulley, J.P.; Cavanagh, H.D. Severe reactive ischemic posterior segment inflammation in Acanthamoeba keratitis: A new potentially blinding syndrome. Ophthalmology 2007, 114, 313–320. [Google Scholar] [CrossRef] [PubMed]
- Herz, N.L.; Matoba, A.Y.; Wilhelmus, K.R. Rapidly progressive cataract and iris atrophy during treatment of Acanthamoeba keratitis. Ophthalmology 2008, 115, 866–869. [Google Scholar] [CrossRef] [PubMed]
- Roth, M.; Balasiu, A.; Daas, L.; Holtmann, C.; Servera, A.; Walckling, M.; MacKenzie, C.R.; Fuchsluger, T.A.; Geerling, G. 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. [Google Scholar] [CrossRef] [PubMed]
- Sagerfors, S.; Ejdervik-Lindblad, B.; Söderquist, B. Does the sampling instrument influence corneal culture outcome in patients with infectious keratitis? A retrospective study comparing cotton tipped applicator with knife blade. BMJ Open Ophthalmol. 2020, 4, e000363. [Google Scholar]
- Muiño, L.; Rodrigo, D.; Villegas, R.; Romero, P.; Peredo, D.E.; Vargas, R.A.; Liempi, D.; Osuna, A.; Jercic, M.I. Effectiveness of sampling methods employed for Acanthamoeba keratitis diagnosis by culture. Int. Ophthalmol. 2019, 39, 1451–1458. [Google Scholar] [CrossRef]
- Marines, H.M.; Osato, M.S.; Font, R.L. The value of calcofluor white in the diagnosis of mycotic and Acanthamoeba infections of the eye and ocular adnexa. Ophthalmology 1987, 94, 23–26. [Google Scholar] [CrossRef]
- Grossniklaus, H.E.; Waring, G.O., 4th; Akor, C.; Castellano-Sanchez, A.A.; Bennett, K. Evaluation of hematoxylin and eosin and special stains for the detection of Acanthamoeba keratitis in penetrating keratoplasties. Am. J. Ophthalmol. 2003, 136, 520–526. [Google Scholar] [CrossRef]
- Elhardt, C.; Schweikert, R.; Hartmann, L.M.; Vounotrypidis, E.; Kilani, A.; Wolf, A.; Wertheimer, C.M. The role of the calcofluor white staining in the diagnosis of Acanthamoeba keratitis. J. Ophthalmic Inflamm. Infect. 2023, 12, 23. [Google Scholar] [CrossRef]
- Bharathi, M.J.; Ramakrishnan, R.; Meenakshi, R.; Mittal, S.; Shivakumar, C.; Srinivasan, M. Microbiological diagnosis of infective keratitis: Comparative evaluation of direct microscopy and culture results. Br. J. Ophthalmol. 2006, 90, 1271–1276. [Google Scholar] [CrossRef]
- Thebpatiphat, N.; Hammersmith, K.M.; Rocha, F.N.; Rapuano, C.J.; Ayres, B.D.; Laibson, P.R.; Eagle, R.C., Jr.; Cohen, E.J. Acanthamoeba keratitis: A parasite on the rise. Cornea 2007, 26, 701–706. [Google Scholar] [CrossRef]
- Kaufman, S.C.; Musch, D.C.; Belin, M.W.; Cohen, E.J.; Meisler, D.M.; Reinhart, W.J.; Udell, I.J.; Van Meter, W.S. Confocal microscopy: A report by the American Academy of Ophthalmology. Ophthalmology 2004, 111, 396–406. [Google Scholar] [CrossRef]
- De Craene, S.; Knoeri, J.; Georgeon, C.; Kestelyn, P.; Borderie, V.M. Assessment of Confocal Microscopy for the Diagnosis of Polymerase Chain Reaction-Positive Acanthamoeba keratitis: A Case-Control Study. Ophthalmology 2018, 125, 161–168. [Google Scholar] [CrossRef] [PubMed]
- Yera, H.; Ok, V.; Lee Koy Kuet, F.; Dahane, N.; Ariey, F.; Hasseine, L.; Delaunay, P.; Martiano, D.; Marty, P.; Bourges, J.L. PCR and culture for diagnosis of Acanthamoeba keratitis. Br. J. Ophthalmol. 2021, 105, 1302–1306. [Google Scholar] [CrossRef]
- Padhi, T.R.; Das, S.; Sharma, S.; Rath, S.; Rath, S.; Tripathy, D.; Panda, K.G.; Basu, S.; Besirli, C.G. Ocular parasitoses: A comprehensive review. Surv. Ophthalmol. 2017, 62, 161–189. [Google Scholar] [CrossRef] [PubMed]
- Hammersmith, K.M. Diagnosis and management of Acanthamoeba keratitis. Curr. Opin. Ophthalmol. 2006, 17, 327–331. [Google Scholar] [CrossRef] [PubMed]
- Garg, P.; Kalra, P.; Joseph, J. Non-contact lens related Acanthamoeba keratitis. Indian J. Ophthalmol. 2017, 65, 1079–1086. [Google Scholar] [CrossRef]
- Clarke, D.W.; Alizadeh, H.; Niederkorn, J.Y. Failure of Acanthamoeba castellanii to produce intraocular infections. Investig. Ophthalmol. Vis. Sci. 2005, 46, 2472–2478. [Google Scholar] [CrossRef]
- Shigeyasu, C.; Shimazaki, J. Ocular surface reconstruction after exposure to high concentrations of antiseptic solutions. Cornea 2012, 31, 59–65. [Google Scholar] [CrossRef]
- Pfister, D.R.; Cameron, J.D.; Krachmer, J.H.; Holland, E.J. Confocal microscopy findings of Acanthamoeba keratitis. Am. J. Ophthalmol. 1996, 121, 119–128. [Google Scholar] [CrossRef]
- Kobayashi, A.; Yokogawa, H.; Yamazaki, N.; Ishibashi, Y.; Oikawa, Y.; Tokoro, M.; Sugiyama, K. In vivo laser confocal microscopy findings of radial keratoneuritis in patients with early stage Acanthamoeba keratitis. Ophthalmology 2013, 120, 1348–1353. [Google Scholar] [CrossRef]
- Alomar, T.; Matthew, M.; Donald, F.; Maharajan, S.; Dua, H.S. In vivo confocal microscopy in the diagnosis and management of Acanthamoeba keratitis showing new cystic forms. Clin. Exp. Ophthalmol. 2009, 37, 737–739. [Google Scholar] [CrossRef] [PubMed]
- Chidambaram, J.D.; Prajna, N.V.; Palepu, S.; Lanjewar, S.; Shah, M.; Elakkiya, S.; Macleod, D.; Lalitha, P.; Burton, M.J. In Vivo Confocal Microscopy Cellular Features of Host and Organism in Bacterial, Fungal, and Acanthamoeba keratitis. Am. J. Ophthalmol. 2018, 190, 24–33. [Google Scholar] [CrossRef] [PubMed]
- Cavanagh, H.D.; Petroll, W.M.; Alizadeh, H.; He, Y.G.; McCulley, J.P.; Jester, J.V. Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology 1993, 100, 1444–1454. [Google Scholar] [CrossRef] [PubMed]
- Ting, D.S.J.; Gopal, B.P.; Deshmukh, R.; Seitzman, G.D.; Said, D.G.; Dua, H.S. Diagnostic armamentarium of infectious keratitis: A comprehensive review. Ocul. Surf. 2022, 23, 27–39. [Google Scholar] [CrossRef]
- Agarwal, M.; Asokan, R.; Therese, K.L.; Lakshmipathy, M. Bilateral Acanthamoeba keratitis with radial keratoneuritis—Utility of AS-OCT in management and treatment. Clin. Exp. Optom. 2021, 104, 871–873. [Google Scholar] [CrossRef]
- Park, Y.M.; Lee, J.S.; Yoo, J.M.; Park, J.M.; Seo, S.W.; Chung, I.Y.; Kim, S.J. Comparison of anterior segment optical coherence tomography findings in Acanthamoeba keratitis and herpetic epithelial keratitis. Int. J. Ophthalmol. 2018, 11, 1416–1420. [Google Scholar]
- Liu, H.Y.; Hopping, G.C.; Vaidyanathan, U.; Ronquillo, Y.C.; Hoopes, P.C.; Moshirfar, M. Polymerase Chain Reaction and Its Application in the Diagnosis of Infectious Keratitis. Med. Hypothesis Discov. Innov. Ophthalmol. 2019, 8, 152–155. [Google Scholar]
- Yera, H.; Zamfir, O.; Bourcier, T.; Ancelle, T.; Batellier, L.; Dupouy-Camet, J.; Chaumeil, C. Comparison of PCR, microscopic examination and culture for the early diagnosis and characterization of Acanthamoeba isolates from ocular infections. Eur. J. Clin. Microbiol. Infect. Dis. 2007, 26, 221–224. [Google Scholar] [CrossRef]
- Booton, G.C.; Kelly, D.J.; Chu, Y.W.; Seal, D.V.; Houang, E.; Lam, D.S.; Byers, T.J.; Fuerst, P.A. 18S ribosomal DNA typing and tracking of Acanthamoeba species isolates from corneal scrape specimens, contact lenses, lens cases, and home water supplies of Acanthamoeba keratitis patients in Hong Kong. J. Clin. Microbiol. 2002, 40, 1621–1625. [Google Scholar] [CrossRef]
- Goh, J.W.Y.; Harrison, R.; Hau, S.; Alexander, C.L.; Tole, D.M.; Avadhanam, V.S. Comparison of In Vivo Confocal Microscopy, PCR and Culture of Corneal Scrapes in the Diagnosis of Acanthamoeba keratitis. Cornea 2018, 37, 480–485. [Google Scholar] [CrossRef]
- Ung, L.; Bispo, P.J.M.; Shanbhag, S.S.; Gilmore, M.S.; Chodosh, J. The persistent dilemma of microbial keratitis: Global burden, diagnosis, and antimicrobial resistance. Surv. Ophthalmol. 2019, 64, 255–271. [Google Scholar] [CrossRef] [PubMed]
- Somerville, T.F.; Herbert, R.; Neal, T.; Horsburgh, M.; Kaye, S.B. An Evaluation of a Simplified Impression Membrane Sampling Method for the Diagnosis of Microbial Keratitis. J. Clin. Med. 2021, 10, 5671. [Google Scholar] [CrossRef] [PubMed]
- Sawada, Y.; Yuan, C.; Huang, A.J. Impression cytology in the diagnosis of Acanthamoeba keratitis with surface involvement. Am. J. Ophthalmol. 2004, 137, 323–328. [Google Scholar] [CrossRef] [PubMed]
- Siddiqui, R.; Khan, N.A. Biology and pathogenesis of Acanthamoeba. Parasit. Vectors. 2012, 10, 5–6. [Google Scholar] [CrossRef]
- Lim, N.; Goh, D.; Bunce, C.; Xing, W.; Fraenkel, G.; Poole, T.R.; Ficker, L. Comparison of polyhexamethylene biguanide and chlorhexidine as monotherapy agents in the treatment of Acanthamoeba keratitis. Am. J. Ophthalmol. 2008, 145, 130–135. [Google Scholar] [CrossRef]
- Pérez-Santonja, J.J.; Kilvington, S.; Hughes, R.; Tufail, A.; Matheson, M.; Dart, J.K. Persistently culture positive Acanthamoeba keratitis: In vivo resistance and in vitro sensitivity. Ophthalmology 2003, 110, 1593–1600. [Google Scholar] [CrossRef]
- Dart, J.K.G.; Papa, V.; Rama, P.; Knutsson, K.A.; Ahmad, S.; Hau, S.; Sanchez, S.; Franch, A.; Birattari, F.; Leon, 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. [Google Scholar] [CrossRef]
- Papa, V.; Rama, P.; Radford, C.; Minassian, D.C.; Dart, J.K.G. Acanthamoeba keratitis therapy: Time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases. Br. J. Ophthalmol. 2020, 104, 575–581. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.Q.; Li, R.; Zhang, C.; Luo, S.Y.; Sun, X.G.; Jin, X.Y. Morphological characteristics in corneal smear of Acanthamoeba keratitis. Zhonghua Yan Ke Za Zhi 2010, 46, 432–436. [Google Scholar]
- Zhou, W.; Warrilow, A.G.; Thomas, C.D.; Ramos, E.; Parker, J.E.; Price, C.L.; Vanderloop, B.H.; Fisher, P.M.; Loftis, M.D.; Kelly, D.E.; et al. Functional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii. Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids 2018, 1863, 1164–1178. [Google Scholar] [CrossRef]
- Tu, E.Y.; Joslin, C.E.; Shoff, M.E. Successful treatment of chronic stromal Acanthamoeba keratitis with oral voriconazole monotherapy. Cornea 2010, 29, 1066–1068. [Google Scholar] [CrossRef] [PubMed]
- Musayeva, A.; Riedl, J.C.; Schuster, A.K.; Wasielica-Poslednik, J.; Pfeiffer, N.; Gericke, A. Topical Voriconazole as Supplemental Treatment for Acanthamoeba keratitis. Cornea 2020, 39, 986–990. [Google Scholar] [CrossRef] [PubMed]
- Bagga, B.; Joseph, J.; Garg, P.; Chandran, K.; Jayabhasker, P.; Manjulatha, K.; Sharma, S. Efficacy of Topical Miltefosine in Patients with Acanthamoeba keratitis: A Pilot Study. Ophthalmology 2019, 126, 768–770. [Google Scholar] [CrossRef]
- Thulasi, P.; Saeed, H.N.; Rapuano, C.J.; Hou, J.H.; Appenheimer, A.B.; Chodosh, J.; Kang, J.J.; Morrill, A.M.; Vyas, N.; Zegans, M.E.; et al. Oral Miltefosine as Salvage Therapy for Refractory Acanthamoeba keratitis. Am. J. Ophthalmol. 2021, 223, 75–82. [Google Scholar] [CrossRef]
- McClellan, K.; Howard, K.; Niederkorn, J.Y.; Alizadeh, H. Effect of steroids on Acanthamoeba cysts and trophozoites. Investig. Ophthalmol. Vis. Sci. 2001, 42, 2885–2893. [Google Scholar]
- Carnt, N.; Robaei, D.; Watson, S.L.; Minassian, D.C.; Dart, J.K. The Impact of Topical Corticosteroids Used in Conjunction with Antiamoebic Therapy on the Outcome of Acanthamoeba keratitis. Ophthalmology 2016, 123, 984–990. [Google Scholar] [CrossRef] [PubMed]
- Somani, S.N.; Ronquillo, Y.; Moshirfar, M. Acanthamoeba keratitis. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: http://www.ncbi.nlm.nih.gov/books/NBK549863/ (accessed on 9 April 2025).
- Parasitic Ulcer Treatment Trial (PUTT). Available online: https://clinicaltrials.gov/study/NCT06213649 (accessed on 6 May 2025).
- Di Zazzo, A.; Kheirkhah, A.; Abud, T.B.; Goyal, S.; Dana, R. Management of high-risk corneal transplantation. Surv. Ophthalmol. 2017, 62, 816–827. [Google Scholar] [CrossRef]
- Sarnicola, E.; Sarnicola, C.; Sabatino, F.; Tosi, G.M.; Perri, P.; Sarnicola, V. Early Deep Anterior Lamellar Keratoplasty (DALK) for Acanthamoeba keratitis Poorly Responsive to Medical Treatment. Cornea 2016, 35, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Szentmáry, N.; Daas, L.; Shi, L.; Laurik, K.L.; Lepper, S.; Milioti, G.; Seitz, B. Acanthamoeba keratitis—Clinical signs, differential diagnosis and treatment. J. Curr. Ophthalmol. 2018, 31, 16–23. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Graffi, S.; Peretz, A.; Jabaly, H.; Koiefman, A.; Naftali, M. Acanthamoeba keratitis: Study of the 5-year incidence in Israel. Br. J. Ophthalmol. 2013, 97, 1382–1383. [Google Scholar] [CrossRef]
- Maycock, N.J.; Jayaswal, R. Update on Acanthamoeba keratitis: Diagnosis, Treatment, and Outcomes. Cornea 2016, 35, 713–720. [Google Scholar] [CrossRef] [PubMed]
- Essalat, M.; Abolhosseini, M.; Le, T.H.; Moshtaghion, S.M.; Kanavi, M.R. Interpretable deep learning for diagnosis of fungal and Acanthamoeba keratitis using in vivo confocal microscopy images. Sci. Rep. 2023, 13, 8953. [Google Scholar] [CrossRef]
- Shareef, O.; Soleimani, M.; Tu, E.; Jacobs, D.S.; Ciolino, J.B.; Rahdar, A.; Cheraqpour, K.; Ashraf, M.; Habib, N.B.; Greenfield, J.; et al. A novel artificial intelligence model for diagnosing Acanthamoeba keratitis through confocal microscopy. Ocul. Surf. 2024, 34, 159–164. [Google Scholar] [CrossRef] [PubMed]
- Koyama, A.; Miyazaki, D.; Nakagawa, Y.; Ayatsuka, Y.; Miyake, H.; Ehara, F.; Sasaki, S.-I.; Shimizu, Y.; Inoue, Y. Determination of probability of causative pathogen in infectious keratitis using deep learning algorithm of slit-lamp images. Sci. Rep. 2021, 11, 22642. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.; Wang, H.; Wang, S.; Wei, Z.; Zhang, Y.; Wang, Z.; Chen, K.; Ou, Z.; Liang, Q. Deep learning-based classification of infectious keratitis on slit-lamp images. Ther. Adv. Chronic Dis. 2022, 13, 20406223221136071. [Google Scholar] [CrossRef]
- Mouncey, P.R.; Osborn, T.M.; Power, G.S.; Harrison, D.A.; Sadique, M.Z.; Grieve, R.D.; Jahan, R.; Tan, J.C.; Harvey, S.E.; Bell, D.; et al. Protocolised Management In Sepsis (ProMISe): A multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock. Health Technol. Assess. 2015, 19, 97. [Google Scholar] [CrossRef]
- Sharma, N.; Sahay, P.; Maharana, P.K.; Singhal, D.; Saluja, G.; Bandivadekar, P.; Chako, J.; Agarwal, T.; Sinha, R.; Titiyal, J.S.; et al. Management algorithm for fungal keratitis: The TST (topical, systemic, and targeted therapy) protocol. Cornea 2019, 38, 141–145. [Google Scholar] [CrossRef]
- Dart, J.K.G.; Papa, V.; Rama, P.; Knutsson, K.A.; Ahmad, S.; Hau, S.; Sanchez, S.; Franch, A.; Birattari, F.; Leon, P.; et al. Acanthamoeba keratitis treatment outcomes compared for drug delivery by protocol versus physician s individualised treatment. Ocul. Surf. 2025, in press. [Google Scholar] [CrossRef]
- Abbouda, A.; Abicca, I.; Alió, J.L. Current and Future Applications of Photoactivated Chromophore for Keratitis-Corneal Collagen Cross-Linking (PACK-CXL): An Overview of the Different Treatments Proposed. Semin. Ophthalmol. 2018, 33, 293–299. [Google Scholar] [CrossRef]
- Atalay, H.T.; Dogruman-Al, F.; Sarzhanov, F.; Özmen, M.C.; Tefon, A.B.; Arıbaş, Y.K.; Bilgihan, K. Effect of Riboflavin/Rose Bengal-Mediated PACK-CXL on Acanthamoeba Trophozoites and Cysts in Vitro. Curr. Eye Res. 2018, 43, 1322–1325. [Google Scholar] [CrossRef]
- Atalay, H.T.; Uysal, B.S.; Sarzhanov, F.; Usluca, S.; Yeşilırmak, N.; Özmen, M.C.; Erganiş, S.; Tefon, A.B.; Dogruman-Al, F.; Bilgihan, K. Rose Bengal-Mediated Photodynamic Antimicrobial Treatment of Acanthamoeba keratitis. Curr. Eye Res. 2020, 45, 1205–1210. [Google Scholar] [CrossRef] [PubMed]
- Ding, D.S.J.; Henein, C.; Said, D.G.; Dua, H.S. Photoactivated chromophore for infectious keratitis—Corneal cross-linking (PACK-CXL): A systematic review and meta-analysis. Ocul. Surf. 2019, 17, 624–634. [Google Scholar]
- Hager, T.; Hasenfus, A.; Stachon, T.; Seitz, B.; Szentmáry, N. Crosslinking and corneal cryotherapy in Acanthamoeba keratitis—A histological study. Graefes Arch. Clin. Exp. Ophthalmol. 2016, 254, 149–153. [Google Scholar] [CrossRef] [PubMed]
Diagnostic Technique | Advantages | Disadvantages | Target Detected |
---|---|---|---|
Corneal scrape/ Culture | Good sensitivity High specificity The only method for detecting viable Acanthamoeba | In co-infection, there is a risk of misdiagnosis. Corneal scrapes cannot access deeper stroma, where AK can infiltrate. | Cysts and trophozoites |
PCR | High sensitivity Rapid turnaround | False positives due to amplification of non-viable Acanthamoeba genomes. | Cysts and trophozoites |
In Vivo Confocal Microscopy (IVCM) | Sensitivity and specificity are both high; a rapid and non-invasive test | Significant learning curve required and operator-dependent. A small area of the cornea is covered per scan, and there is limited availability. | Primarily cysts |
Impression Cytology | High specificity | Requires expertise in cytopathology and specialized stains. Cannot detect deep Acanthamoeba cysts. | Superficial cysts only |
AS-OCT | Useful for differential diagnosis, non-invasive | Current machines cannot detect Acanthamoeba trophozoites and cysts directly. | Indirect structural signs only |
Treatment Category | Agent(s) | Main Point | Cidal/Static Activity and Target |
---|---|---|---|
Biguanides | Polyhexamethylene biguanide (PHMB) | First-line therapy; effective as monotherapy or in combination | Cidal—cysts and trophozoites |
Chlorhexidine | Smaller molecule allows deeper corneal penetration; comparable outcomes to PHMB. | Cidal—cysts and trophozoites | |
Aromatic Diamidines | Propamidine, Hexamidine | Used in combination with biguanides; not effective as monotherapy | Static—primarily trophozoites |
Antifungal Agents | Voriconazole, Posaconazole | Antifungal agents with anti-amoebic activity; used in refractory or co-infected cases | Cidal—primarily cysts |
Phosphocholine Analog | Miltefosine | Used in refractory cases; topical and oral forms trialed; limited accessibility | Cidal—cysts and trophozoites (variable efficacy) |
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Fu, L.; Wasielica-Poslednik, J.; Geerling, G.; Robbie, S.; D’Esposito, F.; Musa, M.; Tognetto, D.; Giglio, R.; Gagliano, C.; Zeppieri, M. Navigating the Challenges of Acanthamoeba Keratitis: Current Trends and Future Directions. Life 2025, 15, 933. https://doi.org/10.3390/life15060933
Fu L, Wasielica-Poslednik J, Geerling G, Robbie S, D’Esposito F, Musa M, Tognetto D, Giglio R, Gagliano C, Zeppieri M. Navigating the Challenges of Acanthamoeba Keratitis: Current Trends and Future Directions. Life. 2025; 15(6):933. https://doi.org/10.3390/life15060933
Chicago/Turabian StyleFu, Lanxing, Joanna Wasielica-Poslednik, Gerd Geerling, Scott Robbie, Fabiana D’Esposito, Mutali Musa, Daniele Tognetto, Rosa Giglio, Caterina Gagliano, and Marco Zeppieri. 2025. "Navigating the Challenges of Acanthamoeba Keratitis: Current Trends and Future Directions" Life 15, no. 6: 933. https://doi.org/10.3390/life15060933
APA StyleFu, L., Wasielica-Poslednik, J., Geerling, G., Robbie, S., D’Esposito, F., Musa, M., Tognetto, D., Giglio, R., Gagliano, C., & Zeppieri, M. (2025). Navigating the Challenges of Acanthamoeba Keratitis: Current Trends and Future Directions. Life, 15(6), 933. https://doi.org/10.3390/life15060933