Background: Histological analysis of two Acanthamoeba keratitis eyes with anterior and posterior segment inflammation and blindness. Methods: Two eyes of 2 patients (age 45 and 51 years) with acanthamoeba keratitis (PCR of epithelial abrasion positive) were analysed. Patients underwent triple-topical therapy (polyhexamethilen-biguanide, propamidin-isethionat and neomycin) with failed recovery, subsequent crosslinking, corneal cryotherapy, repeat penetrating keratoplasties, amniotic membrane transplantations and phacoemulsification with posterior chamber lens implantation. The patients developed ocular hypotony with central vein/artery occlusion, retinal/choroidal detachment and had no light perception, therefore, the inflamed eyes were enucleated. Histological analysis was performed using haematoxilin-eosin, periodic acid- Schiff and Gömöri-methenamine silver staining. Results: We could not observe acanthamoeba trophozoites or cysts neither in the cornea nor in other ocular tissues. Anterior synechiae was detected in the chamber angle of both globes and lymphocytic infiltration was observed around central retinal artery and vein, associated with fibrous metaplasia of the retinal pigment epithelium. We found perivascular inflammatory cell infiltration (mainly lymphocytes) in the episclera and around ciliary nerves, when analysing the first globe. This was associated with non-granulomatous uveitis, cilioschisis and tractional retinal detachment. Cross sections of the optic nerve revealed gliosis and optic nerve atrophy. Histopathologic studies of the second globe revealed a multifocal, non-granulomatous choroiditis with lymphocytic infiltration. Conclusions: In long-standing, recalcitrant acanthamoeba keratitis, uveititis, retinal vasculitis and scleritis may occur and result in blindness, even without further persistence of acanthamoeba trophozoites or cysts. In this stage of acanthamoeba keratitis, systemic immune suppression may be necessary for a longer time period.