Infectious keratitis (IK) represents a significant global health concern, ranking as the fifth leading cause of blindness worldwide despite being largely preventable and treatable. Elderly populations are particularly susceptible due to age-related changes in immune response and corneal structure. However, research on IK in this demographic remains scarce. Age-related alterations such as increased permeability and reduced endothelial cell density further compound susceptibility to infection and hinder healing mechanisms. Additionally, inflammaging, characterized by chronic inflammation that develops with advanced age, disrupts the ocular immune balance, potentially exacerbating IK and other age-related eye diseases. Understanding these mechanisms is paramount for enhancing IK management, especially in elderly patients. This review comprehensively assesses risk factors, clinical characteristics, and management strategies for bacterial, viral, fungal, and acanthamoeba keratitis in the elderly population, offering crucial insights for effective intervention.

Ophthalmologists\' diagnostic and treatment competence in Acanthamoeba keratitis varies widely. This investigator-initiated, retrospective, single-center chart review examined the electronic patient files regarding PCR-positive Acanthamoeba keratitis. We included corneal and contact lens assessments. We further reviewed the patient\'s medical history, corneal scraping results regarding viral or fungal co-infections, and the duration from symptom onset to final diagnosis. We identified 59 eyes of 52 patients from February 2010 to February 2023, with 31 of 52 (59.6%) being female patients. The median (IQR, range) patient age was 33 (25.3 to 45.5 [13 to 90]) years, and the mean (SD, range) time to diagnosis after symptom onset was 18 (10.5 to 35 [3 to 70]) days. Overall, 7 of 52 (7.7%) patients displayed a bilateral Acanthamoeba infection, and 48 (92.3%) used contact lenses at symptom onset. Regarding other microbiological co-infections, we found virologic PCR testing in 45 of 52 (86.5%) patients, with 3 (6.7%) positive corneal scrapings. Fungal cultures were performed in 49 of 52 (94.2%) patients, with 5 (10.2%) positive corneal scrapings. The medical treatment success rate was 45/46 (97.8%). This study raises awareness of patient education in contact lens handling and screens for further microbial co-infections in suspected Acanthamoeba cases.

Natural products play a significant role in providing the current demand as antiparasitic agents, which offer an attractive approach for the discovery of novel drugs. The present study aimed to evaluate in vitro the potential impact of seaweed Padina pavonica (P. pavonica) extract in combating Acanthamoeba castellanii (A. castellanii). The phytochemical constituents of the extract were characterized by Gas chromatography-mass spectrometry. Six concentrations of the algal extract were used to evaluate its antiprotozoal activity at various incubation periods. Our results showed that the extract has significant inhibition against trophozoites and cysts viability, with complete inhibition at the high concentrations. The IC50 of P. pavonica extract was 4.56 and 4.89 µg/mL for trophozoites and cysts, respectively, at 24 h. Morphological alterations of A. castellanii trophozoites/cysts treated with the extract were assessed using inverted and scanning electron microscopes and showed severe damage features upon treatment with the extract at different concentrations. Molecular Docking of extracted compounds against Acanthamoeba cytochrome P450 monooxygenase (AcCYP51) was performed using Autodock vina1.5.6. A pharmacokinetic study using SwissADME was also conducted to investigate the potentiality of the identified bioactive compounds from Padina extract to be orally active drug candidates. In conclusion, this study highlights the in vitro amoebicidal activity of P. pavonica extract against A. castellanii adults and cysts and suggests potential AcCYP51 inhibition.

Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl2 or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na+/K+ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.

BACKGROUND: Proteases produced by Acanthamoeba spp. play an important role in their virulence and may be the key to understanding Acanthamoeba pathogenesis; thus, increasing attention has been directed towards these proteins. The present study aimed to investigate the lytic factors produced by Acanthamoeba castellanii during the first hours of in vitro co-culture with human corneal epithelial cells (HCECs).
METHODS: We used one old and one recent Acanthamoeba isolate, both from patients with severe keratitis, and subsets of these strains with enhanced pathogenic potential induced by sequential passaging over HCEC monolayers. The proteolytic profiles of all strains and substrains were examined using 1D in-gel zymography.
RESULTS: We observed the activity of additional proteases (ranging from 33 to 50 kDa) during the early interaction phase between amoebae and HCECs, which were only expressed for a short time. Based on their susceptibilities to protease inhibitors, these proteases were characterized as serine proteases. Protease activities showed a sharp decline after 4 h of co-incubation. Interestingly, the expression of Acanthamoeba mannose-binding protein did not differ between amoebae in monoculture and those in co-culture. Moreover, we observed the activation of matrix metalloproteinases in HCECs after contact with Acanthamoeba.
CONCLUSIONS: This study revealed the involvement of two novel serine proteases in Acanthamoeba pathogenesis and suggests a pivotal role of serine proteases during Acanthamoeba-host cell interaction, contributing to cell adhesion and lysis.

OBJECTIVE: To report first clinical use of novel medical treatment for Acanthamoeba keratitis.
METHODS: Interventional observational case series. Two patients with Acanthamoeba keratitis were unsuccessfully treated with polihexanide (PHMB) 0.02% and propamidine 0.1% for 6 weeks, then all were shifted in a compassionate use of PHMB 0.08% with novel standardized protocol. The postinterventional follow-up of patients was at least 7 months.
RESULTS: PHMB 0.08% eyedrops in a novel standardized protocol improved infection resolution and led to complete healing of the lesion after 4 weeks in the two cases. Corneal opacities and neovascularization decreased slowly, best-corrected visual acuity slightly improved and progressively increased in the further 7 months, and no infection recurrence occurred.
CONCLUSIONS: This preliminary report of two cases shows promising response to polihexanide 0.08% lowering drastically the illness duration, with reduced chance of recurrence, and mostly improving patients\' quality of life.

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening corneal infection caused by the Acanthamoeba parasite. This microorganism is found ubiquitously in the environment, often in freshwater, soil, and other sources of moisture. Despite its low incidence, AK presents significant challenges due to delayed diagnosis and the complex nature of therapeutic management. Early recognition is crucial to prevent severe ocular complications, including corneal ulceration and vision loss. Diagnostic modalities and treatment strategies may vary greatly depending on the clinical manifestation and the available tools. With the growing reported cases of Acanthamoeba keratitis, it is essential for the ophthalmic community to thoroughly understand this condition for its effective management and improved outcomes. This review provides a comprehensive overview of AK, encompassing its epidemiology, risk factors, pathophysiology, clinical manifestations, diagnosis, and treatment.

BACKGROUND: Infectious Keratitis is one of the most common ocular emergencies seen by ophthalmologists. Our aim is to identify the risk factors and clinical features of Acanthamoeba Keratitis (AK).
METHODS: This retrospective chart review study was conducted at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, and included all the microbial keratitis cases, male and female patients of all ages. The main outcome is the differentiation between various microbial keratitis types.
RESULTS: We included 134 consecutive eyes of 126 persons. We had 24 cases of acanthamoeba keratitis, 22 bacterial keratitis, 24 fungal keratitis, 32 herpetic keratitis, and 32 bacterial co-infection. Contact lens wear was found in 33 eyes (24.6%). Among acanthamoeba keratitis patients, 73% were ≤ 39 years of age, and 73% were females (P <0.001). Also, in AK cases, epithelial defect was found in all cases (100%), endothelial plaques were found in 18 eyes (69.2%), 12 cases had radial keratoneuritis (46.2%), and ring infiltrate was found in 53.8% of AK cases.
CONCLUSIONS: We determined the factors that increase the risk of acanthamoeba infection and the clinical characteristics that help distinguish it from other types of microbial keratitis. Our findings suggest that younger females and patients who wear contact lenses are more likely to develop acanthamoeba keratitis. The occurrence of epitheliopathy, ring infiltrate, radial keratoneuritis, and endothelial plaques indicate the possibility of acanthamoeba infection. Promoting education on wearing contact lenses is essential to reduce the risk of acanthamoeba infection, as it is the most significant risk factor for this infection.

This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical features, diagnosis, medical and surgical therapy, as well as outcomes of Acanthamoeba keratitis (AK). AK is a significant cause of ocular morbidity, and early diagnosis with timely institution of appropriate therapy is the key to obtaining good outcomes. The varied presentations result in frequent misdiagnosis, and co-infections can increase the morbidity of the disease. The first line of therapy continues to be biguanides and diamidines, with surgery as a last resort.

Acanthamoeba infection is associated with keratitis in humans; however, its association with keratitis in dogs remains unclear. To investigate this possibility, we collected 171 conjunctival swab samples from dogs with eye-related diseases (65 with keratitis and 106 without keratitis) at Chungbuk National University Veterinary Teaching Hospital, Korea, from August 2021 to September 2022. Polymerase chain reaction identified 9 samples (5.3%) as Acanthamoeba positive; of these, 3 were from dogs with keratitis (4.6%) and 6 were from dogs without keratitis (5.7%). Our results indicated no significant association between Acanthamoeba infection and keratitis, season, sex, or age. All Acanthamoeba organisms found in this study had the genotype T4, according to 18S ribosomal RNA analysis. Acanthamoeba infection in dogs might have only a limited association with keratitis.