Acanthamoeba keratitis (AK) is a rare, but devastating eye disease (Dart, Saw, and Kilvington 2009). The condition is caused by the infiltration of the protozoan parasite Acanthamoeba castelanii. The parasite can shift between a mobile amebic state, called a trophozoite, and a dormant cystic state. The cyst is highly resilient. Studies have demonstrated its ability to survive conditions such as pH 2.0, freezing, gamma and UV radiation, moist heat (60°C) for 60 minutes, 24 years at 4°C in water and desiccation for more than 20 years (Sriram et al. 2008). Consequently, cysts are difficult to eradicate from the human cornea, and cases often become protracted. Outcome is poor and 30 % of AK cases ultimately need surgical intervention (Papa et al. 2020). It is possible to visualize acanthamoeba organisms directly using in vivo confocal microscopy (IVCM) making this technique valuable in diagnosing AK (De Craene et al. 2018). Using IVCM, we present a case where the acanthamoeba cysts have persisted for 12 years in a human cornea.
In June, 2009, a 52-year-old male was referred for urgent evaluation at the Department of Ophthalmology Aarhus University Hospital, a tertiary unit for corneal care. The patient had a history of a painful red left eye for 3 days. The patient normally wore contact lenses for mild myopia and had type 2 diabetes. There was no prior eye disease.
Best corrected visual acuity (BCVA) was 0.2 logMAR (0.6 Snellen decimal units,) and the eye presented with ciliary injection, and a dendritic ulcer on the central cornea. Treatment was initiated using topical antiherpetic (aciclovir) ointment 5 times daily and antibiotic (chloramphenicol, 10 %) ointment 4 times daily. Bacterial cultures and PCR analysis for herpes visus were negative. Small subepithelial infiltrates persisted despite ongoing treatment. Five months after presentation, AK was suspected. The central 8 mm of the corneal epithelium was removed and sent for both polymerase chain reaction (PCR) analysis for Acanthamoeba castelanii specific DNA and microscopy. The PCR was positive, and the microscopy was negative. Treatment was changed to topical 0.2 % Polyhexamethylbiguanid (PHMB) drops every hour and topical 0.1 % propamidine isetionate (Brolene) drops 4 times daily.
A central 8 mm diameter deep stromal corneal infiltrate developed gradually within a year after presentation. BCVA declined to 0.8 logMAR (0.16 Snellen Decimal units). IVCM monitoring confirmed acanthamoeba cysts located in deep in stromal layers from about 300 µm and deeper (figure 1A). There was no pain and the eye was quiet. The condition was unchanged, and drops were slowly tapered over a course of 3.5 years and then stopped. This unusually slow tapering was done as IVCM demonstrated sustained presence of acanthamoeba cysts in the corneal stroma from 300 µm and deeper towards the endothelium (figure 1B). Corresponding to the deep corneal infiltrate, a stromal scar developed. BCVA increased to 0.5 logMAR (0.32 Snellen Decimal units).
In 2021, 8 years after the cessation of AK treatment, the patient was reexamined. The BCVA had improved to 0.3 logMAR (0.5 Snellen Decimal Units). The corneal scar was largely unchanged in the deep stroma, and the eye was quiet (figure 1D+E). A repeat IVCM exam revealed that the acanthamoeba cysts were still present in unchanged density corresponding the stromal scar (figure 1 C).
This case demonstrates the continued presence of acanthamoeba cysts inside a human cornea for 12 years. This is in line with a recent paper that noted ongoing presence of acanthamoeba cysts in the corneal stroma despite apparent resolution of the clinical infection (Wang et al. 2019). The authors noted several cases in which acanthamoeba cysts persisted throughout the follow-up period which lasted to about 13 months. The location of cysts deeper in the corneal stroma may account for the unusually long treatment period noted here, as well as the persistence of cysts. This is in line with a previous study which noted that eyes with deeper cyst penetration were more likely to require penetrating keratoplasty (Huang et al. 2017).
However, it has not yet been reported whether cysts may persist years after the primary infection has been resolved. As such, it remains unclear how long acanthamoeba cysts can remain inside the living human cornea. Importantly, it is unclear whether the cysts are actually viable in the case presented here. This could in theory be answered with a surgical biopsy and a subsequent cultivation attempt, but this was not undertaken for ethical reasons. It is unclear why the host immune system does not interact with the acanthamoeba cysts, and it is also curious why the cysts refrain from entering their active trophozoic state without ongoing treatment. This matter remains unclear. Throughout the years, IVCM has proven valuable in diagnosing AK, but as this case demonstrates, monitoring the condition with IVCM can add important knowledge about this rare but serious condition.
Conflicts of Interest
The authors have no proprietary or financial interests to disclose