RESUMO
BACKGROUND: Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322-5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy. METHODS: This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT. DISCUSSION: We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. TRIAL REGISTRATION: NCT, NCT05110001 , Registered on November 5, 2021.
Assuntos
Ceratite por Acanthamoeba , Infecções Oculares Fúngicas , Fotoquimioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rosa Bengala , Humanos , Rosa Bengala/uso terapêutico , Fotoquimioterapia/métodos , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/diagnóstico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Método Duplo-Cego , Resultado do Tratamento , Acuidade Visual , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Multicêntricos como Assunto , Luz VerdeRESUMO
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.
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Ceratite , Humanos , Ceratite/tratamento farmacológico , Idoso , Fatores de Risco , Envelhecimento , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/terapia , CórneaRESUMO
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.
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Ceratite por Acanthamoeba , Acanthamoeba castellanii , Simulação de Acoplamento Molecular , Extratos Vegetais , Acanthamoeba castellanii/efeitos dos fármacos , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antiprotozoários/farmacologia , Antiprotozoários/química , Trofozoítos/efeitos dos fármacos , Animais , HumanosRESUMO
Although rare, amoebic keratitis (AK) is a disease caused by Acanthamoeba spp. that can lead to blindness. The drugs currently available for its treatment are very toxic, which has motivated the investigation for more effective and safe therapeutic options. In this study, the in vitro activity of ß-caryophyllene (BCP) was exploited taking into account its action against other protozoans as well as its well-known healing and anti-inflammatory properties (aspects relevant for the AK pathogenesis). On the other hand, high volatilization and oxidation phenomena are found for this compound, which led to its incorporation into nanoemulsions (NEs). Two emulsifying agents were tested, resulting in monodisperse systems with reduced droplet size (<265 nm) and high surface charge (positive and negative for NEs prepared with cetrimonium bromide -CTAB and Phosal® 50+, respectively). NEs prepared with CTAB were shown to be more stable after long-term storage at 4 and 25 °C than those prepared with Phosal®. Pure BCP, at the highest concentration (500 µM), resulted in a level of inhibition of Acanthamoeba trophozoites equivalent to that of reference drug (chlorhexidine). This activity was even greater after oil nanoencapsulation. The reduced droplet size could improve the interaction of the oil with the microorganism, justifying this finding. Changes in surface charge did not impact the activity. Positively charged NEs improved the interaction and retention of BCP in the cornea and thus should be prioritized for further studies.
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Ceratite por Acanthamoeba , Emulsões , Sesquiterpenos Policíclicos , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Sesquiterpenos Policíclicos/química , Nanopartículas , Administração Oftálmica , Cetrimônio/química , Animais , Acanthamoeba/efeitos dos fármacos , Estabilidade de Medicamentos , Tamanho da Partícula , Soluções Oftálmicas , HumanosRESUMO
PURPOSE: 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.
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Ceratite por Acanthamoeba , Biguanidas , Adulto , Feminino , Humanos , Masculino , Ceratite por Acanthamoeba/tratamento farmacológico , Antiprotozoários/uso terapêutico , Benzamidinas/uso terapêutico , Biguanidas/uso terapêutico , Soluções Oftálmicas , Acuidade Visual , AdolescenteRESUMO
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.
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Acanthamoeba castellanii , Biguanidas , Ouabaína , Biguanidas/farmacologia , Acanthamoeba castellanii/efeitos dos fármacos , Ouabaína/farmacologia , Ceratite por Acanthamoeba/parasitologia , Ceratite por Acanthamoeba/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Humanos , Sinergismo Farmacológico , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/efeitos dos fármacos , Desinfetantes/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidoresRESUMO
Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening complication of corneal collagen crosslinking (CXL) for keratoconus. In this report, we describe an early adolescent male who underwent routine CXL for progressive keratoconus in his left eye. Preprocedural left visual acuity (VA) was 6/9. At day 5 postprocedure, multifocal corneal infiltrates were identified. Corneal scrape, bandage contact lens cultures and herpetic and Acanthamoeba PCR were negative. In vivo, confocal microscopy (IVCM) identified Acanthamoeba cysts within the corneal stroma. Intensive amoebicidal therapy was initiated, but recovery was complicated by significant inflammation, resulting in widespread aggressive corneal vascularisation necessitating topical steroids and steroid-sparing agents. At 10 months, his left VA was 6/24. This report emphasises the importance of maintaining a high index of suspicion for AK in cases of post-CXL microbial keratitis and highlights the diagnostic value of IVCM, particularly in culture-negative and PCR-negative cases.
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Ceratite por Acanthamoeba , Ceratocone , Microscopia Confocal , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Humanos , Masculino , Ceratocone/tratamento farmacológico , Ceratocone/diagnóstico , Adolescente , Riboflavina/uso terapêutico , Colágeno , Fármacos Fotossensibilizantes/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Acuidade Visual , Córnea/parasitologia , Córnea/patologia , Acanthamoeba/isolamento & purificação , Substância Própria/patologia , Substância Própria/parasitologiaAssuntos
Ceratite por Acanthamoeba , Fosforilcolina , Voriconazol , Humanos , Ceratite por Acanthamoeba/tratamento farmacológico , Administração Tópica , Antifúngicos/uso terapêutico , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Quimioterapia Combinada , Fosforilcolina/análogos & derivados , Fosforilcolina/administração & dosagem , Fosforilcolina/uso terapêutico , Resultado do Tratamento , Voriconazol/administração & dosagem , Voriconazol/uso terapêutico , Pessoa de Meia-IdadeRESUMO
PURPOSE: To compare the outcomes of big-bubble deep anterior lamellar keratoplasty (BB-DALK) and penetrating keratoplasty (PKP) in the management of medically unresponsive Acanthamoeba keratitis (AK). METHODS: This retrospective study included 27 eyes of BB-DALK and 24 eyes of PKP from a tertiary ophthalmology care centre. Glucocorticoid eye drops were subsequently added to the treatment plan 2 months postoperatively based on the evaluation using confocal laser scanning microscopy. The clinical presentations, best-corrected visual acuity (BCVA), postoperative refractive outcomes, graft survival, and Acanthamoeba recurrence were analyzed. RESULTS: The AK patients included in the study were in stage 2 or stage 3, and the percentage of patients in stage 3 was higher in the PKP group (P = 0.003). Clinical presentations were mainly corneal ulcers and ring infiltrates, and endothelial plaques, hypopyon, uveitis and glaucoma were more common in the PKP group (P = 0.007). The BCVA and the graft survival rate showed no statistically significant differences between the two groups at 1 year after surgery. However, 3 years postoperatively, the BCVA of 0.71 ± 0.64 logMAR, the graft survival rate of 89.5%, and the endothelial cell density of 1899 ± 125 cells per square millimeter in the BB-DALK group were significantly better than those of the PKP group (P = 0.010, 0.046, and 0.032, respectively). 3 eyes (11.1%) in the BB-DALK group and 2 eyes (8.3%) in the PKP group experienced Acanthamoeba recurrence, but the rates showed no statistically significant difference between the two groups (P = 1.000). In the PKP group, immune rejection and elevated intraocular pressure were observed in 5 and 6 eyes, respectively. CONCLUSION: Corneal transplantation is recommended for AK patients unresponsive to antiamoebic agents. The visual acuity and graft survival can be maintained after BB-DALK surgery. Acanthamoeba recurrence is not related to the surgical approach performed, whereas complete dissection of the infected corneal stroma and delayed prescribing of glucocorticoid eye drops were important to prevent recurrence.
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Ceratite por Acanthamoeba , Transplante de Córnea , Glaucoma , Humanos , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/cirurgia , Ceratoplastia Penetrante , Glucocorticoides , Estudos Retrospectivos , Soluções OftálmicasRESUMO
PURPOSE: The aim of this study was to describe 3 cases of recalcitrant Acanthamoeba keratitis (AK) that were successfully treated using in vivo corneal confocal microscopy (IVCM) to guide excimer laser ablation depth with adjunctive mitomycin C 0.02%. METHODS: Three patients diagnosed with AK did not respond to several weeks of intensive topical therapy with antiamoebic agents. The patient underwent phototherapeutic keratectomy with topical mitomycin C 0.02% application. The maximum stromal depth of cysts measured by IVCM was 80 µm, 100 µm, and 240 µm, and the stromal ablation depths were 80 µm, 100 µm, and 100 µm, respectively. RESULTS: In all 3 eyes, AK resolved after a single excimer laser application, and topical treatment was gradually discontinued within 6 weeks afterward. In 1 eye, penetrating corneal transplantation was performed 6 weeks after phototherapeutic keratectomy because of ongoing severe corneal pain. IVCM and histology of the corneal transplant did not reveal any Acanthamoeba cysts within the excised corneal button. No recurrence was observed during the follow-up period of 19 to 34 months. CONCLUSIONS: IVCM-guided phototherapeutic keratectomy with mitomycin C 0.02% seems to be a safe and successful approach for the treatment of AK, especially in cases of resistance to topical treatment. Corneal IVCM should be performed before laser application to measure cyst depth, determine ablation depth, and assess postoperative treatment success.
Assuntos
Ceratite por Acanthamoeba , Ceratectomia Fotorrefrativa , Humanos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/cirurgia , Mitomicina/uso terapêutico , Lasers de Excimer/uso terapêutico , Córnea/patologia , Microscopia ConfocalRESUMO
PURPOSE: To report clinical findings and prognostic factors for visual and morphological outcomes in patients with Acanthamoeba keratitis (AK). METHODS: Single-center, retrospective, longitudinal study of 51 cases of AK diagnosed by real-time polymerase chain reaction (RT-PCR) between March 2010 and October 2022. The primary outcome was the final best corrected visual acuity (BCVA). Poor visual outcome was defined as a final BCVA ≥ 1 logMAR unit, while good visual outcome was defined as a final BCVA < 1 logMAR unit. Eyes from these two groups were compared, regarding demographic and initial clinical variables, anti-Acanthamoeba treatment used, and complications of the disease. Early diagnosis was defined as ≤ 14 days from symptom onset to diagnostic confirmation and initiation of Acanthamoeba medical treatment. Multivariable logistic regression was used to determine predictors of poor visual outcome. RESULTS: A total of 51 eyes from 46 patients diagnosed with AK, all contact lens (CL) wearers, were included in this study. Average follow-up was 39.0 ± 30.2 [total range 14-120] months. Thirty-one eyes (60.8 %) presented good visual outcome, with a lower baseline age (30.5 ± 9.0 vs. 42.3 ± 15.8; p = 0.020), better initial BCVA (0.8 ± 0.7 logMAR units vs. 1.3 ± 0.9 logMAR units; p = 0.047), higher rate of early diagnosis (45.2 % vs. 5.6 %; p = 0.004), and higher rate of therapeutic epithelial debridement (64.5 % vs. 10 %; p < 0.001). 20 eyes (39.2 %) presented poor visual outcome, with 12 eyes undergoing evisceration/enucleation (23.5 %). These 20 eyes presented a higher rate of complications (90 % vs. 61.3 %; p = 0.031). In multivariable analysis, early diagnosis of AK (OR 19.78; 95 % CI 2.07-189.11; p = 0.010) and therapeutic epithelial debridement (OR 19.02; 95 % CI 3.27-110.57; p = 0.001) were associated with a good visual outcome. CONCLUSIONS: In the present study, poor visual outcome was present in 39 % of affected eyes. Early AK diagnosis (≤14 days from symptom onset) and therapeutic epithelial debridement were associated with good final visual outcome.
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Ceratite por Acanthamoeba , Acanthamoeba , Humanos , Ceratite por Acanthamoeba/terapia , Ceratite por Acanthamoeba/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Estudos Longitudinais , Fatores de RiscoRESUMO
PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Ceratite por Acanthamoeba , Benzamidinas , Biguanidas , Humanos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Produção de Droga sem Interesse Comercial , Estudos ProspectivosRESUMO
PURPOSE: To summarize the evidence base on the use of topical corticosteroids for infectious keratitis. METHODS: Narrative review. RESULTS: Infectious keratitis is a painful condition that often results in visually significant corneal stromal scarring, even when antimicrobial therapy is successful. Corticosteroids may reduce inflammation and subsequent scar formation and while relieving the acute ocular pain associated with a corneal ulcer. However, corticosteroids also reduce the host immune response, which could hinder the ability to clear infection. The safety and effectiveness of corticosteroids depends to a large part on the efficacy of the antimicrobials being used to treat the underlying infection. Randomized trials have found that corticosteroids are safe and effective for herpetic keratitis when used with appropriate antiviral therapy, and are safe for bacterial keratitis when used with broad spectrum topical antibiotics. The effectiveness of corticosteroids for bacterial keratitis has not been shown conclusively, although more advanced bacterial corneal ulcers may do better with corticosteroids. No randomized trials have assessed the safety and effectiveness of steroids for fungal or acanthamoeba keratitis. Animal studies suggest corticosteroids may be harmful in fungal keratitis, and observational human studies have found that steroids are harmful for fungal and acanthamoeba keratitis when started prior to anti-amoebics. CONCLUSIONS: Topical corticosteroids, when used as an adjunct to antimicrobial therapy, may be beneficial if the antimicrobial being used can effectively clear or suppress the infection, such as in bacterial and herpetic keratitis. Randomized trials would be helpful to further delineate the role of corticosteroids for infectious keratitis.
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Ceratite por Acanthamoeba , Úlcera da Córnea , Infecções Oculares Bacterianas , Ceratite Herpética , Humanos , Ceratite por Acanthamoeba/tratamento farmacológico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Ceratite Herpética/tratamento farmacológico , Corticosteroides , Glucocorticoides/uso terapêutico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Esteroides , Antibacterianos/uso terapêuticoRESUMO
ABSTRACT: A 42-year-old female contact lens wearer presented to a local emergency department with a 3-day history of decreased vision and ocular discomfort in her right eye. She was started on topical fluorometholone and oral acyclovir with initial diagnosis of herpes simplex keratitis. After 3 weeks of worsening symptoms, she was diagnosed with bacterial corneal ulcer and treated with levofloxacin eye drops every 2 hr. After 14 days of no improvement, she was referred to our clinic for further workup. Slitlamp examination demonstrated a solitary dense 3×3-mm infiltration involving anterior and central corneal stroma. The overlying epithelium was intact, and there was no subepithelial infiltration, radial perineuritis, keratic precipitates, or anterior chamber reaction. Corneal sensation was normal. Confocal microscopy and corneal biopsy were definitive for Acanthamoeba infection. The patient received polyhexamethylene biguanide 0.02% every 2 hr and oral ketoconazole 200 mg twice a day, which resulted in improvement in her signs and symptoms within 10 days. The medications were gradually tapered off over 5 months per clinical response. At the 9-month follow-up visit, the best-corrected visual acuity was 5/10 with a superficial central stromal scar at slitlamp examination. Acanthamoeba infection should be considered in contact lens wearers who present with intrastromal corneal abscess.
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Ceratite por Acanthamoeba , Amebíase , Lentes de Contato Hidrofílicas , Humanos , Feminino , Adulto , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/etiologia , Abscesso/complicações , Abscesso/patologia , Lentes de Contato Hidrofílicas/efeitos adversos , Córnea/patologia , Amebíase/complicações , Amebíase/patologiaRESUMO
Acanthamoeba keratitis (AK) is an eye disease often occurring in contact lens wearers. AK treatment is prolonged and requires multiple drugs, which can lead to adverse effects. Our study aimed to compare the in vitro activities and safety of Miltefosine with that of conventional antimicrobial agents used to treat AK. Acanthamoeba castellanii genotype T4 was obtained from a patient with keratitis and subjected to in vitro susceptibility testing with various antimicrobial agents, including Chlorhexidine (CHX), Pentamidine isethionate (PI)Polyhexamethylene biguanide (PHMB), and Miltefosine to assess their efficacy against Acanthamoeba trophozoites and cyst. The cytotoxicity of the agents was evaluated in Vero cells, and their selectivity indexes (SI) were calculated. Chlorhexidine exhibited the highest amoebicidal activity with the highest selectivity index against the trophozoite and cyst, ranging from 1.17 to 8.35. The selectivity index of PHMB is slightly comparable to Chlorhexidine, exhibiting significant anti-Acanthamoeba activity. On the other hand, Pentamidine isethionate and Miltefosine displayed low SI among the compounds. Pentamidine isethionate was effective at high concentrations, which was toxic. Miltefosine exhibited the lowest cytotoxicity; nevertheless, due to the lowest anti-Acanthamoeba activity presented a low selectivity against the parasite. Further studies on more clinical samples and prolonged incubation time should be done to investigate the effectiveness and toxicity of drugs in both in vitro and in vivo conditions.
Assuntos
Ceratite por Acanthamoeba , Acanthamoeba , Anti-Infecciosos , Cistos , Chlorocebus aethiops , Animais , Humanos , Clorexidina/farmacologia , Trofozoítos , Pentamidina , Células Vero , Ceratite por Acanthamoeba/tratamento farmacológicoRESUMO
PURPOSE: The purpose of this study was to describe the management of a case of recurrent scleritis and Acanthamoeba -positive scleral abscess in a patient after the use of miltefosine for recalcitrant Acanthamoeba keratitis. METHODS: This is a case study. RESULTS: In this study, we report a case of advanced Acanthamoeba keratitis with resultant corneal perforation with therapeutic keratoplasty and associated scleritis who later developed a scleral abscess after treatment with oral miltefosine. The scleral abscess was positive for Acanthamoeba cysts and trophozoites, and after treatment for an additional several months, the patient had complete resolution of her disease. CONCLUSIONS: Acanthamoeba scleritis is a rare complication associated with Acanthamoeba keratitis. It has traditionally been treated as an immune reaction and associated inflammation, especially with the use of miltefosine. Management can require a multitude of different approaches, and in this situation, it has been demonstrated that scleritis can be infectious and that conservative management can be effective.
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Ceratite por Acanthamoeba , Acanthamoeba , Doenças da Esclera , Esclerite , Humanos , Feminino , Ceratite por Acanthamoeba/tratamento farmacológico , Esclerite/complicações , AbscessoRESUMO
OBJECTIVE: To examine the microbial distribution and antimicrobial susceptibility of culture-positive microbial keratitis at a large tertiary referral center in the mid-Atlantic region of the United States. METHODS: Retrospective review of culture-positive microbial keratitis cases at the Wilmer Eye Institute from 2016 through 2020. RESULTS: Of the 474 culture-positive microbial keratitis cases, most were bacterial (N=450, 94.9%), followed by fungal (N=48, 10.1%) and Acanthamoeba keratitis (N=15, 3.1%). Of the 450 bacterial isolates, 284 (69.5%) were gram-positive organisms, whereas 157 (28.4%) were gram-negative organisms. The most common bacterial species isolated was coagulase-negative Staphylococcus spp (N=154, 24.8%), and the most common gram-negative isolate was Pseudomonas aeruginosa (N=76, 12.3%). Among fungi, the most common isolates were Candida (N=25, 45.4%), whereas Fusarium (N=6, 10.9%) and Aspergillus (N=3, 5.5%) were less common. Of the 217 bacterial isolates tested for erythromycin susceptibility, 121 (55.7%; â¼60% of coagulase-negative staphylococci and corynebacteria tested) showed resistance to erythromycin. CONCLUSIONS: Microbial keratitis in the Baltimore Mid-Atlantic region of the United States is most commonly caused by bacteria, with fungi and acanthamoeba being less common. Gram-positive bacterial infections predominate. Among fungal keratitis cases, Candida species are more commonly encountered than are filamentous species. Use of erythromycin as infection prophylaxis should be reexamined. Findings from our study may guide empiric treatment in this geographic region.
Assuntos
Ceratite por Acanthamoeba , Infecções Oculares Bacterianas , Humanos , Coagulase/uso terapêutico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Bactérias , Staphylococcus , Mid-Atlantic Region , Ceratite por Acanthamoeba/tratamento farmacológico , Estudos Retrospectivos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Eritromicina/uso terapêutico , Testes de Sensibilidade MicrobianaRESUMO
Acanthamoeba spp. are pathogens that cause Acanthamoeba keratitis (AK), a serious cornea inflammation that can lead to gradual loss of vision, permanent blindness, and keratoplasty. The efficacy of AK treatment depends on the drug's ability to reach the target tissue by escaping the protective eye barrier. No single drug can eradicate the living forms of the amoeba and be non-toxic to the cornea tissue. The treatment aims to eradicate both forms of protozoan life but is hampered by the resistance of the cysts to the most available drugs, leading to prolonged infection and relapses. Drug therapy is currently performed mainly using diamidines and biguanides, as they are more effective against cysts. However, they are cytotoxic to corneal cells. Drugs are applied topically, and hourly. Over time, the frequency of administration decreases, but the treatment time varies from month to years. This study aims to obtain an up-to-date summary of the literature since 2010, allowing us to identify the trends and gaps and address future research involving new alternatives for treating AK. The results were divided into three phases, pre-treatment, empirical treatment, and the treatment after diagnosis confirmation. The drugs prescribed were stratified into antiamoebic, antibiotic, antifungal, antivirals, and steroids. It was possible to observe the transition in drug prescription during three different stages until the diagnosis was confirmed. There were more indications for antibiotic, antifungal, and antiviral drugs in the early stages of the disease. The antiamoebic drugs were only prescribed after exhausting other treatments. This can be directly involved in developing complications and no responsiveness to medical treatment.
Assuntos
Ceratite por Acanthamoeba , Acanthamoeba , Humanos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Antifúngicos/uso terapêutico , Córnea , Antibacterianos/uso terapêuticoRESUMO
As the number of contact lens users increases, contact lens induced corneal infection is becoming more common. Acanthamoeba keratitis (AK) is a type of those which is caused by Acanthamoeba species, and may cause severe ocular inflammation and visual loss. We evaluated whether Torreya nucifera (T. nucifera) extract has an anti-amoebic effect and studied its mechanism of action on Acanthamoeba lugdunensis (A. lugdunensis). Cell viability was tested using the alamarBlue™ method, and the cell death mechanism was confirmed using the Tali® Apoptosis Kit. The SYTOX® Green assay was performed to check the plasma membrane permeability. The JC-1 dye was used to measure the mitochondrial membrane potential. A CellTiter-Glo® Luminescent Assay was used to measure the adenosine-triphosphate (ATP) level. Morphological changes in the mitochondria were examined by transmission electron microscopy (TEM). Cystic changes and a decrease in cell viability after treatment with T. nucifera were observed. Both apoptotic and necrotic cells were found in the Tali® Apoptosis assay. There was no significant difference in plasma membrane permeability between the control and T. nucifera treated groups. The collapse of the mitochondrial membrane potential and reduced ATP level in A. lugdunensis was confirmed in the groups treated with T. nucifera. Structural damage to the mitochondria was observed on TEM in the groups treated with T. nucifera. T. nucifera showed an anti-amoebic effect on A. lugdunensis, by inducing the loss of mitochondrial membrane potential. Thus, it could be a future therapeutic agent for AK.