Clinical Aspects and Immunobiology of Acanthamoeba Keratitis

Abstract

Acanthamoeba keratitis (AK) is a rare, severe, debilitating infection of the cornea that results in loss of vision and poor quality of life. Contact lens wearers and farm workers are most at risk of AK, due to increased environmental and ocular surface exposure. Timely diagnosis is important to good prognosis but is complicated by the similarity of AK clinical features to other corneal infections especially Herpes Simplex Keratitis, which is more common. Acanthamoeba species are free living protozoa that can adapt to the environment by forming a mobile, feeding trophozoite in favorable conditions and a dormant cyst when threatened. Both forms are not susceptible to antibiotics and are treated by disinfectants which can be toxic. Cysts are more difficult to treat and can lie dormant in the cornea for many months, leading to a waxing and waning disease course. Furthermore, Acanthamoeba species can host other micro-organisms leading to dual infection and increased severity. As most people have developed humoral immunoglobulin G (IgG) antibodies, although AK patients exhibit lower levels of tear secretory IgA antibodies. This could be linked with the Th17 pathway, in which genomic DNA and tear protein patient studies, show some association. There are also genetic associations between AK patients with single nucleotide polymorphisms (SNPs) in CXCL8 (the gene that codes for interleukin-8, IL-8) and toll-like receptor 4 (TLR4) and severe inflammatory outcomes. IL-8 is a strong neutrophil attractant and activator and TLR4 is associated with detection of Acanthamoeba and cytokine signaling. These studies show promise for biomarker identification and better understanding of the pathophysiology to design better treatments for AK patients.