Some studies have revealed that granulomatous inflammation and the immune response are critical mechanisms in the course of AK.
19–21 Macrophages and polymorphonuclear leukocytes seem to be the predominant cells in the inflammatory infiltrate of AK.
19 In the present study, a significant increase in DC density was shown in patients with AK, especially in the mild and moderate AK subgroups. Compared to controls, a three times increase in DC size and dendrite length was found in AK cases. A similar result was observed by Cruzat et al.,
7 who demonstrated a significant increase in DC density in cases with infectious keratitis compared to controls (672.9 ± 791.5 vs. 49.3 ± 39.6;
P < 0.0001). In addition, some studies have shown that mature DCs can be recognized by morphologic changes, including numerous long dendrites and increased size.
14,22 Zhivov et al.
14 used IVCM to examine DC distribution in 200 normal corneas of 112 healthy volunteers and found that mature DCs appeared in the peripheral cornea with numerous long dendrites. In the central cornea, DCs often lacked or had only a few small dendrites. Consequently, the size and length of DCs might be used to evaluate the degree of maturity of DCs. In the present study, the size and dendrite length of DCs increased with increasing AK severity. This suggests that amoebic cysts might induce cell-mediated immunity and an inflammatory response. Cell-derived cytokines and chemokines (tumor necrosis factor α, IL-1, and macrophage inflammatory protein (MIP)-1α and MIP-β) can regulate the movement of DCs from the periphery toward the center.
22 In a mouse model, cysts induced a lymphoproliferative response in splenic T cells from mice immunized against
Acanthamoeba cysts.
23 Although the adaptive immune response cannot kill the cysts, antiparasite antibodies or complement induced by cysts help to stimulate a neutrophil-mediated inflammatory response. Therefore, integration of both the innate and adaptive immune response is very important to remove amoeba from the cornea. Unfortunately, it is not possible to distinguish the detailed characteristics of round cells such as neutrophils, basophils, or eosinophils by IVCM. DC density and maturation increased with the size of the corneal ulcer in the mild and moderate stages of AK. However, in the severe subgroup, while DC exhibited a highly mature stage, the DC density was lower. As more cysts transform into trophozoites in the severe stage of AK, neutrophil inflammation might downregulate any subsequent lymphoproliferative response to cyst antigens.
5 Clarke and Niederkorn
20 suggested that cell-mediated immunity may not be very effective in controlling severe AK. Consequently, at this stage, corticosteroid use may increase tissue damage and induce or worsen chronic AK.
24 In all AK cases, ulcer size was positively correlated with cyst density and DC density, emphasizing the link between inflammation and infection in AK. Although we did not find a significant correlation between cyst density and DC density, cyst density was positively correlated with DC size and DC length. Using IVCM, it might be possible to monitor inflammatory conditions by detecting DC maturation. Although not widely accepted, anti-inflammatory and immunosuppressive treatments have been reported in some studies on AK management.
25–27 Based on the present results, it would be interesting to evaluate in vivo corneal inflammatory conditions by IVCM.