Acanthamoeba Ocular Infection: Anomalous Presentation of a Potentially Vision-Threatening Condition
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Acanthamoeba keratitis (AK) is a rare and potentially severe corneal infection. In rich countries, AK is often related to contact lens (CL) wearing, poor contact lens hygiene and prolonged CL wearing . Soft CL are known to be at increased risk than rigid gas permeable (RGP) lenses . AK may have a proteiform presentation [3, 4]. At the onset, signs and symptoms are often aspecific and the clinical picture may be mistaken as a fungal, bacterial or viral infection leading to a delay in the diagnosis. In absence of a prompt treatment, devastating complications as perilimbar scleritis [5, 6] and severe ischemic posterior segment inflammation  may occur and lead to complete vision loss. Therefore, if possible, an early diagnosis should be always made  and more than a single investigation should be performed to detect either the parasite vegetative forms (trophozoites) or the typical double-walled cysts (dormant forms) .
In this article, we describe two cases of amoebic keratitis with uncommon presentation in which a proper diagnosis was established after multiple and repetitive diagnostic procedures including conventional cultures, microscopic smears, polymerase chain reaction (PCR) and even tissue biopsy.
Two patients with clinical features of keratitis of unknown origin were referred to the Corneal Service at the Catholic University of the Sacred Heart in Rome for consultation between 2016 and 2017. For each patient, a complete ophthalmological history focusing on keratitis risk factors was obtained and multiple diagnostic procedures were performed in order to detect the specific pathogen.
In case of corneal and/or anterior segment involvement several laboratory diagnostic procedures are available in our centre, divided in first- and second-level or advanced diagnostic procedures.
First-level investigations include microscopic examinations of smears and incubation of cultures following large corneal debridement. In case of negative results, more advanced procedures, normally performed, are polymerase chain reaction (PCR) and in vivo confocal microscopy (IVCM). In case of negative results, a sclero-corneal biopsy may be required.
Since laboratory diagnostic procedures may take several days and even weeks for final results, a temporary wide spectrum antibiotic therapy was administered in both cases according to the clinical presentation and severity of the corneal involvement.
Acanthamoeba keratitis is a rare and vision-threatening condition . The clinical picture may be various but some findings are believed to be typical: the unilateral presentation, a history of CL wearing, diffuse corneal haze, radial keratoneuritis and a ring-shaped stromal infiltrate [1, 2, 4]. Among symptoms, blurred vision and disproportionate pain are frequently reported, with the latter being largely considered pathognomonic of AK . Nevertheless, atypical presentation may be the rule and, in developing countries, exposure to contaminated soil or water, and a history of ocular trauma are the main predisposing factors, whereas CL wearing has lower importance [12, 13]. In a recent published series, a typical presentation with disproportionate pain, ring infiltrates, and radial keratoneuritis was observed in less than a third of cases . Cases of painless AK with normal vision have also been reported [14, 15, 16]. The first patient of our series presented with severe anterior segment involvement, with no complain of ocular pain even after the onset of scleritis. The absence of pain together with persistently negative cultures led to a delay in the diagnosis and thus proper therapy could not be administered. At first, to explain corneal anaesthesia and the absence of pain, a neurotrophic keratitis was supposed, but when sclerokeratitis arose, it was clear that neurotrophic keratopathy could not be the proper diagnosis and a sclero-corneal biopsy was therefore necessary.
Moreover, patient habits and environmental exposure were investigated and it was found that he had been exposed for a long time to capsaicin, a molecule extracted from chili pepper with well-documented analgesic properties [17, 18]. The patient later referred that he was still engaged in agriculture and that chili-pepper farming was his main employment. He used to wash his hands and face with the same water that he had collected in a little basin before. It is reasonable to suppose that slight ocular trauma with an exposure to contaminated soil could have been the predisposing factor for AK, whereas the exposure to capsaicin might explain corneal analgesia. Capsaicin analgesic effect can be explained by the activation of its receptor transient receptor potential vanilloid subtype 1 (TRVP1) with a subsequent loss of function of the somatic nociceptive fibres. Nerve endings collapse because of the calcium overload induced by activation of TRPV1, with loss of mitochondrial function, metabolic inhibition and disruption of the integrity of the terminal membrane . In previously published cases series, enucleation was recommended as the definitive surgical solution in presence of scleritis with limbar stem cells deficiency, in order to control a painful condition in an otherwise blind eye [19, 20, 21]. In our case, the absence of pain due to the prolonged capsaicin exposure made it possible to perform an “eye-sparing” surgery.
The second patient of our series was a young, contact lens-wearer female who presented with a nummular keratitis and an otherwise intact epithelium. Moderate ocular pain was also referred. This case, according to the classification proposed by Tu et al. , may be considered a mild but atypical form of AK; indeed, in clinical practice, amoebic keratitis with no epithelium defects are not the rule .
The reported cases both remark how an etiological diagnosis can be challenging in some cases of infectious keratitis, especially for AK. It has been reported that traditional cultures effectiveness in isolating Acanthamoeba ranges between 30% and 60%  and it may take some weeks for final results . Recently newer diagnostic procedures, as IVCM and PCR have been largely adopted, but it was found that they may integrate but not completely substitute amoebic cultures [25, 26]. On the other hand, IVCM is a long spending procedure in which any single frame of the scan needs to be evaluated by an expert operator in order to detect lesions that may be related to Acanthamoeba. Furthermore, cases of PCR-negative but culture-positive AK have been described [25, 27]. Scheid reported a case in which Acanthamoeba involvement was detected with traditional cultures, whereas PCR was persistently negative . To explain this finding, the author postulated that nucleotides substitutions in the highly-conserved region of the 18S rRNA gene (the molecular target) may prevent binding of commonly used primers for molecular detection . Moreover, in a large series of 125 patients diagnosed with keratitis, Kowalski et al. found that only 14 out of 125 patients (11.2%) had their diagnosis of AK confirmed with both PCR and cultures, whereas 4 out of 125 patients (3.2%) and 3 out of 125 patients (2.4%) were respectively “culture-negative PCR-positive” and “culture-positive PCR negative” . It was also remarkable that the vast majority of cases (104 out of 125 patients; 83.2%) were both “culture and PCR negative” for Acanthamoeba spp., and among these a different causative pathogen was isolated in only 19 cases (18.3%) .
The above-mentioned studies confirm the assumption that an etiological diagnosis may be challenging to make in case of corneal infection and that quite often the causative agent remains unknown. Our cases and the aforementioned studies highlighted the current role of the “clinical diagnosis” that in our opinion cannot be entirely replaced by the “laboratory diagnosis”. Similarly, Goh and co-workers with the definition of “clinical AK” referred to those cases in which robust clinical signs of AK were present or otherwise it was possible to observe a complete disease resolution after amoebicidal drugs administration . Therefore, if a high grade of AK suspicion is present, we suggest anti-amoebic agents administration even in case of multiple negative laboratory investigations, in order to avoid devastating complications related to an unrecognized Acanthamoeba ocular infection, considering also the low risk of toxicity of anti-amoebic treatments .
Atypical presentation of AK is quite common and sometimes may be the rule. Despite several diagnostic procedures have been developed to improve its identification rate, multiple negative results from different procedures cannot completely rule out amoebic involvement. Therefore, anti-amoebic drugs administration seems recommendable in case of patients with a high grade of suspicion for AK despite persistently negative laboratory results, in order to prevent severe vision loss.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Research Involving Human Participants
All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 17.Frias B, Merighi A. Capsaicin, nociception and pain. Molecules. 2016;21(6). doi: https://doi.org/10.3390/molecules21060797.